Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in ter...Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.展开更多
Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Meth...Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was ...Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was investigated by utilizing various phenotypic assays,including colony morphological characterization,crystal violet staining,Cyclic di-GMP(c-di-GMP)quantification,and swimming motility assay.The regulation of the VCA0560 gene by Fur and Hap R was analyzed by luminescence assay,electrophoretic mobility shift assay,and DNase I footprinting.Results VCA0560 gene mutation did not affect biofilm formation,motility,and c-di-GMP synthesis in V.cholerae,and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity.The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator Hap R.Conclusion Overexpressed VCA0560 functions as an active DGC in V.cholerae,and its transcription is repressed by Fur and Hap R.展开更多
Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family.To our knowledge,this is the first report of a carbapenem-resistant L.adecarboxylata strain isolated from a healthy newb...Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family.To our knowledge,this is the first report of a carbapenem-resistant L.adecarboxylata strain isolated from a healthy newborn.The L.adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes.Plasmids 2 and 4 did not harbor any antimicrobial resistance genes.Plasmid 3 is a novel plasmid containing three resistance genes.The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level,with a similarity of 99.4%(737/741).This case highlights the importance of considering L.adecarboxylata as a potential cause of infections in children.展开更多
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,le...Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.展开更多
Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of act...Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.展开更多
Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on th...Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.展开更多
Objective: To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis. Methods: The puochitis rat model was established and the faeces sample and the mucous membrane sample were collected regul...Objective: To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis. Methods: The puochitis rat model was established and the faeces sample and the mucous membrane sample were collected regularly, in which the bacterial nucleic acids were extracted for quantitative analysis of the intestinal flora in the samples through using the real-time quantitative PCR technique and high energy sequencing technology. Results: The disorder phenomenon of the intestinal flora appeared at the 7th day of the experiment, and the pouchitis was presented at the 21 th day of the experiment. At the 31 th day of the experiment, compared to control group and non-pouchitis group, the quantity of Bifidobacterium and the Lactobacillusof the pouchitis model rats in the mucous membrane sample and the faeces sample were significantly decreased(P<0.05), and the Bacteroidetes, Faecalibacterium prausnitzii and 桛 Clostridium leptum subgroup in the mucous membrane of pouchitis were significantly decreased(P<0.05). The Clostridium coccoides group was the main flora in the mucous membrane of pouchitis, the bacterial diversity of non-puochitis group and control group was significantly higher than that of the puochitis group(P<0.05). Conclusions: The intestinal flora imbalance is one of the factors that cause the incidence of the pouhitis; this study provides a clue of the pathogenesis and treatment direction of the intestinal inflammatory disease.展开更多
In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h p...In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus particles were spherical, 70 nm in diameter, and enveloped; they also featured surface fibers.展开更多
AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chroni...AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTS Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load(P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores(P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3(severe liver fibrosis) and 4(cirrhosis). CONCLUSION Iron metabolism disorders occur in patients with HBVrelated liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.展开更多
Objective Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this ...Objective Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this study, we explored whether coxsackievirus B3(CVB3) infection induced autophagy through endoplasmic reticulum(ER) stress. Methods In CVB3-infected HeLa cells, the specific molecules of ER stress and autophagy were detected using Western blotting, reverse transcription polymerase chain reaction(RT-PCR), and confocal microscopy. Then PKR-like ER protein kinase(PERK) inhibitor, inositol-requiring protein-1(IRE1) inhibitor, or activating transcription factor-6(ATF6) inhibitor worked on CVB3-infected cells, their effect on autophagy was assessed by Western blotting for detecting microtubule-associated protein light chain 3(LC3). Results CVB3 infection induced ER stress, and ER stress sensors PERK/eIF2α, IRE1/XBP1, and ATF6 were activated. CVB3 infection increased the accumulation of green fluorescent protein(GFP)-LC3 punctuation and induced the conversion from LC3-Ⅰ to phosphatidylethanolamine-conjugated LC3-1(LC3-Ⅱ). CVB3 infection still decreased the expression of mammalian target of rapamycin(mTOR) and p-mTOR. Inhibition of PERK, IRE1, or ATF6 significantly decreased the ratio of LC3-Ⅱ to LC3-Ⅰ in CVB3-infected HeLa cells. Conclusion CVB3 infection induced autophagy through ER stress in HeL a cells, and PERK, IRE1, and ATF6 a pathways participated in the regulation of autophagy. Our data suggested that ER stress may inhibit mTOR signaling pathway to induce autophagy during CVB3 infection.展开更多
This study projected dengue distribution risk map using representative concentration pathways(RCP2.6,RCP4.5,RCP6.0,RCP8.5)in China in 2020s,2030s,2050s and 2100s.Based on the biological characteristics of Aedes albopi...This study projected dengue distribution risk map using representative concentration pathways(RCP2.6,RCP4.5,RCP6.0,RCP8.5)in China in 2020s,2030s,2050s and 2100s.Based on the biological characteristics of Aedes albopictus and the dengue epidemic process,dengue transmission biological model was developed to project the risk epidemic areas.Observational temperature data in 1981-2016 at 740 stations and grid data of 0.5°×0.5°(15°-55.5°N,70°-140.5E)under selected RCPs in 2020s,2030s,2050s and 2100s were used.Relative to 142 counties and 168 million people living in the projected high risk area of dengue in the climate condition of 1981-2016,dengue high risk areas in China would expand under same RCP scenarios in the 21st century with time past except RCP2.6 with a turning down point in 2050s.Especially under RCP8.5 which global mean temperature would increase by 4.9 C till 2100s,the high risk area and population for dengue transmission would expand additional 34 counties(20 million)in 2020s,114 counties(60 million)in 2030s,208 counties(160 million)in 2050 and 456 counties(490 million)in 2100s respectively than those of 1981-2016.For RCP8.5 in 2100s,the population and expanded high risk areas would increase 4.2-fold and 2.9-fold than the 1981-2016 mean.The newly added high risk areas should prepare for controlling and preventing dengue in different period according to projected dengue risk map.展开更多
Pseudorabies virus(PRV),a veterinary pathogen that infects domestic animals as well as wild animals such as wild boar and feral swine,was recently reported to infect human and led to endophthalmitis and encephalitis.A...Pseudorabies virus(PRV),a veterinary pathogen that infects domestic animals as well as wild animals such as wild boar and feral swine,was recently reported to infect human and led to endophthalmitis and encephalitis.A retrospective seroepidemiologic survey was conducted using 1,335 serum samples collected from patients with encephalitis and ELISA positive rates were 12.16%,14.25%,and 6.52%in 2012,2013,and 2017,respectively.展开更多
In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people...In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people living with HIV, amounting to59% of HIV patients worldwide, were receiving antiretroviral therapy(ART)[1]. In China, the National Free Antiretroviral Treatment Program(NFATP),which was initiated in 2002, continued to progress.展开更多
Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the...Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. Results In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat(36.5%) was higher than that in cattle meat(1.1%). However, the prevalence in poultry cloacal swabs(27.0%) was lower than that in cattle stool(57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST-21(11.9%), ST-22(10.3%), and ST-403(7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin(89.7%), followed by tetracycline(74.6%), and nalidixic acid(69.0%). Conclusion This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.展开更多
Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtain...Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtained from Ma’anshan,Anhui province,China,and subjected to multi-locus sequence typing(MLST)with six housekeeping genes.Their taxonomy was investigated using concatenated gyr B-cpn60 sequences,while their resistance to 12 antibiotics was evaluated.Ten putative virulence factors and several resistance genes were identified by PCR and sequencing.Results The 90 Aeromonas isolates were divided into 84 sequence types,80 of which were novel,indicating high genetic diversity.The Aeromonas isolates were classified into eight different species.PCR assays identified virulence genes in the isolates,with the enterotoxin and hemolysin genes act,aer A,alt,and ast found in 47(52.2%),13(14.4%),22(24.4%),and 12(13.3%)of the isolates,respectively.The majority of the isolates(≥90%)were susceptible to aztreonam,imipenem,cefepime,chloramphenicol,gentamicin,tetracycline,and ciprofloxacin.However,several resistance genes were detected in the isolates,as well as a new mcr-3 variant.Conclusions Sequence type,virulence properties,and antibiotic resistance vary in Aeromonas isolates from clinical patients,tap water systems,and food.展开更多
文摘Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.
基金sponsored by National Science and Technology Major Project No. 2016ZX10004222-001。
文摘Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
基金supported by grants from the National Natural Science Foundation of China[Grant No.81471917]the National Basic Research Priorities Program[Grant 2015CB554201]the Science Foundation for the State Key Laboratory for Infectious Disease Prevention and Control of China[Grant No.2015SKLID509]
文摘Objective This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase(DGC)in Vibrio cholerae and how its transcription is regulated by Fur and Hap R.Methods The roles of VCA0560 was investigated by utilizing various phenotypic assays,including colony morphological characterization,crystal violet staining,Cyclic di-GMP(c-di-GMP)quantification,and swimming motility assay.The regulation of the VCA0560 gene by Fur and Hap R was analyzed by luminescence assay,electrophoretic mobility shift assay,and DNase I footprinting.Results VCA0560 gene mutation did not affect biofilm formation,motility,and c-di-GMP synthesis in V.cholerae,and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity.The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator Hap R.Conclusion Overexpressed VCA0560 functions as an active DGC in V.cholerae,and its transcription is repressed by Fur and Hap R.
基金supported by Chinese Field Epidemiology Training Programthe National Natural Science Foundation of China [81861138053]。
文摘Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family.To our knowledge,this is the first report of a carbapenem-resistant L.adecarboxylata strain isolated from a healthy newborn.The L.adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes.Plasmids 2 and 4 did not harbor any antimicrobial resistance genes.Plasmid 3 is a novel plasmid containing three resistance genes.The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level,with a similarity of 99.4%(737/741).This case highlights the importance of considering L.adecarboxylata as a potential cause of infections in children.
基金supported by the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(Grant No.:2020YFE0205100)+13 种基金the National Natural Science Foundation of China(Grant Nos.:82104480,82004248,82141001,82274182,82074098,82173914)the Fundamental Research Funds for the Central public welfare research institutes(Grant Nos.:ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,ZXKT19018,ZXKT19021,ZXKT19022,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10,ZZ16-ND-10-19)the Beijing Municipal Natural Science Foundation(Grant No.:7214287)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002)the Young Elite Scientists Sponsorship Program by CACM(Grant No.:2021QNRC2B29)the CACMS Innovation Fund(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)Shenzhen Governmental Sustainable Development Fund(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Grant No.:SZGSP001)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open Fund(Grant No.:SKL2020Z0302).
文摘Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.
基金funded by the National Natural Science Foundation of China(82273881 and 82304386)Guangdong Basic and Applied Basic Research Foundation(2022A1515110476)+1 种基金the Open Fund of Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology(GDKL202214)SUMC Scientiffc Research Initiation Grant(510858046 and 510858056).
文摘Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.
基金National Key R&D Program of China,Grant/Award Number:2022YFA1304101CAS,Grant/Award Number:XDB29050400+1 种基金National Natural Science Foundation of China,Grant/Award Number:32030003Shenzhen‐Hong Kong Innovation Circle Plan,Grant/Award Number:SGDX2019081623060946。
文摘Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.
基金supported by Natural Science Foundation of China(Grant Number:8150041674)
文摘Objective: To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis. Methods: The puochitis rat model was established and the faeces sample and the mucous membrane sample were collected regularly, in which the bacterial nucleic acids were extracted for quantitative analysis of the intestinal flora in the samples through using the real-time quantitative PCR technique and high energy sequencing technology. Results: The disorder phenomenon of the intestinal flora appeared at the 7th day of the experiment, and the pouchitis was presented at the 21 th day of the experiment. At the 31 th day of the experiment, compared to control group and non-pouchitis group, the quantity of Bifidobacterium and the Lactobacillusof the pouchitis model rats in the mucous membrane sample and the faeces sample were significantly decreased(P<0.05), and the Bacteroidetes, Faecalibacterium prausnitzii and 桛 Clostridium leptum subgroup in the mucous membrane of pouchitis were significantly decreased(P<0.05). The Clostridium coccoides group was the main flora in the mucous membrane of pouchitis, the bacterial diversity of non-puochitis group and control group was significantly higher than that of the puochitis group(P<0.05). Conclusions: The intestinal flora imbalance is one of the factors that cause the incidence of the pouhitis; this study provides a clue of the pathogenesis and treatment direction of the intestinal inflammatory disease.
基金supported by grants from National Natural Science Foundation of China(81290342 and 81501757)Development Grant of State Key Laboratory of Infectious Disease Prevention and Control(2014SKLID103)the Special National Project on Research and Development of Key Biosafety Technologies(2016YFC1201900),China
文摘In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus particles were spherical, 70 nm in diameter, and enveloped; they also featured surface fibers.
基金Supported by the National Science and Technology Major Project,No.2014ZX10002002 and No.2017ZX10202202the National Key Research Plan "Precision Medicine Research" Key Project,No.2017YFC0908103+1 种基金the National Natural Science Foundation of China,No.81700534Program for JLU Science and Technology Innovative Research Team,No.2017TD-08
文摘AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTS Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load(P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores(P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3(severe liver fibrosis) and 4(cirrhosis). CONCLUSION Iron metabolism disorders occur in patients with HBVrelated liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.
基金supported by the China Mega-project for Infectious Disease [2018ZX10102001,2018ZX10711001,2018ZX10734401,and 2018ZX10734404]the SKLID Development Grant [2011SKLID104]
文摘Objective Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this study, we explored whether coxsackievirus B3(CVB3) infection induced autophagy through endoplasmic reticulum(ER) stress. Methods In CVB3-infected HeLa cells, the specific molecules of ER stress and autophagy were detected using Western blotting, reverse transcription polymerase chain reaction(RT-PCR), and confocal microscopy. Then PKR-like ER protein kinase(PERK) inhibitor, inositol-requiring protein-1(IRE1) inhibitor, or activating transcription factor-6(ATF6) inhibitor worked on CVB3-infected cells, their effect on autophagy was assessed by Western blotting for detecting microtubule-associated protein light chain 3(LC3). Results CVB3 infection induced ER stress, and ER stress sensors PERK/eIF2α, IRE1/XBP1, and ATF6 were activated. CVB3 infection increased the accumulation of green fluorescent protein(GFP)-LC3 punctuation and induced the conversion from LC3-Ⅰ to phosphatidylethanolamine-conjugated LC3-1(LC3-Ⅱ). CVB3 infection still decreased the expression of mammalian target of rapamycin(mTOR) and p-mTOR. Inhibition of PERK, IRE1, or ATF6 significantly decreased the ratio of LC3-Ⅱ to LC3-Ⅰ in CVB3-infected HeLa cells. Conclusion CVB3 infection induced autophagy through ER stress in HeL a cells, and PERK, IRE1, and ATF6 a pathways participated in the regulation of autophagy. Our data suggested that ER stress may inhibit mTOR signaling pathway to induce autophagy during CVB3 infection.
文摘This study projected dengue distribution risk map using representative concentration pathways(RCP2.6,RCP4.5,RCP6.0,RCP8.5)in China in 2020s,2030s,2050s and 2100s.Based on the biological characteristics of Aedes albopictus and the dengue epidemic process,dengue transmission biological model was developed to project the risk epidemic areas.Observational temperature data in 1981-2016 at 740 stations and grid data of 0.5°×0.5°(15°-55.5°N,70°-140.5E)under selected RCPs in 2020s,2030s,2050s and 2100s were used.Relative to 142 counties and 168 million people living in the projected high risk area of dengue in the climate condition of 1981-2016,dengue high risk areas in China would expand under same RCP scenarios in the 21st century with time past except RCP2.6 with a turning down point in 2050s.Especially under RCP8.5 which global mean temperature would increase by 4.9 C till 2100s,the high risk area and population for dengue transmission would expand additional 34 counties(20 million)in 2020s,114 counties(60 million)in 2030s,208 counties(160 million)in 2050 and 456 counties(490 million)in 2100s respectively than those of 1981-2016.For RCP8.5 in 2100s,the population and expanded high risk areas would increase 4.2-fold and 2.9-fold than the 1981-2016 mean.The newly added high risk areas should prepare for controlling and preventing dengue in different period according to projected dengue risk map.
基金supported by Ten-thousand Talents Program [Dr.Xiangdong Li]National Key Research and Development Program 2018ZX10101002,2016YFD0500401+1 种基金the Development Grant of State Key Laboratory of Infectious Disease Prevention and Control 2015SKLID505Scientific Research Project of China CDC JY18-1-01。
文摘Pseudorabies virus(PRV),a veterinary pathogen that infects domestic animals as well as wild animals such as wild boar and feral swine,was recently reported to infect human and led to endophthalmitis and encephalitis.A retrospective seroepidemiologic survey was conducted using 1,335 serum samples collected from patients with encephalitis and ELISA positive rates were 12.16%,14.25%,and 6.52%in 2012,2013,and 2017,respectively.
基金supported by the Research Project of Chongqing Municipal Science and Technology Bureau[cstc2019jscx-msxm X0225]Medical Research Project of Chongqing Municipal Health Commission [2017ZDXM001,2019ZDXM005]。
文摘In an effort to end the HIV epidemic by 2030, the Joint United Nations Program on HIV/AIDS(UNAIDS)set the ‘90-90-90’ target and aimed to expand the timely use of ART worldwide. By the end of 2017,21.7 million people living with HIV, amounting to59% of HIV patients worldwide, were receiving antiretroviral therapy(ART)[1]. In China, the National Free Antiretroviral Treatment Program(NFATP),which was initiated in 2002, continued to progress.
基金supported by Sanming Project of Medicine in Shenzhen[SZSM201803081]Shenzhen Technology and Innovation Plan,China[JCYJ 20140416095154399]Nanshan District Technology and Innovation Plan,Shenzhen,China[2016064]
文摘Objective To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni(C. jejuni) isolated from Shenzhen. Methods Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. Results In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat(36.5%) was higher than that in cattle meat(1.1%). However, the prevalence in poultry cloacal swabs(27.0%) was lower than that in cattle stool(57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST-21(11.9%), ST-22(10.3%), and ST-403(7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin(89.7%), followed by tetracycline(74.6%), and nalidixic acid(69.0%). Conclusion This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.
基金supported by the National Natural Science Foundation of China grant numbers NSFC 81861138053 and NSFC 31761133004。
文摘Objective This study aimed to evaluate the genetic diversity,virulence,and antimicrobial resistance of Aeromonas isolates from clinical patients,tap water systems,and food.Methods Ninety Aeromonas isolates were obtained from Ma’anshan,Anhui province,China,and subjected to multi-locus sequence typing(MLST)with six housekeeping genes.Their taxonomy was investigated using concatenated gyr B-cpn60 sequences,while their resistance to 12 antibiotics was evaluated.Ten putative virulence factors and several resistance genes were identified by PCR and sequencing.Results The 90 Aeromonas isolates were divided into 84 sequence types,80 of which were novel,indicating high genetic diversity.The Aeromonas isolates were classified into eight different species.PCR assays identified virulence genes in the isolates,with the enterotoxin and hemolysin genes act,aer A,alt,and ast found in 47(52.2%),13(14.4%),22(24.4%),and 12(13.3%)of the isolates,respectively.The majority of the isolates(≥90%)were susceptible to aztreonam,imipenem,cefepime,chloramphenicol,gentamicin,tetracycline,and ciprofloxacin.However,several resistance genes were detected in the isolates,as well as a new mcr-3 variant.Conclusions Sequence type,virulence properties,and antibiotic resistance vary in Aeromonas isolates from clinical patients,tap water systems,and food.