A protocol was established for simultaneous measurements of zircon U-Pb ages and trace elements by LA-ICP-MS at spot sizes of 16 32 μm.This was accomplished by introducing N 2 into ICP to increase the sensitivity.The...A protocol was established for simultaneous measurements of zircon U-Pb ages and trace elements by LA-ICP-MS at spot sizes of 16 32 μm.This was accomplished by introducing N 2 into ICP to increase the sensitivity.The obtained U-Pb ages for zircon standards GJ-1,TEMORA and SK10-2 are consistent with the preferred values within about 1% uncertainty (2σ) by simple external calibration against zircon standard 91500.Different data reduction softwares could yield different uncertainties for calculation of U-Pb ages.The commercially available program GLITTER4.4 could apply an improper uncertainty calculation strategy,but it may yield artificial high precisions for single analyses.Our trace element analyses indicate that Si is not an ideal internal standard for zircon when calibrated against the NIST glasses.Calibration against the NIST glasses using Si as an internal standard,a systematic deviation of 10% 30% was found for most trace elements including Zr.However,the trace element compositions of zircon can be accurately measured by calibration against multiple reference materials with natural compositions (e.g.,BCR-2G,BHVO-2G and BIR-1G),or calibration against NIST SRM 610 and using Zr as an internal standard.Analyses of two pieces of GJ-1 demonstrate that it is relatively homogenous for most trace elements (except for Ti).展开更多
Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and o...Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.展开更多
Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden...Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should inc展开更多
Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found...Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found to be linked to a large seafood and animal market in Wuhan,and measures for sanitation and disinfection were taken swiftly by the local government agency.The Centers for Disease Control and Prevention(CDC)and Chinese health authorities later determined and announced that a novel coronavirus(CoV),denoted as 2019-nCoV,had caused the pneumonia outbreak in Wuhan city(CDC,2020).Scientists from multiple groups had obtained the virus samples from hospitalized patients(Normile,2020).The isolated viruses were morphologically identical when observed under electron microscopy.展开更多
Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide r...Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide reference for policy planning and contribute to improving cancer control measures.In this study,we reviewed the rates and trends of cancer incidence and mortality and disability-adjusted life year(DALY)burden in China,and compared them with those in the United States(US)and the United Kingdom(UK).Methods:Cancer incidence,mortality,and DALY data for China,US and UK were obtained fromtheGLOBOCAN2020 online database,Global Burden of Disease(GBD)2019 study,and Cancer Incidence in Five Continents plus database(CI5 plus).Trends of cancer incidence and mortality in China,US,and UK were analyzed using Joinpoint regression models to calculate annual percent changes(APCs)and identify the best-fitting joinpoints.Results:An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020.Additionally,cancers resulted in 67,340,309 DALYs in China.Compared to the US and UK,China had lower cancer incidence but higher cancer mortality andDALY rates.Furthermore,the cancer spectrum of China was changing,with a rapid increase incidence and burden of lung,breast,colorectal,and prostate cancer in addition to a high incidence and heavy burden of liver,stomach,esophageal,and cervical cancer.Conclusions:The cancer spectrum of China is changing from a developing country to a developed country.Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China.Therefore,the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well-established in the developed countries,and taking consideration of the diversity of cancer types by of different regions in China at the same time.展开更多
Land-use/land-cover changes （LUCCs） have links to both human and nature inter- actions. China＇s Land-Use/cover Datasets （CLUDs） were updated regularly at 5-year inter- vals from the late 1980s to 2010, with stand...Land-use/land-cover changes （LUCCs） have links to both human and nature inter- actions. China＇s Land-Use/cover Datasets （CLUDs） were updated regularly at 5-year inter- vals from the late 1980s to 2010, with standard procedures based on Landsat TM／ETM＋ im- ages. A land-use dynamic regionalization method was proposed to analyze major land-use conversions. The spatiotemporal characteristics, differences, and causes of land-use changes at a national scale were then examined. The main findings are summarized as fol- lows. Land-use changes （LUCs） across China indicated a significant variation in spatial and temporal characteristics in the last 20 years （1990-2010）. The area of cropland change de- creased in the south and increased in the north, but the total area remained almost un- changed. The reclaimed cropland was shifted from the northeast to the northwest. The built-up lands expanded rapidly, were mainly distributed in the east, and gradually spread out to central and western China. Woodland decreased first, and then increased, but desert area was the opposite. Grassland continued decreasing. Different spatial patterns of LUC in China were found between the late 20th century and the early 21st century. The original 13 LUC zones were replaced by 15 units with changes of boundaries in some zones. The main spatial characteristics of these changes included （1） an accelerated expansion of built-up land in the Huang-Huai-Hai region, the southeastern coastal areas, the midstream area of the Yangtze River, and the Sichuan Basin; （2） shifted land reclamation in the north from northeast China and eastern Inner Mongolia to the oasis agricultural areas in northwest China; （3） continuous transformation from rain-fed farmlands in northeast China to paddy fields; and （4） effective- ness of the ＂Grain for Green＂ project in the southern agricultural-pastoral ecotones of Inner Mongolia, the Loess Plateau, and southwestern mountainous areas. In the last two decades, although climate change展开更多
Using the in situ zircon U-Pb dating method of LA-ICPMS, we analyzed the 31 Ma old SHRIMP U-Pb age of the Yongsheng nepheline syenite from southern Jilin Province under different spot sizes. The obtained ages are comp...Using the in situ zircon U-Pb dating method of LA-ICPMS, we analyzed the 31 Ma old SHRIMP U-Pb age of the Yongsheng nepheline syenite from southern Jilin Province under different spot sizes. The obtained ages are comparable with that of SHRIMP in both accuracy and precision. The age is also identical to that of the Yinmawanshan gabbro from the Liaodong Peninsula within error. Both the Yongsheng nepheline syenite and the Yinmawanshan gabbro represent the youngest known exposed intrusions in northeastern and even eastern China. The results indicate the Eocene mantle-derived magmatic underplating, and the rapid crustal uplifting of this region since 30 Ma. The analyses also document extremely high LREE concentrations and relatively flat REE patterns for the zircons from the Yongsheng nepheline syenite, which represent a new type of zircon REE pattern.展开更多
China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading cause...China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and展开更多
During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or transdifferentiation （EMT）. In this process, the cells lose ...During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or transdifferentiation （EMT）. In this process, the cells lose their epithelial characteristics, including their polarity and specialized cell-cell contacts, and acquire a migratory behavior, allowing them to move away from their epithelial cell community and to integrate into surrounding tissue, even at remote locations. EMT illustrates the differentiation plasticity during development and is complemented by another process, called mesenchymal to epithelial transition （MET）. While being an integral process during development, EMT is also recapitulated under pathological conditions, prominently in fibrosis and in invasion and metastasis of carcinomas. Accordingly, EMT is considered as an important step in tumor progression. TGF-β signaling has been shown to play an important role in EMT. In fact, adding TGF-β to epithelial cells in culture is a convenient way to induce EMT in various epithelial cells. Although much less characterized, epithelial plasticity can also be regulated by TGF-β-related bone morphogenetic proteins （BMPs）, and BMPs have been shown to induce EMT or MET depending on the developmental context. In this review, we will discuss the induction of EMT in response to TGF-β, and focus on the under- lying signaling and transcription mechanisms.展开更多
This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multis...This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.展开更多
As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, envir...As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, environmental pollution, and ultimately human health, timely and higher resolution land cover information is urgently needed to achieve the sustainable development goals of the United Nations.展开更多
A National Science Foundation of China （NSFC） major research project, Destruction of the North China Craton （NCC）, has been carried out in the past few years by Chinese scientists through an in-depth and systemati...A National Science Foundation of China （NSFC） major research project, Destruction of the North China Craton （NCC）, has been carried out in the past few years by Chinese scientists through an in-depth and systematic observations, experiments and theoretical analyses, with an emphasis on the spatio-temporal distribution of the NCC destruction, the structure of deep earth and shallow geological records of the craton evolution, the mechanism and dynamics of the craton destruction. From this work the foUowing conclusions can be drawn： （1） Significant spatial heterogeneity exists in the NCC lithospheric thickness and crustal structure, which constrains the scope of the NCC destruction. （2） The nature of the Paleozoic, Mesozoic and Cenozoic sub-continental lithospheric mantle （CLM） underneath the NCC is characterized in detail. In terms of water content, the late Mesozoic CLM was rich in water, but Cenozoic CLM was highly water deficient. （3） The correlation between magmatism and surface geological response confirms that the geological and tectonic evolution is governed by cratonic destruction processes. （4） Pacific subduction is the main dynamic factor that triggered the destruction of the NCC, which highlights the role of cratonic destruction in plate tectonics.展开更多
The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,an...The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.展开更多
There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and ...There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.展开更多
Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, how...Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk 展开更多
Land use and land cover change as the core of coupled human-environment systems has become a potential field of land change science （LCS） in the study of global environmental change. Based on remotely sensed data of...Land use and land cover change as the core of coupled human-environment systems has become a potential field of land change science （LCS） in the study of global environmental change. Based on remotely sensed data of land use change with a spatial resolution of 1 km × 1 km on national scale among every 5 years, this paper designed a new dynamic regionalization according to the comprehensive characteristics of land use change including regional differentiation, physical, economic, and macro-policy factors as well. Spatial pattern of land use change and its driving forces were investigated in China in the early 21 st century. To sum up, land use change pattern of this period was characterized by rapid changes in the whole country. Over the agricultural zones, e.g., Huang-Huai-Hai Plain, the southeast coastal areas and Sichuan Basin, a great proportion of fine arable land were engrossed owing to considerable expansion of the built-up and residential areas, resulting in decrease of paddy land area in southern China. The development of oasis agriculture in Northwest China and the reclamation in Northeast China led to a slight increase in arable land area in northern China. Due to the ＂Grain for Green＂ policy, forest area was significantly increased in the middle and western developing regions, where the vegetation coverage was substantially enlarged, likewise. This paper argued the main driving forces as the implementation of the strategy on land use and regional development, such as policies of ＂Western Development＂, ＂Revitalization of Northeast＂, coupled with rapidly economic development during this period.展开更多
In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a n...In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.展开更多
The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous d...The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.展开更多
Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human ...Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear （3PN） zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene （HBB）. However, the efficiency of homologous recombination directed repair （HDR） of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene （HBD）, which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.展开更多
基金supported by the National Natural Science Foundation of China (GrantNos. 40821061,90914007,40576030 and 90714010)the State Administration of Foreign Expert Affairs of China (Grant No. B07039)the Special Fund for Basic Scientific Research of Central Colleges,China University of Geosciences
文摘A protocol was established for simultaneous measurements of zircon U-Pb ages and trace elements by LA-ICP-MS at spot sizes of 16 32 μm.This was accomplished by introducing N 2 into ICP to increase the sensitivity.The obtained U-Pb ages for zircon standards GJ-1,TEMORA and SK10-2 are consistent with the preferred values within about 1% uncertainty (2σ) by simple external calibration against zircon standard 91500.Different data reduction softwares could yield different uncertainties for calculation of U-Pb ages.The commercially available program GLITTER4.4 could apply an improper uncertainty calculation strategy,but it may yield artificial high precisions for single analyses.Our trace element analyses indicate that Si is not an ideal internal standard for zircon when calibrated against the NIST glasses.Calibration against the NIST glasses using Si as an internal standard,a systematic deviation of 10% 30% was found for most trace elements including Zr.However,the trace element compositions of zircon can be accurately measured by calibration against multiple reference materials with natural compositions (e.g.,BCR-2G,BHVO-2G and BIR-1G),or calibration against NIST SRM 610 and using Zr as an internal standard.Analyses of two pieces of GJ-1 demonstrate that it is relatively homogenous for most trace elements (except for Ti).
基金Acknowledgments We thank Drs Fengyong Liu and Sheng Luan at UC Berkeley, USA, for their discussion and help with the writing of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （no. 30225037, 30471991, 30570731）, National Basic Research Program of China （973 Program） （no. 2006CB503909, 2004CB518603）, the ＂111＂ Project, and the Natural Science Foundation of Jiangsu Province （no. BK2004082, BK2006714）.
文摘Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
文摘Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should inc
基金This work was supported in part by grants from the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(directed by Dr.Song Li)(2018ZX09711003)of Chinathe National Key R&D Program(2018YFC0310600)of China+1 种基金the National Natural Science Foundation of China(31771412)Special Fund for strategic bio-resources from Chinese Academy of Sciences(ZSYS-014).
文摘Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found to be linked to a large seafood and animal market in Wuhan,and measures for sanitation and disinfection were taken swiftly by the local government agency.The Centers for Disease Control and Prevention(CDC)and Chinese health authorities later determined and announced that a novel coronavirus(CoV),denoted as 2019-nCoV,had caused the pneumonia outbreak in Wuhan city(CDC,2020).Scientists from multiple groups had obtained the virus samples from hospitalized patients(Normile,2020).The isolated viruses were morphologically identical when observed under electron microscopy.
文摘Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide reference for policy planning and contribute to improving cancer control measures.In this study,we reviewed the rates and trends of cancer incidence and mortality and disability-adjusted life year(DALY)burden in China,and compared them with those in the United States(US)and the United Kingdom(UK).Methods:Cancer incidence,mortality,and DALY data for China,US and UK were obtained fromtheGLOBOCAN2020 online database,Global Burden of Disease(GBD)2019 study,and Cancer Incidence in Five Continents plus database(CI5 plus).Trends of cancer incidence and mortality in China,US,and UK were analyzed using Joinpoint regression models to calculate annual percent changes(APCs)and identify the best-fitting joinpoints.Results:An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020.Additionally,cancers resulted in 67,340,309 DALYs in China.Compared to the US and UK,China had lower cancer incidence but higher cancer mortality andDALY rates.Furthermore,the cancer spectrum of China was changing,with a rapid increase incidence and burden of lung,breast,colorectal,and prostate cancer in addition to a high incidence and heavy burden of liver,stomach,esophageal,and cervical cancer.Conclusions:The cancer spectrum of China is changing from a developing country to a developed country.Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China.Therefore,the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well-established in the developed countries,and taking consideration of the diversity of cancer types by of different regions in China at the same time.
基金National Basic Research Program of China,No.2010CB950900No.2014CB954302+1 种基金National Key Technol-ogy R&D Program,No.2013BAC03B00The Key Research Program of the Chinese Academy of Sciences,No.KSZD-EW-Z-021-02
文摘Land-use/land-cover changes （LUCCs） have links to both human and nature inter- actions. China＇s Land-Use/cover Datasets （CLUDs） were updated regularly at 5-year inter- vals from the late 1980s to 2010, with standard procedures based on Landsat TM／ETM＋ im- ages. A land-use dynamic regionalization method was proposed to analyze major land-use conversions. The spatiotemporal characteristics, differences, and causes of land-use changes at a national scale were then examined. The main findings are summarized as fol- lows. Land-use changes （LUCs） across China indicated a significant variation in spatial and temporal characteristics in the last 20 years （1990-2010）. The area of cropland change de- creased in the south and increased in the north, but the total area remained almost un- changed. The reclaimed cropland was shifted from the northeast to the northwest. The built-up lands expanded rapidly, were mainly distributed in the east, and gradually spread out to central and western China. Woodland decreased first, and then increased, but desert area was the opposite. Grassland continued decreasing. Different spatial patterns of LUC in China were found between the late 20th century and the early 21st century. The original 13 LUC zones were replaced by 15 units with changes of boundaries in some zones. The main spatial characteristics of these changes included （1） an accelerated expansion of built-up land in the Huang-Huai-Hai region, the southeastern coastal areas, the midstream area of the Yangtze River, and the Sichuan Basin; （2） shifted land reclamation in the north from northeast China and eastern Inner Mongolia to the oasis agricultural areas in northwest China; （3） continuous transformation from rain-fed farmlands in northeast China to paddy fields; and （4） effective- ness of the ＂Grain for Green＂ project in the southern agricultural-pastoral ecotones of Inner Mongolia, the Loess Plateau, and southwestern mountainous areas. In the last two decades, although climate change
基金co-supported by the National Natural Science Foundation of China(Grant Nos.40133020 and 40272045)the Chinese Ministry of Science and Technology of China(Grant No.G1999043202)the Chinese Academy of Sciences and the Key Laboratory of Continental Dynamics,Northwest University,the Ministry of Education of China.
文摘Using the in situ zircon U-Pb dating method of LA-ICPMS, we analyzed the 31 Ma old SHRIMP U-Pb age of the Yongsheng nepheline syenite from southern Jilin Province under different spot sizes. The obtained ages are comparable with that of SHRIMP in both accuracy and precision. The age is also identical to that of the Yinmawanshan gabbro from the Liaodong Peninsula within error. Both the Yongsheng nepheline syenite and the Yinmawanshan gabbro represent the youngest known exposed intrusions in northeastern and even eastern China. The results indicate the Eocene mantle-derived magmatic underplating, and the rapid crustal uplifting of this region since 30 Ma. The analyses also document extremely high LREE concentrations and relatively flat REE patterns for the zircons from the Yongsheng nepheline syenite, which represent a new type of zircon REE pattern.
基金This study was funded by Ministry of Science and Technology of the People’s Republic of China,National Key R&D Programme of China(2017YFC1310901,2016YFC0901002,2017YFC1307905,and 2015BAI12B00)the Youth Programme(QML20180501)+1 种基金National Natural Science Foundation of China(81801152)Beijing Talents Project(2018000021223ZK03 and 2018A13).
文摘China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and
文摘During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or transdifferentiation （EMT）. In this process, the cells lose their epithelial characteristics, including their polarity and specialized cell-cell contacts, and acquire a migratory behavior, allowing them to move away from their epithelial cell community and to integrate into surrounding tissue, even at remote locations. EMT illustrates the differentiation plasticity during development and is complemented by another process, called mesenchymal to epithelial transition （MET）. While being an integral process during development, EMT is also recapitulated under pathological conditions, prominently in fibrosis and in invasion and metastasis of carcinomas. Accordingly, EMT is considered as an important step in tumor progression. TGF-β signaling has been shown to play an important role in EMT. In fact, adding TGF-β to epithelial cells in culture is a convenient way to induce EMT in various epithelial cells. Although much less characterized, epithelial plasticity can also be regulated by TGF-β-related bone morphogenetic proteins （BMPs）, and BMPs have been shown to induce EMT or MET depending on the developmental context. In this review, we will discuss the induction of EMT in response to TGF-β, and focus on the under- lying signaling and transcription mechanisms.
基金supported by the National Health Commission of the People’s Republic of China (201302002,Clinical Trial NCT02200679)。
文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
基金partially supported by the National Key Research and Development Program of China(2016YFA0600103)Delos Living LLCthe Cyrus Tang Foundation
文摘As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, environmental pollution, and ultimately human health, timely and higher resolution land cover information is urgently needed to achieve the sustainable development goals of the United Nations.
基金supported by National Natural Science Foundation of China (Grant Nos.90714001,90714004,90714008,90714009,91014006,91114206)
文摘A National Science Foundation of China （NSFC） major research project, Destruction of the North China Craton （NCC）, has been carried out in the past few years by Chinese scientists through an in-depth and systematic observations, experiments and theoretical analyses, with an emphasis on the spatio-temporal distribution of the NCC destruction, the structure of deep earth and shallow geological records of the craton evolution, the mechanism and dynamics of the craton destruction. From this work the foUowing conclusions can be drawn： （1） Significant spatial heterogeneity exists in the NCC lithospheric thickness and crustal structure, which constrains the scope of the NCC destruction. （2） The nature of the Paleozoic, Mesozoic and Cenozoic sub-continental lithospheric mantle （CLM） underneath the NCC is characterized in detail. In terms of water content, the late Mesozoic CLM was rich in water, but Cenozoic CLM was highly water deficient. （3） The correlation between magmatism and surface geological response confirms that the geological and tectonic evolution is governed by cratonic destruction processes. （4） Pacific subduction is the main dynamic factor that triggered the destruction of the NCC, which highlights the role of cratonic destruction in plate tectonics.
基金This work was supported by the National Science and Technology Major Project(2017ZX10103011 and 2017ZX10204401)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-1-009)+1 种基金Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581 and JCYJ20170413141236903)China Postdoctoral Science Foundation(2019T120147).
文摘The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
文摘There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.
文摘Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk
基金National Basic Research Program of China, No.2009CB421105National Key Technology R&D Program, No.2006BAC08B00Knowledge Innovation Program of the CAS, No.KSCX1-YW-09-01
文摘Land use and land cover change as the core of coupled human-environment systems has become a potential field of land change science （LCS） in the study of global environmental change. Based on remotely sensed data of land use change with a spatial resolution of 1 km × 1 km on national scale among every 5 years, this paper designed a new dynamic regionalization according to the comprehensive characteristics of land use change including regional differentiation, physical, economic, and macro-policy factors as well. Spatial pattern of land use change and its driving forces were investigated in China in the early 21 st century. To sum up, land use change pattern of this period was characterized by rapid changes in the whole country. Over the agricultural zones, e.g., Huang-Huai-Hai Plain, the southeast coastal areas and Sichuan Basin, a great proportion of fine arable land were engrossed owing to considerable expansion of the built-up and residential areas, resulting in decrease of paddy land area in southern China. The development of oasis agriculture in Northwest China and the reclamation in Northeast China led to a slight increase in arable land area in northern China. Due to the ＂Grain for Green＂ policy, forest area was significantly increased in the middle and western developing regions, where the vegetation coverage was substantially enlarged, likewise. This paper argued the main driving forces as the implementation of the strategy on land use and regional development, such as policies of ＂Western Development＂, ＂Revitalization of Northeast＂, coupled with rapidly economic development during this period.
基金supported(in part)by the Entrusted Project of National Center for Medical Service Administration,National Health and Family Planning Commission China(No.[2019]099)the First Level Funding of the Second Medical Leading Talent Project in Hubei Provincethe Special Project for Emergency of the Ministry of Science and Technology(2020YFC0841300)。
文摘In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
基金This work was supported by the Fundamental Research Funds for the Central Universities(WK2070000191,WK9110000037)the fellowship of China National Postdoctoral Program for Innovative Talents(BX20200325)the Natural Science Foundation of Anhui province(1808085QH244).
文摘The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.
基金This study was supported by the National Basic Research Program （973 Program） （Nos. 2010CB945401 and 2012CB911201）, the National Natural Science Foundation of China （Grant Nos. 91019020, 81330055, and 31371508）.
文摘Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear （3PN） zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene （HBB）. However, the efficiency of homologous recombination directed repair （HDR） of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene （HBD）, which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
