Reading: win8.1 System Version Activation Key win8 Professional Edition Activation Code win8.1 System Version Activation Key win8 Professional Edition Activation Code

  Now it is said that the market share of that windows8 system has risen the fastest, and that it is the win8 system. More and more people install win8 system after being recognized by the market. However, because the time for free upgrade of win8 has passed, many people have not activated the system after installing it. Many functions of the system without activation cannot be used. In order to solve this problem, Xiaobian collected activation codes of various versions of win8 system for everyone to use. With activation code tutorial.

  I. How to use the activation code, taking win8 Professional Edition as an example:

  1. Press Win +X at the same time, and then select the command prompt (Administrator).

  2. Enter in turn at the command prompt:

  Slmgr.vbs /upk (at this time, the pop-up window shows "Product key successfully uninstalled")

  Slmgr/ipkw269n-wfgwx-yvc9b-4j6c9-T83gx (pop-up window prompts: "Product key successfully installed")

  Slmgr /skms zh.us.to (pop-up window prompts: "The computer name of key management service is successfully set to zh.us.to")

  Slmgr /ato (pop-up window prompts: "Product successfully activated")

  Second, the activation keys of each version of win8

  Professional Edition: W269N-WFGWX-YVC9B-4J6C9-T83GX

  Education Edition: NW6C2-QMPWW-D7KKK-3KGT6-VCFB2

  Professional edition n: mh37w-n47xk-v7xm9-c7227-gcqg9

  Enterprise edition n: dph2v-ttnvb-4x9q3-tjr4h-khjw4

  Education edition n: 2wh4n-8qgbv-h22jp-ct43q-mdwwj

  Enterprise edition: NPPR9-FWDCX-D2C8J-H872K-2YT43

  Home Edition: TX9XD-98N7V-6WMQ6-BX7FG-H8Q99

  Enterprise version lstb: wnmtr-4c88c-jk8yv-hq7t2-76df9

  Enterprise version lstb n: 2f77b-tnfgy-69f-b8ykp-d69tj

  The above is how to use the activation keys and keys of each version of win8. Friends who need to activate can refer to this tutorial for operation.

Online payment real-name registration system’s single-day and annual transaction volume will be restricted from now on.

  BEIJING, Beijing, July 1 (Qiu Yu) On the 1 ST, the Measures for the Administration of Online Payment Services of Non-bank Payment Institutions (hereinafter referred to as the Measures) came into effect, and payment institutions will implement real-name management for customers. After the implementation of the new regulations, when users use Alipay balance and WeChat change to conduct transactions, the single-day and annual transaction amount will be restricted.

  What is real-name authentication?

  You can’t transfer money and send and receive red envelopes without authentication.

  Ms. Tian recently tried to transfer money to her son through Alipay, but she failed because "real name authentication has not been carried out". She successfully completed the transfer after uploading photos of her ID card.

  According to the Measures, payment institutions should implement real-name management of customers, register and take effective measures to verify the basic information of customers’ identities, check valid identity documents as required and keep copies or photocopies of valid identity documents.

  Without real-name authentication, the user experience will be affected. Alipay said that it will not be able to receive red envelopes, rewards, transfers, etc. from others without real-name authentication. According to the WeChat payment team, if the user does not have a real name, functions such as collecting money and using change to send red envelopes may be restricted.

  Real-name accounts account for about half of personal accounts for online payment. According to China Payment and Clearing Industry Operation Report (2016), by the end of 2015, there were 2.630 billion personal payment accounts opened by non-bank payment institutions, and 1.346 billion payment accounts had completed real-name authentication, accounting for 51.07%.

  What are the ways of real-name authentication?

  Many external authentication channels do not need to open a "I am me" certificate.

  The "Measures" stipulate that in real-name authentication, users need to verify their basic identity information through external channels.

  A related person from the public relations department of Ant Financial told the reporter of Zhongxin.com (WeChat WeChat official account: cns2012) that there are many external channels used by Alipay to verify identity, such as uploading ID cards and binding bank cards; Pay water, electricity, gas and cable TV fees in Alipay; Buy insurance in Alipay; Open sesame credit and so on.

  The relevant person in charge of the central bank said earlier that in the process of identity verification, customers only need to fill in and upload relevant information online according to the requirements of payment institutions, and do not need to go to relevant departments to prove that "I am me".

  What kind of account do you belong to?

  Associating the mobile phone number with the bank card and paying the electricity fee can improve the account authority.

  The Measures divide individual payment accounts of non-bank payment institutions into three categories, and manage the balance payment transaction amount separately.

  Specifically, Class I accounts are the most restricted, and the balance payment transactions have not exceeded 1000 yuan since the account was opened; The annual accumulative payment transaction of the balance of Class II account shall not exceed 100,000 yuan; The annual accumulative payment transaction of the balance of Class III account shall not exceed 200,000 yuan.

  Among them, the limit of Class II and Class III accounts does not include the transfer from the payment account to the customer’s own bank account with the same name, and Class I accounts include.

  The classification is based on the number of external channels in real-name authentication. If the face-to-face method is adopted, the external channels required for the above three types of accounts are one, three and five respectively.

  For example, if you upload an ID card to a payment account, associate a real-name mobile phone number, bind a bank card, buy a train ticket, and pay the electricity bill, even if there are five external channels, it belongs to a Class III account. If two bank cards of different banks are bound, it is considered as two external channels.

  What if the balance payment amount is not enough?

  200,000 yuan/year is a hard rule, and the quota cannot be increased after it is used up.

  The reporter noticed that the Alipay client has hung up the prompt of "current balance payment amount". For example, the Class III account will display "existing amount of 200,000 yuan/year" and the remaining amount.

  What if the annual quota of 100,000 or even 200,000 yuan is not enough? In this regard, Alipay said that if the balance payment amount of Class I and Class II accounts exceeds the limit, it can continue to increase the amount by improving the identity information; If the balance payment amount is already 200,000 yuan/year, it will be impossible to continue to increase the amount.

  The relevant person in charge of the central bank said that after statistical analysis, the annual accumulated limit of 100,000 yuan and 200,000 yuan for Class II and III personal payment accounts can meet the needs of most customers to use the "balance" of payment accounts for payment.

  What should I do if the single-day balance transaction is excessive?

  Can be combined with payment tools such as bank cards.

  The Measures set a limit for one-day transactions. For transactions verified by payment institutions with two or more effective elements, excluding digital certificates and electronic signatures, the cumulative amount of all payment accounts of a single customer in a single day should not exceed 5,000 yuan (excluding the transfer from the payment account to the customer’s own bank account with the same name).

  If you use Alipay to buy goods with a price of 7,000 yuan online, because it exceeds 5,000 yuan, you can’t pay with the balance of Alipay. How should users pay? According to the explanation of Alipay client, transfer, consumption and wealth management through other payment methods such as bank card express payment, online banking and ant flower garden are not subject to this quota.

  Similarly, if you transfer money to someone else’s account, more than 5000 yuan, you can’t transfer money with Alipay balance, but there is no restriction on fast payment by bank card.

  Will personal information be leaked?

  Payment institutions shall not store sensitive customer information.

  Some users are worried that real-name authentication will reveal too much personal information and there are security risks. In this regard, the public relations department of Ant Group said that after the identity information is more perfect, users can not only enjoy more comprehensive services, but also improve the security level of accounts and better protect their rights and interests.

  Li Jiquan, a senior partner and lawyer of Beijing Junbang Law Firm, said in an interview that after real-name authentication, it means that everyone who makes online payment is transparent, and everyone’s traces are traceable, which will help to trace after problems appear, but will increase the security of online transactions.

  The relevant person in charge of the central bank pointed out earlier that in terms of information security, the Measures require payment institutions to formulate customer information protection measures and risk control mechanisms to ensure that they and special merchants do not store sensitive customer information, and bear the losses and responsibilities caused by information disclosure according to law.

New consumption observation | reshaping the market structure, "striving for progress" in the change of high-end women’s wear

Source: PEACEBIRD Taiping Bird Women’s Dress Weibo

How long has it been since you bought clothes at the mall?

Recently, a topic # I dare not buy clothes in the mall with a monthly salary of 20,000 # rushed to Weibo for hot search. The problem that fewer and fewer people buy clothes in shopping malls and stores has aroused public concern.

People are not only discussing the reasons for this phenomenon, but also wondering, are those high-end clothing stores in shopping malls, especially those women’s clothing brands that have led the trend of the times, still doing well after being closed and closed down?

It is worth noting that recently, a number of high-end fashion apparel groups in China disclosed their 2023 financial reports. From the data point of view, the revenue and net profit of several mainstream brands achieved double growth, and their performance was improving.

At the same time, the slow growth of net profit has also exposed many problems, such as the loss of young consumer groups, serious product homogeneity, high-end mass clothing and accelerated competition, and high-end women’s wear brands have entered a new stage that needs to be transformed urgently.

The pressure of good performance, "hard to hide"

There is basically a fashion group behind the common brand stores that consumers visit in shopping malls.

Domestic mainstream mid-to high-end women’s wear groups, such as Langzi (with LANCY FROM25, LIME FLARE, etc.), Gelisi (with ELLASSAY, Laurèl, etc.), Winner Fashion (with La Koradior, CADIDL, etc.) and Local Fashion (with DAZZLE, DIAMOND DAZZLE, etc.). In addition, there are VGRASS parent company Jinhong Group, JNBY women’s parent company Jiangnan Buyi, and PEACEBIRD women’s parent company Taiping Bird.

Combing the financial report data of these companies in 2023, we will find that "year-on-year growth" is almost the same keyword.

Specifically, in 2023, Langzi’s revenue was 5.145 billion yuan, a year-on-year increase of 24.41%, and its net profit was 225 million yuan, a year-on-year increase of 953.37%; Winner’s fashion revenue was 6.912 billion yuan, a year-on-year increase of 22.1%, and net profit was 838 million yuan, a year-on-year increase of 119.2%; Gelisi’s operating income was 2.915 billion yuan, up 21.73% year on year, and its net profit was 106 million yuan, up 41.7% year on year …

At the same time, the brands under the group also performed well. Among them, the winners, Koradior, NAERSI and NEXY.CO, all earned more than 1 billion yuan, which were 2.387 billion yuan, 1.464 billion yuan and 1.004 billion yuan respectively.

With the improvement of domestic consumption environment and the return of offline passenger flow, high-end women’s brand stores have gradually stepped out of the "cold winter period" and ushered in a small "warm sun". However, it should be noted that behind the growth is the performance under pressure.

Judging from the growth base, the "starting line" of the group’s performance is the "trough period" in 2022, and the profitability of many brands has not returned to the state before the epidemic.

From the business sector, the growth of women’s clothing sector is weak and obvious. In 2023, the most representative of Langzi Co., Ltd., the medical beauty business sector of the group achieved an operating income of 2.127 billion yuan, surpassing the original main business of women’s clothing for the first time.

Source: Langzi shares LANCY Weibo

The demand is more yuan, the scenes are richer, and the exquisite white-collar workers have changed their minds.

In the 1990s, high-end women’s wear brands such as MORELINE, Brother, JNBY and DAZZLE sprouted and developed in the tide of international clothing brands entering China, and attracted the attention of a large number of urban beauties, white-collar workers and exquisite women with their classic collocation and boutique positioning.

As far as mass clothing is concerned, high-end women’s wear is far ahead in terms of brand awareness and market influence, forming a high industry barrier. But in recent years, the business problems of these brands have become more and more obvious.

Internally, many people still have the same impression of the brand, such as slim suits, lightly cooked long skirts and three-dimensional shirts … After the new Chinese style, cool style and BM spice girl style set off wave after wave of fashion trends, this unified and orderly "temperament" will be labeled as "old-fashioned".

Externally, fast fashion brands represented by Uniqlo, ZARA, UR and Hot Air have diverted consumers with their high cost performance, high innovation rate and fashionable style. In order to withdraw funds, Chanel and Dior high-end international clothing brands that began to sell at a discount, as well as mass clothing brands that have turned to high-end products, are dividing their market share.

The reason is that the market has changed and the audience has changed.

Xu Lizhao, head of the Shopex market, pointed out that as the core consumer group of high-end women’s wear, elite women have more diverse roles in the workplace, and their demand for clothing is more diverse, and they are considerate and comfortable while being fashionable and casual. Some younger elite women want to make professional clothes more sweet and romantic.

In addition, outdoor sports and tourism and fitness fever have driven clothing to "grow into a new scene", and clothing brands such as Archaeopteryx, Disante, Beifang, Angpao, lululemon and Jiaoxia Outdoor have led the new trend and become the "bright spot" of the whole high-end clothing industry.

From the perspective of the consumer market, he said that in the era of "the ratio of heart to price is greater than cost performance", "emotional value" has become a hot spot to promote women’s consumption, such as the popularity of "dopamine wearing". Focusing on the demand of female groups for "emotional value", clothing brands are also actively solving problems.

Let young people fall in love with "class flavor" and find a breakthrough from diversification.

When any brand develops to a certain stage, it needs to make corresponding adjustments in product design, marketing strategy and service characteristics according to market changes, even high-end women’s wear with sufficient resources is not included.

Recently, in Little Red Book, Brother, a high-end Taiwan, China women’s clothing brand, became popular. A brand that was once labeled as "wearing within the system" made many young people lament that it was "both earthy and expensive".

The reason for turning red is very simple. The combination of "full of class flavor" forced young women who entered the workplace to buy a set, and later found that brother had good quality and service. Looking back at the popularity of my brother, it is not just that consumers are "old".

The younger brother who started off the line set up the live broadcast matrix such as Tik Tok live broadcast room, video number live broadcast room, Taobao live broadcast room and Aauto Quicker live broadcast room very early, which strengthened the ability of online operation and sales. At the same time, in terms of products, Brother has obvious cultural characteristics and collocation style, which meets the requirements of consumers for the tonality of high-end brands. The brand has a good reputation and customers are willing to pay for the high premium.

"Most mid-to-high-end women’s wear brands mainly sell offline stores, and the target consumers usually need to try them on and feel the material and design." Xu Lizhao said that brands need to provide better customer service and deepen emotional communication.

At the same time, he also pointed out that WeChat applet mall, short video official account, Tik Tok account and Xiaohongshu account have become the necessary infrastructure for middle and high-end clothing brands to face consumers, and brands have more channels and contacts to carry out DTC business in order to obtain more direct decision-making data for consumers.

In addition to brothers, high-end women’s fashion groups have also undergone brand transformation.

Gelisi began to expand its categories, and made great efforts to develop luxury brands, forming a brand matrix with many attributes such as fashion, trendy brand, luxury and online celebrity. Similarly, Winner Fashion said that it will start to prepare a new brand in 2024, which will "meet the cross-scene clothing needs of high-net-worth people for sports, leisure and business commuting".

In addition, at the marketing level, Xu Lizhao introduced that some brands began to directly compare with international luxury brands, dig deep into brand-specific DNA, and penetrate brand stories into all dimensions from products, visual communication, marketing and retail terminals.

For example, he said that when Hermes Orange and Tiffany Blue became classic cases in the luxury goods industry, the high-end women’s brand Koradior took rose red as the brand’s exclusive color, and then cooperated with innovative roses to meet the design, inviting sweet stars from Europe and America to speak. This marketing method has made it a hot and well-recognized high-end women’s clothing brand in China.

"The top high-end women’s wear brands still have some room for market growth. Brands need to keep up with market changes, gain insight into the needs of target customers, and conduct flexible product design to meet the diversified product needs of women in different roles in different scenarios. " Xu Lizhao concluded. (Text/Ji Xiaoling)

National Health Commission: Five emergency medical teams in China have been certified by WHO.

Cctv newsOn the morning of September 9, the National Health and Wellness Commission held a press conference to introduce the progress and effectiveness of international cooperation and exchange on health and wellness since the 18th National Congress of the Communist Party of China. It was introduced at the meeting that in the past ten years, China has actively participated in international organizations and regional cooperation mechanisms in the field of health and shared China’s experience. Actively participate in and host international conferences at ministerial level and above, and successfully co-host the 9th Global Health Promotion Conference with WHO in 2016; At the World Health Assembly, he promoted and passed many resolutions such as safe medication for children and traditional medicine, and took the lead in holding side events on health system, health and poverty alleviation; Five emergency medical teams in China have been certified by WHO; Successfully passed the WHO malaria elimination certification, and China’s malaria prevention and control experience was included in the WHO technical guide; Traditional medicine has been formally incorporated into the latest International Classification of Diseases, which provides a Chinese plan for promoting global health.

From 2014 to 2015, China sent more than 1,200 clinical and public health experts to fully assist countries in West Africa to control the Ebola epidemic and successfully achieve the goal of "winning the battle and zero infection". Since the outbreak of the COVID-19 epidemic, China has maintained close communication with WHO and relevant countries and regions, shared information such as Covid-19’s gene sequence as soon as possible, announced the diagnosis and treatment plan and prevention and control plan as soon as possible, promptly and openly reported the epidemic information, held technical exchange activities with more than 180 countries and more than 10 international organizations around the world, sent anti-epidemic medical experts to 34 countries, and shared China’s experience in fighting the epidemic with all parties without reservation. Over the past decade, we have carried out pragmatic cooperation with countries and international organizations around the world, and carried out pragmatic cooperation projects such as joint prevention and control of malaria and dengue fever and maternal and child health in neighboring countries. Over the past ten years, we have continuously sent China medical team members to countries in need to provide assistance, cooperated with 46 hospitals in 41 countries in Africa, and conducted free clinics for cataract recovery and heart surgery in more than 30 countries, treating 22 million patients and saving countless lives. More than 2,000 medical team members have won national honors at home and abroad. In addition, we also support Hong Kong and Macao to integrate into the overall situation of national health and healthy development, actively implement various policies of benefiting Taiwan in the field of health and health, and work together with Hong Kong, Macao and Taiwan to fight the COVID-19 epidemic and protect the health and well-being of all people.

Master Han Meilin: A Hard Journey of Art Achieves a Beautiful Life.

  He presided over the design of the emblem and mascot "Fuwa" of the 2008 Beijing Olympic Games, and people affectionately called him "the father of Fuwa".

  He was awarded the title of "Artist of Peace" by UNESCO, "Coubertin Award" by the International Olympic Committee, "Cultural Medal of the President of Korea" and "Honorary Academician" by the University of Venice.

  He has four personal art galleries in Hangzhou, Beijing, Yinchuan and Yixing, and his works involve painting, calligraphy, sculpture, ceramics, design and many other aspects, and all thousands of works have been donated to the country for future generations to study.

  His achievements in painting, calligraphy, sculpture, ceramics and other artistic fields have attracted worldwide attention. He is called "China’s Picasso" because of his wide cross-border, profound artistic attainments, distinctive personality and great social influence, but he claims to be "the successor of grandma in northern Shaanxi".

  He is Mr. Han Meilin, a UNESCO peace artist, a senior professor of liberal arts in Tsinghua University and a professor at Tsinghua University Academy of Fine Arts.

Han Meilin

  Born in Jinan, Shandong, China in 1936. In 1955, he was admitted to the Central Academy of Fine Arts (in 1956, he became the first student of the Central Academy of Arts and Crafts with the adjustment of departments). He is currently a senior professor of liberal arts in Tsinghua University, a librarian in central research institute of culture and history, honorary director of ceramic art committee of China Artists Association, vice president of World Chinese Association and honorary president of China Arts and Crafts Association.

  In recent years, "Han Meilin Art Museum" has been established in Hangzhou, Beijing and Yinchuan, and "Han Meilin Zisha Art Museum" has been established in Yixing, actively promoting social aesthetic education and international cultural exchanges. Establish "Han Meilin Art Foundation" and devote yourself to artistic public welfare and social charity. In 2015, he was awarded the title of "Peace Artist" by UNESCO. 2016 "The World of Merrill Lynch • Han Meilin’s Global Tour was launched, and he held solo exhibitions in Venice, Beijing, Paris, Liechtenstein, Seoul and Bangkok, and was awarded the title of "Honorary Academician" by the University of Venice. In 2018, he won the "Coubertin" Medal and the "Korean Cultural Medal" of the International Olympic Committee. In 2019, he won the "Lifetime Achievement Award for Influencing the World Chinese Award".

  Why did suffering make his life beautiful? Why is his life’s creation not the same? Where did his confidence come from? Why should artists learn to think independently about the world? Why do artists have to have great love?

  On March 22nd, at 7: 00 pm, Mr. Han Meilin, a UNESCO peace artist, a senior professor of liberal arts in Tsinghua University and a professor of Tsinghua University Academy of Fine Arts, gave a special performance "Taking Heaven as a Painting", which took you into the wonderful art world of this master!

  In the winter of 1936, Han Meilin was born in a family of four in Huangjinxiang, Jinan. His parents loved each other and lived with his grandmother who had been widowed for many years. Three generations lived happily in three tile houses in the alley. But the good times didn’t last long. My father died of tuberculosis two years later, leaving Han Meilin’s mother, two widows and three brothers who were not yet adults. At that time, the youngest brother was only born for more than a month. Two young widowed women resolutely shouldered the burden of life, helped each other to raise three children and never remarried. But even in such a difficult situation, two women in bad karma still attach importance to education and insist on sending their children to school.

  When Han Meilin was five years old, his mother sent him to a private school to practice calligraphy. Mr. Wang found Han Meilin’s square and tough personality and thought that he was the most suitable for Yan Zhenqing, a famous minister in the Tang Dynasty. Since then, he has laid the foundation for Han Meilin’s calligraphy all his life. At the same time, he began to show his talent for painting. He painted on the wall of his neighbor’s house with lime, and was beaten by his mother for destroying the newly painted wall. A little longer, Han Meilin entered Jinan Authentic Relief Society Primary School for the Poor. The school was founded by famous gentry and wealthy businessmen who worked in Jinan. It not only exempted tuition fees, but also invited Li Yuanqing, Zhao Yuanren, Chen Shuliang, Qin Hongyun and other famous artists to offer sports, music, art and other stylistic courses for students. The school is not far from home. It is a rare beauty for Han Meilin to grab a handful of tea dregs poured out of the teahouse for breakfast on the way to school on foot. Compared with the lack of material life, the school’s aesthetic education has given Han Meilin the best enlightenment in his artistic life. He loves painting more, and his teachers affectionately call him a "little painter".

  In 1948, Jinan ushered in liberation, and Han Meilin, who had just entered junior high school, decided to drop out of school to work to reduce the burden on his family. Shortly after the liberation of Jinan, the government planned to build a memorial tower for revolutionary martyrs on Sili Mountain in the south of the city. With the help of the Civil Affairs Department, Han Meilin, who was only 13 years old, became the correspondent of commander Wan Chunpu in the preparatory office. At that time, the relief group of the Tower Building Committee gathered a group of well-known domestic artists. Han Meilin, who was fascinated by painting since childhood, followed these artists for advice. Later, he was simply sent to the relief group by Commander Wan as a correspondent. He followed Wang Zhaoshan, Liu Su and Mud to make sculptures. In order to understand the human body structure, he made human skeleton specimens together with Xue Junlian. In the example of the artists, Han Meilin’s artistic level was rapidly improved.

Mr. Han Meilin, who just joined the army in the Tower Building Committee.

  After the War to Resist U.S. Aggression and Aid Korea started, Han Meilin transferred to Jinan Repertory Theatre as an actor, and also volunteered to work part-time in the propaganda work of the troupe. Soon, the Repertory Theatre was dissolved, and Han Meilin was assigned by the Bureau of Culture and Education to serve as an art teacher in Nanchenggen Primary School in Jinan. At that time, Han Meilin was less than 15 years old, but he used his painting strength to subdue students about his own age, and also attracted primary school art teachers in the whole region to observe the teaching. At the beginning of the founding of the People’s Republic of China, new China was in ruins, and there was even a blank in primary school art education in China. Shandong People’s Publishing House came here to compile his lesson plans into two textbooks, Basic Knowledge of Painting and Reference Album of Primary School Painting Teaching. Han Meilin got 400 yuan for this. In that era when 10 cents could buy four eggs, this fee was a huge sum. Han Meilin used this money to buy gifts for his family and a bicycle for going out on weekends.

Mr. Han Meilin’s youth

  Han Meilin’s passion for fine arts touched Li Shuhua, a Chinese teacher at the same school. He introduced Han Meilin to his cousin Le Wei, who was studying at Shanghai Academy of Fine Arts. With the encouragement of Le Wei, Han Meilin decided to apply for the middle school attached to Central Academy of Fine Arts. Newborn calves are not afraid of tigers. Han Meilin went to Beijing with enthusiasm to catch the exam. He was unexpectedly received by Mr. Pang Xunqin, the director of the Department of Arts and Crafts of the Academy of Fine Arts and a master figure in the art world. Mr. Pang saw the talent of this young man from Han Meilin’s daily works and suggested that he directly apply for the university. In Mr. Pang’s expectant eyes, Han Meilin was heated and took on this seemingly impossible task. Han Meilin, who had only been in junior high school for three months, finished the senior high school course in 21 days with a strong momentum. Even his eyes were temporarily blind because of overuse. He finally got the eighth place in the Central Academy of Fine Arts. Under the guidance of Bole, this wild-growing swift horse finally embarked on the professional road of art. In college, although Han Meilin majored in design, his paintings were recognized by many people.

Mr. Han Meilin is the first class teacher in the Central Academy of Arts and Crafts (third from the left in the front row).

  In 1960, after graduating from Han Meilin University, he wanted to respond to the college’s call to go to Yunnan ethnic minority areas when filling out his assignment, but he was left as a teaching assistant in the Decoration Department of the Academy of Fine Arts because of his excellent performance. After teaching, Han Meilin created many excellent works and became a rising star in Ran Ran at that time.

  In 1963, Han Meilin was transferred to Anhui to organize the Academy of Fine Arts, and was involved in the catastrophe of the times. He was unjustly imprisoned, and his body and mind were greatly devastated. But even in prison, he tried his best to draw. Without a pen and paper, he painted rice soup on his pants. When the rice soup dried, his white pants became "drawing paper", and he painted on it with branches, which became his light in the dark.

  In 1972, Han Meilin was released from prison and was assigned to work in Huainan Ceramic Factory. The factory assigned him a crude dormitory of 6 square meters. Because there was a buttonwood tree outside the house, Han Meilin felt the vitality of the trees and named his hut Tongzhai. In the next six years, he lived in Tongzhai to create.

After he was released from prison, Mr. Han Meilin weighed only 36 kilograms.

  After he was released from prison, although his living conditions improved, he still couldn’t afford the high cost of ink painting. In order to make ink painting paper show the ink smudge effect similar to expensive rice paper, Han Meilin combined traditional ink painting with modern watercolor painting and created a new technique of brush painting — — Brush a layer of water on the hard paper first, and when the paper is half dry, quickly draw a pen to make the ink pigment "smudge" along the water potential. This kind of creation is not achieved overnight. Too much water brushing will make the ink flow away with the water, and it is impossible to maintain the shape. Too little water brush will make the drawing paper dry too fast, which will affect the blooming effect. After thousands of adjustment attempts, Han Meilin finally found the balance point between water and paper, and even created a new ink and wash color matching method.

Mr. Han Meilin’s painting "Friends in Need"

  "Love" is the eternal theme of Han Meilin’s art. He said: "Artists should love the world, our society, our children, animals, plants and everything with love." Although he suffered a lot, Han Meilin never showed his suffering in his works of art, from Erhei, a close friend of poodle in times of trouble, to a monkey, a fox and a squirrel … … The animal shapes in Han Meilin’s brush painting are smart, and the fuzzy effect of ink and wash combined with blooming adds a cuteness.

  In 1978, Han Meilin was finally rehabilitated, transferred to Anhui Artists Association to engage in professional art creation, and later served as vice president of Anhui Painting Academy. The spring breeze of reform and opening-up blew away the gloom that had shrouded Han Meilin for many years, and his artistic life ushered in spring.

  In 1979, Han Meilin held his first solo art exhibition in China Art Museum, and published the first collection of animal paintings "Still on Earth" in the following year. In the same year, Han Meilin was invited to be the first China painter to hold a solo exhibition in the United States after the reform and opening up, starting from new york, he toured 21 cities including Boston, and became famous at home and abroad.

  In college, both the teachings of Chai Fei, Pang Xunqin and Zheng Ke and the friendship with Shen Congwen, who works in the Palace Museum, made Han Meilin deeply realize the profoundness of China arts and crafts. At that time, he was determined to follow the will of gentlemen, base himself on tradition and folk, and draw inspiration from land and history.

In 2003, the "Han Meilin Art Caravan" was held in Kaili, Guizhou.

  Han Meilin was inspired by an Indian film "Caravan", in which a group of actors sat in a caravan, and his heart yearned for the action of collecting wind wherever they went. Since 1977, Han Meilin led his own art caravan members to "drive" on the land of China, with the purpose of "helping the poor through culture and collecting wind through art", and went to the fields to learn various folk art techniques, and at the same time helped local difficult manufacturers to revive with his own creations. His interests seem to have no boundaries, from exquisite Henan Jun porcelain and Yixing purple sand to simple straw weaving and wall hanging. "Weaving, dyeing, engraving, carving, painting, writing, cloth, wood, stone, grass and metal, all contact, learning and teaching", he has gained endless artistic inspiration from the people, and his own creative path is also.

In September 2018, "Han Meilin Art Caravan" was in Nantong.

  Han Meilin always believes that image is the key to artistic creation. With image in mind, all kinds of materials can be used by him. He swims freely among ink, ceramics and bronze. When the times endow him with a new mission, he can devote himself to new creation at any time, so can painting and design.

  In 1980, China Post began to issue the first series of stamps on the zodiac, and the fourth set of special stamps on the zodiac in the year of pig in Guihai, which was issued in 1983, was designed by Han Meilin. The green leaves of hearts painted on pigs are very eye-catching, which not only has the traditional paper-cut and shadow play style, but also means a happy life with hearts, full of folk joy and festive atmosphere. This simple and exaggerated style of folk art has attracted worldwide attention.

In 1983, Mr. Han Meilin designed the special zodiac stamp for the Year of the Pig.

  Since then, Han Meilin has integrated his understanding of traditional Chinese zodiac culture into vivid animal images, not only taking charge of the design of special stamps and commemorative medals of Chinese zodiac for many times, but also gradually formed the Han Meilin zodiac art with both national charm and modern aesthetics, leading China traditional culture to go abroad again.

  The Zodiac in Han Meilin’s Works

  In 1989, Han Meilin Studio of China Artists Association was formally established, which is the first and only studio named after artists by China Artists Association. As a pilot project of market economy reform in the art field, Han Meilin led his team to create giant sculptures in 58 cities, such as Long Whistling in the Wind, Dashun Farming, Five Clouds and Nine Rus, Qian Jianglong, Qianwang Shooting the Tide, Huafeng Yingxiang, Hundreds of Birds Facing the Phoenix and Danfeng Chaoyang, etc., with more than 1,500 studio members at most. Han Meilin marks the rise of modern cities after China’s reform and opening up with a unique way of artists’ sculpture works.

Shenzhen Shekou Sculpture "The Golden Bull"

  In 1996, the Atlanta Olympic Games was held in the United States, which coincided with the centenary of the modern Olympic Games. Han Meilin was invited to participate in the design competition of Olympic symbolic sculptures. It took him less than a month to complete the artistic conception and integrate the two Chinese elements, Tenglong and Huabiao, into the urban sculpture. Finally, the Five Dragon Bell Tower he designed stood out from the design schemes of 17 countries and was successfully selected.

The sculpture "Five Dragon Bell Tower" designed by Mr. Han Meilin for the 1996 Atlanta Olympic Games.

  Han Meilin’s fate with the Olympic Games naturally continued in the process of China’s bid for hosting the Olympic Games. He successively presided over the design of the emblem, Olympic logo and mascot for the 2008 Beijing Olympic Games, making indelible contributions to the smooth hosting of the 2008 Beijing Olympic Games.

  In 2000, after continuous creation and revision, we finally had the "Chinese knot" with simple and smooth lines and rich meanings that we see today.

Mr. Han Meilin designed the logo of Beijing Olympic bid.

  The success of the Olympic bid is only the beginning, and greater challenges will follow. In 2005, the revision team composed of top experts such as Han Meilin began to revise the design scheme of mascots collected from all over the world, but the individual images such as rattle, panda and loong that entered the "final circle" could not perfectly show the theme of the 5,000-year Chinese civilization and the modern Beijing Olympic Games. When the design came to a deadlock, Han Meilin boldly proposed to design the mascot with a combined image instead of a single image. The new creative thinking found the key to the design of the mascot, and the embryonic form of "Fuwa" was born. After more than two months, Han Meilin closed the studio to further revise and improve the design scheme of "Fuwa", and was once taken to the hospital for a heart attack caused by sleepless nights.

Mr. Han Meilin and Fuwa "Huanhuan"

  In 2018, the International Olympic Committee awarded Han Meilin the "Coubertin Medal" in recognition of his outstanding contribution to promoting the Olympic spirit. It can be said that he is still active in the front line of artistic creation in his octogenarian years, which is a true portrayal of the Olympic spirit.

  Since ancient times, China’s calligraphy and painting have paid attention to "the same origin of calligraphy and painting", while Han Meilin became famous for his paintings, but he has long been attached to calligraphy. When I was a child, my family was poor, and I found ancient books such as Four-body Thousand-character Writing, Six-book Classification, Shuowen Gushua, etc. When I didn’t understand their meaning, I was able to regard them as picture books and appreciate the beauty of words and images. In the travel activities, Han Meilin picked up the lost ancient Chinese characters from the ancient rock paintings of Helan Mountain, and from the fragments of ceramics, bronzes, tortoise shells and stone carvings scattered all over the country. He called these ancient Chinese characters, whose pronunciation and interpretation can’t be tested, "deaf-mute beauty", and recorded them almost instinctively in his own conception book. After decades of accumulation, they have reached tens of thousands. Once in Hong Kong, Mr. Qi Gong came across the ancient Chinese characters written by Han Meilin in his notebook, and suggested that he create them artistically, as if to wake up the dreamer in a word, and Han Meilin was determined to create a "heavenly book".

Mr Han Meilin is writing a gobbledygook.

  In 2007, Han Meilin spent 34 years collecting and writing the ancient Chinese character catalogue "Tianshu", which finally came out. He did not research the origin and interpretation of the characters, but pursued the visual beauty of the characters themselves, and performed it with modern aesthetics on the premise of retaining the structure and font of the characters. Huang Miaozi, a master of calligraphy and painting, wrote a poem for it, "Cangjie makes words and ghosts cry at night, and Merrill Lynch’s Tianshu is a god’s costume". "Tianshu" is also a book and a painting. After the first book was published, Han Meilin continued to collect, sort out and re-create, giving more modern life to ancient Chinese characters. He said that if his body permits, he would like to write the translated words, which is a gift that Han Meilin really wants to leave to the nation.

Gobbledygook size: 370*120cm Year: 2015

  Like most artists, Han Meilin has made great efforts in his creation, but he doesn’t care much about business affairs. In 2001, Han Meilin was admitted to the hospital for bypass surgery due to heart problems. When his life was dying, there were thousands of works left in the studio and he didn’t know what to do with them. After his recovery, Han Meilin, who didn’t want to get close to business, decided to donate his works to the country for future generations to study. Under the direction of his wife, Zhou Jianping, Han Meilin Art Museum was built in Beijing and Hangzhou at both ends of the Grand Canal. Subsequently, Yinchuan Pavilion was completed and opened in 2015. Han Meilin became the first China contemporary artist with three art galleries (Beijing, Hangzhou and Yinchuan). Its scale, category and quantity are vast, and it is known as "Dunhuang for one person". Han Meilin has a mantra: "I am making progress every day!" The growth of age can’t stop him from pursuing art. Under the impetus of continuous creation, Han Meilin Zisha Art Museum was established in Yixing, the birthplace of Zisha Pot, in 2019. At present, the expansion projects of Beijing, Hangzhou and Yinchuan have also been carried out in an orderly manner.

Han Meilin Art Museum in Hangzhou, Beijing and Yinchuan

  Over the years, Han Meilin has supported charity by donating money and works. In 2013, the Han Meilin Art Foundation was formally established, which enabled it to carry out art-related public welfare undertakings more systematically, regularly and continuously, promote cultural education and cultural inheritance by setting up scholarships, and donated funds to build Merrill Hope Primary School and Merrill Lynch classrooms in many places to promote the popularization of basic education and aesthetic education.

Donation ceremony of "Fuwa Nini Hope Primary School"

  In 2015, Han Meilin was awarded the title of "Peace Artist" by UNESCO, becoming the first person in China art circle to win this honor. Since then, Han Meilin has more actively participated in the cause of promoting cultural exchanges and cultural inheritance in various countries and regions, and in 2016, launched the "Merrill Lynch’s World Han Meilin Global Tour Exhibition", with the purpose of "paying tribute to the Renaissance, returning to the roots of the nation, and performing cultural duties", and carrying forward the "peaceful" and "pluralistic" cultural world outlook with art, and promoting the great ideal of "truth, goodness and beauty" in human society.

Irina bokova, then Director-General of UNESCO, awarded Mr. Han Meilin the certificate of "peace artist".

  Today, Han Meilin, who is 87 years old, still insists on writing and drawing every day, and maintains strong artistic creativity. Together with the art foundation he founded, he continues to promote the inheritance of national culture and international cultural exchanges. He calls himself a "time poor", so he should make up for the lost time in turbulent times with more diligent creation.

  Han Meilin’s life is so rich that it is difficult for us to define him in one word. He has made outstanding contributions in painting, calligraphy, sculpture, ceramics and other fields. Even his life itself has been carved into a masterpiece of art in the pursuit of goodness and beauty for decades. Such a master is a wonderful blessing from God to the world and to China.

Jiangsu issued blue warning of blizzard and yellow warning of road icing.

  CCTV News:Issued by Jiangsu Meteorological Observatory at 08: 46 on December 18th, 2023.Blizzard blue warningIt is estimated that there will be more than 12 hours and 4 millimeters of snowfall in most areas of central and southern Nanjing, Zhenjiang, Changzhou, southern Taizhou and southwestern Wuxi from day to night today. The Provincial Emergency Department (Provincial Disaster Reduction Office) and the Provincial Meteorological Bureau reminded to take precautions.

  Defense guide:

  1. The government and relevant departments shall, in accordance with their duties, make preparations for snow disaster prevention and freezing injury prevention;

  2 transportation, railway, electric power, communications and other departments should carry out road, railway and line inspection and maintenance, and do a good job in road cleaning and snow melting;

  3. Pedestrians should pay attention to cold prevention and anti-skid, drivers should drive carefully, and vehicles should take anti-skid measures;

  4. Farming and pastoral areas and breeding industries should reserve feed and prepare for snow disaster prevention and freezing injury prevention;

  5. Reinforce temporary structures that are easily crushed by snow, such as scaffolding.

  In addition, Jiangsu Meteorological Observatory issued it at 08: 19 on December 18, 2023.Yellow warning of road icingIt is estimated that there will be road icing in Nanjing, Xuzhou, Lianyungang, Suqian, Huai ‘an, Yancheng, Yangzhou, Taizhou, Zhenjiang, Changzhou and Wuxi that will have an impact on traffic today and tomorrow. The Provincial Emergency Department (Provincial Disaster Reduction Office) and the Provincial Meteorological Bureau reminded to take precautions.

  Defense guide:

  1. Traffic, public security and other departments should prepare for road icing according to their duties;

  2. Drivers should pay attention to road conditions and drive safely;

  3. Pedestrians should ride bicycles as little as possible when going out, and pay attention to anti-skid.

In the future, will bytes make music "shorter"?

Author | Li Beichen

Source | Whale Fall Business Review

As we all know, today’s Chinese music scene is called "Shaking".

At the end of last year, Tencent Music made the top ten hot songs of the year, namely: Cloud and the Sea, Bai Yueguang and Zhu Shazhi, Gossip of the Prodigal Son, Dream that Can’t Wake Up, Treading on the Mountains and Rivers, Qian Qian Never Will Fall, Shepherd of Coco Tuohai, Emptying, and Obsession.

Almost all of them are Tik Tok Divine Comedy.

Yes, the most popular part of Chinese music has become the accompaniment of Tik Tok.

In the face of traffic, QQ Music and Netease Cloud Music also chose to bow their heads, with a special list of popular songs in Tik Tok, and QQ Music regarded "Tik Tok Hot Search" as a recommended option for searching songs.

Whether you like it or not, the subversion and controversy brought by Tik Tok to China’s music industry have become increasingly apparent. Those Tik Tok Divine Comedy haunts your mind, which has made the music market in China undergo an unpredictable evolution.

Obviously, Byte himself realized this, and then suddenly realized: "Why should I give up my own traffic?"

So they left the stage and entered the music market in person, which may completely change the appearance of the music market-and even the whole "music".

Traffic coordination in ByteDance

From the moment of its birth, Tik Tok has a close relationship with music-Tik Tok has a "sound" in his name, and the icon is also a note.

Looking back, Tik Tok’s predecessor, A.me, positioned itself as "short music video", which was quite similar to musical.ly, which was popular among American teenagers at that time, and created short videos by guiding users to lip-synch with music or dance. By the end of 2017, musical.ly had more than 200 million registered users.

Also in 2017, musical.ly was acquired by ByteDance, and then merged into the overseas version of TikTok in TikTok, which brought many active users and creators to TikTok and laid a good foundation for its rapid expansion in the global market.

ByteDance’s "formal" entry into the music market began two years ago.

In March, 2020, Byte officially launched the music playing software Resso in India and Indonesia. You can understand it as "Tik Tok in Music". Once the App is opened, it will be personalized song recommendation. If you don’t like this song, you can swipe the screen up and down like a Tik Tok and quickly cut to the next one.

Resso has been online for half a year, and the download volume has exceeded 15 million times. With this experience, in 2021, a music division was established within Byte, and a key task was to open up the music community of Resso and TikTok.

However, due to various reasons, Resoo has not expanded its territory to more countries and regions. At present, only a few countries such as India, Indonesia and Brazil are open.

In terms of music, perhaps the next force point of Byte is the domestic market.

In the spring of 2022, ByteDance launched an online music app-soda music in China.

The interface of soda music is very similar to Resso, which also uses sliding up and down to cut songs. Compared with the familiar left and right key switching, sliding up and down can greatly improve the speed of cutting songs. Under this interactive logic, people are not so much listening to songs as "brushing songs".

More importantly, according to media reports, most of the data of soda music and Tik Tok are synchronized. Soda music can help people to collect the divine comedy heard in Tik Tok synchronously, and find more similar songs in ByteDance’s proud algorithm recommendation.

Byte’s intention to engage in music is obvious, that is, to cooperate with the flow of Tik Tok and soda music.—— It is foreseeable that the soda concert will be more deeply bound with Tik Tok to form a closed loop of flow: Tik Tok can hatch the Tik Tok Divine Comedy and guide it to soda music; Those minority songs in soda music can also be hatched into "soda divine comedy" with the help of recommendation algorithm, which can be used to feed back short video with vibrato and become Tik Tok divine comedy, thus further consolidating Tik Tok’s position in the field of short video.

It does look wonderful.

In the future, music will eventually become shorter.

As for the penetration of bytes into the music field, what it means to the music market in China is a matter of opinion.

Please note that this article has no intention to talk about the vulgarization tendency of Chinese music. After all, there is no need to argue about the reality. The whole Chinese music presents a dangerous prosperity that will collapse once the coarse gravel foundation is removed. Huang Shujun has a song called "Change 1995", and there is a lyric that won my heart: "Only pop, no music, I think it is a good thing that you are out of sight."

So today, we are out of sight, avoiding "music quality" and talking about "music length".

Have you ever thought about it,When music can be "brushed", people will inevitably leave less and less time for a song, and they will become more and more stingy, so that they will never give you "time for a song" again.

Yes, now is not the era of "slow in the past". In the past, everyone was sincere: a song is a song; Movies, one is another. This is not the case now. People’s interest cycle is getting shorter and shorter, and the content carrier is also getting shorter and shorter, so that they can be embedded in people’s increasingly fragmented nothingness life at any time.

Therefore, just as people have become more and more impatient to watch the whole movie and are used to watching the short video of "watching a movie in X minutes", people have become more and more impatient to listen to the whole song and are used to going straight to the climax and only listening to the chorus (especially for new songs).

I even think,One day in the future, the online music platform will be completely "chorus", that is, every song that people brush will only have a climax.

If this is the case, then this new technology carrier will change the music-the time of a song is bound to become shorter, and the "memory points" such as melody and rhythm are bound to become more accurate-as much as the music was changed when vinyl was born.

You know, nowadays, a song usually lasts only a few minutes, thanks to vinyl. At first, there was no time limit for church music and court music (Beethoven’s Ninth Symphony lasted about 70 minutes), but as music can be stored, copied and distributed by new technology, a piece of music is also "framed" in the poor capacity of 4 minutes when vinyl was born. Musicians can choose not to compromise on technology, but as long as you want to seize the dividend of new technology, you must make the work shorter and make the melody and rhythm more accurate to meet the increasingly impatient attention of the audience.

Well, whether you like it or not, this process is repeating itself. The emergence of new technical media such as bytes makes human attention shorter than before, which also makes the time of a song shorter than before.

Maybe a hundred years later, the new generation of young people will look back at Jay Chou in the 21st century, just as we look back at Beethoven in the 18th century-"It’s just a song, why did you write it so long?"

Author: Li Beichen (WeChat: Whale Fall Business Review)

How to handle gait password verification business in the bank?

In today’s digital age, the bank’s security verification methods are constantly innovating. As a relatively novel and efficient verification method, gait password verification service brings more convenience and security for users. The following is a detailed introduction to how to handle the gait password verification business in the bank.

First, you need to go to the bank’s business outlets. Before you go, it is recommended that you prepare relevant identification documents, such as ID card and passport, in advance to ensure that the business process can go smoothly.

When you arrive at the bank, tell the lobby manager or counter staff that you want to do gait password verification. The staff will provide you with the corresponding application form, and you need to fill in your personal information carefully, including your name, ID number and contact information.

After completing the application form, give it to the staff. The bank will verify and verify your identity. This process may require you to provide some additional proof materials or answer some security questions to ensure that your identity is true and valid.

After passing the authentication, the bank will arrange professional technicians to collect gait data for you. This usually requires you to walk a certain distance and way on a specific device, so that the system can accurately record your gait characteristics.

After the gait data is collected, the bank’s system will analyze and process the collected data, and associate and bind it with your account.

In the whole process, you may need to wait patiently for a period of time, depending on the bank’s business processing speed and the complexity of the system.

It should be noted that different banks may have slightly different procedures for gait password verification business. The following is a list of the handling characteristics of several common banks:

Bank name Handling characteristics Industrial and Commercial Bank of China (ICBC) Standardized service flow, strong technical support and advanced acquisition equipment. China Construction Bank Pay attention to customer experience, and have special guides to assist in handling. agricultural bank The processing efficiency is high and the data processing is safe and reliable.

In addition, after completing the gait password verification business, you need to take good care of your personal information and password to avoid revealing it to others. At the same time, pay attention to the relevant notices and tips of the bank regularly to understand the updates and changes of the business.

In a word, it may take some time and steps to handle the gait password verification business of the bank, but it can provide a higher level of protection for your account security and make you feel more at ease while enjoying the banking services.

(Editor in charge: difference extension)

[Disclaimer] This article only represents the author’s own views and has nothing to do with Hexun. Hexun.com is neutral about the statements and opinions in this article, and does not provide any express or implied guarantee for the accuracy, reliability or completeness of the contents. Readers are requested for reference only, and please take full responsibility. Email: news_center@staff.hexun.com.

Guests discussed how to improve medical services: seeing a doctor is more comfortable and services are more considerate.

Group photo of guests

People’s Daily Online, Beijing, March 19 (Wang Xiaohua) This year’s government work report puts forward that "people-centered development ideas should be adhered to, and efforts should be made to safeguard and improve people’s livelihood, and the people’s sense of gain has been continuously enhanced." Since the first three-year "Action Plan for Further Improving Medical Services" was officially launched in 2015, hospitals at all levels have made positive achievements in innovating service measures and improving people’s medical experience in view of the "bottleneck" problem of medical treatment. With the launch of the new round of improving medical service plan, how to make "seeing a doctor more comfortable, providing more considerate services and increasing people’s sense of obtaining medical treatment"?

During the two sessions of the National People’s Congress in 2018, People’s Daily Online and People’s Health jointly organized a series of roundtable forums on "Healthy Chinese". In the special session of "Further Improving Medical Services" held on March 15th, five guests from government agencies and medical institutions gathered at People’s Daily Online to discuss the beneficial measures of "Further Improving Medical Services".

Innovating medical service mode and improving patients’ accessibility to medical treatment

Jiao Yahui, deputy director of the Medical Administration and Hospital Authority of the National Health and Family Planning Commission, said that after the expiration of the first three-year "Medical Service Improvement Plan", patients’ access and satisfaction were improved through the extensive application of information technology, improvement of service quality, acceleration of sinking of resources and continuous improvement of medical services.

Jiao Yahui introduced that since China launched the first three-year "Action Plan for Further Improving Medical Services" in 2015, the service process has been optimized by means of Internet informationization, which has alleviated the long-standing problem of "three long and one short" (long waiting time for medical treatment, long payment time, long time for taking medicine and short time for seeing a doctor). Through the innovative service model, the number of patients going to and from the hospital, repeated queuing in the hospital, the whole waiting time for outpatient service and the average length of stay were effectively reduced.

According to the data of 5.87 million valid questionnaires of real-time online satisfaction survey, the overall satisfaction of outpatients and inpatients in tertiary hospitals in China reached 90.7 points and 93.9 points; The analysis of 28.83 million pieces of information related to medical services on the Internet shows that netizens’ overall feelings about medical services are positive, which fully reflects the positive results achieved in improving medical services in the past three years.

Building emergency specialist alliance and opening up the "green channel" for emergency patients

Li Weimin, deputy to the National People’s Congress and president of west china hospital, said that this year, Huaxi Hospital will focus on optimizing the medical treatment mode and improving the satisfaction of emergency patients. At the same time, through the construction of emergency specialist alliance, the information triage before emergency admission can be realized, and the rescue and treatment resources can be dispatched in time, so as to truly open a green channel for emergency patients to check and be admitted to hospital.

Li Weimin introduced that since the establishment of the telemedicine network in West China Hospital in 2001, more than 640 hospitals in 20 provinces and cities across the country have joined the telemedicine network, providing telemedicine education and multidisciplinary joint consultation for difficult cases in remote areas and ethnic minority areas, which not only enables grassroots patients to get timely diagnosis and quality treatment programs, but also improves the local medical service level.

Take effective measures to promote the appointment and medical association system

Feng Guosheng, chairman of Beijing Chaoyang Hospital affiliated to Capital Medical University, introduced the effective measures taken by Beijing Chaoyang Hospital in improving medical services in recent years. He pointed out that in terms of appointment diagnosis and treatment, since 2012, Chaoyang Hospital has adopted various forms to carry out appointment registration services to facilitate patients to see a doctor. In the process of diagnosis and treatment, the appointment time, including the examination time, is accurate to 15 minutes, which greatly reduces the waiting time of patients in the hospital and obviously improves the medical environment.

In terms of vigorously developing the construction of medical associations, in 2012, Chaoyang Hospital established a medical association with Chaoyang Hospital as the core and secondary hospitals and community medical centers as participants under the guidance of the government. Through the standardized operation within the medical association, more patients with common diseases and chronic diseases can enjoy the high-quality medical resources of large hospitals at their doorsteps.

Feng Guosheng said that Chaoyang Hospital has also realized telemedicine through information technology, and further strengthened the innovation of outpatient services, such as setting up symptom clinics and special disease clinics to facilitate patients to seek medical treatment.

Extend the service to the grassroots level and let more children enjoy health.

Ni Xin, dean of Beijing Children’s Hospital affiliated to Capital Medical University, pointed out that Beijing Children’s Hospital has implemented a comprehensive appointment system for non-emergency patients since June 2015. Through a variety of ways, patients are guided and facilitated to make appointments and time-sharing visits, so that the waiting time of patients is shortened, the peak flow of outpatients is reduced, and the medical experience is significantly improved. These methods mainly include: dynamically adjusting staff and improving service space; Implement centralized appointment for large-scale examinations to reduce patients’ running back and forth; Increase voluntary service and improve the online and offline guidance system; Open professional outpatient service and expert team outpatient service to make the process of treating intractable diseases more convenient.

Ni Xin introduced that in order to facilitate children to seek medical treatment nearby, Beijing Children’s Hospital and Children’s Research Institute took the lead to promote the common development of pediatrics in 16 municipal general hospitals in Beijing. By hosting three children’s hospitals, the medical level of local hospitals has been further improved. Beijing Children’s Hospital and 23 provincial children’s hospitals across the country set up a cross-provincial specialist alliance to achieve the goal of "doctors move and patients don’t move". In the next step, we will use artificial intelligence to comprehensively improve the level of medical services, extend services to the grassroots, increase support for poor areas, and let more children enjoy health.

Carry out the comprehensive upgrade of information system for the construction of smart hospitals

Jiang Lihong, deputy to the National People’s Congress and president of the First People’s Hospital of Yunnan Province, said that in the past three years, the First People’s Hospital of Yunnan Province has actively implemented the improvement of medical services, mainly focusing on two themes, and has achieved certain results: First, the construction of smart hospitals. The hospital information system has been upgraded in an all-round way, and the people’s appointment registration rate has increased from about 30% to more than 91% after the new system goes online. The hospital implemented the one-card service, and invested in the construction of 126 self-service machines. Patients can register for ID cards or medical insurance cards.

The second is the construction of medical association and graded diagnosis and treatment. People in Yunnan Province, especially in mountainous areas, live in scattered areas, and fewer patients in Yunnan Province are transferred to other provinces for medical treatment. The demand for medical associations and graded diagnosis and treatment is more urgent. The First People’s Hospital of Yunnan Province and 215 state (city) and county hospitals in the province formed a medical association, and 3-5 specialists were selected from 33 state-level hospitals to form a specialist alliance. At the same time, 6 provincial-level expert grass-roots workstations and 66 secondary hospitals and community expert teams were set up to build a "joint laboratory for precision medicine and eugenics" with the hospitals in the medical association, forming a multi-level assistance mechanism such as hospitals, specialist alliances and expert teams.

Expression of nano-antibody in different systems

?  Foreword  

In 1993, Belgian scientists discovered a new antibody-nano-antibody (VHHs) in camel serum, which is different from the traditional antibody structure and only consists of heavy chain variable regions. Compared with traditional antibodies, nano-antibodies have the advantages of stable physical and chemical properties, low immunogenicity, strong tissue permeability, and can recognize epitopes that traditional antibodies cannot recognize, which makes them a strong and beneficial supplement to traditional antibodies.

Nano-antibody is only composed of heavy chain variable region, with small molecular weight and simple structure, which enables it to realize stable expression in various expression systems. So far, VHHs has been expressed in many expression systems, from prokaryotic cells, yeast, fungi, insect cells, mammalian cell lines to plants. This paper mainly introduces the expression of nano-antibody in different expression systems, and the present situation and development trend in the field of this system.

Prokaryotic expression system Prokaryotic expression system is the earliest mature protein expression system studied. Obtaining foreign proteins through prokaryotes can obtain gene expression products in a short time, and the cost required is relatively low. The expression system mainly includes Escherichia coli expression, Bacillus subtilis expression and Streptomyces expression. Among them, Escherichia coli system is the most widely used, and the prokaryotic system generally refers to the expression of Escherichia coli.

Escherichia coli expression system Escherichia coli expression system is the most important expression platform of recombinant protein in laboratory environment, and the expression is controlled by lactose operon. The host of Escherichia coli system has the advantages of fast growth, simple culture, low price, clear genetic background and high protein expression. However, it can not modify the expression product after translation, and the expression product contains a lot of endotoxin and is easy to form inclusion bodies.

Common host bacteria of Escherichia coli expression system

35221657261595373

Periplasmic space, as the only compartment with oxidation environment in Escherichia coli, is the most commonly used expression system of nano-antibodies containing specific disulfide bonds. In addition to aerobic environment, there are many partners and isomerases in the periplasmic space, which can promote the correct formation of disulfide bonds and help protein fold. Nano-antibody protein is first produced in the cytoplasmic space, and then secreted into the periplasmic space through Sec pathway, SPR pathway or Tat pathway. After signal peptide is removed by signal peptidase, the target protein can be obtained [1].

Up to now, many VHHs have been successfully expressed in periplasm, some of which can reach tens of milligrams per liter, but there are still a lot of VHHs with low yield. This is because many fusion proteins can not be effectively secreted in the periplasmic space, and cytoplasmic expression seems to be the only expression mode of such fusion proteins [8].

The cytoplasm is a reduced compartment, so that the proteins expressed through the cytoplasm can not be folded correctly, and most of them are inclusion body proteins. The proteins are protected from the degradation of intracellular enzymes and are easy to be separated in high purity and concentration. However, there are many kinds of proteins in cytoplasm, and it is difficult to purify them. At the same time, nonfunctional inclusion proteins need to be completely denatured and refolded to be recovered from these inclusions, but the recovery of VHHs is usually inefficient [1]. In order to solve the problem of cytoplasmic expression, Xue X and others designed a new dialysis-dilution device in 2016. Using this device, researchers refolded VHHs and achieved a recovery rate of 85%, while the conventional dialysis and dilution methods only reached 13%[9]. Bacterial cytoplasm can be an effective compartment to produce correctly folded nanoparticles when expressed by recombinant vectors with sulfhydryl oxidase and disulfide isomerase activities. Larger volume and wider cytoplasm of chaperone/folding enzyme can achieve high yield of nano-antibody [6]. At the same time, double mutants with defects in thioredoxin and glutathione pathways have been developed. Some of these strains have been sold commercially in recent years, such as Origami (Novagen), Rosetta-gami (Novagen) and SHuffle?T7 (New England Biolabs) [10]. Among them, Shufflet 7 overexpresses a critical periplasmic isomerase DsbC, which can effectively catalyze the isomerization of disulfide bonds. Some studies have found that,The activity of isomerase DsbC can increase the yield of functional recombinant protein in periplasmic research [11].  

Kavousipour Soudabeh and other modified vectors added four different signal peptide sequences to guide the secretion and expression of nano-antibodies, and found that TrBC signal peptide had the best effect [5]. Jianli Yu et al. used repetitive amino acid sequence motifs (GAGAGS) found in silk fibroin (SFP) as a new fusion tag (SF-tag) to enhance the expression of nanosomes in E.coli.. The transcription level of labeled protein is 2.3-7.0 times that of unlabeled protein, and the yield is increased by 2.5-7.1 times [27]. Xi Xie and others tried to select antifreeze protein AXX, and obtained its reverse transcription protein XXA by synthesizing XXA gene, which was used to develop new soluble fusion tags. It was found that the solubility ratio of fusion protein expressed by XXA fusion tag reached 86%, which was much higher than that of other tags [12].

Other prokaryotic expression systems Lactic acid bacteria are the most common intestinal probiotics, which are generally considered to be harmless to human body and are very suitable for the production host of therapeutic molecules. However, the existing expression data show that the yield of VHHS produced by lactic acid bacteria is low, about 1-3mg/L, which is much lower than that of Escherichia coli [13,14]. Lactobacillus rhamnosus DSM14870, as a normal flora in human vagina, can express HIV antibody in the form of soluble or cell wall anchor fixation, and is a suitable expression host for HIV antibody [2]. When Bacillus brevis choshinensis was used for 3L fed-batch fermentation, the yield was as high as 3g/L[15]. This system is easy to manipulate genes, has no endotoxin and shows weak protease activity, so it is a very noteworthy system.

Eukaryotic expression system 

Due to the defects of prokaryotic expression system, such as difficult purification of inclusion body protein and incomplete protein modification, people began to use eukaryotic expression system to study genes. At present, eukaryotic expression systems commonly used in genetic engineering research include yeast expression system, insect cell expression system and mammalian cell expression system.

Yeast expression system Yeast system has clear genetic background, simple operation, easy genetic operation, perfect eukaryotic protein expression control system and advantages of both prokaryotic and eukaryotic expression systems. Yeast eukaryotic protein expression systems include methanol yeast expression system, Saccharomyces cerevisiae expression system, Schizosaccharomyces expression system and Kluyveromyces expression system [17].

Saccharomyces cerevisiae is the first yeast fermented by human beings, which has no specific virus and low cost. At present, it is the largest yeast expression system in shake flask culture, with the output exceeding 100mg/L[16]. Some amino acids in VHHs can participate in the recruitment of molecular chaperones in endoplasmic reticulum, thus narrowing the difference of molecular chaperones between Saccharomyces cerevisiae and mammalian cells, which is beneficial to the folding kinetics of nano-antibodies and improving the yield of nano-antibodies in Saccharomyces cerevisiae [17]. The protein expressed by Saccharomyces cerevisiae is prone to hyperglycosylation, and a large number of endogenous proteins are produced during fermentation, so the secretion efficiency of the target protein is low [1]. Considering the above problems, Saccharomyces cerevisiae is gradually replaced by methanol yeast represented by Pichia pastoris.

Pichia pastoris expression system is an efficient expression system of foreign proteins. This microorganism does not accumulate toxic ethanol, but only secretes a few endogenous proteins, and its glycosylation degree is the same as that of mammalian cells, so its immunogenicity is weak, so it is the most commonly used eukaryotic expression system. Pichia pastoris has a strictly regulated methanol inducible AOX1 promoter, which is suitable for high expression of foreign proteins [1]. But methanol is a highly toxic and dangerous chemical product. The GAP promoter without methanol induction is used instead of AXOI, and the carbon source does not need to be changed during the culture process, so the operation is simpler and the time for foreign proteins to reach the peak level can be shortened. The yield and affinity of nanoparticles produced by this system are similar to those produced by methanol-induced expression. It has been studied that the yield of nano-antibody expressed by this system in shake flask is 51.71mg/L[18] and 16mg/L[19].

Fungal expression system 

Some filamentous fungi, such as Trichoderma and Aspergillus, can secrete a large number of foreign proteins in the culture medium. However, the fungal system not only expresses protein of interest, but also produces many proteases, which affects the yield. Joosten et al. obtained only 1.5 mg/L VHHs in Aspergillus awamori medium. After adding 0.25% BSA, it reached 7 mg/L. It is reported that more than 80% of VHH is degraded or adhered to the cell wall compared with endogenous xylanase secreted efficiently in this system, and researchers believe that the low secretion efficiency of VHHs is the bottleneck of fungal expression [20]. In order to overcome this limitation and protect VHHs from degradation, other researchers fused VHH with the high amylase A signal sequence (sTAA) of Rhizopus oryzae lipase (N28) and the N-terminal 28 amino acid fragment (N28), so that the highest yield of VHHs expressed in Aspergillus oryzae reached 73mg/L, which was 300-800 mg/L lower than that of Escherichia coli [21]. The final yield of GlaB-VHH fusion protein in Aspergillus oryzae can reach 610mg/L, which provides the possibility for high expression of nano-antibody, but its stability needs to be verified [22]. In addition, VHH[23] was expressed by maize head smut in unconventional secretion pathway.

Insect cell expression system 

Insect cells are a widely used eukaryotic expression system, and recombinant baculovirus vectors (such as AcMNPV) can specifically transfect insect cells. Its survival in nature is short, and the strong promoter is inactivated in mammals and cannot infect vertebrates, so the recombinant baculovirus is safe for human beings. Proteins with complex structures under the control of strong promoters may not be able to form correct folding and post-translation modification, which may lead to the aggregation of target proteins and reduce antibody production, so the expression yield of VHHs in this system is much higher than that of other types of antibodies [17].

Gómez-Sebastián and others used the improved baculovirus expression system (IBES? technology) to express VHHs for the first time. The chigger larvae were inoculated with different recombinant baculovirus inoculation methods. The yield of VHH extracted from larvae is 257 mg/L, and the recovery rate after purification is 50%[7]. When expressing anti-endothelial cell selection protein, Drosophila cell SC-2 secreted 12-14mg/L, but the target protein was not detected when expressed in Escherichia coli at the same time, which may be related to the processing and modification ability of insect cells [26].

Mammalian cell expression system Mammalian cells are the best expression system for therapeutic antibodies, because the produced antibodies have the weakest immunogenicity. At present, the main cell lines include CHO, NS0, Sp2/0, HEK293 and per C6 [17]. Among them, CHO cells grow rapidly and adapt to serum-free suspension culture, which is the most popular host. They can express VHHS up to 100mg/L in shake flask [24]. HEK293 cells are more commonly used in the laboratory because of transient transfection and semi-stable expression, because they require less time and labor. However, monoclonal antibodies approved for the treatment of human diseases are only produced by CHO, NS0 and SP2/0. So far, HEK293 cells have not been used to produce VHHs, and there are few reports about producing antibody fragments by this method [17]. In most literatures, CHO is used to produce antibody fragments. Up to now, 50% of the therapeutic proteins produced in industry are still produced by CHO [1]. The production costs associated with mammalian cell lines are much higher than those associated with any other laboratory research platform.

Common host cells of mammalian expression system

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Plant expression system Compared with other expression systems, plant production platform (stable and transient expression system) is cheap, safe, capable of folding and assembling complex proteins and post-translation modification, easy to expand, and unaffected by human pathogens and diseases. It is an ideal protein expression host and is usually used as an alternative method for mammalian expression systems. In addition, plant expression products can be concentrated in specific organs, such as leaves or seeds, and can be taken orally directly. Tobacco leaves are the most common hosts for expressing VHHs, while the proteins expressed in Arabidopsis and rice seeds have attracted much attention because of their direct oral input of VHHs[1]. The stable transformation methods commonly used in plant system expression have some problems, such as the recombinant gene escaping to nature or the time-consuming transformation. Therefore, some studies have proposed the transient expression system of plant virus expression vector as an alternative method, and the nano-body content with correct conformation reaches 0.45% of the total soluble protein [25].

Present situation and development of nano-antibody expression 

Escherichia coli expression system is the most commonly used expression system of nano-antibody, which has two expression modes: periplasmic expression and cytoplasmic expression, each with its own advantages and disadvantages. Some oxidation engineering strains have been modified, but more experimental support is needed. In addition, various methods of modifying vectors, such as adding labels or signal peptides, have been put forward and have been verified by experiments. Compared with Escherichia coli, Pichia pastoris has excessive glycosylation, which may lead to immunogenicity and ultimately affect its clinical application. The expression systems of fungi, insects, plants and mammals are much more complicated than prokaryotic and eukaryotic expression systems, and are generally not easily adopted after considering the production time, cost and laboratory conditions.

Escherichia coli system is fast, convenient and cheap, and it is the first choice for VHH expression under most laboratory conditions. When some types of VHHs can’t be successfully produced in E.coli, other systems will be used instead.

List of nano-antibody expression

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