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N Engl J Med. 2011 Apr 21;364(16):1523-32.
Fever with thrombocytopenia associated with a novel bunyavirus in China.
Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, Zhang L, Zhang QF, Popov VL, Li C, Qu J, Li Q, Zhang YP, Hai R, Wu W, Wang Q, Zhan FX, Wang XJ, Kan B, Wang SW, Wan KL, Jing HQ, Lu JX, Yin WW, Zhou H, Guan XH, Liu JF, Bi ZQ, Liu GH, Ren J, Wang H, Zhao Z, Song JD, He JR, Wan T, Zhang JS, Fu XP, Sun LN, Dong XP, Feng ZJ, Yang WZ, Hong T, Zhang Y, Walker DH, Wang Y, Li DX.
Chinese Center for Disease Control and Prevention, Beijing, China.
BACKGROUND: Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.
METHODS: We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples.
RESULTS: We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness.
CONCLUSIONS: A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Lancet. 2011 May 28;377(9780):1855-61.
A global reference for fetal-weight and birthweight percentiles.
Mikolajczyk RT, Zhang J, Betran AP, Souza JP, Mori R, Gülmezoglu AM, Merialdi M.
Department of Clinical Epidemiology, Bremen Institute for Prevention Research and Social Medicine, Bremen, Germany.
BACKGROUND: Definition of small for gestational age in various populations worldwide remains a challenge. References based on birthweight are deficient for preterm births, those derived from ultrasound estimates might not be applicable to all populations, and the individualised reference can be too complex to use in developing countries. Our aim was to create a generic reference for fetal weight and birthweight that overcame these deficiencies and could be readily adapted to local populations.
METHODS: We used the fetal-weight reference developed by Hadlock and colleagues and the notion of proportionality proposed by Gardosi and colleagues and made the weight reference easily adjustable according to the mean birthweight at 40 weeks of gestation for any local population. For application and validation, we used data from 24 countries in Africa, Latin America, and Asia that participated in the 2004-08 WHO Global Survey on Maternal and Perinatal Health (237,025 births). We compared our reference with that of Hadlock and colleagues (non-customised) and with that of Gardosi and colleagues (individualised). For every reference, the odds ratio (OR) of adverse perinatal outcomes (stillbirths, neonatal deaths, referral to higher-level or special care unit, or Apgar score lower than 7 at 5 min) for infants who were small for gestational age versus those who were not was estimated with multilevel logistic regression.
FINDINGS: OR of adverse outcomes for infants small for gestational age versus those not small for gestational age was 1.59 (95% CI 1.53-1.66) for the non-customised fetal-weight reference compared with 2.87 (2.73-3.01) for our country-specific reference, and 2.84 (2.71-2.99) for the fully individualised reference.
INTERPRETATION: Our generic reference for fetal-weight and birthweight percentiles can be easily adapted to local populations. It has a better ability to predict adverse perinatal outcomes than has the non-customised fetal-weight reference, and is simpler to use than the individualised reference without loss of predictive ability.
Lancet. 2011 May 28;377(9780):1812-4.
Fetal growth standards: individual and global perspectives.
West Midlands Perinatal Institute, Birmingham B6 5RQ, UK.
Lancet. 2011 Aug 6;378(9790):457.
China's major health challenge: control of chronic diseases.
In Toward a Healthy and Harmonious Life in China, a report issued last week, the World Bank urged China to step up efforts to tackle its rising tide of non-communicable diseases (NCDs), warning of not only the social but the economic consequences of inaction. NCDs are China's number one health threat, contributing to more than 80% of the country's 10.3 million annual deaths and nearly 70% of its total disease burden. Projections made in the report, which was produced in collaboration with the Chinese Ministry of Health and WHO, make for rather grim reading. If effective control and prevention strategies are not implemented, the prevalence of cardiovascular disease, chronic obstructive pulmonary disease, diabetes, and lung cancer in individuals older than 40 years will double or even triple during the next two decades. Resultant increases in treatment costs and a reduction in workforce productivity, the report warns, will increase the chances of future economic slowdown and pose a substantial social problem.
A headline statistic in the report is that reduction of mortality from cardiovascular disease by only 1% per year between 2010 and 2040 will save the country a staggering US$10.7 trillion—68% of China's real gross domestic product in 2010. But mortality from NCDs is just the tip of the iceberg. NCD-related morbidity accounts for more than 90% of China's total NCD burden, and the increasing prevalence of disease is likely to severely reduce the number of healthy workers in China. This reduction in productivity does not stop at only those with disease. Their family members—who will also suffer from reduced household income—may need to take time off work to care for their dependants. This knock-on effect is particularly pertinent to China, because its one-child policy means that family carers will have proportionately more added responsibility than would individuals in other countries where care of a sick parent can be shared among siblings.
The rising trend in NCDs is rooted in social, economic, and environmental changes that have taken place in China during the past couple of decades. China has undoubtedly done an excellent job in lifting many millions of its population out of poverty, but the same efforts have not yet been put into the improvement of population health. Indeed, many people's incomes have risen, which has improved the health status of much of the population, but the trappings of rapid urbanisation have meant increases in unhealthy behaviours and pollution, leading to a sharp rise in NCD-related risk factors, especially among the poor.
China's health-care system—traditionally geared towards the treatment of acute and infectious disorders—has been ill-equipped to deal with NCDs, but is undergoing reform. Central to these reforms are improvements in primary care. In 2010, China issued a capacity-building plan to address its serious shortage of general practitioners—in the next 10 years they plan to train an ambitious 300 000 general practitioners, who will certainly be needed if the reduction of NCDs is to become a priority. Furthermore, much-needed improvement in the professional status of doctors in China could strengthen their political voice. Such political empowerment would improve opportunities to influence public debate about the industries that contribute risk factors to NCDs—tobacco, food, and alcohol manufacturers, in particular. Nationwide reduction of air and water pollution is another area in need of urgent attention.
At this year's World Health Assembly, Chen Zhu, China's Minister of Health, spoke of the great urgency with which China must act to prevent chronic disease—any such actions will certainly need a multisectoral approach. This World Bank report, with its emphasis on the economic effects of these diseases, might just be what is needed to engage all stakeholders in China's economy. Put simply, investment into the prevention of NCDs will not only be good for the health and wellbeing of China's population, but will result in a substantial financial return for the country.
The report outlines some worrying problems, but presents an exciting challenge. If China—known to be a world leader in business and technology—can achieve progress in the effective prevention and control of NCDs, it can also become a world leader in health. Admittedly, compared with space exploration and advances in biotechnology, the control of NCDs lacks futuristic-chic, but, in the face of this bottleneck to China's social and economic development, it can certainly be considered equally as forward-thinking.
AIDS. 2011 Sep 24;25(15):1925-7.
Detection of HIV-1 viruses in tears of patients even under long-term HAART.
Han Y, Wu N, Zhu W, Li Y, Zuo L, Ye J, Qiu Z, Xie J, Li T.
Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
To determine whether HIV-1 viruses exist in tears of patients under HAART, a cross-sectional study was designed. All participants who underwent long-term HAART with undetectable plasma viral load had detectable HIV-1 viral load in tears (n = 16) and had no difference from the controls (n = 5). Our data suggested that the lacrimal gland and/or other tear-associated tissues could be new reservoirs for HIV-1 and precautions should be taken when doing eye examinations.
J Clin Oncol. 2011 Dec 20;29(36):4781-8.
Plasma MicroRNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma.
Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, Wang JF, Zhang Z, Lu S, Huang X, Wang Z, Qiu S, Wang X, Yang G, Sun H, Tang Z, Wu Y, Zhu H, Fan J.
136 Yi Xue Yuan Rd, Shanghai 200032, People's Republic of China.
PURPOSE More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) -related HCC. PATIENTS AND METHODS Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively. CONCLUSION We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.
复旦大学脑科学研究院、复旦大学医学神经生物学国家重点实验室杨振纲教授的研究团队发现成年猕猴和人类的大脑中存有神经干细胞和新生的神经元，并详细描述了由神经干细胞生成的新生神经元的特征及迁移路线，该成果为人类脑损伤后神经再生带来新希望。相关系列论文已陆续发表在《神经科学杂志》（J Neurosci 2011，31:8450）、《细胞研究》（Cell Research 2011年5月17日在线发表）和《欧洲神经科学杂志》（Eur J Neurosci 2011，33:819）上。
J Neurosci. 2011 Jun 8;31(23):8450-5.
The transcription factor Sp8 is required for the production of parvalbumin-expressing interneurons in the olfactory bulb.
Li X, Sun C, Lin C, Ma T, Madhavan MC, Campbell K, Yang Z.
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Interneurons in the olfactory bulb (OB) represent a heterogeneous population, which are first produced at embryonic stages and persisting into adulthood. Using the BrdU birthdating method combined with immunostaining for several different neuronal markers, we provide the integrated temporal patterns of distinct mouse OB interneuron production from embryonic day 14 to postnatal day 365. We show that although the majority of OB interneuron subtypes continue to be generated throughout life, most subtypes show a similar "bell-like" temporal production pattern with a peak around birth. Tyrosine hydroxylase and calretinin-expressing interneurons are produced at a relatively low rate in the adult OB, while parvalbumin-expressing (PV+) interneuron production is confined to later embryonic and early postnatal stages. We also show that Dlx5/6-expressing progenitors contribute to PV+ interneurons in the OB. Interestingly, all PV+ interneurons in the external plexiform layer (EPL) express the transcription factor Sp8. Genetic ablation of Sp8 by cre/loxP-based recombination severely reduces the number of PV+ interneurons in the EPL of the OB. Our results suggest that Sp8 is required for the normal production of PV+ interneurons in the EPL of the OB. These data expand our understanding of the temporal and molecular regulation of OB interneuron neurogenesis.
Cell Res. 2011 Nov;21(11):1534-50.
Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain.
Wang C, Liu F, Liu YY, Zhao CH, You Y, Wang L, Zhang J, Wei B, Ma T, Zhang Q, Zhang Y, Chen R, Song H, Yang Z.
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and βIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.
Eur J Neurosci. 2011 Mar;33(5):819-30.
Emx1-expressing neural stem cells in the subventricular zone give rise to new interneurons in the ischemic injured striatum.
Wei B, Nie Y, Li X, Wang C, Ma T, Huang Z, Tian M, Sun C, Cai Y, You Y, Liu F, Yang Z.
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032 China.
Neural stem cells from different regions within the subventricular zone (SVZ) are able to produce several different subtypes of interneurons in the olfactory bulb throughout life. Previous studies have shown that ischemic stroke induces the production of new neurons in the damaged striatum from the SVZ. However, the origins and genetic profiles of these newborn neurons remain largely unknown as SVZ neural stem cells are heterogeneous. In the present study, using a mouse model of perinatal hypoxic-ischemic (H/I) brain injury combined with BrdU labeling methods, we found that, as in rat brains, virtually all newborn neuroblasts that migrate from the SVZ into the ischemic injured striatum exclusively express the transcription factor Sp8. Furthermore, although newborn neuroblasts are plentiful in the damaged striatum, only a few can differentiate into calretinin-expressing (CR+) interneurons that continuously express Sp8. Genetic fate mapping reveals that newly born CR+ interneurons are generated from Emx1-expressing neural stem cells in the dorsal-lateral SVZ. These results suggest that the fate of the Emx1-expressing lineage in the ischemic damaged striatum is restricted. However, when Sp8 was conditionally inactivated in the Emx1-lineage cells, Pax6 was ectopically expressed by a subpopulation of Emx1-derived CR+ cells in the normal and damaged striatum. Interestingly, these cells possessed large cell bodies and long processes. This work identifies the origin of the newly born CR+ interneurons in the damaged striatum after ischemic brain injury.