Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in I...Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byflow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and verified.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.展开更多
AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the P...AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation.展开更多
Three global datasets, the History Database of the Global Environment （HYDE）, Kaplan and Krurnhardt （KK） and Pongratz of reconstructed anthropogenic land cover change （ALCC） were introduced and compared in this ...Three global datasets, the History Database of the Global Environment （HYDE）, Kaplan and Krurnhardt （KK） and Pongratz of reconstructed anthropogenic land cover change （ALCC） were introduced and compared in this paper. The HYDE dataset was recon- structed by Goldewijk and his colleagues at the National institute of Public ttealth and the Environment in Netherland, covering the past 12 000 years. The KK dataset was reconstructed by Kaplan and his colleagues, the Soil-Vegetation-Atmosphere Research Group at the Institute of Environmental Engineering in Switzerland, covering the past 8000 years. The Pongratz dataset was reconstructed by Pon- gratz and her colleagues at the Max Planck Institute for Meteorology in Germany, coveting AD 800-1992. The results show that the reconstructed datasets are quite different from each other due to the different methods used. The three datasets all allocated the historical ALCC according to human population density. The main reason causing the differences among the three datasets lies on the different relationships between population density and land use used in each reconstructed dataset. The KK dataset is better than the other two datasets for two important reasons. First, it used the nonlinear relationship between population density and land use, while the other two used the linear relationship. Second, Kaplan and his colleagues adopted the technological development and intensification parameters and considered the wood harvesting and the long-term fallow area resulted from shifting cultivation, which were neglected in the recon- structions of the other two datasets. Therefore, the KK dataset is more suitable as one of the anthropogenic forcing fields for climate simulation over the past two millennia that is recently concerned by two projects, the National Basic Research Program and the Strategic and Special Frontier Project of Science and Technology of the Chinese Academy of Sciences.展开更多
BACKGROUND Understanding a virus shedding patterns in body fluids/secretions is importantto determine the samples to be used for diagnosis and to formulate infectioncontrol measures.AIM To investigate the severe acute...BACKGROUND Understanding a virus shedding patterns in body fluids/secretions is importantto determine the samples to be used for diagnosis and to formulate infectioncontrol measures.AIM To investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)shedding patterns and its risk factors.METHODS All laboratory-confirmed coronavirus disease 2019 patients with completemedical records admitted to the Shenzhen Third People’s Hospital from January28, 2020 to March 8, 2020 were included. Among 145 patients (54.5% males;median age, 46.1 years), three (2.1%) died. The bronco-alveolar lavage fluid(BALF) had the highest virus load compared with the other samples. The viralload peaked at admission (3.3 × 108 copies) and sharply decreased 10 d afteradmission.RESULTS The viral load was associated with prolonged intensive care unit (ICU) duration.Patients in the ICU had significantly longer shedding time compared to those inthe wards (P < 0.0001). Age > 60 years [hazard ratio (HR) = 0.6;95% confidenceinterval (CI): 0.4-0.9] was an independent risk factor for SARS-CoV-2 shedding,while chloroquine (HR = 22.8;95%CI: 2.3-224.6) was a protective factor.CONCLUSION BALF had the highest SARS-CoV-2 load. Elderly patients had higher virus loads,which was associated with a prolonged ICU stay. Chloroquine was associatedwith shorter shedding duration and increased the chance of viral negativity.展开更多
On the basis of the analysis of main problems existing in current agricultural meteorological service in China,for the purpose of exploring a solution to the "last kilometer" problem in rural meteorological ...On the basis of the analysis of main problems existing in current agricultural meteorological service in China,for the purpose of exploring a solution to the "last kilometer" problem in rural meteorological service,this article designed four short message service products with the business brand name "meteorology for agricultural condition",including "weather prediction for farming season","weather forecast for farming","weather alert",and "meteorological hazards of agriculture".By taking advantage of telecom operators' market,these products have been spread to more than 1 million rural mobile phone users and widely welcomed.They also contributed enormously to disaster prevention and peasants' income growth,and achieved good social and economic benefits.展开更多
A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm...A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm and bilateral ground glass opacities. Echocardiography confirmed cardiomyopathy. With anti-TB drugs, high-dose prednisone and surgery, the life of this patient was successfully prolonged for more than four months. The concomitant disorders of aortic pseudoaneurysm, alveolar hemorrhage and cardiomyopathy in pulmonary tuberculosis are intriguing. We postulate that immune-mediated small vessel vasculitis triggered by pathogens plays an important role in the pathogenesis of this disease, rather than a direct TB infection.展开更多
Vaccinium bracteatum Thunb.,an important native Chinese wild blueberry species,is widely used as a rootstock and in blueberry cultivar breeding,as well as in traditional medicine and local food.We report here the geno...Vaccinium bracteatum Thunb.,an important native Chinese wild blueberry species,is widely used as a rootstock and in blueberry cultivar breeding,as well as in traditional medicine and local food.We report here the genome sequence of V.bracteatum using a combination of Oxford Nanopore Technologies long-read and Illumina HiSeq short-read sequencing technologies to obtain 65.30 Gb of clean data,achieving 114.60-fold genome coverage.The assembled genome has a total sequence length of 569.81 Mb and consists of 36,756 predicted genes.Repetitive DNA sequences represent 57.78%of the genome sequence.Comparative genomic analysis revealed that a total of 336 gene families had expanded and that 298 candidate genes had undergone positive selection during evolution in V.bracteatum.The divergence of V.bracteatum from the related Rhododendron williamsianum and Rhododendron delavayi occurred~13−85 million years ago.The genome sequence of V.bracteatum allowed us to identify some important genes associated with traits involved in fruit development,such as flavonoid biosynthesis,sugar and acid metabolism,MYB transcription factor gene expression,and hormone regulation.The differential expression patterns of genes encoding flavonoid biosynthesis enzymes and MYB transcription factors might explain the high flavonoid content of V.bracteatum.This chromosome-level genome assembly provides reference sequences for the identification and characterization of genes important in the improvement of blueberry and related research.展开更多
Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are i...Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.展开更多
Studying foreign language attrition is important in the context of Chinese language learning because, in light of a growing worldwide interest in learning Chinese languages, language professionals need to understand t...Studying foreign language attrition is important in the context of Chinese language learning because, in light of a growing worldwide interest in learning Chinese languages, language professionals need to understand the complexities of Chinese language acquisition. However, little research exists to date on foreign language attrition among Chinese language learners. In this study, we examined the features of language attrition,especially phonological attrition, among Mandarin learners in a higher educational institution in Brunei Darussalam. Additionally, we sought to test, in a Bruneian context,prominent theories and hypotheses about language attrition, including markedness theory and functional load theory. Our sample consisted of 86 beginner Mandarin students who spoke Malay as their native language and English as the academic language. Participants were 18-20 years old and studied Mandarin formally 4 hours per week for 14 consecutive weeks, during which they were also required to study for 8 hours per week on their own.Subsequently, they took a 3-month break from studying. We tested participants before and after the break and computed descriptive statistics to compare the results of the two tests. Our results showed the greatest attrition rates in tones and special structures of Mandarin, with less attrition in final and initial sounds. We discuss specific phonological findings as they relate to native Malay speakers, and we describe how our findings confirm or contradict,within the Bruneian context, existing theories. We conclude that markedness theory is applicable in our research context, but our findings failed to support functional load theory.展开更多
Background and Aims:Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells(HSCs)and leads to a poor outcome.Artesunate(Art)is an ester derivative of artemisinin that can induce ...Background and Aims:Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells(HSCs)and leads to a poor outcome.Artesunate(Art)is an ester derivative of artemisinin that can induce ferroptosis in HSCs,and activated transcriptional factor 3(ATF3)is an ATF/CREB transcription factor that is induced in response to stress.In this study,we examined the role of the Rho-associated protein kinase 1(ROCK1)/ATF3 axis in Art-induced ferroptosis in HSCs.Methods:HSC activation and ferroptosis were studied in vitro by western blotting,polymerase chain reaction,immunofluorescence,and other assays.ATF3 electrophoretic mobility and ROCK1 protein stability were assayed by western blotting.Immunoprecipitation was used to detect the interaction of ROCK1 and ATF3,as well as ATF3 phosphorylation.A ubiquitination assay was used to verify ROCK1 degradation.Atf3-interfering and Rock1-overexpressing mice were constructed to validate the anti-hepatic fibrosis activity of Art in vivo.Results:Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro.Art also decreased carbon tetrachloride-induced liver fibrosis in mice,which was reversed by interfering with Atf3 or overexpressing Rock1.Conclusions:The ROCK1/ATF3 axis was involved in liver fibrosis and regulation of ferroptosis,which provides an experimental basis for further study of Art for the treatment of liver fibrosis.展开更多
To the Editor:Lipohypertrophy(LH)is the most common local complication caused by multiple overlapping insulin injections.Clinically,LH manifests as prominent and/or thickened tissue at injection or infusion sites,some...To the Editor:Lipohypertrophy(LH)is the most common local complication caused by multiple overlapping insulin injections.Clinically,LH manifests as prominent and/or thickened tissue at injection or infusion sites,sometimes resulting in lump formation under the skin.Histologically,LH is characterized by decreased vascularity,fibrosis,and adipocyte enlargement and proliferation in the subcutaneous tissue at insulin injection sites.Because of this,the existing screening methods for LH are mainly based on clinical examination and ultrasound scanning(USS).A recent systematic review revealed that only limited information is available for detection sensitivity among the different methods used to identify LH to date.Thus far,the gold standard examination for LH diagnosis remains debatable and there has been insufficient research on which patients require both kinds of examination.Currently,the detection sensitivity of USS vs.clinical examination for LH has not been reported in large sample-based studies.The present study aimed to compare the detection accuracy between USS and clinical examination using a large patient cohort and to determine the influencing factors for inconsistent detection results of LH between the two methods.展开更多
Chronic disseminated intravascular coagulation （DIC） is a rare but devastating complication of aortic aneurysm （AA）. This study investigated the clinical manifestations, laboratory findings, and treatment of patie...Chronic disseminated intravascular coagulation （DIC） is a rare but devastating complication of aortic aneurysm （AA）. This study investigated the clinical manifestations, laboratory findings, and treatment of patients with AA-associated chronic DIC （AA-DIC） and explored the mechanisms, duration, and therapeutic response of AA-DIC. We retrospectively reviewed the medical records of 235 AA patients admitted at the Peking Union Medical College Hospital between September 2009 and January 2015. The patients were classified as those with DIC （AA-DIC） and those without DIC （non-DIC）. The AA-DIC group showed a significantly higher proportion of female patients and a significantly longer AA disease course than the non-DIC group did. The AA-DIC patients presented mural thrombi, dissecting aneurysms, a family history of AA, and diabetes significantly more frequently than the non-DIC patients did. Furthermore, multiple regression analyses revealed that sex, mural thrombus, aneurysm type, diabetes, and stent surgery are possible independent risk factors for AA-DIC patients. Fifty-two （22.1%） patients presented AA-DIC. Among these patients, 43 had non-typical DIC and 9 had typical DIC; the mortality rate of the latter was 22.2%. The mean age of the patients with typical DIC was significantly higher than of that of patients with non-typical DIC. The non-typical DIC patients also presented abnormal coagulation disorders of varying degrees. Furthermore, heparin or low-molecular-weight heparin improved the clinical symptoms and laboratory parameters in patients with AA and typical DIC. Thus, chronic DIC should be considered in patients with AA.展开更多
Background and Aims:Recognition of excessive activa-tion of hepatic stellate cells(HSCs)in liver fibrosis prompt-ed us to investigate the regulatory mechanisms of HSCs.We aimed to examine the role of O-GlcNAcylation m...Background and Aims:Recognition of excessive activa-tion of hepatic stellate cells(HSCs)in liver fibrosis prompt-ed us to investigate the regulatory mechanisms of HSCs.We aimed to examine the role of O-GlcNAcylation modifica-tion of alanine,serine,cysteine transporter 2(ASCT2)in HSCs and liver fibrosis.Methods:The expression of O-Glc-NAcylation modification in fibrotic mice livers and activated HSCs was analyzed by western blotting.Immunoprecipita-tion was used to assess the interaction of ASCT2 and O-Glc-NAc transferase(OGT).In addition,ASCT2 protein stability was assayed after cycloheximide(CHX)treatment.The O-GlcNAcylation site of ASCT2 was predicted and mutated by site-directed mutagenesis.Real-time PCR,immunofluores-cence,kit determinations and Seahorse assays were used to clarify the effect of ASCT2 O-GlcNAcylation on HSC glu-taminolysis and HSC activation.Western blotting,immuno-chemistry,and immunohistofluorescence were used to ana-lyze the effect of ASCT2 O-GlcNAcylation in vivo.Results:We observed significantly increased O-GlcNAcylation modi-fication of ASCT2.ASCT2 was found to interact with OGT to regulate ASCT2 stability.We predicted and confirmed that O-GlcNAcylation of ASCT2 at Thr122 site resulted in HSCs activation.We found Thr122 O-GlcNAcylation of ASCT2 me-diated membrane trafficking of glutamine transport and attenuated HSC glutaminolysis.Finally,we validated the expression and function of ASCT2 O-GlcNAcylation after in-jection of AAV8-ASCT2 shRNA in CCl4-induced liver fibrosis mice in vivo.Conclusions:Thr122 O-GlcNAcylation regu-lation of ASCT2 resulted in stability and membrane traf-ficking-mediated glutaminolysis in HSCs and liver fibrosis.Further studies are required to assess its role as a putative therapeutic target.展开更多
Background：Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus （SLE）.This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis （LM） and to determi...Background：Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus （SLE）.This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis （LM） and to determine risk factors of LM in hospitalized Chinese patients with SLE.Methods：We conducted a retrospective case-control study.A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group,and 1 O0 patients with SLE but without LM were randomly pooled as the control group.Univariable analysis was performed using Chi-square tests for categorical variables,and the Student＇s t-test or Mann-Whitney U-test was performed for continuous variables according to the normality.Results：LM presented as the initial manifestation of SLE in 7 patients （28％） and occurred mostly at earlier stages compared to the controls （20.88 ± 35.73 vs.44.08 ± 61.56 months,P =0.008）.Twenty-one patients （84％） experienced episodes of symptomatic heart failure.Echocardiography showed that 23 patients （92％） had decreased left ventricular ejection fraction （＜50％） and all patients had wall motion abnormalities.A high SLE Disease Activity Index was the independent risk factor in the development of LM （odds ratio =1.322,P ＜ 0.001）.With aggressive immunosuppressive therapies,most patients achieved satisfactory outcome.The in-hospital mortality was not significantly higher in the LM group than in the controls （4％ vs.2％,P =0.491）.Conclusions：LM could result in cardiac dysfunction and even sudden death.High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE.Characteristic echocardiographic findings could confirm the diagnosis of LM.Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM.展开更多
Hair analysis has been mainly used to document drug use history in abusers,drug-facilitated crime cases,doping control analysis and postmortem toxicology in the fields of forensic toxicology,clinical toxicology,and do...Hair analysis has been mainly used to document drug use history in abusers,drug-facilitated crime cases,doping control analysis and postmortem toxicology in the fields of forensic toxicology,clinical toxicology,and doping control.Hair analysis has also gained more attention in the last 30 years in China.Relevant technology has been promoted as more research has appeared concerning hair analysis,and consensus has been sought among forensic toxicologists regarding aspects such as hair decontamination treatment,detection of abused substances in hair,segmental hair analysis and interpretation of analytical results.However,there are still some limitations in the estimation of drug intake time and frequency by segmental hair analysis due to the different growth cycles evident within a bundle of hairs,the drug incorporation mechanism and sampling errors.Microsampling and imaging mass spectrometry(iMS)technology based on a single hair may be a good choice to estimate drug intake time more accurately.Analysis of hair root samples may also be used to document acute poisoning in postmortem toxicology,and the analysis of the hair shaft can document long-term use of drugs depending on the length of the hair being evaluated.展开更多
基金Supported by Ningbo Health Technology Project,Nos.2020Y12 and 2022Y12.
文摘Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byflow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and verified.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.
基金Supported by National Science Technology Pillar Program in the 11th Five-Year Plan,No. 2008BAI59B03Research Special Fund for the Public Welfare Industry of Health,No.201202004
文摘AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation.
基金Under the auspices of Strategic and Special Frontier Project of Science and Technology of Chinese Academy of Sciences (No. XDA05080800)National Basic Research Program of China (No. 2010CB950102)National Natural Science Foundation of China (No. 40871007)
文摘Three global datasets, the History Database of the Global Environment （HYDE）, Kaplan and Krurnhardt （KK） and Pongratz of reconstructed anthropogenic land cover change （ALCC） were introduced and compared in this paper. The HYDE dataset was recon- structed by Goldewijk and his colleagues at the National institute of Public ttealth and the Environment in Netherland, covering the past 12 000 years. The KK dataset was reconstructed by Kaplan and his colleagues, the Soil-Vegetation-Atmosphere Research Group at the Institute of Environmental Engineering in Switzerland, covering the past 8000 years. The Pongratz dataset was reconstructed by Pon- gratz and her colleagues at the Max Planck Institute for Meteorology in Germany, coveting AD 800-1992. The results show that the reconstructed datasets are quite different from each other due to the different methods used. The three datasets all allocated the historical ALCC according to human population density. The main reason causing the differences among the three datasets lies on the different relationships between population density and land use used in each reconstructed dataset. The KK dataset is better than the other two datasets for two important reasons. First, it used the nonlinear relationship between population density and land use, while the other two used the linear relationship. Second, Kaplan and his colleagues adopted the technological development and intensification parameters and considered the wood harvesting and the long-term fallow area resulted from shifting cultivation, which were neglected in the recon- structions of the other two datasets. Therefore, the KK dataset is more suitable as one of the anthropogenic forcing fields for climate simulation over the past two millennia that is recently concerned by two projects, the National Basic Research Program and the Strategic and Special Frontier Project of Science and Technology of the Chinese Academy of Sciences.
基金Supported by Startup Fund forYouth Faculty of ShenzhenUniversity, No. 2018009.
文摘BACKGROUND Understanding a virus shedding patterns in body fluids/secretions is importantto determine the samples to be used for diagnosis and to formulate infectioncontrol measures.AIM To investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)shedding patterns and its risk factors.METHODS All laboratory-confirmed coronavirus disease 2019 patients with completemedical records admitted to the Shenzhen Third People’s Hospital from January28, 2020 to March 8, 2020 were included. Among 145 patients (54.5% males;median age, 46.1 years), three (2.1%) died. The bronco-alveolar lavage fluid(BALF) had the highest virus load compared with the other samples. The viralload peaked at admission (3.3 × 108 copies) and sharply decreased 10 d afteradmission.RESULTS The viral load was associated with prolonged intensive care unit (ICU) duration.Patients in the ICU had significantly longer shedding time compared to those inthe wards (P < 0.0001). Age > 60 years [hazard ratio (HR) = 0.6;95% confidenceinterval (CI): 0.4-0.9] was an independent risk factor for SARS-CoV-2 shedding,while chloroquine (HR = 22.8;95%CI: 2.3-224.6) was a protective factor.CONCLUSION BALF had the highest SARS-CoV-2 load. Elderly patients had higher virus loads,which was associated with a prolonged ICU stay. Chloroquine was associatedwith shorter shedding duration and increased the chance of viral negativity.
文摘On the basis of the analysis of main problems existing in current agricultural meteorological service in China,for the purpose of exploring a solution to the "last kilometer" problem in rural meteorological service,this article designed four short message service products with the business brand name "meteorology for agricultural condition",including "weather prediction for farming season","weather forecast for farming","weather alert",and "meteorological hazards of agriculture".By taking advantage of telecom operators' market,these products have been spread to more than 1 million rural mobile phone users and widely welcomed.They also contributed enormously to disaster prevention and peasants' income growth,and achieved good social and economic benefits.
文摘A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm and bilateral ground glass opacities. Echocardiography confirmed cardiomyopathy. With anti-TB drugs, high-dose prednisone and surgery, the life of this patient was successfully prolonged for more than four months. The concomitant disorders of aortic pseudoaneurysm, alveolar hemorrhage and cardiomyopathy in pulmonary tuberculosis are intriguing. We postulate that immune-mediated small vessel vasculitis triggered by pathogens plays an important role in the pathogenesis of this disease, rather than a direct TB infection.
基金supported by Anhui Provincial Natural Science Foundation(2008085QC129 and 2008085MC77)the 17th Huo Yingdong Education Fund Project(171022)Key Research and Development Program in Anhui Province(202204c06020029).
文摘Vaccinium bracteatum Thunb.,an important native Chinese wild blueberry species,is widely used as a rootstock and in blueberry cultivar breeding,as well as in traditional medicine and local food.We report here the genome sequence of V.bracteatum using a combination of Oxford Nanopore Technologies long-read and Illumina HiSeq short-read sequencing technologies to obtain 65.30 Gb of clean data,achieving 114.60-fold genome coverage.The assembled genome has a total sequence length of 569.81 Mb and consists of 36,756 predicted genes.Repetitive DNA sequences represent 57.78%of the genome sequence.Comparative genomic analysis revealed that a total of 336 gene families had expanded and that 298 candidate genes had undergone positive selection during evolution in V.bracteatum.The divergence of V.bracteatum from the related Rhododendron williamsianum and Rhododendron delavayi occurred~13−85 million years ago.The genome sequence of V.bracteatum allowed us to identify some important genes associated with traits involved in fruit development,such as flavonoid biosynthesis,sugar and acid metabolism,MYB transcription factor gene expression,and hormone regulation.The differential expression patterns of genes encoding flavonoid biosynthesis enzymes and MYB transcription factors might explain the high flavonoid content of V.bracteatum.This chromosome-level genome assembly provides reference sequences for the identification and characterization of genes important in the improvement of blueberry and related research.
文摘Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.
文摘Studying foreign language attrition is important in the context of Chinese language learning because, in light of a growing worldwide interest in learning Chinese languages, language professionals need to understand the complexities of Chinese language acquisition. However, little research exists to date on foreign language attrition among Chinese language learners. In this study, we examined the features of language attrition,especially phonological attrition, among Mandarin learners in a higher educational institution in Brunei Darussalam. Additionally, we sought to test, in a Bruneian context,prominent theories and hypotheses about language attrition, including markedness theory and functional load theory. Our sample consisted of 86 beginner Mandarin students who spoke Malay as their native language and English as the academic language. Participants were 18-20 years old and studied Mandarin formally 4 hours per week for 14 consecutive weeks, during which they were also required to study for 8 hours per week on their own.Subsequently, they took a 3-month break from studying. We tested participants before and after the break and computed descriptive statistics to compare the results of the two tests. Our results showed the greatest attrition rates in tones and special structures of Mandarin, with less attrition in final and initial sounds. We discuss specific phonological findings as they relate to native Malay speakers, and we describe how our findings confirm or contradict,within the Bruneian context, existing theories. We conclude that markedness theory is applicable in our research context, but our findings failed to support functional load theory.
基金supported by the National Natural Science Foundation of China(No.82000572,82073914,82173874,82274185)the Natural Science Foundation of Jiangsu Province(No.BK20220467,BK20200840)+4 种基金the Major Project of the Natural Science Research of Jiangsu Higher Education Institutions(No.22KJB310013,19KJA310005)the Joint Project of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica and Yangtze River Pharmaceutical(No.JKLPSE202005)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY82000572)Nanjing Pharmaceutical Association-Changzhou Fourth Pharmaceutical Hospital Pharmaceutical Research Fund(NO.2021YX030)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX22_0792).
文摘Background and Aims:Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells(HSCs)and leads to a poor outcome.Artesunate(Art)is an ester derivative of artemisinin that can induce ferroptosis in HSCs,and activated transcriptional factor 3(ATF3)is an ATF/CREB transcription factor that is induced in response to stress.In this study,we examined the role of the Rho-associated protein kinase 1(ROCK1)/ATF3 axis in Art-induced ferroptosis in HSCs.Methods:HSC activation and ferroptosis were studied in vitro by western blotting,polymerase chain reaction,immunofluorescence,and other assays.ATF3 electrophoretic mobility and ROCK1 protein stability were assayed by western blotting.Immunoprecipitation was used to detect the interaction of ROCK1 and ATF3,as well as ATF3 phosphorylation.A ubiquitination assay was used to verify ROCK1 degradation.Atf3-interfering and Rock1-overexpressing mice were constructed to validate the anti-hepatic fibrosis activity of Art in vivo.Results:Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro.Art also decreased carbon tetrachloride-induced liver fibrosis in mice,which was reversed by interfering with Atf3 or overexpressing Rock1.Conclusions:The ROCK1/ATF3 axis was involved in liver fibrosis and regulation of ferroptosis,which provides an experimental basis for further study of Art for the treatment of liver fibrosis.
基金This work was supported by grants from the Jiangsu Provincial Medical Innovation Team(No.CXTDA2017019)the Clinical Ability Improvement Project of Jiangsu Province Hospital(No.JSPH-NB-2020-2)。
文摘To the Editor:Lipohypertrophy(LH)is the most common local complication caused by multiple overlapping insulin injections.Clinically,LH manifests as prominent and/or thickened tissue at injection or infusion sites,sometimes resulting in lump formation under the skin.Histologically,LH is characterized by decreased vascularity,fibrosis,and adipocyte enlargement and proliferation in the subcutaneous tissue at insulin injection sites.Because of this,the existing screening methods for LH are mainly based on clinical examination and ultrasound scanning(USS).A recent systematic review revealed that only limited information is available for detection sensitivity among the different methods used to identify LH to date.Thus far,the gold standard examination for LH diagnosis remains debatable and there has been insufficient research on which patients require both kinds of examination.Currently,the detection sensitivity of USS vs.clinical examination for LH has not been reported in large sample-based studies.The present study aimed to compare the detection accuracy between USS and clinical examination using a large patient cohort and to determine the influencing factors for inconsistent detection results of LH between the two methods.
文摘Chronic disseminated intravascular coagulation （DIC） is a rare but devastating complication of aortic aneurysm （AA）. This study investigated the clinical manifestations, laboratory findings, and treatment of patients with AA-associated chronic DIC （AA-DIC） and explored the mechanisms, duration, and therapeutic response of AA-DIC. We retrospectively reviewed the medical records of 235 AA patients admitted at the Peking Union Medical College Hospital between September 2009 and January 2015. The patients were classified as those with DIC （AA-DIC） and those without DIC （non-DIC）. The AA-DIC group showed a significantly higher proportion of female patients and a significantly longer AA disease course than the non-DIC group did. The AA-DIC patients presented mural thrombi, dissecting aneurysms, a family history of AA, and diabetes significantly more frequently than the non-DIC patients did. Furthermore, multiple regression analyses revealed that sex, mural thrombus, aneurysm type, diabetes, and stent surgery are possible independent risk factors for AA-DIC patients. Fifty-two （22.1%） patients presented AA-DIC. Among these patients, 43 had non-typical DIC and 9 had typical DIC; the mortality rate of the latter was 22.2%. The mean age of the patients with typical DIC was significantly higher than of that of patients with non-typical DIC. The non-typical DIC patients also presented abnormal coagulation disorders of varying degrees. Furthermore, heparin or low-molecular-weight heparin improved the clinical symptoms and laboratory parameters in patients with AA and typical DIC. Thus, chronic DIC should be considered in patients with AA.
基金the Leading Talent Project of Ji-angsu Province Traditional Chinese Medicine(SLJ0216)the National Natural Science Foundation of China(82073914,81870423)+2 种基金the Major Project of the Natural Science Research of Jiangsu Higher Education Institutions(19KJA310005)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,Grant/Award Number:KYCX20_1493the Joint Project of Jiangsu Key Laboratory for Pharmacol-ogy and Safety Evaluation of Chinese Materia Medica and Yangtze River Pharmaceutical(JKLPSE202005)。
文摘Background and Aims:Recognition of excessive activa-tion of hepatic stellate cells(HSCs)in liver fibrosis prompt-ed us to investigate the regulatory mechanisms of HSCs.We aimed to examine the role of O-GlcNAcylation modifica-tion of alanine,serine,cysteine transporter 2(ASCT2)in HSCs and liver fibrosis.Methods:The expression of O-Glc-NAcylation modification in fibrotic mice livers and activated HSCs was analyzed by western blotting.Immunoprecipita-tion was used to assess the interaction of ASCT2 and O-Glc-NAc transferase(OGT).In addition,ASCT2 protein stability was assayed after cycloheximide(CHX)treatment.The O-GlcNAcylation site of ASCT2 was predicted and mutated by site-directed mutagenesis.Real-time PCR,immunofluores-cence,kit determinations and Seahorse assays were used to clarify the effect of ASCT2 O-GlcNAcylation on HSC glu-taminolysis and HSC activation.Western blotting,immuno-chemistry,and immunohistofluorescence were used to ana-lyze the effect of ASCT2 O-GlcNAcylation in vivo.Results:We observed significantly increased O-GlcNAcylation modi-fication of ASCT2.ASCT2 was found to interact with OGT to regulate ASCT2 stability.We predicted and confirmed that O-GlcNAcylation of ASCT2 at Thr122 site resulted in HSCs activation.We found Thr122 O-GlcNAcylation of ASCT2 me-diated membrane trafficking of glutamine transport and attenuated HSC glutaminolysis.Finally,we validated the expression and function of ASCT2 O-GlcNAcylation after in-jection of AAV8-ASCT2 shRNA in CCl4-induced liver fibrosis mice in vivo.Conclusions:Thr122 O-GlcNAcylation regu-lation of ASCT2 resulted in stability and membrane traf-ficking-mediated glutaminolysis in HSCs and liver fibrosis.Further studies are required to assess its role as a putative therapeutic target.
文摘Background：Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus （SLE）.This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis （LM） and to determine risk factors of LM in hospitalized Chinese patients with SLE.Methods：We conducted a retrospective case-control study.A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group,and 1 O0 patients with SLE but without LM were randomly pooled as the control group.Univariable analysis was performed using Chi-square tests for categorical variables,and the Student＇s t-test or Mann-Whitney U-test was performed for continuous variables according to the normality.Results：LM presented as the initial manifestation of SLE in 7 patients （28％） and occurred mostly at earlier stages compared to the controls （20.88 ± 35.73 vs.44.08 ± 61.56 months,P =0.008）.Twenty-one patients （84％） experienced episodes of symptomatic heart failure.Echocardiography showed that 23 patients （92％） had decreased left ventricular ejection fraction （＜50％） and all patients had wall motion abnormalities.A high SLE Disease Activity Index was the independent risk factor in the development of LM （odds ratio =1.322,P ＜ 0.001）.With aggressive immunosuppressive therapies,most patients achieved satisfactory outcome.The in-hospital mortality was not significantly higher in the LM group than in the controls （4％ vs.2％,P =0.491）.Conclusions：LM could result in cardiac dysfunction and even sudden death.High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE.Characteristic echocardiographic findings could confirm the diagnosis of LM.Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM.
基金National Natural Science Foundation of China[grant number 81772022]Shanghai Key Laboratory of Forensic Medicine[grant number 17DZ2273200]Shanghai Forensic Service Platform[grant number 19DZ2292700].
文摘Hair analysis has been mainly used to document drug use history in abusers,drug-facilitated crime cases,doping control analysis and postmortem toxicology in the fields of forensic toxicology,clinical toxicology,and doping control.Hair analysis has also gained more attention in the last 30 years in China.Relevant technology has been promoted as more research has appeared concerning hair analysis,and consensus has been sought among forensic toxicologists regarding aspects such as hair decontamination treatment,detection of abused substances in hair,segmental hair analysis and interpretation of analytical results.However,there are still some limitations in the estimation of drug intake time and frequency by segmental hair analysis due to the different growth cycles evident within a bundle of hairs,the drug incorporation mechanism and sampling errors.Microsampling and imaging mass spectrometry(iMS)technology based on a single hair may be a good choice to estimate drug intake time more accurately.Analysis of hair root samples may also be used to document acute poisoning in postmortem toxicology,and the analysis of the hair shaft can document long-term use of drugs depending on the length of the hair being evaluated.
