Chen Z.,University of Oxford |
Peto R.,University of Oxford |
Zhou M.,Chinese Center for Disease Control and PreventionBeijing |
Iona A.,University of Oxford |
And 16 more authors.
The Lancet | Year: 2015
Background Chinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in previous generations. We assess the oppositely changing effects of tobacco on male and female mortality. Methods Two nationwide prospective studies 15 years apart recruited 220 000 men in about 1991 at ages 40-79 years (first study) and 210 000 men and 300 000 women in about 2006 at ages 35-74 years (second study), with follow-up during 1991-99 (mid-year 1995) and 2006-14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers. Findings Two-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 [95% CI 1·24-1·41] vs 1·65 [1·53-1·79]; rural: RR 1·13 [1·09-1·17] vs 1·22 [1·16-1·29]), as did the smoking-attributed fraction of deaths at ages 40-79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79-2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11-16·15), lung cancer (RR 3·78, 2·78-5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66-2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30 943, 3265/62 246, 2339/97 344, and 1068/111 933). The smoker versus non-smoker RR of 1·51 (1·40-1·63) for all female mortality at ages 40-79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840 000 male, 130 000 female) deaths in China. Interpretation Smoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation. © 2015 Chen et al.
News Article | November 3, 2016
FAIRPORT, NY, November 03, 2016-- William Y. Chey, MD, DSc, has been included in Marquis Who's Who. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.With more than 50 years of experience as a physician, educator and research scientist in gastrointestinal medicine, Dr. Chey is widely recognized for his expertise in the field of gastroenterology and hepatology. Prior to his retirement in 2000, he served as a professor of medicine and director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center, and as a consultant gastroenterologist at Canandaigua VA Medical Center. He is a fellow of the American College of Gastroenterology and the American Gastroenterological Association, a member of the AGA Legacy Society, and was a member of the American Association for the Advancement of Science and American Physiological Society, among other medical organizations. In addition, he is the former president of the American Pancreatic Association and the American Society of Acupuncture. He was invited nationally and internationally as a visiting professor by numerous prestigious institutions in the United States, Europe, Asia and Mid-Eastern countries. In particular, he holds the titles of Honorary Professor at the Catholic University College of Medicine, Seoul, Korea and Visiting Professor at Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China and Korea University College of Medicine, Seoul, Korea.After completing his medical education in 1953 through the two top medical schools in Seoul, Korea, Seoul National University and Yonsei University in Seoul, Korea, and serving as a medical officer of the Republic of Korea in the Korean War, Dr. Chey emigrated to the United States in 1954 and had his post-graduate training including internship and residency in internal medicine at City Hospital of New York, fellowship in pathology at Mount Sinai Hospital, New York, and fellowship in hepatology at Jersey City Medical Center, Seton Hall University School of Medicine and Dentistry, Jersey City, NJ. Then he received advanced degrees of Master of Science in Gastroenterology in 1962 and Doctor of Science in Medicine in 1966 from the University of Pennsylvania School of Medicine. At Temple University Medical Center and the Samuel S. Fel's Research Institute, Temple University School of Medicine, Philadelphia, PA, he finished a fellowship in gastroenterology and became a faculty member in 1963. He was an Associate Professor of Medicine and Head of Gastrointestinal Research in 1971 when he was recruited by the University of Rochester School of Medicine and Dentistry, Rochester, NY. He was the Founding Director of the Isaac Gordon Center for Digestive Diseases and Nutrition at the Genesee Hospital and Attending Physician at Strong Memorial Hospital, Rochester, NY. In 1992, he became Director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center. He was also the Founding Director of the William and Sheila Konar Center for Digestive and Liver Diseases at Strong Memorial Hospital until his retirement in 2000. During his tenure, he trained numerous clinical and research fellows from the United States and abroad, including Asia, Europe, South America, Mid-East and Africa. The majority of them returned to their native countries and are active in their leadership positions. During the following ten years, he enjoyed practicing gastrointestinal medicine at the Rochester Institute for Digestive Diseases and Sciences and was also actively involved in the American Gastroenterological Association and the American Pancreatic Association. He has been married to Fan K. Tang since 1959. They have 4 children; William D. married to Janine Zwiren, Donna married to Dale Hoellrich, Richard married to Maura Bauman, and Laura married to Richard Warren, and 9 grandchildren; Cameron, Brandon (deceased), Samuel, Megen, Russell, Paris, Wyatt, Josephine and LiLi.He contributed numerous articles to competitive scientific journals, and published many chapters in text-books and two books of his specialty and research. He was a member of the editorial board of the Pancreas and American Journal of Physiology, and has been the Editor-In-Chief of Clinical Endoscopy since 2011. He served as an active member of the National Institute of Health, Surgery and Bioengineering Study Section and a consultant to the Gastrointestinal Drug Advisory Committee, Food and Drug Administration, Department of Health and Human Services.In recognition of his contributions to medicine, Dr. Chey received a wide variety of honors and awards. He was the recipient of the V.L. William and Frisca Go Award for Life Time Achievement from the American Pancreatic Association, the Governor's Award for Excellence in Clinical Research from the American College of Gastroenterology, Distinguished Clinician Award and Mentor's Research Scholar Award from the American Gastroenterological Association, Distinguished Service Award from the Rochester Academy of Medicine and American Top Physicians Award in 2008 from the Consumers' Research Council of America. He has been cited in Marquis Who's Who in America, in Medicine and Health Care, in Science and Engineering, and in the World.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis now publishes many Who's Who titles, including Who's Who in America , Who's Who in the World , Who's Who in American Law , Who's Who in Medicine and Healthcare , Who's Who in Science and Engineering , and Who's Who in Asia . Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com
News Article | December 16, 2015
During the past two decades, Chinese science has undergone profound growth. China's investment in research and development surpassed that of the European Union in 2013, and it is predicted to overtake that of the United States by the end of the decade (see Nature http://doi.org/w5r; 2014).The proportion of published scientific papers that include Chinese co-authors has jumped from 2.4% in 1997 to 19% in 2014 — second only to the US contribution last year of 25%. Those statistics are impressive. But if China is to become a true scientific superpower, it must be able to produce great scientists who are not just knowledgeable but also creative and skilled in innovation. And great scientists need great mentors to lead the way. In recognition of the vision, dedication and hard work of those charged with nurturing the next generation of Chinese researchers, this year's Nature Awards for Mentoring in Science honour five researchers in China. The winners, feted in an 8 December ceremony, were chosen by panels composed of Chinese scientists and Springer Nature editorial representatives (see go.nature.com/hdi5k7). Submissions included statements from five people who had been mentored by the nominee and statements from the nominees reflecting their own thoughts on mentoring. Owing to China's size, submissions were divided into 'north' and 'south', with awards for lifetime and mid-career achievement in each. The 50,000-yuan (US$7,815) lifetime-achievement award for northern China was shared between immunologist Xuetao Cao, who is president of the Chinese Academy of Medical Sciences, and plant scientist Xingwang Deng, dean of the School of Advanced Agricultural Sciences at Peking University. The winner for southern China is Hongyuan Chen, an electroanalytical chemist and director of the Institute of Chemical Biology at Nanjing University. In the mid-career category, the 50,000-yuan awards for northern and southern China went, respectively, to Yigong Shi, a structural biologist and dean of life sciences at Tsinghua University in Beijing, and Hongbing Shu, an immunologist at Wuhan University. Like many Asian nations, China is often seen as a place of rigid hierarchies rooted in deference to power. One trait shared by all the winners, and indeed by all those nominated, is an understanding that the only authority in science is evidence — and that conventional wisdom must always be open to question. Shi, who was named a chair professor of molecular biology at Princeton University in New Jersey before he returned to China in 2008, thinks that most Chinese students are too wary of contradicting senior researchers and accepted scientific ideas. “I encourage my students to think critically and to challenge the authorities, including myself, so that they can learn that established rules can be broken, and with that, new fields of research can be built,” he says. Cao agrees. “We should inspire students to have confidence to challenge the dogma in the textbook and address fundamental questions in science,” he says. The lesson is not lost on the winners' protégés. “The scientific literature is a baffling mass of conflicting ideas and results, accepted wisdom and false assumptions,” notes Weilin Chen, a cancer immunologist at Zhejiang University and one of Cao's former PhD students at the Second Military Medical University in Shanghai. “Professor Cao often said that creativity comes from different directions with different views,” she says. “And he treats everyone, regardless of whether they are a PhD student or a visiting scholar, with the same high regard.” In the past, most Chinese labs were indeed quite rigid, with a single senior professor directing junior professors, postdocs and students along strictly hierarchical lines. With the rapid expansion of research institutes, however — fuelled by a large influx of researchers returning from overseas — the structure of many labs has begun to follow a less-hierarchical model, with many independent principal investigators all pursuing their own agendas and research directions. The mentors honoured by Nature have recognized the importance of instilling young researchers with the self-confidence that they need to establish their own intellectual identity and to make their own way in the world. “In my opinion, simply imparting knowledge is not enough,” says Hongyuan Chen. “A mentor should teach students the way of thinking. In the area of science, I guide my students to think in a scientific way, and give them the opportunity to solve problems independently.” He thinks that a good mentor must have a keen sense of when a student requires guidance and when he or she needs freedom. “For students who are just starting out, we need to give them more-detailed instructions to let them get used to research gradually,” he says. “And for those who have a solid knowledge base, strong independence and creativity, I let them think and practise in their own ways.” Jingjuan Xu, a former PhD student of Hongyuan Chen's and now an analytical chemist at Nanjing University, says that Chen provided an open environment that fostered imagination and creativity. “He encouraged us to read philosophy and literature, and think from different aspects,” recalls the chemist. “He said that every student is an independent, thinking being; a good mentor should nurture them to become 'horses' rather than 'sheep'.” Good mentors also recognize that it is not enough to produce successful scientists — it is just as important to teach others how to be effective, inspiring leaders themselves. Lei Li, a postdoc of Deng's at Yale University in New Haven, Connecticut, and now a professor in the School of Life Sciences at Peking University, recounts her own training in Deng's lab. “As I became more senior in the lab, Professor Deng started to ask me to help others in their lab techniques and in reading their manuscripts, which I soon realized was part of a system,” she says. “When he discovered performance issues, he never just criticized; he took time to find the root of the problem. And in several instances, he delegated me to do the pep talk.” The testimonials for the award winners all strongly reflect the scientists' unwavering dedication to the success of their protégés. But one story in particular stands out. In 2005, immunologist Bo Zhong, now at Wuhan University, applied to do a PhD in Hongbing Shu's lab after graduating with a major in English. “I was determined to study biology after graduation because I was interested in nature,” says Zhong. At Wuhan, “Dr Shu had recently been appointed as dean of life sciences, and his group [at the National Jewish Medical and Research Center in Denver, Colorado] had just published a milestone discovery in Molecular Cell. Every student with ambition wanted to join his lab — and so did I”. Zhong knew that it wouldn't be easy. “I had to admit that my background was much weaker than those who majored in biology,” he says. “I downloaded all his publications but found that I could hardly understand them. I knocked on the door to his office, and asked many naive questions. He patiently explained the details, recommended more publications to me and encouraged me to ask him if I had any difficulty in understanding the studies. Following his instructions, I read more papers, and wrote a five-page summary about pattern recognition and signalling, and asked whether I could join his lab. To my surprise, he agreed.” Shu admits that he was unsure about Zhong's potential at first, but after seeing his determination, Shu felt that Zhong deserved a chance to show what he could do. He doesn't regret the decision. “After I was convinced of his ambition and drive for a scientific career, I took him without hesitation. He has so far proved himself as one of the most successful students trained in my lab.” After taking him on, Shu asked Zhong to turn the summary that he had written into a full review paper, which became the first publication to come out of the newly formed lab. Shu thinks that patience and perseverance are among the most important traits of good mentorship, something he learnt from one of his own mentors: his PhD supervisor, Harish Joshi, a cell biologist at Emory University in Atlanta, Georgia. “I have always remembered what he told me when I was in his lab. 'Do not fire them; fire them up!',” Shu recalls. “In my 17- years' mentoring life, I have never given up on any one of my students.” A well-known Chinese saying goes, “If someone is your teacher for just one day, you should regard that person as your parent for the rest of your life.” The influence that great mentors have does indeed live long — and not just in their students, but in their students' students. “When I started my own lab in 2012, I often asked myself what Yigong would do,” says Liang Feng, a structural biologist at Stanford University in California and a former PhD student of Shi's. “I kept all e-mail communications Yigong sent to me or to the lab, and often went back to read them. They are like a 'how-to' guide for running a lab. For me and many others, Yigong was not only a great mentor and a role model, but also a relentless supporter and a lifelong friend.” The word used to describe the most revered teachers, shifu — a portmanteau of the words for teacher, laoshi, and father, fuqin — echoes the deep connection that forms between exceptional mentors and their protégés. None of the scientists who nominated their mentors for an award takes this filial bond for granted. In the words of Hongyuan Chen's protégé Jing-juan Xu, “I think that 'father' is really too high a standard to expect from a teacher. But we are the lucky children, because Professor Chen treated us like his own kids.”
News Article | January 6, 2016
Formidable capacity in genome sequencing, access to millions of patients and the promise of solid governmental support: those are the assets that China hopes to bring to the nascent field of precision medicine, which uses genomic, physiological and other data to tailor treatments to individuals. Almost exactly one year after US President Barack Obama announced the Precision Medicine Initiative, China is finalizing plans for its own, much larger project. But as universities and sequencing companies line up to gather and analyse the data, some observers worry that problems with the nation’s health-care infrastructure — in particular a dearth of doctors — threaten the effort’s ultimate goal of improving patient care. Precision medicine harnesses huge amounts of clinical data, from genome sequences to health records, to determine how drugs affect people in different ways. By enabling physicians to target drugs only to those who will benefit, such knowledge can cut waste, improve health outcomes using existing treatments, and inform drug development. For example, it is now clear that individuals with a certain mutation (which is mostly found in Asian people) respond better to the lung-cancer drug Tarceva (erlotinib; W. Pao et al. Proc. Natl Acad. Sci. USA 101, 13306–13311; 2004), and the discovery of a mutation that causes 4% of US cystic fibrosis cases led to the development of the drug Kalydeco (ivacaftor). The Chinese government is expected to officially announce the initiative after it approves its next five-year plan in March. Just how much the effort will cost is unclear — but it will almost certainly be larger and more expensive than the US$215-million US initiative. Since last spring, Chinese media has been abuzz with estimates of a 60-billion yuan (US$9.2-billion) budget, spread over 15 years. But this figure is not finalized, cautions Zhan Qimin, director of the State Key Laboratory of Molecular Oncology at Peking Union Medical College in Beijing, who is involved in the initiative. He says that the effort will consist of hundreds of separate projects to sequence genomes and gather clinical data, with support for each ranging from tens of millions of yuan to more than 100 million yuan. Anticipating the initiative, leading institutes — including Tsinghua University, Fudan University and the Chinese Academy of Medical Sciences — are scrambling to set up precision-medicine centres. Sichuan University’s West China Hospital, for instance, plans to sequence 1 million human genomes itself — the same goal as the entire US initiative. The hospital will focus on ten diseases, starting with lung cancer. Both the US and the Chinese efforts will focus on genetic links to diseases that are particularly deadly, such as cancer and heart disease. But China will target specific cancers, such as stomach and liver cancer, which are common there. The Chinese initiative is part of a series of research-funding efforts that will replace two major grant programmes, known as 863 and 973, that are due to be phased out by 2017. The new programmes will be “more organized, more efficient”, says Zhan. Genome-sequencing companies are already vying to provide services to deal with the anticipated demand. For several years, China has boasted high genome-sequencing capacity. In 2010, the genomics institute BGI in Shenzhen was estimated to host more sequencing capacity than the entire United States. This was thanks to its equipment, purchased from Illumina of San Diego, California, which at the time represented state-of-the-art technology. But Illumina has since sold upgraded machines to at least three other genomics firms — WuXi PharmaTech and Cloud Health, both in Shanghai, and the Beijing-based firm Novogene. Jason Gang Jin, co-founder and chief executive of Cloud Health, says that this trio, rather than BGI, will be the main sequencing support for China’s precision-medicine initiative — although BGI’s director of research, Xu Xun, disagrees. Xu says that precision medicine is a priority for BGI and that the organization has a diverse portfolio of sequencers that still gives it an edge. “If you are talking about real data output, BGI is still leading in China, maybe even globally,” he says. BGI has already established a collaboration with the Zhongshan Hospital’s Center for Clinical Precision Medicine in Shanghai, which opened in May 2015 with a budget of 100 million yuan and is run by Fudan University. Regardless of the details, Jin thinks that China will be faster than the United States at sequencing genomes and identifying mutations that are relevant to personalized medicine because China’s larger populations of patients for each disease will make it easier to find sufficient numbers to study. Still, it remains to be seen whether China has the resources to apply these insights to the individualized care of patients. “China wants to do it, and everybody is very excited,” says Ta Jen Liu, project director at the MD Anderson Cancer Center in Houston, Texas, who helps to establish collaborations in China and is familiar with the precision-medicine scene there. But there are hurdles. He notes that Chinese researchers and pharmaceutical companies have not had much success in developing drugs so far; that the pathologists needed to diagnose specific diseases are scarce in China; and that physicians there are notoriously overworked. “Doctors are always overwhelmed with patients, seeing 60 or 70 a day,” he says. “They don’t have time to sit down and think about what is best for specific patients.” David Weitz, a physicist at Harvard University who is starting a company in Beijing to develop diagnostic instruments for use in precision medicine, agrees that there will be obstacles, but notes the initiative’s assets. “We need lots of data to validate ideas, to validate tests,” he says. “There’s lots of data here.” He thinks that this, combined with the Chinese government’s determination to succeed, will mean that the effort will ultimately win out. “They really seem devoted to meeting the needs of the society,” he says. “It’s an exciting thing, to try to help that many people.”
News Article | November 4, 2016
By removing the protein galectin-3 (Gal3), a team of investigators led by University of California School of Medicine researchers were able to reverse diabetic insulin resistance and glucose intolerance in mouse models of obesity and diabetes. By binding to insulin receptors on cells, Gal3 prevents insulin from attaching to the receptors resulting in cellular insulin resistance. The team led by Jerrold Olefsky, MD, professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego School of Medicine, showed that by genetically removing Gal3 or using pharmaceutical inhibitors to target it, insulin sensitivity and glucose tolerance could be returned to normal, even among older mice. However, obesity remained unchanged. "This study puts Gal3 on the map for insulin resistance and diabetes in mouse model," said Olefsky, associate dean for scientific affairs and senior author of the study. "Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach." Olefsky and other researchers have been studying how chronic tissue inflammation leads to insulin resistance in type 2 diabetes. In the paper, published in the journal Cell on November 3, researchers explain that inflammation requires macrophages -- specialized cells that destroy targeted cells. In obese adipose tissue (fat), for example, 40 percent of cells are macrophages. Macrophages in turn secrete Gal3, which then acts as a signaling protein attracting more macrophages, thus resulting in the production of even more Gal3. Furthermore, investigators identified bone marrow-derived macrophages as the source of Gal3 that leads to insulin resistance. More importantly, researchers found that Gal3 is secreted by macrophages, and can then cause insulin resistance in liver, fat cells, and muscle cells independent of inflammation. Gal3 has previously been connected to other diseases. Olefsky will continue to study Gal3 depletion as a possible therapeutic target for nonalcoholic steatohepatitis as well as heart and liver fibrosis. Study co-authors include: Pingping Li, Chinese Academy of Medical Sciences, Peking Union Medical College and UC San Diego; Shuainan Liu, Zhufang Shen, Bing Cui, Lijuan Kong, Shaocong Hou, Xiao Liang, Chinese Academy of Medical Sciences, Peking Union Medical College; Min Lu, UC San Diego, and Merck Research Laboratories; Gautum Bandyyopadhyay, Dayoung Oh, Andrew M. Johnson, Dorothy Sears, Wei Ying, Olivia Osborn, Joshua Wollam, UC San Diego; Takeshi Imamura, Shiga University of Medical Science; Salvatore Iovino, Martin Brenner, Merck Research Laboratories; Steven M. Watkins, Lipomics Technologies, Inc. This research was funded, in part, by grants from the National Institutes of Health (DK033651, DK074868, DK063491, DK09062) and Merck (LKR159915).
News Article | April 20, 2016
An hour's drive from Kunming in southwestern China, past red clay embankments and sprawling forests, lies an unusual zoo. Inside the gated compound is a quiet, idyllic campus; a series of grey, cement animal houses stack up on the lush hillside, each with a clear plastic roof to let in the light. This is the Yunnan Key Laboratory of Primate Biomedical Research, and its inhabitants are some 1,500 monkeys, all bred for research. The serenity of the facility belies the bustle of activity within. Since it opened in 2011, this place has quickly become a Mecca for cutting-edge primate research, producing valuable disease models and seminal publications that have made its director, Ji Weizhi, a sought-after collaborator. Its campus houses a collection of gene-edited monkeys that serve as models of Duchenne muscular dystrophy, autism and Parkinson's disease. Ji plans to double the number of group leaders working there from 10 to 20 in the next 3 years, and to seek more international collaborations — he already works with scientists in Europe and the United States. “In terms of a technology platform, Ji is just way ahead,” says one collaborator, cardiologist Kenneth Chien at the Karolinska Institute in Stockholm. Ji is not alone in his ambitions for monkey research. With support from central and local governments, high-tech primate facilities have sprung up in Shenzhen, Hangzhou, Suzhou and Guangzhou over the past decade. Last month, the science ministry approved the launch of a facility at the Kunming Institute of Zoology that is expected to cost millions of dollars to build. These centres can provide scientists with monkeys in large numbers, and offer high-quality animal care and cutting-edge equipment with little red tape. A major brain project, expected to be announced in China soon, will focus much of its efforts on using monkeys to study disease. The enthusiasm stands in stark contrast to the climate in the West, where non-human-primate research is increasingly stymied by a tangle of regulatory hurdles, financial constraints and bioethical opposition. Between 2008 and 2011, the number of monkeys used in research in Europe declined by 28%, and some researchers have stopped trying to do such work in the West. Many have since sought refuge for their experiments in China by securing collaborators or setting up their own laboratories there. Some of the Chinese centres are even advertising themselves as primate-research hubs where scientists can fly in to take advantage of the latest tools, such as gene editing and advanced imaging. “It could be like CERN in Switzerland, where they set up a large facility and then people come from all over the world to get data,” says Stefan Treue, a neuroscientist who heads the German Primate Center in Göttingen, Germany. With China fast becoming a global centre for primate research, some scientists fear that it could hasten the atrophy of such science in the West and lead to a near monopoly, in which researchers become over-reliant on one country for essential disease research and drug testing. “Governments and politicians don't see this, but we face a huge risk,” says Erwan Bezard, who is director of the Institute of Neurodegenerative Diseases at the University of Bordeaux in France, and has set up his own primate-research company, Motac, in Beijing. Europe and the United States still have the lead in primate research, he says, but this could change as expertise migrates eastwards. “China will become the place where all therapeutic strategies will have to be validated. Do we want that? Or do we want to stay in control?” For decades, researchers have relied on monkeys to shed light on brain function and brain disease because of their similarity to humans. Growth in neuroscience research has increased demand, and although high costs and long reproductive cycles have limited the use of these animals in the past, new reproductive technologies and genetic-engineering techniques such as CRISPR–Cas9 are helping researchers to overcome these drawbacks, making monkeys a more efficient experimental tool. China has an abundance of macaques — the mainstay of non-human-primate scientific research. Although the population of wild rhesus macaques (Macaca mulatta) has declined, the number of farmed animals has risen. According to data from the Chinese State Forestry Administration, the number of businesses breeding macaques for laboratory use rose from 10 to 34 between 2004 and 2013, and the quota of animals that those companies could sell in China or overseas jumped from 9,868 to 35,385 over that time. Farm populations of marmosets, another popular research animal, are also on the rise. Most monkeys are shipped to pharmaceutical companies or researchers elsewhere in the world, but the growing appreciation among scientists of monkey models has prompted investment by local governments and private companies in dedicated research colonies. The country's 2011 five-year plan singled out primate disease models as a national goal; the science ministry followed up by pumping 25 million yuan (US$3.9 million) into the endeavour in 2014. Scientists visiting China are generally pleased with the care given to animals in these facilities, most of which have, or are trying to get, the gold-standard recognition of animal care — accreditation by AAALAC International. Ji's Yunnan Key Laboratory is the most active primate facility, but others are giving it competition. The new monkey facility at the Kunming Institute of Zoology was funded as part of the national development scheme for big science equipment that includes telescopes and supercomputers. The money will help the institute to double its colony of 2,500 cynomolgus monkeys (Macaca fascicularis) and rhesus macaques. Zhao Xudong, who runs the primate-research facility, says that the plan is to “set it up like a hospital, with separate departments for surgery, genetics and imaging”, and a conveyer belt to move monkeys between departments. There will be systems for measuring body temperature, heart rate and other physiological data, all to analyse the characteristics, or 'phenotypes', of animals, many of which will have had genes altered. “We are calling it the 'genotype versus phenotype analyser',” says Zhao. It will take ten years to finish, but he hopes to begin building this year and to start research within three. Other facilities, although smaller, are also expanding and diversifying. The Institute of Neuroscience in Shanghai plans to increase its population of 600 Old World monkeys to 800 next year and expand its 300-strong marmoset colony. Outside China, the numbers are heading in the opposite direction. Harvard Medical School closed its affiliated primate facility in May 2015 for 'strategic' reasons. Last December, the US National Institutes of Health decided to phase out non-human-primate experiments at one of its labs and subsequently announced that it would review all non-human-primate research that it funds. In Europe, researchers say, the climate is also growing colder for such research. Costs are a major disincentive. In 2008, Li Xiao-Jiang, a geneticist at Emory University in Atlanta, Georgia, helped to create the world's first transgenic monkey model of Huntington's disease1 with colleagues at Yerkes National Primate Research Centre. But Li says that it costs $6,000 to buy a monkey in the United States, and $20 per day to keep it, whereas the corresponding figures in China are $1,000 and $5 per day. “Because the cost is higher, you have to write a bigger grant, and then the bar will be higher when they judge it,” says Li. Funding agencies “really do not encourage large-animal research”. For Li, the solution was simple: go to China. He now has a joint position at the Institute of Genetics and Developmental Biology in Beijing, where he has access to around 3,000 cynomolgus monkeys at a farm in Guangzhou and some 400 rhesus monkeys at the Chinese Academy of Medical Sciences' monkey facility in Beijing. He has churned out a series of publications on monkeys with modified versions of the genes involved in Duchenne muscular dystrophy2 and Parkinson's disease3. Neuroscientist Anna Wang Roe says that red tape drove her to China. Roe's team at Vanderbilt University in Nashville, Tennessee, is attempting to work out how modules in the brain are connected, and she estimates that she and her colleagues have spent 25% of their time and a good deal of cash documenting the dosage and delivery-method for each drug they administered to their monkeys, as required by regulations. “We record something every 15 minutes,” she says. “It's not that it's wrong. It's just enormously time-consuming.” In 2013, impressed by the collaborative atmosphere at Zhejiang University in Hangzhou, she proposed that it build a neuroscience institute. The next day the university agreed, and she soon had a $25-million, 5-year budget. “Once the decision is made, you can start writing cheques,” she says. She is now closing her US laboratory to be the director of the Zhejiang Interdisciplinary Institute of Neuroscience and Technology, where she hopes to open a suite of the latest brain-analysis tools, including a powerful new 7-tesla functional magnetic resonance imaging device that she says will give images of the primate brain at unprecedented resolution. Bob Desimone was similarly impressed with the speed at which China moves. As a neuroscientist who heads the McGovern Institute for Brain Research at the Massachusetts Institute of Technology in Cambridge, in January 2014, he had a 'meet and greet' with the mayor of Shenzhen. In March, the mayor donated a building on the Shenzhen Institute of Advanced Technology campus for a monkey-research facility, and the centre's soon-to-be director, Liping Wang, promised that it would be ready by summer. Thinking that impossible, Desimone bet two bottles of China's prized mind-numbing liquor, maotai, that it wouldn't be done in time. He lost. The group raised most of the $10 million needed from city development grants, along with a small input from McGovern, and soon the first animals were being installed in the Brain Cognition and Brain Disorder Research Institute. “This place just makes things happen quickly,” Desimone says. But money and monkeys alone are not enough to lead to discovery. Researchers say that China is short on talented scientists to take advantage of the opportunities provided by animal research. That's why the organizers of the country's new primate centres hope to attract an influx of foreigners to permanent posts or as collaborators. So far, many of those moving to China have been Chinese or foreigners with a previous connection to the country, but others are expressing interest, says neuroscientist Guoping Feng, also at the McGovern Institute. Already, the Shenzhen primate centre has recruited from Europe and the United States, and Desimone says that it will be “an open technology base. Anyone who wants to work with monkeys can come.” The rapid spread of CRISPR–Cas9 and TALEN gene-editing tools is likely to accelerate demand for monkey research: they are turning the genetic modification of monkeys from a laborious and expensive task into a relatively quick, straightforward one. Unlike engineered mice, which can be bred and sent around the world, “monkeys are difficult to send, so it will be easier for the PI or postdoc to go there”, says Treue. Already, competition is fierce as researchers are racing for the low-hanging fruit — engineering genes with established roles in human disease or development. Almost all reports of gene-edited monkeys produced with these techniques have come from China. Desimone predicts that the pursuit of monkey disease models “could give China a unique niche to occupy in neuroscience”. The cages of Ji's facility are already full of the products of gene editing. One troop of animals has had a mutation genetically engineered into the MECP2 gene, which has been identified as the culprit in humans with Rett's syndrome, an autism spectrum disorder. An animal sits listless and unresponsive, holding tight to the bars of the cage as her normal twin sister crawls all over her. In another cage, a monkey with the mutation pumps its arm, reminiscent of repetitive behaviour seen in the human disorder. Some incessantly suck their thumbs. “I've never seen that in a monkey before — never so constant,” says Ji. Among the range of other disease models in Ji's menagerie are monkey versions of cardiovascular disease, which he is working on in collaboration with the Karolinska Institute. And last year, Ji made the world's first chimeric monkeys using embryonic stem cells4, an advance that could make the production of genetically modified animals even easier. The question now is whether these genetically modified monkeys will propel understanding of human brain function and dysfunction to a higher level. “You can't just knock out one gene and be sure you'll have human-like disease phenotype,” says Ji. Researchers see an opportunity to understand human evolution as well as disease. Su Bing, a geneticist at the Kunming Institute of Zoology, is working with Ji to engineer monkeys that carry the human version of a gene called SRGAP2, which is thought to endow the human brain with processing power by allowing the growth of connections between neurons. Su also plans to use CRISPR–Cas9 to introduce human versions of MCPH1, a gene related to brain size, and the human FOXP2 gene, which is thought to give humans unique language ability. “I don't think the monkey will all of a sudden start speaking, but will have some behavioural change,” predicts Su. Although the opportunities are great, there are still obstacles for scientists who choose to locate their animal research in China. Trying to keep a foot in two places can be challenging, says Grégoire Courtine, a spinal-cord-injury researcher based at the Swiss Federal Institute of Technology in Lausanne, who travels almost monthly to China to pursue his monkey research at Motac. He has even flown to Beijing, done a couple of operations on his experimental monkeys, then returned that night. “I'm 40 years old, I have energy in my body. But you need to really will it,” he says. Another downside, says Li, is that policies can change suddenly in China. “There is uncertainty. That makes us hesitate to commit,” says Li, who has retained his post at Emory University. And the immunity that China's primate researchers have had to animal-rights activism could start to erode, warns Deborah Cao, who researches law at Griffith University in Brisbane, Australia, and last year published a book on the use of animals in China5. People are starting to use Chinese social-media sites to voice outrage at the abuse of animals, Cao says. China has competition in its bid to dominate primate research, too. Japan has launched its own brain project focused on the marmoset as a model: the animal reaches sexual maturity in a year and a half, less than half the time it takes a macaque. Some research facilities in China are now building marmoset research colonies — but Japan is considered to be several years ahead. And some researchers want to ensure that such work continues outside Asia. Courtine says that he's “fighting to keep alive” a monkey-research programme he has at Fribourg, Switzerland, because he thinks it's important to have a division of labour. “Research that requires quantity, I'll do in China. I would like to do sophisticated work in Fribourg,” he says. Back at his primate centre in Yunnan, Ji is sure that such work is already taking place. His dream, he says is “to have an animal like a tool” for biomedical discovery. He knows there is a lot of competition in this field, especially in China. But he feels confident: “The field is wide, and there are many, many projects we can do.”
News Article | November 3, 2016
By removing the protein galectin-3 (Gal3), a team of investigators led by University of California School of Medicine researchers were able to reverse diabetic insulin resistance and glucose intolerance in mouse models of obesity and diabetes. By binding to insulin receptors on cells, Gal3 prevents insulin from attaching to the receptors resulting in cellular insulin resistance. The team led by Jerrold Olefsky, MD, professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego School of Medicine, showed that by genetically removing Gal3 or using pharmaceutical inhibitors to target it, insulin sensitivity and glucose tolerance could be returned to normal, even among older mice. However, obesity remained unchanged. "This study puts Gal3 on the map for insulin resistance and diabetes in mouse model," said Olefsky, associate dean for scientific affairs and senior author of the study. "Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach." Olefsky and other researchers have been studying how chronic tissue inflammation leads to insulin resistance in type 2 diabetes. In the paper, published in the journal Cell on November 3, researchers explain that inflammation requires macrophages -- specialized cells that destroy targeted cells. In obese adipose tissue (fat), for example, 40 percent of cells are macrophages. Macrophages in turn secrete Gal3, which then acts as a signaling protein attracting more macrophages, thus resulting in the production of even more Gal3. Furthermore, investigators identified bone marrow-derived macrophages as the source of Gal3 that leads to insulin resistance. More importantly, researchers found that Gal3 is secreted by macrophages, and can then cause insulin resistance in liver, fat cells, and muscle cells independent of inflammation. Gal3 has previously been connected to other diseases. Olefsky will continue to study Gal3 depletion as a possible therapeutic target for nonalcoholic steatohepatitis as well as heart and liver fibrosis. Study co-authors include: Pingping Li, Chinese Academy of Medical Sciences, Peking Union Medical College and UC San Diego; Shuainan Liu, Zhufang Shen, Bing Cui, Lijuan Kong, Shaocong Hou, Xiao Liang, Chinese Academy of Medical Sciences, Peking Union Medical College; Min Lu, UC San Diego, and Merck Research Laboratories; Gautum Bandyyopadhyay, Dayoung Oh, Andrew M. Johnson, Dorothy Sears, Wei Ying, Olivia Osborn, Joshua Wollam, UC San Diego; Takeshi Imamura, Shiga University of Medical Science; Salvatore Iovino, Martin Brenner, Merck Research Laboratories; Steven M. Watkins, Lipomics Technologies, Inc.
News Article | September 7, 2016
Backed by rich private investors, proton therapy, a highly precise but expensive form of radiation used to treat cancer, is booming in China. The country has gone from having no operating proton therapy centers two and a half years ago to having two in operation today plus at least 43 more proton projects in various stages of development, according to China Particle Therapy News, an industry newsletter. “Proton therapy is going into overdrive,” says Zeng Xianwen, a leading radiation oncologist with 60 years of experience in the field. Zeng is positive on the development but cautions that the treatment is not a cure-all. Advocates hold that proton-beam therapy is better than conventional radiation treatment based on X-rays because protons release most of their energy on the tumor and then stop, causing less damage to nearby healthy tissue. And researchers, including Zeng, are looking for ways to further improve the therapy by minimizing its impact on skin and other tissue the radiation travels through to reach the tumor. But studies of proton therapy have been limited, and their authors say more work in this area is needed. For example, a 2014 study of childhood brain tumor survivors supports the idea that proton therapy may lead to a better quality of life for patients when compared to conventional radiation, but its authors say more study is needed to prove that. Another paper published earlier this year concludes that despite its higher cost, proton therapy “offers promising cost-effectiveness” for childhood brain tumors and some types of breast, lung, and head and neck cancer. This study, however, was based on limited data, and its authors warn that the conclusion could change as more evidence becomes available. Proton centers are far more expensive to build than conventional radiation suites. Traditionally centers cost hundreds of millions of dollars to build. Even new, more compact designs cost between $25 million and $30 million per system. Rather than stemming from demand from the medical community, this building spree in China originates from the country’s shifting economic winds. Chinese investors have seen returns from traditionally lucrative stakes in manufacturing and real estate decline in recent years, and that has made investment in medical centers, particularly ones focused on a cutting-edge technology, an area of increasing popularity, says Yu Hongxia, general manager of APH Medical, a subsidiary of a medical supplies company that is investing 1.6 billion yuan ($240 million) in a proton center in southeastern China. Further encouraging this interest is a 2015 decision by the government to relax restrictions on the importing of medical equipment. That made it easy to purchase proton-beam systems from foreign manufacturers. Some worry these centers could further worsen the existing disparity of health care between what the rich and well-connected receive and the average citizen. Although detailed pricing information for the new centers is not yet available, it is certain to be expensive. The going rate for an average treatment at a proton center in Shanghai, one of two operating today, is 278,000 yuan ($41,636). Patients pay for that out of their own pocket. No insurance policy covers proton therapy in China today. Others question whether China has the medical expertise needed to staff so many centers. Some of the hospitals that have teamed up with private investors to build proton centers have never had radiation oncology departments, and there are few professionals experienced with providing proton therapy. As a result, Hu Yimin, chief medical physicist at Cancer Hospital Chinese Academy of Medical Sciences, worries that patients may suffer. “We should develop proton therapy, but not in such haste,” he says. Chao, a 28-year-old who underwent proton therapy treatment two years ago, would argue the centers can’t open quickly enough. In early 2014, when a doctor told her that a rare cancerous tumor nestled at the base of her skull had begun to grow again after two surgeries, Chao, who declined to have her full name published in order to protect her privacy, says she didn’t know what to do. A second doctor suggested proton therapy, but it wasn’t then available in China. That fall, her family scratched together 200,000 yuan ($29,954) and took her to a cancer center in Japan for treatment. “I was lucky,” says Chao, seated recently in her brightly lit office in Beijing. Her tumor is no longer growing, and she’s working full-time again.
Zhang J.,Chinese Academy of Medical Sciences
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011
To investigate the effect and safety of early intervention and delayed intervention therapy on elderly patients and younger patients with non-ST segment elevation acute coronary syndrome. The patients with non-ST segment elevation acute coronary syndrome were randomly divided into early intervention group (coronary angiography taken within 24 hours after grouping) and delayed intervention group (coronary angiography taken after 36 hours after grouping). The primary endpoint was a composite endpoint of death, myocardial infarction and stroke during 180 days follow-up. A total of 815 patients were enrolled, including 198 elderly patients aged 75 years and above, and 617 younger patients aged below 75 years. The elderly patients had a greater incidence of the primary endpoint than that of younger patients (P = 0.00). The primary endpoint of early intervention group were obviously lower than that of delayed intervention group of younger patients (P = 0.01). There was no significant difference in primary endpoint incidence of early intervention group and delayed intervention group of the elderly patients (P = 0.39). The elderly patients with non-ST segment elevation acute coronary syndrome who underwent intervention had greater incidence of death and myocardial infarction. Early intervention reduced the rate of myocardial infarction for the younger patients. There was no significant difference in primary endpoint incidence between early intervention and delayed intervention among elderly patients.
PubMed | Chinese Academy of Sciences and Chinese Academy of Medical Sciences
Type: | Journal: Molecular pharmacology | Year: 2017
Activation of Liver X receptor (LXR) is associated with cholesterol metabolism and anti-inflammatory processes, which makes beneficial to anti-atherosclerosis. Nevertheless, existing agonists which target LXR, for example TO901317, are related to unwanted side-effects. In the present study, using a screening method we identified IMB-808, which displayed potent dual LXR/ agonistic activity. In vitro, IMB-808 effectively increased the expressing quantity of genes related to reverse cholesterol transport process as well as those associated with cholesterol metabolism pathway in multiple cell lines. Additionally, IMB-808 remarkably promoted cholesterol efflux from RAW264.7 as well as THP-1 macrophage cells and reduced cellular lipid accumulation accordingly. Interestingly, compared with TO901317, IMB-808 almost did not increase the expressing quantity of genes related to lipogenesis in HepG2 cells, which indicated that IMB-808 could exhibit fewer internal lipogenic side-effects with a characteristic of selective LXR agonist. Furthermore, in comparison to the full LXR agonist TO901317, IMB-808 recruits co-regulators differently and possesses distinct predictive binding pattern for the LXR ligand-binding domain. In summary, our study demonstrated that IMB-808 could act as an innovative partial LXR agonist avoiding common lipogenic side-effects, providing insight for the design of novel LXR modulators. Our data indicate that this compound might be used as a promising therapeutic agent for the prospective treatment of atherosclerosis in the future.