It’s a common practice for college students to keep in good health. People who work too hard can’t run far.

  Recently, according to the China Youth Daily, "Ginger Soaks Foot" and "Drinking Tea for Beauty" … … With the increasing pressure of life, not only the post-90s generation who entered the workplace, but also many college students have begun to try various methods of health preservation. Health preservation is no longer the exclusive word of the elderly or middle-aged people, and the young campus groups represented by college students are constantly adjusting their lifestyles and advocating a healthier life and rest. Why are this wave of college students "trapped in health care" and "selling the old"? Many college students said that this is a way of "self-mockery" to fight anxiety and pressure.

  In many people’s cognition, college students are relaxed and chic, and can have fun relatively freely. But in fact, many college students are very bitter and tired now. It is not unusual to do homework, research and activities in class until early morning or even later.

  Under such a realistic background, it is not difficult to understand that many college students are "trapped in health preservation". Recently, a "2018 Life Consumption Trend Report" shows that based on the search volume of "Lycium barbarum" on the e-commerce platform of all ages, the proportion of search volume after 1995 increased significantly in September 2017. Honey, Lycium barbarum, whey protein, health tea and enzymes are the health foods that are keen on after 1995.

  When I was in college, I was also a "busy maniac". I was really working hard. My meals and sleep were irregular, and I also had a tendency to overeat. At that time, I thought I was still young, so I indulged myself too much and was indifferent to some early warning signals of my body. But now, nearly a year after graduation, all kinds of physical and mental discomforts have emerged, and I realize that "karma" has come and I want to "pay my debts". Therefore, now I will also force myself to keep fit, such as drinking more hot water, going to massage, eating more healthy food and running to and from work.

  The meaning of life is not temporary, but long-term. To quote a very fashionable online buzzword recently, "People who work too hard can’t run far". Who doesn’t want to "run away" on the road of life? So, please do it and cherish it.

  Of course, it is not enough to rely solely on the self-awakening of young people, but also to exert efforts at the social level. To put it bluntly, in addition to focusing on the "burden reduction" of primary and secondary school students, the social level should also focus on the "burden reduction" of young people represented by college students. There is no denying that the latter should be under pressure and responsible, and strive hard to realize their own value and social value, but all this should not be at the expense of health. It should be a social consensus that only a good body and a healthy lifestyle can create more shocking values.

  Mocheng

Illegal addition of western medicine to Chinese patent medicine is harmful and deadly. "Tangzhining" rings the alarm bell.

  On January 17th and 19th, two patients in Xinjiang died after taking Tangzhining Capsule (batch number "081101") labeled "Guangxi Pingnan Pharmaceutical Factory". After investigation, the "Tangzhining Capsule" that caused the patient’s death was a counterfeit drug, and the chemical component "glibenclamide" was illegally added. According to industry analysts, patients with chronic diseases such as diabetes and hypertension are huge, which has become a "gold mine" for many black-hearted drug dealers to make money. Some products advertised as pure Chinese medicine have illegally mixed western medicine ingredients, or added pharmaceutical ingredients to health foods, which is harmful to patients’ health. This has also become a focus of supervision by law enforcement departments in various places, including Guangdong Province.


  Three chemical components are often illegally added.


  According to reports, although the current medical level has made rapid progress, there is no major breakthrough in some difficult diseases, such as diabetes, chronic hepatitis, malignant tumors, etc., and neither traditional Chinese medicine nor western medicine can achieve a complete cure. Wei Hua, deputy director of the Department of Endocrinology, Guangdong Provincial Hospital of Traditional Chinese Medicine, said that as far as Chinese medicine is concerned, its composition is complex and its effect is mild and slow, while western medicine has continuously developed some chemical drugs which are more effective, but its side effects are relatively large. In this regard, some lawless people, taking advantage of the psychological trust of patients in traditional Chinese medicine, promote so-called pure Chinese medicine and health food, and secretly add western medicine chemical components to them, so that patients feel obvious curative effect after taking it, thus increasing sales. For example, the "Tangzhining Capsule" that went wrong this time is under the banner of Chinese patent medicine.


  Wei Hua said that in addition to the glibenclamide added in the "Tangzhining Capsule" that went wrong this time, gliclazide and glipizide are the most commonly added hypoglycemic western medicine ingredients in those illegal products. According to the relevant regulations, chemical substances are not allowed to be added to traditional Chinese medicine. "Glibenclamide" has a strong hypoglycemic effect, and its pharmacological function is to promote insulin secretion and improve human insulin deficiency through metabolism after entering the blood. However, serious overdose may cause shock and even death.


  It is understood that the Xinjiang Uygur Autonomous Region Institute for Drug Inspection found that the drugs taken by the deceased during his lifetime contained about 10.33 mg of "glibenclamide" per pill. "Glibenclamide" is a second-generation sulfonylurea, which has a strong hypoglycemic effect, but adults should not take more than l5 mg per day, otherwise it will endanger the life safety of users. According to the instructions of the seized drugs, the normal dosage is 9 capsules per day, which has exceeded the maximum daily dosage by 6 times.


  You can’t add western medicine to Chinese medicine at random.


  A person in charge of a pharmaceutical factory told reporters that the incident was not accidental, and illegal drugs, health foods, western medicines and illegal propaganda occurred from time to time. According to National Medical Products Administration, they found that it is not uncommon to add sildenafil, a component of Viagra, to the "pure Chinese medicine" for treating male sexual dysfunction, and to add thyroid hormone to diet food, which can cause hyperthyroidism, so that patients who don’t know the truth suffer from side effects of drugs for no reason. This exposes a problem: most Chinese people believe that "natural drugs" have the advantages of low toxicity and side effects, and it is inevitable that they are not alert to side effects such as dependence.


  Wang Dahong, Secretary-General of the Market Working Committee of China Health Food Association, said that illegal addition of western medicine ingredients in traditional Chinese medicine or chemical ingredients in health food will do great harm to patients and should not be added indiscriminately. Doctors and patients use mixed Chinese and western medicines without knowing it, which can easily lead to repeated adverse drug reactions. For example, if diabetic patients don’t know that the Chinese patent medicine for lowering blood sugar is added with glibenclamide, they mistakenly think it is a "Chinese medicine with no toxic and side effects" and take it in excess, or take the western medicine for lowering blood sugar at the same time for "integrated Chinese and western medicine treatment", which will lead to overdose of hypoglycemic drugs and hypoglycemia, and even lead to blood sugar fluctuation of patients if they stop taking the medicine suddenly. Therefore, Wang Dahong said that the timely discovery and investigation of the problem "Tangzhining Capsule" has eliminated another safety hazard that harms consumers’ health, and the industry has been further eliminated.


  Illegal addition has four characteristics.


  Most Chinese patent medicines or health foods illegally added with western medicine ingredients have the following characteristics: First, they claim that they can cure or greatly improve certain diseases in a short period of time, and their efficacy is remarkable. Second, most drugs are sold through online advertisements, mail advertisements or health knowledge lectures. Third, most drugs or health care products are covered with legal coats. Some products are pure Chinese medicine ingredients when applying for batch number, but western medicine ingredients are added during production. Fourth, the means of addition is very secret. Knowing that the routine drug testing only examines the internal substances of drugs, criminals add western medicine ingredients to the external carriers of drugs such as capsule shell. Finally, it is suggested that consumers can check the authenticity of drugs through the official website of the State Food and Drug Administration.


  -Medical files


  glibenclamide


  Glibenclamide, alias glibenclamide, Daanning, etc., is a prescription drug and must be taken under the guidance of a doctor. It is an islet hormone and a drug that affect blood sugar, and can be used to treat mild and moderate non-insulin-dependent diabetes mellitus with unsatisfactory therapeutic effect only by diet control, but the patient’s islet β cells need to have certain insulin secretion function without serious complications, such as diarrhea, nausea, headache, stomachache, liver function damage, thrombocytopenia and other adverse symptoms. If you take glibenclamide in large quantities for a long time, it will eventually lead to hypoglycemia, nephropathy and even death.


  -Related links


  Which drugs illegally add glibenclamide?


  According to experts, in the drug treatment of diabetes, except insulin, most of them are oral drugs. Oral hypoglycemic drugs are usually divided into three categories: western medicine hypoglycemic drugs, pure Chinese medicine hypoglycemic drugs and Chinese and Western medicine hypoglycemic drugs. Generally, pure Chinese medicine has weak hypoglycemic effect, slow onset and high safety. Western medicine hypoglycemic agents take effect quickly and have great toxic and side effects. The combination of Chinese and western hypoglycemic agents is based on the pure traditional Chinese medicine hypoglycemic agents, and incorporates the ingredients of western medicine hypoglycemic agents, which not only has the advantages of rapid hypoglycemic effect of western medicine, but also has the advantages of high safety of traditional Chinese medicine. According to the person in charge of the provincial drug evaluation center, at present, only three kinds of oral hypoglycemic drugs, such as Yikai Xiaoke Pill, are officially registered in China. It is not the first time to illegally add glibenclamide. In 2005, the Ministry of Health investigated and dealt with two cases-


  ○ On June 15th, 2005, the Ministry of Health issued a notice, requiring all localities to investigate and deal with some batch numbers of "Ku Le Kang Capsule" produced by Liaoning Healthy Weiye Biotechnology Co., Ltd.. The Ministry of Health pointed out that when the relevant departments of Jilin Province supervised and inspected the health food "Ku Le Kang" capsules (approval number: Wei Shi Jian Zi [2002] No.0588) produced by Liaoning Health Weiye Biotechnology Co., Ltd., they found that the products marked with certain batch numbers contained chemical drugs. The capsule shells of samples with batch numbers of 20041201 (not for sale), 20040902 and 20041201 contain the chemical drug glibenclamide, and the capsule contents with batch number of 20050401 contain the chemical drug gliclazide.


  ○ On October 9, 2005, Jiangxi Food and Drug Administration announced that the law enforcement officers of Nanchang Food and Drug Administration had tested the drug "Tangbikang Jiangtangning Capsule" labeled as batch number 20050403082 produced by Jilin Shenhui Pharmaceutical Co., Ltd.: glibenclamide was illegally added to this Chinese patent medicine. (Reporter Roger Lee)

Editor: Liu Li

Golden Horse Poster Gong Li Hou Xiaoxian’s side face is so beautiful! Creative signboard has not been smashed for ten years.

The 55th Golden Horse Poster


1905 movie network news Today, the main visual poster of the 55th Golden Horse Award was released, which once again firmly attracted the attention. This poster with blue and gold as the main color looks like staring at the sleeping sand dunes in the middle of the night from a distance. If you look closely, you will find that it is four faces lined up in turn. This poster was designed by Fang Xuzhong, the poster designer and visual director of the ceremony last year. It extends the concept of "everyone plays a supporting role in the film" and draws the facial contours of Ang Lee (Chairman of the Executive Committee of Taipei Golden Horse Film Festival), Hou Xiaoxian (Dean of Golden Horse Film Academy), Gong Li (Chairman of the Golden Horse Award Jury) and Xiao Ye (Judge of Golden Horse Venture Capital Conference) into dune shapes. The picture made up of tiny particles of light and shadow also seems to imply the ambiguous connection between retaining the instantaneous image with light and shadow and the passing time.

 

The main visual posters of the Golden Horse Awards pay attention to convey the understanding of Chinese movies with rich imagination and bold creativity, which has always been a highlight of the Golden Horse Awards. In recent years, almost all the main visual posters have paid tribute to Taiwan Province’s old films and filmmakers.

 

In 2017, the main visual posters of the 54th Golden Horse Awards were the "Shadow Idiot Edition" and "Fan Edition" posters with the stills of "Spring Breeze" as the main elements. The two posters project the pictures from the stills onto various screens to convey the real and illusory feeling brought by the film, which is similar to the 53rd brighter summer day designed by Huang Hai, in which the junior four illuminates the night sky with a flashlight to show that "the light of the film never goes out".

 "Shadow Idiot Edition" (54th edition) by square sequence

"Fan Edition" (54th session)


The 53rd Tribute to Guling Street by Yellow Sea

Even more amazing is the 50th Golden Horse, a Maggie Cheung-themed poster designed by Taiwan Province graphic designer Nie Yongzhen (who designed album covers for Jay Chou, Yoga Lin and others). The image of Maggie Cheung is partially cut to show different areas of the face, which means that the film is like a slice of time, so it can’t really keep time, so it can only intercept fragments.

 The 50th Maggie Cheung by Nie Yongzhen

In addition, it is worth noting that cartoonist Jimmy has designed the main visual poster for the Golden Horse Award twice. At the 39th Taipei Golden Horse Film Festival, he gathered his characters in the cinema and opened a small door under it. It not only means that the film blurs the boundary between reality and illusion, but also outlines the pleasant atmosphere of watching movies.

How many meters is the 39th by?

Another time was the 49th Golden Horse Award 10 years later. He created in oil painting for the first time in public and handed in three design drawings at one time. Two of them are a pair of dressed-up "hot horses and handsome horses", and the final picture is the picture of a little boy and a horse flying on the sea. According to Jimmy himself, this means "the pursuit of light and shadow".

 How many meters is the 49th by?

Next, please enjoy the main visual poster of the Golden Horse Award from 2008 to this decade — —


The 45th Session (2008), which rejected complexity and chose simple color blocks.

The 45th by Nie Yongzhen


         A camera head who is always running, 46th (2009)

The 46th by Wang Zhihong


          Seconds of Glass Breaking, 47th (2010)

The 47th by Wang Zhihong

       Inspired by Hou Hsiao-hsien, the 48th session (2011) is based on the essential old camera which may be closer to gaze.

The 48th by Lin Xiaoyi (cover designer of Kawabata Yasunari series)


      The Pursuit of Light and Shadow, 49th (2012)

The 51st by Xiao Qingyang (album cover artist)


       Chivalrous women with stick figures, hidden in gilded lines, 52nd (2015).

The 52nd, by Zhang Shuping.


        "The Light of Movies: Looking Back, Illuminating Forward", 53rd (2016)

The 53rd Tribute to Guling Street by Yellow Sea


       To pay tribute to the 20th anniversary of the publication of "Spring Break", selected by Wong Kar-wai himself, the 54th (2017).

The 54th session By square order

        The 2018 Golden Horse Film Festival will be held from November 8 to 25.

 

Consumer goods are "trade-in"! What do you want to change?

Citizens are buying TV sets (photo by reporter Gao Qian)

The public is buying a refrigerator (photo by reporter Gao Qian)

  Editor’s Note: A few days ago, the Provincial Department of Commerce and other 19 departments jointly issued the "Implementation Plan for Promoting Trade-in of Consumer Goods in Henan Province", which will focus on the implementation of three major projects: trade-in of automobiles, trade-in of household appliances and "rejuvenation" of home improvement and kitchen and bathroom. As soon as this news came out, it was widely concerned by consumers. What are consumers’ expectations and concerns? What is the situation of the consumer market? The reporter interviewed this.

  New kinetic energy-

  Find a "home" for waste materials

  In life, many people have seen such a scene in residential areas: old toilets, old furniture, waste household appliances, etc. are abandoned beside the trash can, waiting for someone to take them away. What should I do with these big household items? Is there a smooth recycling channel? Yesterday, the reporter started an interview.

  The netizen had the experience of handling large household items. He told reporters that his old house needed to be renovated and he wanted to get rid of some old things. But because of the high floor and no elevator, things were bulky and heavy, and many masters who collected waste products were unwilling to pick them up. Selling these things not only won’t get money, but also requires paying a "disposal fee". "In the end, I had to bundle things that can still be used at home and can be sold with these items, and some people reluctantly agreed to clear them." This netizen is emotional.

  With the continuous improvement of living standards, citizens’ demand for integrated upgrading of large household items is constantly increasing, and where to go for the eliminated large household items has become a difficult problem. "The public area in the hospital is limited. If these large items are discarded in the hospital, it will not only occupy the road, but also increase the burden on sanitation workers. I feel guilty in my heart, and I am afraid of causing conflicts in my neighborhood. I really hope that the relevant departments can provide a’ home’ for the eliminated household items. " The netizen said "the flag is victorious". "The electronic components in some household appliances will release harmful substances after aging and expiration, causing invisible harm to the human body." Ms. Shi, who is engaged in the environmental protection industry, said that she had done market research, and many residents did have the demand for recycling large household items.

  The reporter learned that due to the lack of convenient recycling points, these eliminated large household items were either discarded at will or dismantled by some illegal dismantling points. An old man who walks the streets to recycle old household appliances told reporters that these old things are worthless, and washing machines, old computers, etc. are tens of dollars regardless of good or bad. Dealing with these things takes up space and time, and he takes them back and sells them in parts.

  Previously, the relevant ministries and commissions of the state jointly issued the Notice on Encouraging Household Appliance Manufacturers to Carry out the Action of Responsibility System for Recycling Targets, and put forward a series of policies to encourage household appliance manufacturers to implement recycling. Nowadays, many home appliance manufacturers are carrying out "trade-in" activities, and some enterprises can even provide disassembly services for free.

  For a long time, the recycling level of large household items is low, the management is not standardized, and the necessary recycling facilities are lacking. The "last mile" of recycling has never been opened. Recently, the Henan Provincial Department of Commerce and other 19 departments jointly issued the "Implementation Plan for Promoting Trade-in of Consumer Goods in Henan Province", which mentioned that the recycling network of household appliances should be upgraded, and the construction of recycling outlets, sorting centers, dismantling facilities and other projects should be supported to improve the efficiency of recycling, transit and distribution. The staff of an environmental protection enterprise in our city told the reporter that they have paid attention to this problem and are considering establishing a recycling channel and management system with some qualified enterprises to realize the reduction, harmlessness and resource disposal of large household items.

  Automobile energy conversion-

  Double subsidies are more favorable.

  Automobile consumption is an important part of household consumption. At present, the automobile trade-in project has begun. What is the trend of the consumer market? What new weather has it presented? On May 11th, the reporter went to the automobile market in northern Henan for an interview.

  There are used car trading places in the market, and more are new car sales stores. In a new car sales store at the entrance of the market, different styles of cars are parked. Duan Wenbin, the manager of the automobile sales and marketing department, is sorting out the automobile sales information. He said: "The new round of automobile trade-in has begun, which will definitely drive the automobile market consumption. We have prepared enough sources to meet the diversified needs of consumers as much as possible."

  On May 7, the "Implementation Plan for Promoting Trade-in of Consumer Goods in Henan Province" jointly issued by the Provincial Department of Commerce and other 19 departments mentioned that from May 7 to the end of this year, individual consumers will be scrapped with fuel vehicles or new energy passenger vehicles with national emission standards of Grade III and below, and they will be subsidized by 10,000 yuan for purchasing new energy passenger vehicles; For individual consumers, the fuel vehicles with national emission standards of Grade III and below will be scrapped, and the fuel passenger cars with a displacement of less than 2.0 will be subsidized by 7,000 yuan. At the same time, cities and counties are encouraged to give subsidies to consumers who replace old cars with new ones, and the provincial finance will give appropriate awards; Encourage automobile production enterprises and sales enterprises to independently carry out second-hand car replacement subsidies and superimposed preferential profit-making activities.

  "In fact, we have always had replacement subsidies for car buyers. Old cars are exchanged for new ones, cars of the same brand are subsidized by 5,000 yuan, and subsidies of different brands are 3,000 yuan. Consumers can enjoy subsidies as long as they provide transaction tickets." Duan Wenbin said that now, government departments also have subsidies, coupled with corporate concessions, consumers can save a lot by exchanging old ones for new ones.

  What style of car is more popular with consumers? Duan Wenbin pointed to a small new energy passenger car and said, "It must be a new energy passenger car, especially this small one, which saves energy and is convenient to park in the urban area." Yan Dong, a staff member of an automobile sales department who specializes in selling new energy passenger cars, also told reporters: "It is precisely because of the good market prospects of new energy passenger cars that the manufacturers we sell cars changed from fuel vehicle production to new energy passenger car production last year. Moreover, adding intelligent technology and intelligent management, such as autonomous driving technology, to new energy passenger cars is very popular among young consumers. "

  Cui Zhifeng, a consumer who has transferred to several car stores, is a "post-00" and is preparing to change to a new car. He said: "New energy vehicles are the first choice. I prefer to be intelligent and have a better driving experience. Let’s take a look around today and exchange our old car for a new one in a couple of days. "

  How to apply for car trade-in subsidy? The reporter learned that consumers can enter the application through the website of the "National Automobile Circulation Information Management" system or the "Car Trade-in" applet.

  Replacement of home appliances-

  Merchants let the market get hot.

  "Trade-in" is not a new term for the home appliance market. The difference is that more businesses have joined the trade-in activities this year. On May 11th, the reporter visited some appliance stores in our city.

  The reporter saw that many merchants have advertised "trade-in", and almost all the home appliances in the store have billboards. In the corridors and aisles, the slogan of "trade-in" can be seen everywhere. A staff member told the reporter: "Many commodities can be’ trade-in’. This year, there are more commodities participating in the activities and the publicity is stronger. Generally speaking,’ trade-in’ can be deducted from 200 yuan to 300 yuan, and you can participate in activities regardless of the brand or quality. Some merchants don’t even take away the old machines, and then make profits for consumers. "

  The reporter found that in addition to trade-in, merchants also launched other promotional activities, and some brands launched "group purchase coupons" benefits. After consumers receive coupons online, they can also purchase new products by superimposing in-store promotional activities; Some brands offer services such as "10-year warranty" and free cleaning; Some products focus on intelligence, and users can control them remotely by connecting their mobile phones. Nowadays, intelligent household appliances such as "washing machine+dryer", dishwasher and sweeping robot have entered more and more families. A salesperson told the reporter: "According to the needs of consumers, merchants will launch different products, some of which are economical and applicable, and some of which can meet the needs of high-quality life, but overall, green and energy-saving products sell best."

  "Come in and have a look, this is our new TV set. Its biggest highlight is’ seamless adsorption’, separated design and stereo surround, and the picture and color are even less, which can meet the needs of family viewing. " The clerk said to the consumers who are buying TV sets, "The promotion activities during the May 1 ST period are still going on. As long as they really want to buy them, the price can be negotiated again." "Now many consumers value cost performance, and similar products with low price, good quality and high energy efficiency are more popular." A citizen who just bought a TV set told reporters.

  So, which home appliances do consumers most want to join the trade-in activity? The reporter learned that some consumers hope that the trade-in activities of large household appliances such as refrigerators and washing machines should be implemented so that consumers can really get benefits. Another part of consumers said that the upgrading speed of large household appliances is slow, and it is more affordable for small household appliances to join the activities. "Before replacing the old electric baking pans at home, 50 yuan changed the price for a new one. Small household appliances are broken, which costs a little more to repair, but it is a pity to throw them away. This kind of activity is quite good. " Citizen Gao Min said. Ms. Dong, a citizen, said that there are many broken small household appliances at home. If different types of small household appliances can be exchanged for each other, it would be better to buy the products they need.

  Home improvement kitchen and bathroom "rejuvenation" new-

  Green, intelligent and energy-saving become the first choice.

  With a gentle kick, the toilet lid automatically rises, freeing hands; With a wave of your hand, the range hood hidden in the hanging cabinet can be lowered; Remote control operation, the mattress bends into an S-shape, which makes the body fit and relax … Nowadays, green, intelligent and energy-saving products emerge one after another in home stores. Will the home market be "rejuvenated" with the current trade-in craze? On May 13th, the reporter visited some home markets in our city.

  On the morning of the same day, in a home improvement building materials market in the middle section of Wenming Avenue, the reporter met Ms. Niu, a citizen. "I just bought a new house for my child in March this year, and now the hard clothes will end immediately." She is consulting the whole house customization and told reporters. After a few days of shopping, she realized that there are a lot of wardrobe plates, such as density board, particle board, pine board, multilayer board and solid board, which are dazzling. "The child will get married at the end of the year, so in the choice of building materials, my biggest requirement is that the environmental protection level should be high. This is the case with wardrobes and cabinet plates, as well as the previous latex paint."

  In addition to the popularity of green building materials, smart and energy-saving products have also become popular choices for consumers. In a bathroom shop on the first floor of the building materials market, the latest smart toilets were put in a conspicuous position. "At present, the best selling in our store is the smart toilet. In the past, most young people liked it, but now the customer base is wider. Many middle-aged and elderly people change their clothes and choose smart or light smart toilets. " Zhi Hong, a salesperson of the store, introduced it. Now the smart toilet is no longer "unattainable". You can buy a light smart toilet with heated seat and automatic lid lifting for more than 2,000 yuan, and the price is similar to that of ordinary toilets. "Our smart toilets and light smart toilets are both water-efficient secondary, and its sensing device will discharge water according to the load-bearing time, providing consumers with quality life and saving water at the same time." Zhihong said.

  Kitchen and bathroom is the core area of the family and an important functional area. In addition to the renovation of new houses, many consumers who renovated old houses also started from the renovation of kitchen and bathroom. Ms. Gao, who lives in the Laker Triangle, originally bought a second-hand house, which was already decorated when she bought it. "I didn’t redecorate because of the limited budget. Now that I have a little more money, I want to clean up the kitchen. " Ms. Gao, who is choosing a gas stove, said that at present, the cupboard has been replaced at home, and then a set of more energy-efficient stoves and range hoods should be selected.

  During the interview, the reporter learned that some businesses have launched trade-in activities, and at the same time, businesses are still continuing the "May Day" discount and various combination package promotions. "I saw the trade-in implementation plan issued by the province on the Internet, and I hope that businesses can launch related activities as soon as possible. In this way, the merchants will make some profits and the government will subsidize them. We can also upgrade our consumption and enjoy a higher quality smart home. " Ms. Niu said.

  What did you get in exchange for the old one?

  A few days ago, the Provincial Department of Commerce and other departments jointly issued a document to promote the full implementation of trade-in of consumer goods in Henan Province, focusing on the implementation of three major projects: trade-in of automobiles, trade-in of household appliances and "rejuvenation" of home improvement and kitchen and bathroom. Our city is also promoting this work. What changes have been brought to our production and life by the trade-in of consumer goods?

  Trade-in of consumer goods has brought about an improvement in people’s quality of life. In the new round of trade-in activities of consumer goods, the new products replaced tend to be new energy passenger cars, green smart home appliances, smart electronic products, smart homes and other new products. These new products focus on green and intelligence, bringing convenience and intelligence to people’s lives, especially some aging smart products, which enhance the well-being of the elderly. Trade-in of consumer goods leads the new consumption fashion and improves the quality of life of the people.

  Trade-in of consumer goods has brought a new look to the consumer market. Consumers can exchange old products for new ones and enjoy a certain amount of subsidies at the same time. Subsidies stimulate market consumption, which is bound to set off a new round of consumption boom. Consumer goods, such as automobiles, home appliances, home improvement, kitchen and bathroom, which are included in this trade-in subsidy, are an important part of residents’ consumption and are also bulk consumer products. Subsidies from government departments and concessions from some enterprises will certainly stimulate the consumer market and then set off a consumption boom.

  Trade-in of consumer goods brings about the recycling of resources. At present, after automobiles, household appliances, home improvement, kitchen and bathroom and other household products are abandoned, some residents can’t find special recycling channels, and waste products will be littered, which may bring pollution to the environment. After the unified recycling of waste products, possible environmental pollution is avoided, moreover, waste resources can be recycled, and the quality and level of economic cycle are greatly improved.

  Trade-in of consumer goods has brought about high-quality economic development. Green and intelligence are the vane of the consumer market. Stimulated by the trade-in policy, green and smart products favored by consumers are bound to be popular. This is conducive to promoting investment and promoting enterprises to produce more green and intelligent products, thus promoting the continuous increase of the proportion of advanced production capacity and bringing more high-quality durable consumer goods into residents’ lives. This can also promote local industries to climb "high", make efforts to "new", go "green" and make great strides towards high-quality development.

  Trade-in of consumer goods has brought a new look to consumers’ life and consumption market. Relevant departments of our city should speed up the introduction of relevant policies so that consumers can enjoy the policy dividend as soon as possible and bring new atmosphere and changes.

  (Reporter Deng Wei, Gao Qian, Li Hui)

Buying a house and a car when you are in love, what should I do after breaking up?

one

Illustration Wang Chen Jun

  Transfer money during love, do you need to return it after breaking up? Buying a wedding room and registering your girlfriend’s name is a gift or a joint house purchase? Buying a car before marriage is a bride price or a gift. Can I ask for a return after breaking up? Recently, Haidian court tried many such cases, and the judge explained them in detail and gave a prompt.

  Case:

  Forced by his girlfriend to write an iou? If "coercion" is not proved, it will be returned.

  Xiao Na said that during her love with Xiaolei, Xiaolei borrowed 600,000 yuan from her on the grounds of revolving business, and then repaid 30,000 yuan. In July 2015, Xiaolei issued a debit note to her, promising to repay it at maturity, but failed to fulfill the repayment promise after the expiration. She repeatedly urged for no results, so she sued Xiaolei for repaying the loan principal of 570,000 yuan and paying interest.

  During the trial, Xiao Na submitted the IOUs and transfer records to the court. The content of the loan shows: "Xiaolei borrowed 600,000 yuan from Xiaona today, and has already paid back 30,000 yuan, leaving 570,000 yuan to be paid off before October 2015. On July 30, 2015, the borrower Xiao Lei. " According to the personal account statement of Xiao Na Bank, Xiao Na transferred RMB 600,000 to Xiaolei from 2014 to 2015 by mobile phone.

  Xiaolei recognized the transfer record, but said that he and Xiao Na were originally in love, and they often transferred money to each other during their love. He did not borrow money from Xiaona. The two parties originally planned to hold a wedding in August 2015, but a few days before the wedding, Xiao Na and several people forced him to write this IOU.

  The court held that according to the evidence submitted by Xiao Na, it can be concluded that there is a private loan relationship between her and Xiaolei, and Xiaolei should fulfill the repayment obligation, but the failure to repay all the loans so far has constituted a breach of contract. Xiaolei claimed that the IOU was issued under the coercion of Xiao Na, but no evidence was provided, so the court refused to accept it. Finally, the court ordered Xiaolei to repay Xiao Na’s loan of 570,000 yuan and pay corresponding interest.

  The judge suggested that the lender should keep the payment voucher.

  Hu Meiqing of Haidian Court said that it is very common for lovers to transfer money to each other. After the relationship ends, it is not uncommon for one party to advocate "transferring money to borrow money" and sue. Because many lovers write IOUs to each other for emotional reasons, but no loans actually occur, it is more complicated to identify such loan relationships.

  Is it a loan relationship to transfer money during the relationship? The judge believes that the party who advocates the establishment of the loan relationship generally bears the burden of proof on whether the loan relationship is true and the actual delivery of the loan. Therefore, it is particularly important for lenders to keep relevant payment vouchers. Borrowing between lovers, it is best to leave traces by means of transfer, etc., and at the same time pay attention to keeping the bank’s running water and transaction records. If you need to pay a large amount of cash, you should keep the bank’s withdrawal records, and if necessary, you should ask the other party to issue an iou or sign a loan agreement.

  Case:

  Before marriage, the court awarded 50% of the property rights under the name of one registered person.

  Another pair of lovers, Zhou Yang and Li Ting, have been dating since they were in college, and they broke up in 2015. In October 2012, the two parties jointly invested to buy a house in Haidian District, Beijing. Because Zhou Yang was not qualified to buy a house at that time, they negotiated and signed a sales contract with the real estate company in the name of Li Ting. After that, Zhou Yang paid the down payment of 1,588,519 yuan, the purchase price of 160,000 yuan, and Li Ting paid the remaining house price of 440,000 yuan. The house was registered in the name of Li Ting. On June 30, 2016, after obtaining the qualification to buy a house, Zhou Yang contacted Li Ting to handle the house transfer, but Li Ting ignored it. Zhou Yang found out that she planned to sell the house through an intermediary company.

  In this regard, Zhou Yang believes that the joint purchase of a house by both parties and Li Ting’s unauthorized sale have seriously infringed on their legitimate rights and interests, so he sued his ex-girlfriend and demanded that the house be divided according to law, with himself and Li Ting accounting for 78.3% and 21.7% respectively.

  However, Li Ting said that the house was registered in her personal name and belonged to personal property, and Zhou Yang had no right to divide it; Moreover, the purchase price paid by Zhou Yang is a gift to her, and there is no common property between the two parties.

  During the trial, both of them said that they intended to buy a house as a wedding room, but later they broke up due to emotional reasons, and the house has been occupied by Li Ting. The court held that it was an act of jointly purchasing property with marriage intention to jointly invest and buy a house in the name of Li during their love. Now the two sides have failed to get married and end their love relationship, and the purpose of buying a house has been impossible to achieve. Although the property right is registered in the name of the woman, it should still be recognized as common property. In the end, the court ruled that the house was jointly owned by two people, with each party holding 50% of the property rights, and Li Ting assisted Zhou Yang in the registration of the property rights.

  The judge suggested that buying a house together during love is regarded as common property.

  It is more and more common to buy a house jointly before marriage. Hu Meiqing believes that houses, cars and furniture jointly invested by both parties during the period of love should be regarded as common property. At the termination of the joint ownership relationship, the division of the joint property shall be handled according to the agreement if there is an agreement, and if there is no agreement, the factors such as the contribution of the co-owners, the contribution to the joint property and the actual needs of the co-owners in production and life shall be considered. In order to avoid disputes in the future, we should be cautious in buying a house together during the period of love. We can sign a capital contribution agreement in advance to stipulate their respective shares, and at the same time, we should keep relevant evidence such as bank transfer records and payment vouchers.

  Case:

  Buying a car, registering in the name of the prospective mother-in-law, breaking up, and the court awarded the refund of the car.

  A couple decided to get married. Li Wen said that he spent 226,856.9 yuan to buy an SUV as a wedding gift at the request of his girlfriend Zhang Xia. Because they were not qualified to buy a car in Beijing, they registered the car in the name of Zhang Xia’s mother Wang. However, the two sides broke up soon due to personality and other reasons. Li Wen’s request for Zhang Xia to return the car purchase fee was rejected, so he sued Zhang Xia’s mother and daughter for returning the engagement price of more than 230,000 yuan.

  During the trial, Zhang Xia’s mother and daughter argued that there was no engagement between Li Wen and Zhang Xia, and the vehicle involved in the case that Li Wen invested and registered under Wang’s name was not an engagement bride price. Because of their long relationship, Li Wen mentioned breaking up many times. Before buying a car, Li Wen broke up with Zhang Xia again. This time, he proposed to buy a car for Zhang Xia to make up for his feelings. Moreover, when buying a car, the old car under Wang’s name is discounted to 8000 yuan, so the newly bought car also has Wang’s rights and interests, which should be divided before disposal. The used car has been depreciated and should not be returned at the new car price.

  The court held that the car purchase money should belong to Li Wen’s expenditure for the purpose of marriage and has the nature of bride price. Although Zhang Xia’s mother and daughter claimed that Li Wen’s contribution was a gift, they did not provide sufficient evidence and the court did not support it. In view of their failure to get married, Li Wen has the right to demand that the other party return the corresponding expenses incurred for marriage. Regarding the amount of money to be refunded, it should be judged according to Li Wen’s actual expenses for purchasing the car. Finally, the court ruled that Zhang Xia’s mother and daughter returned Li Wen’s car purchase price of 232,983.79 yuan.

  Judge’s tip: unmarried people ask for the support of the bride price court.

  Hu Meiqing said that the phenomenon of paying bride price before marriage is a custom, which is popular in many parts of China. If both parties fail to go through the marriage registration formalities, and one party requests to return the bride price, it shall be supported. If unmarried men and women have indeed lived together but are not registered to get married in the end, the court can determine whether to return and the amount of the bride price according to the time of their living together, the amount of the bride price and the local rural customs and habits. In addition, the actual payers and recipients of the bride price are not limited to men and women themselves. If the actual recipients of the bride price are the parents of the woman or other people, when the man sues for the return of the bride price, the woman and the actual recipients can be listed as co-defendants. (The parties in the text are all pseudonyms) (Reporter Lin Jing)

The comedian organized a group to drag the opera, and the film "The Great Anti-school" was set.

Today (11th), the official announcement of the comedy film "Big Anti-Faction" will be released nationwide on April 4th. It is reported that the film has assembled more than 20 gold medal comedians, which will bring a relaxed and joyful work to the audience during the Qingming small holiday.

The comedian organized a group to drag the opera, and the film "The Great Anti-school" was set.

The movie "The Great Anti-Faction" tells the story of the little actor Bi Chao (Bao Beier) who finally got the chance to play the big villain after all the hardships. However, Bi Chao accidentally lost his memory and mistakenly thought that he was a suspect in the kidnapping case. With amnesia, he was determined to "go against the sky and change his life" and continue his plan of "kidnapping the richest man", but he did not expect to be crushed in action. Bi Chao, who was unarmed, was not only starved and beaten along the way, but also offended three gangsters who wanted money and didn’t want to die. Can Bi Chao’s goal be achieved in the end, and what kind of jokes will he encounter? It remains to be seen.

In the preview of the film’s "This villain is not very clever" version, a news report confessed that "kidnapper" Bi Chao was running around the city, but it was completely inconsistent with the description of "extremely vicious" in the report. Bi Chao not only had no money to be sent back to his original place by taxi driver, but also was caught by the security guard and ate several "big pockets" in the process of secretly stepping on the spot. The robber Bi Chao experienced all kinds of oolong events in the process of completing the goal of "kidnapping the richest man", and the unreasonable storyline also attracted the audience to burst into laughter, all of which revealed the film purpose of "making fun". And dazzling female stars, resplendent party scenes and other "eye-catching" pictures are also very eye-catching.

At the same time, there are also big scenes of "package stimulation" such as drifting around the corner and flying car blasting, which instantly boost the adrenaline of the audience. At the end of the preview, the richest man was not afraid of the robbers who caught up, and even boasted that "this is bulletproof glass", but he didn’t expect to be backhand. Bi Chao directly opened the car door, raised his pistol and said, "Get off!" It will break the game in an instant, and the relationship between the robbers and the rich will be reversed instantly. Subverting the brain hole and constantly reversing the comedy burden has also made the audience increasingly look forward to what interesting plots will follow.

The film assembled more than 20 golden comedy lineups that made people "smile", and all the performers staged a "drama in the play" that was constantly reversed. Bao Beier, the leading actor, became a distinctive "villain" this time, which was crushed by reality and brought a refreshing hilarious experience to the audience. The actors such as Xiao Spicy Li Jiaqi, Dayong Zhou, Clara, Wei Xiang, Jia Bing, Yang Haoyu and Andrew, who all appeared in the preview, are even more eye-catching. The super comedy lineup joined forces to attack, and everyone collectively shook their burdens and pulled the "laugh" fruit full.

Yangzi Evening News/Zi Niu Journalist Kong Xiaoping

The car will not give way to each other, and the "road anger" man actually instructed the truck to hit the car.

  Guangzhou Daily News (all-media reporters Jessica Fong Ching correspondent Li Xiaoyuan and Zhou Bo) On March 23rd this year, a movie-like "car-chasing and intercepting play" was staged on Jinsha Road in Haizhu District, Guangzhou. In order to stop a car, two large trucks did not hesitate to chase the car for one kilometer, cross the line, turn around and even hit the other car’s head. It turned out that the driver of this car had beaten with another car driver, Zhou, because of the problem of not giving way to each other in the narrow road. When Zhou was angry, he called relatives driving big trucks to intercept each other. On the morning of July 30th, Guangzhou Haizhu District People’s Court held a public hearing on Zhou’s case of suspected trouble-making, and pronounced a sentence in court. Zhou was sentenced to seven months’ imprisonment.

  According to the prosecution’s allegations, at 22: 40 on March 23 this year, when the defendant Zhou drove a car out of Innovation Road via Xinmin Sixth Street in Haizhu District, he met Kuang Mouming driving a car from Innovation Road to Xinmin Sixth Street. Because of the narrow road, two cars cannot pass at the same time. Due to the problem of avoiding the car, the defendant Zhou had an argument with Kuang Mouming and his co-pilot Kuang Mouhua, and then the two sides beat each other.

  After a "scuffle", Kuang Mouming and Kuang Mouhua drove away first, and the defendant Zhou immediately left a voice message on his relatives’ WeChat group using WeChat, claiming that he was injured in Xinmin Sixth Street and asked his relatives to come over to help chase him by car. At the same time, he also called relatives to inform them to drive to the scene.

  Later, two large trucks called by the defendant Zhou arrived at the scene, and Zhou sat on one of the large trucks and commanded to catch up with the car for nearly one kilometer. When chasing after the Jinsha gas station near Jinsha Road in Haizhu District, Zhou’s big truck intercepted the small car driven by Kuang Mouming. When Kuang Mouming saw it, he turned around and fled. At this time, another big truck rushed from the opposite lane and crossed the line and crashed into the small car driven by Kuang Mouming, causing damage to the left front of the car and the left rear mirror.

  After Kuang Mouming was hit and stopped, Zhou’s big truck immediately stepped forward to intercept. Zhou and others got off the cab and wanted to rush to the vehicle driven by Kuang Mouming. When Kuang Mouming saw it, he immediately drove away from the scene and called the police for help. Subsequently, the defendant Zhou was arrested by the police. After identification, the injuries of Kuang Mouming and Kuang Mouhua were all minor injuries, and the loss price of the car driven by Kuang Mouming was RMB 8663.22.

  The prosecutor asked in court, "Do you know the consequences of chasing cars on the main road?" "Why didn’t you call the police immediately?" Zhou argued that the reason why he informed his relatives to chase and intercept Kuang Mouming’s driving vehicle was that Kuang Mouming and Kuang Mouhua beat him and fled. He didn’t remember their license plates, only recognized cars and people, "just wanted to intercept the other vehicle and call the police", but there was no alarm after the collision.

  After trial, Haizhu District People’s Court held that the defendant Zhou chased and intercepted others, and the circumstances were bad; Arbitrary destruction of public or private property, if the circumstances are serious, has constituted the crime of stirring up trouble. The defendant Zhou confessed his crime truthfully after arriving at the case and voluntarily pleaded guilty, which can be given a lighter punishment according to law. The defendant, Zhou, had an altercation with Kuang Mouming’s party because of the meeting, and then beat each other. After Kuang Mouming’s party left, he still called others to drive the truck to catch up with and intercept the vehicle driven by Kuang Mouming. His behavior of catching up and intercepting had a great impact on traffic order, and he was given a heavier punishment as appropriate. Considering that Kuang Mouming was at fault, and the defendant Zhou had actively compensated Kuang Mouming for his losses, he was given a lighter punishment as appropriate. In the end, the court ruled that the defendant Zhou constituted a crime of seeking trouble and sentenced him to seven months in prison.

Test drive Guangzhou Automobile Aian AION Y: 100,000-class pure electric SUV.

In the domestic household scooter market, it is a hot model. Since then, this car has been favored by many consumers because of its close price and good product strength. At present, 16 models have been launched for consumers to choose from, and the price range is 99,800-145,800 yuan. So is this car suitable for starting? Today, we will take the entry-level model with a price of 99,800 yuan-2024 Plus 310 Xingyao Edition as an example to analyze with you.

First of all, look at the appearance. As a new energy vehicle, AION Y does not adopt a closed front face like many pure electric vehicles, but retains the design of the air intake grille. The front of the car adopts front headlights with split design, and the interior presents a fan-shaped arrangement, which improves the recognition of the front of the car.

The side of the car body benefits from its short suspension and long wheelbase design, so when you look at it from the side, there will be an MPV atmosphere. The style of the hub is relatively simple, and it is equipped with 215/55 R17 specifications.

In the rear part, the word "AION Y" is placed in the middle of the tailgate, which looks more conspicuous. The rear design of "AION Y" is simpler, with a rich sense of hierarchy and a fuller look. The tail wing with the same color as the car body at the top has been hollowed out, and the shape of the taillight is relatively slender.

Entering the car, the interior design of AION Y is relatively simple. The center console is mainly covered by a black plaque, and the air outlet of the air conditioner is hidden under this plaque, which looks very regular. It adopts the design style of flat bottom and double spokes, and it feels good to hold. The main driver is equipped with a 10.25-inch full LCD instrument panel, and the display effect is relatively clear.

In addition, AION Y is also equipped with a 14.6-inch central control screen with built-in ADiGO 4.0 intelligent interconnection ecosystem, which supports navigation system, navigation road information display, service, Bluetooth/car phone and other functions. Moreover, the response speed of this system is relatively fast, and it is very convenient for daily use.

In terms of other configurations, AION Y comes standard with practical functions such as body stability system, brake assist, keyless start, remote start, uphill assist, and remote control of mobile App. At the same time, the whole system comes standard, which can detect the working state of tires in real time, and its performance in safety is quite good.

In terms of seats, AION Y is made of imitation leather, the front seats all support manual four-way adjustment, and the main driving seat is equipped with the function of height adjustment. The rear seats support a 40:60 ratio, which can further expand the space of the luggage compartment.

In terms of space, AION Y has a body length of 4,535 mm, a width of 1,870 mm, a height of 1,650 mm and a wheelbase of 2,750 mm. Although it is positioned as a compact SUV, such data performance has reached the new standard. Therefore, the ride space of this car is relatively spacious. The experiencer with a height of 1.75 meters sits in the front row, and after adjusting the seat to a suitable position, the head space is about one punch and three fingers. At this time, the seat is kept still and comes to the back row. There are still more than two punches in the head space and more than two punches in the legs.

In terms of storage capacity, AION Y’s luggage compartment has a volume of 405 liters, a depth of 880 mm, a width of 1020 mm and a height of 700 mm. After putting down two 28-inch suitcases, there is still room for some small items. In addition, the second row of seats in this car can be almost flat after being put down, and it can be easily handled if you need to pull some big items occasionally.

In terms of chassis, AION Y adopts the body structure, the front suspension is McPherson type, and the rear suspension is longitudinal arm torsion beam type. This configuration is also a common configuration at this price. When passing through the potholed road, AION Y’s shock absorption effect is still quite good, without the feeling of "hitting hard", and the comfort performance is not bad. However, due to the high center of gravity, this car will have obvious inclination when cornering at high speed, and its handling is relatively average.

In terms of power, the AION Y we test-drive is equipped with a permanent magnet synchronous single motor, with a total power of 100 kW and a total horsepower of 136, with a total of 176. The transmission system is matched with an electric vehicle single-speed gearbox. The battery pack has a capacity of 37.9 kWh and a pure electric cruising range of 310km, which is enough for urban transportation, and the cost of daily vehicles will be much lower than that of fuel vehicles.
From the perspective of vehicle driving, AION Y provides a smooth, comfortable and sporty driving experience, which is suitable for daily home and work. It has a variety of driving modes and steering modes to meet different driving needs. Suspension system and chassis are tuned to comfort, which can effectively filter road vibration and provide a comfortable ride experience. The power output is linear and delicate, providing a good push back feeling at low speed, and the influence of wind noise and tire noise is relatively amplified at high speed. I-PEDAL mode can adjust the strength of kinetic energy recovery in real time, realize reasonable control of vehicle speed by opening and closing the accelerator pedal in low-speed traffic jams, and provide different driving experiences. The adjustment of accelerator pedal and accelerator pedal is linear, which makes AION Y very comfortable to drive as a whole. Summary: Through this test drive of AION Y, we found that this car does have a good performance in terms of space, and both the riding space and the loading space meet the needs of most people. In terms of driving experience, the power output of this car is relatively linear, and the steering feel is also very light, so it is not difficult to drive. For novice drivers who just got their driver’s license, AION Y should be a good choice. Of course, if you just want to buy a daily scooter, then AION Y is also worth considering.

Predicting the survival benefit and immune response of immunotherapy for multiple cancers based on mutation gene sets.

This issue of the "Precision Frontier" column shared by Zhao Haitao’s research team published inGenome Medicine(IF =11.12) [1], a mutation signature was constructed and verified to predict the prognosis of patients receiving immunotherapy, and the potential immune response of different subtypes was studied by using multidimensional data.

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Research background

Immunocheckpoint inhibitors (ICI) have changed the treatment of many cancers. However, the beneficiaries of ICI treatment are limited, so it is necessary to screen and predict biomarkers to classify patients. At present, many biomarkers, such as tumor mutation load (TMB), have been used as indicative biomarkers in clinic. However, some high TMB patients with gene mutation related to immunotherapy resistance are not sensitive to ICI treatment. Therefore, it is necessary to go beyond TMB and identify the specific genetic determinants of ICI treatment response.

research design

The study included genome and clinical data of 12,647 patients. There were 1572 cases in the training set (immunotherapy patients with 9 kinds of cancer) and 932 cases in the verification set (immunotherapy patients with 5 kinds of cancer). The training set was sequenced by MSK-IMPACT panel containing 468 genes.

The authors identified a set of 11 genes based on mutation, which can divide patients into high-risk and low-risk groups. The mutation of these 11 genes is related to the better response to ICI treatment, and this gene set has been proved to be an independent prognostic factor after ICI treatment.

research results

1. Identify mutant gene sets that can predict the outcome of immunotherapy.

Firstly, the survival differences of 468 genes in the training set were compared between wild type and mutant type, and 98 genes related to OS (global survival) were obtained. After that, LASSO COX regression analysis was further screened and 11 important genes were finally obtained. Through COX regression analysis, the risk score of each patient was quantified on the basis of 11 mutant gene sets. In the training concentration, the OS of patients in the high-risk group is shorter than that of patients in the low-risk group (Figure 1B). In order to study whether the gene set is limited to a specific population or suitable for different populations, the subgroup analysis regardless of age, drug use type and cancer species shows that the gene set is significantly related to the OS of patients treated with ICI (Figure 1C-E).

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Figure 1. Generation and Verification of Gene Set Based on Mutation

2. Verification of predictable immunotherapy results

In order to further confirm the value of mutation-based gene set in predicting the results of immunotherapy, it was found that the OS of low-risk group was higher than that of high-risk group (Figure 1F). The research results of predicting ICI treatment response in gene set show that the DCB(durable clinical benefit) of ICI treatment in low-risk group is significantly increased compared with that in high-risk group (Figure 1G), and low-risk patients are more likely to respond to ICI treatment (Figure 1H). These results get the same results in the verification set (Figure 1I, J).

3. Gene set is an independent prognostic predictor of immunotherapy.

Next, the author verifies whether the gene set based on mutation is an independent predictor of immunotherapy response. In the training and validation set, univariate COX regression analysis showed that the gene set was related to OS. After adjusting for drug type, tumor type and TMB, multivariate COX regression analysis showed that the gene set was still an independent predictor, which confirmed the stability of its independent prediction of ICI prognosis (Figure 2A, B). In order to determine which factor has the best predictive performance, C-index is used to compare the performance of mutation-based gene sets with TMB and drug types. The results of C-index show that the gene set based on mutation can predict the prognosis more accurately than TMB and drug type in both training set and validation set (Figure 2C, D).

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Fig. 2. Relationship between mutation-based gene sets and other characteristics

4. The clinical benefit of ICI treatment can be predicted based on the mutant gene set, disease stage, CTL and 6-IFN-g gene signature.

Considering the stage of disease, CTL and 6-gene IFN-g signature have been proved to be highly predictive of the response to ICI treatment, the authors speculate that they may play a synergistic role in predicting the response to immunotherapy. The author combined the gene set based on mutation with disease stage, CTL and 6-gene IFN-g signature through Nomotograph, and provided a method for clinicians to quantitatively predict the OS of patients treated by ICI. Fig. 2E is the nomogram of Riaz cohort construction, and the calibration curve of fig. 2F shows the consistency of actual and predicted results, indicating that these signature should be integrated into the predicted nomogram of ICI treatment.

5. Potential external immune landscape of high and low risk groups

In order to further explore the relationship between immune system and mutation-based gene set, the authors conducted a multi-group analysis of TCGA cohort, and the risk score divided TCGA cohort into high and low risk groups (Figure 3A). At the genome level, the proportion of white blood cells, lymphocytes and TIL in the low-risk group was significantly higher than that in the high-risk group (Figure 3B-D). The H&E staining results of TIL ratio are consistent with the above results (Figure 3E). In addition, the proportion of immunostimulatory cells (such as CD8 T cells) in the low-risk group is also significantly higher than that in the high-risk group (Figure 3F). The above results were further tested by Danaher et al.’ s immune infiltration score (figure 3G) and immune characteristic score (figure 3H), and it was found that the abundance of immune cells in low-risk group was higher. Then unsupervised clustering was used to cluster the immune characteristic scores of patients in TCGA cohort, and the results were clustered into two immune infiltration modes (Figure 3I), and the high immune infiltration was significantly enriched in the low-risk group (Figure 3J).

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Fig. 3. Immune status of high and low risk population in TCGA cohort.

In addition, the immune signature in the low-risk group was significantly higher than that in the adjacent cancer tissue; On the contrary, the immune signature in the high-risk group was significantly lower than that in the adjacent tissues (Figure 4A). The correlation of immune activity in low-risk group was significantly higher than that in high-risk group (Figure 4B, C). GSEA results showed that 13 pathways were significantly enriched in the low-risk group, including 6 immune-related pathways, such as "cytotoxicity mediated by natural killer cells" (Figure 4D). Tumors in the low-risk group are associated with significantly higher CYT scores, and the number of fibroblasts in the high-risk group is now increasing (Figure 4E, F). According to these results, the low-risk group is rich in immune cells, which can respond to ICI treatment, and fibroblasts may help the high-risk group escape. The expression of chemokines in the low-risk group is higher (Figure 4G, H), so the author speculates that the enrichment of chemokines in the low-risk group may trigger an immune response.

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Figure 4. Potential external immune landscape of high and low risk groups 

6. Potential inherent immune landscape of high and low risk groups

Some potential factors determining tumor immunogenicity between the two groups were compared. Mutation, new antigen load, TCR and BCR diversity in low-risk group were significantly higher than those in high-risk group, but CNV load and aneuploidy in high-risk group were higher than those in low-risk group (Figure 5A). This result is consistent with previous studies, that is, tumor aneuploidy is related to immunotherapy and decreased immune escape marker response. In addition, the heterogeneity of tumor in high-risk group is higher than that in low-risk group, which further supports the view that tumor will promote the development of heterogeneity in the presence of cytolytic activity and less active infiltration of immune cells. In order to further understand the mutation process of high and low risk groups, the mutation characteristics were described according to somatic mutation data, and four different mutation patterns were determined in TCGA cohort (Figure 5B). The frequency of these four mutation signals in the low-risk group is significantly higher than that in the high-risk group (Figure 5C). In addition, it was also found that immune checkpoint molecules (such as PD-1, PD-L1 and CTLA4) and costimulatory molecules were more highly expressed in the low-risk group (Figure 5E).

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Figure 5. Potential innate immune response and escape landscape in high and low risk groups. 

7. Copy number characteristics of high and low risk groups

Significant differences in chromosome variation were detected in high and low risk groups (fig. 6A). Local amplification peaks of immune genes with good characteristics, such as PD-L1 (9p24.1) and PD-L2 (9p24.1), were observed in the low-risk group (fig. 6B, C). GO function annotation of the specifically amplified genes showed that the low-risk group was significantly enriched in two immune-related biological processes, while the high-risk group was significantly enriched in the biological process of "positive regulation of fibroblast proliferation", but not in any immune-related biological processes (Figure 6E). At the level of mRNA expression in TCGA cohort, the expression of PD-L1 and PD-L2 mRNA in low-risk group increased significantly (Figure 6G), which was consistent with CNV data. This finding suggests that CNVs in tumor contributes to the observed difference in immune infiltration.

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Figure 6. Variation of copy number in high and low risk groups

discuss

This study is the first time to use an independent cohort to study the comprehensive mutant gene sets of different tumor types. Through PSM algorithm, hierarchical analysis and multivariate COX regression analysis, the application performance of mutation-based gene sets in different types of tumors was tested, and the results showed that mutation-based gene sets were reliable.

This study has the following innovation and practical application value. First, different types of tumors (such as NSCLC (non-small cell lung cancer), melanoma and renal cell carcinoma) are used, which represent the most common types of cancer treated with ICI. Secondly, the application of multiple biomarker prediction model needs to understand the factors that affect the accuracy and precision of Qualcomm analysis in clinical practice. The risk score formula and threshold of mRNA expression calculation are not suitable for verification with other types of data. Therefore, this study developed a gene set based on mutation to predict the clinical efficacy of ICI treatment. The composition of the above mutations is neither affected by tissue types nor adjusted by any other biomarkers. The risk score formula and threshold of gene set based on mutation can be verified by other tumor analysis methods, such as DNA sequencing and single nucleotide polymorphism microarray analysis. Therefore, mutation-based gene sets are not affected by technological changes, even when different platforms are used in different centers. Thirdly, in practice, gene sets based on mutations avoid exposing patients to potential immune-related adverse reactions when they are unlikely to respond, and enable patients to match to potentially more effective treatments more quickly. Fourthly, the prediction performance of gene set based on mutation is compared with other factors that can predict immunotherapy, and it is found that the prediction performance of gene set based on mutation is better than all these factors.

Several limitations of this study. First of all, because some mutations may be enriched in some tumor types, the initial goal of this study is to create a panel instead of identifying a single gene (such as BRAF), because the former can contain more genes to predict the prognosis of different types of tumors. Secondly, although the immune landscape of 11 genes in the gene set based on mutation has been explored, it is still necessary to clarify the molecular mechanism of each gene affecting immunotherapy in vivo and in vitro functional experiments. Thirdly, the enrichment scores of carcinogenic pathways and the expression patterns of immune checkpoints should also be detected by immunohistochemistry.

tag

The mutation-based gene set proposed in this study is the first comprehensive genomic marker systematically identified, which can be used to evaluate the ICI treatment effect of pan-cancer species. This study is also the largest prognostic model discovery project for cancer patients receiving ICI treatment (whether single drug treatment or combined treatment of anti-PD-1 and anti-CTLA-4). Nomoto, which combines mutation-based gene set with TMB and drug types, can help clinicians choose patients who may have a strong response to ICI treatment. In addition, it also reveals the different immune conditions of high and low risk groups, and specific genomic changes may drive the formation of these microenvironments. In a word, this work puts forward a new tumor classification method, which may guide the decision-making of ICI treatment. END 

References:

[1] Long, J., Wang, D., Wang, A. et al. A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape. G enome Med 14, 20 (2022). https://doi.org/10.1186/s13073-022-01024-y

Write Liu Hua Hua

Editing and typesetting SX

How do new Chinese immigrants overcome the difficulty of studying?

  How do new Chinese immigrants overcome the difficulty of studying?

  When new Chinese immigrants come to foreign countries and work hard, it is often difficult to take care of their children’s studies. In recent years, some young Chinese immigrants have gone abroad to study, but they are also faced with challenges such as different study environments in foreign countries and family financial difficulties, resulting in some dropouts. Let the children of new immigrants and young new immigrants better integrate into the new learning environment and ensure their academic success, which requires better home-school cooperation and better system design at the social level.

Psychological counselors are teaching parents how to ensure that their children get high school diplomas. Photo by Zhu Zeren (World Journal, USA)
Psychological counseling teachers are teaching parents how to ensure that their children get high school diplomas (photo by Zhu Zeren, World Journal, USA))

  It is not common to play truant and work.

  When new Chinese immigrants first arrive in the United States, they face many difficulties, and the education of their children is one of them.

  According to the US "World Journal" report, due to the large number of young shop assistants recruited by Chinese restaurants and retail stores in new york, the problem of many new immigrant Chinese students dropping out of school is more serious.

  According to Zhao Hongfang, a bilingual psychological counselor at Jiangbang High School in Flushing, some Chinese students are in Internet cafes all day and night. When they are familiar with the store, they actually help to watch the store at night. When asked by their parents how they have money to spend, they lie about working after class.

  Some Chinese students don’t get along well with their parents, so they moved out at the age of 17 and watched the shop at night to earn living expenses. In particular, the owners of new Chinese restaurants in Flushing are looking for young clerks who know English, attracting a large number of dropouts. The school said that they would go to the restaurant to bring these students back.

  However, the lack of diplomas will only bring more difficulties for new immigrants to seek a living in the United States in the future. According to the report, a survey in new york in 2015 showed that the annual salary of those without a high school diploma was only $21,121, those with a high school diploma was $31,038 and those with a bachelor’s degree was about $60,000.

  It is worth noting that although new Chinese immigrants have played truant, worked or even dropped out of school, this is not the norm.

  In an interview with this newspaper, Liang Guanjun, chairman of the American East Asian Association, believes that some students in every school play truant or drop out of school for some reason. "Flushing is so big, and employment opportunities are still limited. We can only say that this phenomenon exists among the new immigrants in new york, but the size of the’ large number’ in the report is debatable."

  Even so, the difficulty in adapting to new Chinese immigrants still needs attention.

  Inadvertence in discipline and difficulty in adaptation

  Different from the "Chinese" born and raised in the United States, behind the new Chinese immigrants who came to the United States to work and play truant is the helplessness of their families’ inability to discipline and adapt to the environment.

  "This is an old problem, which exists in big cities in the east and west of the United States and is quite difficult to solve." Chinese lawyer Sun Lantao said in an interview with this newspaper that Chinese in the United States often choose school districts to send their children to school. All the above phenomena occur in bad school districts. There, parents are forced to survive, sometimes working hard for 12 hours every day, and have no time to ask about their children’s learning. Children’s own English is not enough, and they are under bilingual pressure, so they are discouraged and unwilling to learn.

  For new immigrant students, the financial hardship of their families is also a major incentive to play truant and work. "Nowadays, in the United States, it is not easy for restaurants to recruit people, so the salaries are relatively high." Liang Guanjun introduced that the monthly salary of Flushing Restaurant is about 2,800 dollars, which attracts students who can’t go on studying, and there are also cases where individual families have financial difficulties and need their children to make money.

  The educational environment and allocation of educational resources in American society are also very different from those in China.

  Sun Lantao introduced that the US Constitution and the constitutions of all states stipulate that any school-age children must receive compulsory education before the age of 18, regardless of whether they or their parents have immigration status. That is to say, even the children of illegal immigrants, as long as they are school-age children, no matter where they live, public schools must accept them and must not refuse them to go to school on the grounds of poor English and insufficient test scores. However, at the implementation level, the imbalance of educational resources has greatly reduced the effect of ensuring the enrollment rate of immigrant children.

  "American culture is different from that of China, where the whole people attach importance to education. Ordinary public schools often have poor basic education. Psychological counseling and bilingual guidance advocated by the education department cannot be put in place at all because of the lack of human resources. " Sun Taotao introduced.

  The negligence of family discipline and the difference of social environment bring poor communication between home and school, which eventually leads to inefficiency in the academic management cooperation of new immigrant children. "Chinese immigrants, Chinese new immigrants, survival is a problem, and the language is unreasonable. I don’t know how to start." Sun Lantao said that the communication information between parents and school teachers is seriously poor, which reduces the effectiveness of cooperation between schools and parents.

  Multi-party cooperation to promote studies together

  How to help new Chinese immigrants better integrate into the new learning environment and ensure their enrollment rate? Experts said that the joint efforts and effective cooperation of all parties are needed.

  On the one hand, new immigrant families need to integrate into the new study environment more actively. Cai Wenyao, consultant of the American Chinese Chamber of Commerce, said in an interview with this newspaper: "Children need to get out of the comfort zone and consult more local students. Parents can also make good use of community resources and communicate with other immigrant parents who have experienced difficult stages instead of resting on their laurels."

  At the same time, home and school also need to better cooperate, psychologically appease their children, and more effectively prevent students who want to skip classes and work from drilling loopholes in the system.

  In an interview with the World Journal, Zhao Hongfang said that parents can take the initiative to provide contact information to the school and learn to check attendance records and grades online. If parents leave their children completely unattended, the school can report it and ask the Children’s Service Administration to intervene in the investigation.

  On the other hand, the society can also make efforts in promoting the children of Chinese new immigrants to study.

  "In a short time, it is still a luxury to solve the problem of young Chinese immigrants going to school." Lawyer Sun Lantao said that despite this, from the legislative point of view, with the increasing proportion of Chinese in politics, this phenomenon will attract the attention of political circles, and the education department will also strengthen investment in this group and training bilingual teachers. With the increase of corresponding educational resources and infrastructure, the current situation may gradually change.