As small heat shock proteins,α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation ofβ/γ-crystallins.Genetic mutations of CRYAA are associated with protein aggregation and catara...As small heat shock proteins,α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation ofβ/γ-crystallins.Genetic mutations of CRYAA are associated with protein aggregation and cataract occurrence.One possible process underlying cataract formation is that endoplasmic reticulum stress(ERS)induces the unfolded protein response(UPR),leading to apoptosis.However,the pathogenic mechanism related to this remains unexplored.Here,we successfully constructed a cataract-causing CRYAA(Y118D)mutant mouse model,in which the lenses of the CRYAA-Y118D mutant mice showed severe posterior rupture,abnormal morphological changes,and aberrant arrangement of crystallin fibers.Histological analysis was consistent with the clinical pathological characteristics.We also explored the pathogenic factors involved in cataract development through transcriptome analysis.In addition,based on key pathway analysis,up-regulated genes in CRYAAY118D mutant mice were implicated in the ERS-UPR pathway.This study showed that prolonged activation of the UPR pathway and severe stress response can cause proteotoxic and ERS-induced cell death in CRYAA-Y118D mutant mice.展开更多
Summary:Changes of maximum expiratory flow at 25%and 50%of vital capacity(MEF2s and MEFso,respectively),and predominant parameters indicating small airways function in asthmatics before and after bronchodilator(BD)rev...Summary:Changes of maximum expiratory flow at 25%and 50%of vital capacity(MEF2s and MEFso,respectively),and predominant parameters indicating small airways function in asthmatics before and after bronchodilator(BD)reversibility test have been less interpreted.Our study aimed to investigate the clinical role of changes of MEF2s and MEFso before and after BD reversibility test in diagnosing asthma.Forced expiratory volume in the first second(FEV),MEF2s,and MEFso were measured before and after BD reversibility test in 207 asthmatic patients using standard process.Forty healthy individuals were enrolled as controls.Receiver operating characteristic(ROC)curve was used to assess the diagnostic accuracy of reversibility of MEF2s and MEFgo before and after BD reversibility test(OMEF 2s%and AMEF so%,respectively)in diagnosing asthma.Among these functional criteria,AMEF2;%and 0MEFs%≥25%performed the best diagnostic performance.The sensitivity,specificity,and accuracy of AMEF 25%≥25%as an objcctive diagnostic test for asthma were 63.29%,87.50%,and 67.21%,and of AMEFs0%≥25%were 79.23%,85.00%,and 80.16%,respectively.The area under the ROC curve of the indicators was 0.8203 and 0.9104,respectively.By contrast,an increase in FEV≥12%and 200 mL demonstrated a sensitivity of 62.32%,specificity of 82.50%,and accuracy of 65.59%in diagnosing asthma.The changes of MEF2s and MEFso before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma,with cutoff values of 25%being the most.展开更多
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health.With the passing of time,the epidemiology of coronavirus disease 2019 evolves and the know...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health.With the passing of time,the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumulates.To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China,the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission.This recommendations includes the epidemiology,diagnosis,management,maternal care,medication treatment,care of birth and newborns,and psychological support associated with maternal SARS-CoV-2 infection.It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.展开更多
Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started...Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started providing free hepatitis B immunoglobulin for all new-borns born to hepatitis B surface-antigen(HBsAg)positive mothers in 2010.However,few studies have evaluated the effectiveness of the PMTCT programme.Therefore,we aimed to investigate the outcomes of the programme and identify associated factors.Method:Using a cross-sectional study design,we collected data on 4112 pairs of HBsAg-positive mothers and their children aged 7-22 months in four representative provinces through interviews and medical record review.We tested HBsAg and hepatitis B surface antibody(anti-HBs)of children by enzyme-linked immunosorbent assay at designated maternal and child hospital laboratories.We used logistic regression to analyse factors associated with child HBsAg and anti-HBs positivity.Results:Thirty-five children were HBsAg positive,indicating the mother-to-child transmission(MTCT)rate was 0.9%(0.6-1.1%).The anti-HBs positive rate was 96.8%(96.3-97.4%).Children receiving HBvacc between 12 and 24h of birth were 2.9 times more likely to be infected than those vaccinated in less than 12 h(adjusted odds ratio[aOR]=2.9,95%confidence interval[CI]:1.4-63,P=0.01).Maternal hepatitis B e-antigen(HBeAg)positivity was associated with higher MTCT rate(aOR=79.1,95%Cl:10.8-580.2,P<0.001)and lower anti-HBs positive rate(aOR=0.4,95%CI:03-0.6,P<0.001).Children with low birth weight(LBW)were 60%less likely to be anti-HBs positive than those with normal birth weight(aOR=0A,95%CI:02-0.8,P=0.01).Conclusions:The MTCT rate was lower than the 2030 WHO elimination goal,which implies the programme is on track to achieve this target.As earlier HBvacc birth dose(HBvcc-BD)was associated with lower MTCT rate,we suggest that the PMTCT programme work with the Expanded Programme on Immunization(EPI)to modify the current recommendation for early HBvcc-BD to a requirement Our finding that LBW was associated with lower anti-HBs positivity points to the need for further studies to understand factors associated with these risks and opportunities for program strengthening.The programme needs to ensure providing essential test to identify HBeAg-positive mothers and their infants and provide them with appropriate medical care and follow-up.展开更多
Congenital syphilis(CS)is a significant public health problem worldwide.The majority of cases of CS are caused by in utero transmission.The World Health Organization launched the global elimination of CS initiative wi...Congenital syphilis(CS)is a significant public health problem worldwide.The majority of cases of CS are caused by in utero transmission.The World Health Organization launched the global elimination of CS initiative with the goal of reducing mother-to-child transmission of syphilis.The risk for CS is mainly related to three factors:(1)high matemal prevalence,(2)low coverage of antenatal care services,and(3)treatment failure.The long-acting penicillin preparations such as benzathine penicillin G are the preferred therapies for maternal syphilis.There are several challenges in preventing CS from both pregnant women and their health care providers.These problems include that prenatal care lack or delay,syphilis management flaws from health care providers,lacks of basic information,and awareness about maternal syphilis and CS by public.Many efforts have been made to solve the problems.These include that dual elimination of mother-to-child transmission(EMTCT)of both human immunodeficiency virus(HIV)and syphilis or triple EMTCT of HIV,syphilis and hepatitis B,World Health Organization country validation of EMTCT of syphilis and HIV,set up a CS case review board and a National Day to combat syphilis and CS.展开更多
Background:The number of HIV-positive pregnant women accounted for about 10% of China’s total over the past few years in Liangshan Prefecture, Sichuan province in China. Although cost-effectiveness of the PMTCT of HI...Background:The number of HIV-positive pregnant women accounted for about 10% of China’s total over the past few years in Liangshan Prefecture, Sichuan province in China. Although cost-effectiveness of the PMTCT of HIV have been evaluated in other previous studies, no specific study has been conducted in Liangshan prefecture, nor has the expenses paid individually by HIV-positive pregnant women been included. The purpose of this study was to evaluate both the short-term and long-term cost-effectiveness of PMTCT of HIV in Liangshan Prefecture from the social perspective.Methods:From December 2018 to January 2019, individual expenses and the other costs were collected: individual expenses of 133 recruited HIV-positive pregnant women registered in the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis, and HBV, and the other costs from local maternal and child healthcare hospitals, Centers for Disease Control and Prevention, and general hospitals. The costs, the number of pediatric infections averted from being HIV infected were analyzed. And, Life years gained by pediatric infections averted were calculated by using a life table. Besides, Direct benefit was calculated through a Markov mode. Furthermore, One-way sensitivity analysis was conducted for key variables affecting the benefit–cost ratio.Results:The estimated number of pediatric infections averted was 164.The total cost was USD 114.1 million, including direct medical costs, direct non-medical costs, and indirect costs, which were USD 54.2 million, USD 53.4 million, and USD 6.5 million, respectively. 630.6 person-years discounted to 2017 were gained at a 3% annual rate, and cost per life year gained was USD 1809.50. Direct benefits were USD 198.4 million, indirect benefits USD 82.5 million, and the benefit–cost ratio was 1.5. The sensitivity analysis showed that if PMTCT costs hypothetically ranged from USD 85.6 million to USD 142.6 million, benefit–cost ratio would vary from 1.0 to 2.3.Conclusions:PMTCT of HIV in Liangshan Prefecture was very cost-effective. It was a great economic burden of PMTCT on HIV-positive pregnant women and their families to take individual expenses. Therefore, it could be suggested that individual expenses should be covered as much as possible by different types of financing.展开更多
Background:Vaccination is crucial for human immunodeficiency virus(HlV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases.However,studies have shown ...Background:Vaccination is crucial for human immunodeficiency virus(HlV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases.However,studies have shown that they are at high risk of incomplete vaccination.Although China has developed prevention of mother-to-child transmission(PMTCT)of HIV programs substantially over the past decades,few studies have investigated the immunization levels of Chinese HIV-exposed children.Therefore,we aimed to evaluate vaccination coverage and its associated factors among HIV-exposed children in China during 2016-2018.展开更多
基金This study was supported by the National Natural Science Foundation of China(31872724,81900837,81870641,82070939)Zhejiang Province Key Research and Development Program(2019C03091,2020C03035)。
文摘As small heat shock proteins,α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation ofβ/γ-crystallins.Genetic mutations of CRYAA are associated with protein aggregation and cataract occurrence.One possible process underlying cataract formation is that endoplasmic reticulum stress(ERS)induces the unfolded protein response(UPR),leading to apoptosis.However,the pathogenic mechanism related to this remains unexplored.Here,we successfully constructed a cataract-causing CRYAA(Y118D)mutant mouse model,in which the lenses of the CRYAA-Y118D mutant mice showed severe posterior rupture,abnormal morphological changes,and aberrant arrangement of crystallin fibers.Histological analysis was consistent with the clinical pathological characteristics.We also explored the pathogenic factors involved in cataract development through transcriptome analysis.In addition,based on key pathway analysis,up-regulated genes in CRYAAY118D mutant mice were implicated in the ERS-UPR pathway.This study showed that prolonged activation of the UPR pathway and severe stress response can cause proteotoxic and ERS-induced cell death in CRYAA-Y118D mutant mice.
基金This project was supported by the National Natural Science Foundation of China(No.81970024)partly by Scientific Research Project of Wuhan Health Committee(No.WX16C45).
文摘Summary:Changes of maximum expiratory flow at 25%and 50%of vital capacity(MEF2s and MEFso,respectively),and predominant parameters indicating small airways function in asthmatics before and after bronchodilator(BD)reversibility test have been less interpreted.Our study aimed to investigate the clinical role of changes of MEF2s and MEFso before and after BD reversibility test in diagnosing asthma.Forced expiratory volume in the first second(FEV),MEF2s,and MEFso were measured before and after BD reversibility test in 207 asthmatic patients using standard process.Forty healthy individuals were enrolled as controls.Receiver operating characteristic(ROC)curve was used to assess the diagnostic accuracy of reversibility of MEF2s and MEFgo before and after BD reversibility test(OMEF 2s%and AMEF so%,respectively)in diagnosing asthma.Among these functional criteria,AMEF2;%and 0MEFs%≥25%performed the best diagnostic performance.The sensitivity,specificity,and accuracy of AMEF 25%≥25%as an objcctive diagnostic test for asthma were 63.29%,87.50%,and 67.21%,and of AMEFs0%≥25%were 79.23%,85.00%,and 80.16%,respectively.The area under the ROC curve of the indicators was 0.8203 and 0.9104,respectively.By contrast,an increase in FEV≥12%and 200 mL demonstrated a sensitivity of 62.32%,specificity of 82.50%,and accuracy of 65.59%in diagnosing asthma.The changes of MEF2s and MEFso before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma,with cutoff values of 25%being the most.
文摘The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health.With the passing of time,the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumulates.To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China,the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission.This recommendations includes the epidemiology,diagnosis,management,maternal care,medication treatment,care of birth and newborns,and psychological support associated with maternal SARS-CoV-2 infection.It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.
文摘Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started providing free hepatitis B immunoglobulin for all new-borns born to hepatitis B surface-antigen(HBsAg)positive mothers in 2010.However,few studies have evaluated the effectiveness of the PMTCT programme.Therefore,we aimed to investigate the outcomes of the programme and identify associated factors.Method:Using a cross-sectional study design,we collected data on 4112 pairs of HBsAg-positive mothers and their children aged 7-22 months in four representative provinces through interviews and medical record review.We tested HBsAg and hepatitis B surface antibody(anti-HBs)of children by enzyme-linked immunosorbent assay at designated maternal and child hospital laboratories.We used logistic regression to analyse factors associated with child HBsAg and anti-HBs positivity.Results:Thirty-five children were HBsAg positive,indicating the mother-to-child transmission(MTCT)rate was 0.9%(0.6-1.1%).The anti-HBs positive rate was 96.8%(96.3-97.4%).Children receiving HBvacc between 12 and 24h of birth were 2.9 times more likely to be infected than those vaccinated in less than 12 h(adjusted odds ratio[aOR]=2.9,95%confidence interval[CI]:1.4-63,P=0.01).Maternal hepatitis B e-antigen(HBeAg)positivity was associated with higher MTCT rate(aOR=79.1,95%Cl:10.8-580.2,P<0.001)and lower anti-HBs positive rate(aOR=0.4,95%CI:03-0.6,P<0.001).Children with low birth weight(LBW)were 60%less likely to be anti-HBs positive than those with normal birth weight(aOR=0A,95%CI:02-0.8,P=0.01).Conclusions:The MTCT rate was lower than the 2030 WHO elimination goal,which implies the programme is on track to achieve this target.As earlier HBvacc birth dose(HBvcc-BD)was associated with lower MTCT rate,we suggest that the PMTCT programme work with the Expanded Programme on Immunization(EPI)to modify the current recommendation for early HBvcc-BD to a requirement Our finding that LBW was associated with lower anti-HBs positivity points to the need for further studies to understand factors associated with these risks and opportunities for program strengthening.The programme needs to ensure providing essential test to identify HBeAg-positive mothers and their infants and provide them with appropriate medical care and follow-up.
基金This research was supported by the Shenzhen Science and Technology Plan(JCYJ20180228162311024)Shenzhen Health System Key Discipline Construction Capacity Enhancement Project(SZXJ201606001)
文摘Congenital syphilis(CS)is a significant public health problem worldwide.The majority of cases of CS are caused by in utero transmission.The World Health Organization launched the global elimination of CS initiative with the goal of reducing mother-to-child transmission of syphilis.The risk for CS is mainly related to three factors:(1)high matemal prevalence,(2)low coverage of antenatal care services,and(3)treatment failure.The long-acting penicillin preparations such as benzathine penicillin G are the preferred therapies for maternal syphilis.There are several challenges in preventing CS from both pregnant women and their health care providers.These problems include that prenatal care lack or delay,syphilis management flaws from health care providers,lacks of basic information,and awareness about maternal syphilis and CS by public.Many efforts have been made to solve the problems.These include that dual elimination of mother-to-child transmission(EMTCT)of both human immunodeficiency virus(HIV)and syphilis or triple EMTCT of HIV,syphilis and hepatitis B,World Health Organization country validation of EMTCT of syphilis and HIV,set up a CS case review board and a National Day to combat syphilis and CS.
文摘Background:The number of HIV-positive pregnant women accounted for about 10% of China’s total over the past few years in Liangshan Prefecture, Sichuan province in China. Although cost-effectiveness of the PMTCT of HIV have been evaluated in other previous studies, no specific study has been conducted in Liangshan prefecture, nor has the expenses paid individually by HIV-positive pregnant women been included. The purpose of this study was to evaluate both the short-term and long-term cost-effectiveness of PMTCT of HIV in Liangshan Prefecture from the social perspective.Methods:From December 2018 to January 2019, individual expenses and the other costs were collected: individual expenses of 133 recruited HIV-positive pregnant women registered in the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis, and HBV, and the other costs from local maternal and child healthcare hospitals, Centers for Disease Control and Prevention, and general hospitals. The costs, the number of pediatric infections averted from being HIV infected were analyzed. And, Life years gained by pediatric infections averted were calculated by using a life table. Besides, Direct benefit was calculated through a Markov mode. Furthermore, One-way sensitivity analysis was conducted for key variables affecting the benefit–cost ratio.Results:The estimated number of pediatric infections averted was 164.The total cost was USD 114.1 million, including direct medical costs, direct non-medical costs, and indirect costs, which were USD 54.2 million, USD 53.4 million, and USD 6.5 million, respectively. 630.6 person-years discounted to 2017 were gained at a 3% annual rate, and cost per life year gained was USD 1809.50. Direct benefits were USD 198.4 million, indirect benefits USD 82.5 million, and the benefit–cost ratio was 1.5. The sensitivity analysis showed that if PMTCT costs hypothetically ranged from USD 85.6 million to USD 142.6 million, benefit–cost ratio would vary from 1.0 to 2.3.Conclusions:PMTCT of HIV in Liangshan Prefecture was very cost-effective. It was a great economic burden of PMTCT on HIV-positive pregnant women and their families to take individual expenses. Therefore, it could be suggested that individual expenses should be covered as much as possible by different types of financing.
文摘Background:Vaccination is crucial for human immunodeficiency virus(HlV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases.However,studies have shown that they are at high risk of incomplete vaccination.Although China has developed prevention of mother-to-child transmission(PMTCT)of HIV programs substantially over the past decades,few studies have investigated the immunization levels of Chinese HIV-exposed children.Therefore,we aimed to evaluate vaccination coverage and its associated factors among HIV-exposed children in China during 2016-2018.
