BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essent...BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region.Further,SAHA disturbed the Ca^(2+)homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells.Additionally,SAHA decreased the mitochondrial membrane potential levels,thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro.CONCLUSION SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway,thereby enhancing HCC cell death.展开更多
Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a mol...Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.展开更多
Importance:Central line-associated bloodstream infection(CLABSI)is one of the most serious complications of central venous access devices.Reducing the risk of CLABSI is of utmost significance in efforts to improve neo...Importance:Central line-associated bloodstream infection(CLABSI)is one of the most serious complications of central venous access devices.Reducing the risk of CLABSI is of utmost significance in efforts to improve neonatal mortality rates and enhance long-term prognosis.Objective:To determine the dwell time and incidence of CLABSI of umbilical venous catheterization(UVC)for preterm infants in China.Methods:Preterm infants with UVC admitted to 44 tertiary neonatal intensive care units in 24 provinces in China were enrolled.Study period was from November 2019 to August 2021.The end point of observations was 48 h after umbilical venous(UV)catheter removal.The primary outcomes were dwell time of UV catheter and UVC-associated CLABSI.Data between infants with UV catheter dwell time≤7 days and>7 days,and with birth weight(BW)≤1000 g and>1000 g were compared.Results:In total,2172 neonates were enrolled(gestational age 30.0±2.4 weeks,BW 1258.5±392.8 g).The median UV catheter dwell time was 7(6–10)days.The incidence of UVC-associated CLABSI was 3.03/1000 UV catheter days.For infants with UV catheter dwell time≤7 days and>7 days,the UVC-associated CLABSI incidence was 3.71 and 2.65 per 1000 UV catheter days,respectively,P=0.23.For infants with UVC dwell times of 3–6,7–12,and 13–15 days,the UVC-associated CLABSI rates were 0.14%,0.68%,and 2.48%(P<0.01).The Kaplan–Meier plot of UV catheter dwell time to CLABSI showed no difference between infants with BW≤1000 g and>1000 g(P=0.60).Interpretation:The median dwell time of UV catheter was 7 days,and the incidence of UVC-associated CLABSI was 3.03/1000 catheter days in China.The daily risk of UVC-associated CLABSI and other complications increased with the dwell time.展开更多
What is already known about this topic?Elevated gestational weight gain(GWG)during pregnancy among women diagnosed with gestational diabetes mellitus(GDM)is correlated with an increased instance of large for gestation...What is already known about this topic?Elevated gestational weight gain(GWG)during pregnancy among women diagnosed with gestational diabetes mellitus(GDM)is correlated with an increased instance of large for gestational age(LGA)and macrosomia.However,it remains uncertain whether managing weekly GWG following a GDM diagnosis positively impacts fetal birth weight.What is added by this report?Our study found that GWG following GDM diagnosis correlates positively with the risk of LGA and macrosomia among all body mass index(BMI)subgroups,especially for overweight and obese women.What are the implications for public health practice?The results of this research highlight the importance of enforcing a more stringent regulation on GWG on a weekly basis for overweight and obese women diagnosed with GDM,particularly when considering neonatal growth.展开更多
Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn disease...Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.展开更多
Summary What is already known about this topic?Joint effects of gestational weight gain(GWG)and hyperglycemia on adverse pregnancy outcomes suggest that lower optimal GWG is optimal for women with gestational diabetes...Summary What is already known about this topic?Joint effects of gestational weight gain(GWG)and hyperglycemia on adverse pregnancy outcomes suggest that lower optimal GWG is optimal for women with gestational diabetes mellitus(GDM).However,there is still a lack of guidelines.What is added by this report?Optimal weekly GWG range after diagnosis of GDM for underweight,normal-weight,overweight,and obese women was 0.37–0.56 kg/week,0.26–0.48 kg/week,0.19–0.32 kg/week,and 0.12–0.23 kg/week,respectively.What are the implications for public health practice?The findings may be used to inform prenatal counseling regarding optimal gestational weight gain for women with gestational diabetes mellitus,and suggest the need for weight gain management.展开更多
基金the National Natural Science Foundation of China,No.82260127Guizhou Provincial Science and Technology Projects,No.Qiankehe Jichu-ZK[2021]365 and Qiankehe Jichu-ZK[2021]364+2 种基金National Natural Science Foundation Cultivation Project of Guizhou Medical University,No.20NSP016Guizhou Provincial Natural Science Foundation,No.[2021]4029 and[2022]4017Science and Technology Foundation of Guizhou Provincial Health Commission,No.gzwjkj2019-1-102.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region.Further,SAHA disturbed the Ca^(2+)homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells.Additionally,SAHA decreased the mitochondrial membrane potential levels,thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro.CONCLUSION SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway,thereby enhancing HCC cell death.
基金This work was supported by the National Science and Technology Major Projects(Grant Number 2017ZX10104001-005-010,2017ZX10103004-004)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Number 2019-I2M-5-026)。
文摘Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.
基金Capital’s Funds for Health Improvement and Research,Grant/Award Number:2022-2-2095。
文摘Importance:Central line-associated bloodstream infection(CLABSI)is one of the most serious complications of central venous access devices.Reducing the risk of CLABSI is of utmost significance in efforts to improve neonatal mortality rates and enhance long-term prognosis.Objective:To determine the dwell time and incidence of CLABSI of umbilical venous catheterization(UVC)for preterm infants in China.Methods:Preterm infants with UVC admitted to 44 tertiary neonatal intensive care units in 24 provinces in China were enrolled.Study period was from November 2019 to August 2021.The end point of observations was 48 h after umbilical venous(UV)catheter removal.The primary outcomes were dwell time of UV catheter and UVC-associated CLABSI.Data between infants with UV catheter dwell time≤7 days and>7 days,and with birth weight(BW)≤1000 g and>1000 g were compared.Results:In total,2172 neonates were enrolled(gestational age 30.0±2.4 weeks,BW 1258.5±392.8 g).The median UV catheter dwell time was 7(6–10)days.The incidence of UVC-associated CLABSI was 3.03/1000 UV catheter days.For infants with UV catheter dwell time≤7 days and>7 days,the UVC-associated CLABSI incidence was 3.71 and 2.65 per 1000 UV catheter days,respectively,P=0.23.For infants with UVC dwell times of 3–6,7–12,and 13–15 days,the UVC-associated CLABSI rates were 0.14%,0.68%,and 2.48%(P<0.01).The Kaplan–Meier plot of UV catheter dwell time to CLABSI showed no difference between infants with BW≤1000 g and>1000 g(P=0.60).Interpretation:The median dwell time of UV catheter was 7 days,and the incidence of UVC-associated CLABSI was 3.03/1000 catheter days in China.The daily risk of UVC-associated CLABSI and other complications increased with the dwell time.
文摘What is already known about this topic?Elevated gestational weight gain(GWG)during pregnancy among women diagnosed with gestational diabetes mellitus(GDM)is correlated with an increased instance of large for gestational age(LGA)and macrosomia.However,it remains uncertain whether managing weekly GWG following a GDM diagnosis positively impacts fetal birth weight.What is added by this report?Our study found that GWG following GDM diagnosis correlates positively with the risk of LGA and macrosomia among all body mass index(BMI)subgroups,especially for overweight and obese women.What are the implications for public health practice?The results of this research highlight the importance of enforcing a more stringent regulation on GWG on a weekly basis for overweight and obese women diagnosed with GDM,particularly when considering neonatal growth.
基金the Foundation of National Key R&D Program of China of Research on Application Demonstration and Evaluation of Comprehensive Prevention And Control Technology of Birth Defects(Grant No.2018YFC1002700)Zhejiang R&D Research Project Research on New Technologies for Birth Health,Birth Safety and Perinatal Disease Diagnosis and Treatment(Grant No.2021C03099).
文摘Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases.The develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening methodologies.Methods We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.With this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates nationwide.Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were detected.Glucose-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different regions.The positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north China.In addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after recall.Eighty percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional differences.On the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of non-carriers.Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods.Our data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in different regions.
基金funded by the Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences(2020-I2M-2-009,2021-I2M-1-023)the Project of the National Health Commission of the People’s Republic of China(20191901)the National Natural Science Foundation of China(81973053).
文摘Summary What is already known about this topic?Joint effects of gestational weight gain(GWG)and hyperglycemia on adverse pregnancy outcomes suggest that lower optimal GWG is optimal for women with gestational diabetes mellitus(GDM).However,there is still a lack of guidelines.What is added by this report?Optimal weekly GWG range after diagnosis of GDM for underweight,normal-weight,overweight,and obese women was 0.37–0.56 kg/week,0.26–0.48 kg/week,0.19–0.32 kg/week,and 0.12–0.23 kg/week,respectively.What are the implications for public health practice?The findings may be used to inform prenatal counseling regarding optimal gestational weight gain for women with gestational diabetes mellitus,and suggest the need for weight gain management.
