Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.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
Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similaritie...Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.展开更多
In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an ...In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.展开更多
The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferi...The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferior petrosal sinus sampling （BIPSS）. Of the 108 patients 52 underwent BIPSS prior to surgery and 56 did not. Results showed that BIPSS accuracy for the diagnosis of Cushing＇s disease was 86.5% （45/52）, and accuracy for adenoma lateralization during surgery was 76.9% （40/52）. In addition, early remission rate was significantly greater compared to patients without BIPSS. Results demonstrated that BIPSS facilitated localization and diagnosis of Cushing＇s disease and helped to predict adenoma lateralization.展开更多
Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestat...Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).展开更多
Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clin...Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia.Methods Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed.We examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of proteins.Results We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were reported.Female patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 years.The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>T.All mutations lead to spatial conformational changes that affect protein stability.Conclusions Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations.Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations.The correlation between genotype and phenotype needs further study.Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.展开更多
Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We includ...Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.展开更多
The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-...The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.展开更多
INTRODUCTIONHigh-risk population of Type 2 diabetes mellitus （T2DM） includes both euglycemic （normal glucose tolerance [NGT]） population with high risk of diabetes （EPWHROD） and prediabetic population. Between t...INTRODUCTIONHigh-risk population of Type 2 diabetes mellitus （T2DM） includes both euglycemic （normal glucose tolerance [NGT]） population with high risk of diabetes （EPWHROD） and prediabetic population. Between these two groups,展开更多
Cardiovascular disease is the leading cause of mortality in China.Primary prevention of cardiovascular disease with a focus on lifestyle intervention and risk factor control has been shown to effectively delay or prev...Cardiovascular disease is the leading cause of mortality in China.Primary prevention of cardiovascular disease with a focus on lifestyle intervention and risk factor control has been shown to effectively delay or prevent the occurrence of cardiovascular events.To promote a healthy lifestyle and enhance the detection,diagnosis,and treatment of cardiovascular risk factors such as hypertension,dyslipidemia,and diabetes,and to improve the overall capacity of primary prevention of cardiovascular disease,the Chinese Society of Cardiology of Chinese Medical Association has collaborated with multiple societies to summarize and evaluate the latest evidence with reference to relevant guidelines and subsequently to develop recommendations for primary cardiovascular disease prevention in Chinese adults.The guideline consists of 10 sections:introduction,methodology for developing the guideline,epidemiology of cardiovascular disease in China and challenges in primary prevention,general recommendations for primary prevention,assessment of cardiovascular risk,lifestyle intervention,blood pressure control,lipid management,management of type 2 diabetes,and use of aspirin.The promulgation and implementation of this guideline will play a key role in promoting the practice of primary prevention for cardiovascular disease in China.展开更多
The“Chinese guideline on the primary prevention of cardiovascular diseases”(referred to as the Chinese guideline below)has been developed recently by the Chinese Society of Cardiology of Chinese Medical Association ...The“Chinese guideline on the primary prevention of cardiovascular diseases”(referred to as the Chinese guideline below)has been developed recently by the Chinese Society of Cardiology of Chinese Medical Association and other major associations of cardiology by consolidating existing recommendations and scientific statements,expert consensus documents,and clinical practice guidelines into a single guidance document focused on the primary prevention of atherosclerotic cardiovascular disease(ASCVD)in Chinese population.[1]Cardiovascular diseases(CVDs),including stroke and ischaemic heart disease,were the leading causes of death and disability-adjusted life-years in China.[2]Evidence-based decision making for CVDs primary prevention in a country with a fifth of the global population is therefore of the utmost importance.展开更多
Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health proble...Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health problems.The p160 steroid receptor coactivator(SRC)gene family members have been suggested to be involved in energy homeostasis,but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated.In the current study,we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue(WAT)and brown adipose tissue(BAT).Primary cells were cultured to investigate the differentiation ability of both adipocytes.Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis.We observed that SRC-3^(–/–)mice were lean,with reduced WAT and decreased serum leptin levels,mainly due to the smaller white adipocyte size caused by impaired adipo-genesis,presented by decreased peroxisome proliferator activated receptor g(PPARg)expression.In the BAT,the lipid droplets decreased significantly in SRC-3^(–/–)mice as demonstrated by histological analysis and electron micro-scopic observation,which could be explained by enhanced thermogenesis.The expression of thermogenic marker gene PPARg coactivator 1αand uncoupling protein-1 increased in BAT of SRC-3^(–/–)mice,which proved our observations.Collectively,these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.展开更多
A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease...A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in Shanghai,China.After 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed albuminuria.In comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for albuminuria.Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria.In conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip circumference.Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.展开更多
Rare and undiagnosed diseases have been recognized as major public health concerns,despite those being affected accounting for only a small percentage of the global population.Most patients cannot get precise diagnose...Rare and undiagnosed diseases have been recognized as major public health concerns,despite those being affected accounting for only a small percentage of the global population.Most patients cannot get precise diagnoses or effective treatments.This situation thereby causes a heavy burden on healthcare systems,posing huge challenges not only for clinicians,but also for the family members of these patients.展开更多
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
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.
基金supported by grants from the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01)the National Natural Science Foundation of China (81873565 and 82100605)+2 种基金Shanghai Jiao Tong University Transmed Awards Research (20190104)Star Program of Shanghai Jiao Tong University (YG2021QN54)Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (17CSK04 and 15LC06)。
文摘Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
基金supported by a grant from the NIH:DK32333supported by the National Natural Science Foundation of China (81070693 and 81200647)
文摘In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.
基金the Natural Science Foundation of Shanghai,No.08ZR1413800
文摘The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferior petrosal sinus sampling （BIPSS）. Of the 108 patients 52 underwent BIPSS prior to surgery and 56 did not. Results showed that BIPSS accuracy for the diagnosis of Cushing＇s disease was 86.5% （45/52）, and accuracy for adenoma lateralization during surgery was 76.9% （40/52）. In addition, early remission rate was significantly greater compared to patients without BIPSS. Results demonstrated that BIPSS facilitated localization and diagnosis of Cushing＇s disease and helped to predict adenoma lateralization.
基金supported by the National Key Research and Development Program of China(2020YFA0112800,2020YFA0112801)the National Natural Science Foundation of China(82270842,82000829)CAMS Innovation Fund for Medical Sciences(2020-12M-5-002).
文摘Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).
文摘Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia.Methods Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed.We examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of proteins.Results We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were reported.Female patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 years.The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>T.All mutations lead to spatial conformational changes that affect protein stability.Conclusions Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations.Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations.The correlation between genotype and phenotype needs further study.Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.
基金supported by the grants from the National Natural Science Foundation of China(Nos.82088102,91857205,82022011,81970728,and 81930021)the Shanghai Rising-Star Program(No.21QA1408100)+2 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)the National Top Young Scholar Program(Yu Xu),the Innovative Research Team of High-Level Local Universities in Shanghai,the Shanghai Clinical Research Center for Metabolic Diseases(No.19MC1910100)the Shanghai Shen Kang Hospital Development Center(Nos.SHDC2020CR1001A and SHDC2020CR3064B).
文摘Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.
基金supported by the National Major Scientific and Technological Special Project for"Significant New Drugs Development"(No.2017ZX09304007)the National Natural Science Foundation of China(Nos.82088102 and 81970728)+2 种基金the Science and Technology Commission of Shanghai Municipality(Nos.22Y31900300 and 23XD1432600)the Innovative Research Team of High-Level Local Universities in Shanghaisupported by the"National Top Young Talents"program.
文摘The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
文摘INTRODUCTIONHigh-risk population of Type 2 diabetes mellitus （T2DM） includes both euglycemic （normal glucose tolerance [NGT]） population with high risk of diabetes （EPWHROD） and prediabetic population. Between these two groups,
文摘Cardiovascular disease is the leading cause of mortality in China.Primary prevention of cardiovascular disease with a focus on lifestyle intervention and risk factor control has been shown to effectively delay or prevent the occurrence of cardiovascular events.To promote a healthy lifestyle and enhance the detection,diagnosis,and treatment of cardiovascular risk factors such as hypertension,dyslipidemia,and diabetes,and to improve the overall capacity of primary prevention of cardiovascular disease,the Chinese Society of Cardiology of Chinese Medical Association has collaborated with multiple societies to summarize and evaluate the latest evidence with reference to relevant guidelines and subsequently to develop recommendations for primary cardiovascular disease prevention in Chinese adults.The guideline consists of 10 sections:introduction,methodology for developing the guideline,epidemiology of cardiovascular disease in China and challenges in primary prevention,general recommendations for primary prevention,assessment of cardiovascular risk,lifestyle intervention,blood pressure control,lipid management,management of type 2 diabetes,and use of aspirin.The promulgation and implementation of this guideline will play a key role in promoting the practice of primary prevention for cardiovascular disease in China.
基金the grants from the National Key R&D Program of China(2017YFC1310700,2016YFC 1305600).
文摘The“Chinese guideline on the primary prevention of cardiovascular diseases”(referred to as the Chinese guideline below)has been developed recently by the Chinese Society of Cardiology of Chinese Medical Association and other major associations of cardiology by consolidating existing recommendations and scientific statements,expert consensus documents,and clinical practice guidelines into a single guidance document focused on the primary prevention of atherosclerotic cardiovascular disease(ASCVD)in Chinese population.[1]Cardiovascular diseases(CVDs),including stroke and ischaemic heart disease,were the leading causes of death and disability-adjusted life-years in China.[2]Evidence-based decision making for CVDs primary prevention in a country with a fifth of the global population is therefore of the utmost importance.
基金supported by grants from the National Basic Research Program of China(No.2006CB503904)Natural Science Foundation of China(Grant Nos.30725037 and 30971385)Shanghai Committee for Science and Technology(No.07JC14042).
文摘Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health problems.The p160 steroid receptor coactivator(SRC)gene family members have been suggested to be involved in energy homeostasis,but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated.In the current study,we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue(WAT)and brown adipose tissue(BAT).Primary cells were cultured to investigate the differentiation ability of both adipocytes.Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis.We observed that SRC-3^(–/–)mice were lean,with reduced WAT and decreased serum leptin levels,mainly due to the smaller white adipocyte size caused by impaired adipo-genesis,presented by decreased peroxisome proliferator activated receptor g(PPARg)expression.In the BAT,the lipid droplets decreased significantly in SRC-3^(–/–)mice as demonstrated by histological analysis and electron micro-scopic observation,which could be explained by enhanced thermogenesis.The expression of thermogenic marker gene PPARg coactivator 1αand uncoupling protein-1 increased in BAT of SRC-3^(–/–)mice,which proved our observations.Collectively,these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.
基金This work was supported by the grants from the National Key R&D Program of China(Nos.2017YFC1310700,2018YFC1311800,and 2018YFC1311705)the National Natural Science Foundation of China(Nos.81870560,82070880,81941017,81770842,81970706,and 82022011)+6 种基金the National Science and Technology Major Project for"Significant New Drugs Development"(No.2017ZX09304007)Shanghai Municipal Government(No.18411951800)Shanghai Shenkang Hospital Development Center(Nos.SHDC12019101,SHDC2020CR1001A,and SHDC2020CR3069B)the Scientific and Technological Committee of Shanghai(No.19411964200)Shanghai Jiao Tong University School of Medicine(No.DLY201801)Ruijin Hospital(No.2018 CR002)Shanghai Rising-Star Program(No.21QA1408100).
文摘A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in Shanghai,China.After 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed albuminuria.In comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for albuminuria.Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria.In conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip circumference.Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
基金The study is supported by the Major Chronic Non-communicable Disease Prevention and Control Research,National Key R&D Program of China (Nos.2016YFC1305600and 2016YFC1305601), National Natural Science Foundation of China (No.81500610), Shanghai Pujiang Program (No.18PJ1409600)and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No.20171901).
文摘Rare and undiagnosed diseases have been recognized as major public health concerns,despite those being affected accounting for only a small percentage of the global population.Most patients cannot get precise diagnoses or effective treatments.This situation thereby causes a heavy burden on healthcare systems,posing huge challenges not only for clinicians,but also for the family members of these patients.
