Objective: To explore the causal association between dietary components (carbohydrate, fat, protein, and sugar) and 119 genera of known gut microbiota using Mendelian randomization (MR) methods. Methods: Genome-wide association study (GWAS) data for dietary components were collected from the DietGen, while GWAS data for gut microbiota were collected from the MiBioGen. Single nucleotide polymorphism (SNP) loci associated with the four dietary components were used as instrumental variables, and 119 known gut microbiota genera were used as the outcomes. MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. Common genetic pleiotropic genes between dietary components and gut microbiota were identified by MAGMA and PLACO analyses. Results: The MR analysis revealed causal associations between carbohydrates and 4 gut microbiota genera, fats and 14 genera, proteins and 14 genera, and sugars and 11 genera (all P<0.05). The MR-Egger regression analysis showed no horizontal pleiotropy among the selected SNPs, and the MR-PRESSO test did not identify any outliers (all P>0.05). The MAGMA and PLACO analyses revealed that 74.42% (32/43) of the causal associations had pleiotropic genes, with 1 to 10 pleiotropic genes identified. Multiple causal association groups shared the same pleiotropic genes. Conclusion There are potential genetic and causal associations between dietary components and gut microbiota.

Objective: To investigate the association between childhood obesity and type 2 diabetes mellitus (T2DM) as well as coronary artery heart disease (CHD). Methods: Genome-wide association study (GWAS) data for childhood obesity were collected from the ECG consortium, encompassing information on children aged 2 to 18 years, including 18 613 cases and 12 696 controls. GWAS data for T2DM were collected from the DIAGRAM consortium, including 242 283 cases and 1 569 734 controls. GWAS data for CHD were collected from the CARDIoGRAMplusC4D consortium, including 10 801 cases and 137 371 controls. Pleiotropic genes associated with both T2DM and CHD were analyzed using the MAGMA, PLACO and conditional false discovery rate (cFDR) methods. Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) method, exploring the causal relationships among childhood obesity, T2DM and CHD. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. The mediating variables among the three diseases were investigated by using a mediation analysis. Results: The results of MAGMA, PLACO and cFDR analyses identified 80 pleiotropic genes associated with both T2DM and CHD, primarily distributed on chromosomes 3, 17 and 19. The MR analysis revealed that childhood obesity increased the risk of T2DM (OR=1.151, 95%CI: 1.033-1.283) and CHD (OR=1.158, 95%CI: 1.068-1.255), T2DM increased the risk of CHD (OR=1.182, 95%CI: 1.139-1.227), and CHD increased the risk of T2DM (OR=1.124, 95%CI: 1.055-1.198). The MR-Egger regression analysis showed no horizontal pleiotropy, and the MR-PRESSO test did not identify any outliers (all P>0.05). Mediation analysis indicated that childhood obesity directly increased the risk of CHD (effect value=0.096, 95%CI: 0.012-0.180) and indirectly increased the risk of CHD through T2DM (effect value=0.023, 95%CI: 0.005-0.041), with the mediation effect accounting for 15.65% of the total effect. Conclusions There are potential causal associations between childhood obesity and T2DM as well as CHD, with a bidirectional causal relationship between T2DM and CHD. T2DM also plays a mediating role in the association between childhood obesity and CHD.

Objective: To investigate the epidemiological characteristics of hepatitis E in Shaoxing City, Zhejiang Province from 2006 to 2024, so as to provide the evidence for the prevention and control of hepatitis E. Methods: Data on hepatitis E incidence in Shaoxing City from 2006 to 2024 were collected through the Surveillance System of China Information System for Disease Control and Prevention. The epidemiological characteristics were analyzed using descriptive epidemiological methods. The trend in hepatitis E incidence was analyzed using the average annual percent change (AAPC) and annual percent change (APC). The spatial-temporal clustering characteristics of hepatitis E incidence were identified using spatial-temporal scanning analysis. Results: A total of 2 408 hepatitis E cases were reported in Shaoxing City from 2006 to 2024, with an average annual reported incidence of 2.55/100 000. The overall trend was not statistically significant (AAPC=3.181%, P>0.05). Specifically, it showed an upward trend from 2006 to 2011 (APC=17.371%, P<0.05), a downward trend from 2011 to 2019 (APC=-12.497%, P<0.05), and an upward trend from 2019 to 2024 (APC=18.076%, P<0.05). The epidemic season of hepatitis E was from January to May, with seasonal indices of 122.09%, 118.60%, 145.02%, 129.57%, and 106.15%, respectively. The top three average annual reported incidences were identified in Zhuji City, Xinchang County, and Shengzhou City, with rates of 4.18/100 000, 2.85/100 000, and 2.74/100 000, respectively. The average annual reported incidence of hepatitis E was higher in males than in females (3.52/100 000 vs. 1.56/100 000, P<0.05). A relatively large number of hepatitis E cases were reported among individuals aged 40-<70 years, with 1 639 cases (68.06%). Among them, the group aged 60-<70 years had the highest average annual reported incidence of hepatitis E, at 4.92/100 000. Farmers constituted the predominant occupational group, accounting for 1 515 cases (62.92%). Spatial-temporal scanning analysis identified two clusters in Shaoxing City from 2006 to 2024. The class Ⅰ cluster was located in Shengzhou City, with aggregation time from January 1, 2011 to May 1, 2014. The class Ⅱ cluster was located in Xinchang County, with aggregation time from December 1, 2012 to March 31, 2013. Conclusions The reported incidence of hepatitis E in Shaoxing City from 2006 to 2024 exhibited a pattern of an initial increase, followed by a decrease, and then a subsequent rise. The disease demonstrated higher prevalence during the winter and spring seasons. Key populations for targeted control and prevention include males, individuals aged 40-<70 years, and farmers. Shengzhou City and Xinchang County were identified as high-risk areas.

Objective To prepare tubeimoside Ⅲ nanoemulsion(TBMⅢ-NE)and evaluate its adjuvant effect in vaccines.Methods TBMⅢ-NE was prepared using low-energy emulsification.Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE,and transmission electron microscopy(TEM)was employed to observe the morphology.CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells(BMDCs).The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay.The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy.After co-incubation of TBMⅢ-NE with BMDCs,the expression levels of CD40,CD86,MHC-Ⅰ,and CCR7 on the surface of BMDCs were detected using flow cytometry,and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay(ELISA).After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE,ELISA was conducted to determine the serum levels of specific IgG,IgG2a,and IgG1 antibodies.The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot(ELISpot)assay.Results The prepared blank nanoemulsion(BNE)and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm,and a polydispersity index of 0.214 and 0.125,respectively.TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed.When the TBMⅢ-NE adjuvant was diluted by 400-fold,the survival rate of BMDCs was approximately 86%.Compared with free TBMⅢ,the hemolytic toxicity of TBMⅢ-NE was significantly reduced(P<0.01).TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs(P<0.05),indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes.TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs(P<0.05).When combined with RBD,TBMⅢ-NE significantly increased the levels of specific IgG,IgG2a,and IgG1 antibodies in mouse serum(P<0.01)and promoted the secretion of specific IFN-γ in splenocytes(P<0.01),indicating that TBM Ⅲ-NE could enhance specific cellular immune responses.Conclusion A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.

Objective To investigate the interaction between a novel antimicrobial compound,HL-J6,and penicillin-binding protein 1(PBP1)of Staphylococcus aureus.Methods With MRSA252 genomic DNA as the template and PBP1F and PBP1R as primers,the expression plasmid pET30a-pbp1-39-608 was constructed by amplifying the target gene fragment followed by cloning into the Nde I/Xho I restriction sites of the pET30a vector.Then the obtained plasmids were transformed into Escherichia coli for the expression of PBP1-39-608 protein,and the product was purified by affinity chromatography.The inhibitory effect of HL-J6 on the transpeptidase activity of PBP1-39-608 was measured using peptidoglycan side chain backbone peptide,with thiol ester analog S2d as the substrate.The affinity between HL-J6 and PBP1-39-608 was detected using microscale thermophoresis(MST),and the binding interaction was confirmed by cellular thermal shift assay(CETSA).Molecular docking and dynamics simulation were performed using AutoDock Vina and Desmond software,respectively,to elucidate the binding mode of HL-J6 with the PBP1-39-608 protein and the key amino acid residues involved.Results The recombinant plasmid pET30a-pbp1-39-608 was successfully constructed,and PBP1-39-608 protein was produced after induction and purified,yielding a protein with an approximate molecular mass of 65×103.HL-J6 inhibited the transpeptidase activity of PBP1-39-608 in a time-dependent manner(P<0.001).The dissociation constant Kd of the binding between HL-J6 and PBP1-39-608 was 64.92 μmol/L.Molecular docking results showed that HL-J6 bound to the active pocket of PBP1-39-608 by interacting with key residues such as ILE-348,ASN-370,THR-516 and PHE-423,with a binding score of-8.38 kcal/mol(<-5.00 kcal/mol).Dynamics simulation results indicated that the complex became stable after 50 ns.Conclusion HL-J6 effectively inhibits the transpeptidase activity of Staphylococcus aureus PBP1,and shows stable interaction with the protein.

OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.

Objective: To investigate the epidemiological and etiological characteristics of viral diarrhea among children under 5 years of age in Shaoxing City, Zhejiang Province, so as to provide insights into management of viral diarrhea. Methods: The surveillance data on viral diarrhea among children under 5 years of age in Shaoxing City from 2019 to 2022 were collected, including demographics and stool testing results. The epidemiological and etiological characteristics of viral diarrhea were analyzed using a descriptive epidemiological method. Results: A total of 763 diarrheal children under 5 years of age were reported in Shaoxing City from 2019 to 2022, and 236 children were tested positive for virus (30.93%). The detection of virus was 49.01%, 31.61%, 20.43% and 21.89% from 2019 to 2022, which appeared an overall tendency towards a decline (P<0.05). The incidence of viral diarrhea peaked from November to March of the next year and from May to July, and the detection of virus was lower among children with diarrhea living in urban areas (Yuecheng District, Keqiao District and Shangyu District) than among those in suburb areas (Zhuji City, Shengzhou City and Xinchang County) (30.22% vs. 52.00%, P<0.05). There were 206 children tested positive for a single virus, and the detection rates of rotavirus (RV), enteric adenovirus (EAdV), norovirus (NoV), and sapovirus (SaV) were 9.57%, 8.91%, 8.39%, and 0.13%, respectively. There were 25 children with virus co-infections, and the positive rates of EAdV and NoV, RV and EAdV and RV and NoV co-infections were 1.31%, 1.18% and 0.79%, respectively. There were 5 children with triple infections of RV, EAdV and NoV (0.66%). The highest detection of EAdV was seen in April, the highest detection of RV and NoV was seen in January, while SaV was only detected in April. Conclusion The incidence of viral diarrhea among children under 5 years of age peaked in winter and spring in Shaoxing City from 2019 to 2022, and the cases predominantly occurred in urban areas. The detection of virus appeared an overall tendency towards a decline, with high detection of RV, EAdV and NoV.

Objective: To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shaoxing City from 2006 to 2022, so as provide insights into improvements of the HFRS control strategy. Methods: Data pertaining to HFRS cases in Shaoxing City from 2006 to 2022 were captured from the Surveillance System of China Information System for Disease Control and Prevention. The temporal, population and regional distributions of HFRS were analyzed using the descriptive epidemiological method, and the trends in incidence of HFRS were evaluated using annual percent change (APC). Results: Totally 1 022 HFRS cases were reported in Shaoxing City from 2006 to 2022, with annual average incidence of 1.22/105 and three deaths. The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022 (APC=-11.101%, t=-9.930, P<0.001), and the incidence of HFRS peaked from May to June and from November to January of the next year. A higher incidence of HFRS was seen in men than in women (1.76/105 vs. 0.68/105; χ2=201.361, P<0.001). There were 714 HFRS cases at ages of 30 to 59 years (69.86%), and farmers were the predominant occupation (78.18%). The three counties with the largest number of HFRS cases included Zhuji (366 cases), Xinchang (263 cases) and Shengzhou (134 cases). The incidence of HFRS was lower in urban districts (Yuecheng, Keqiao and Shangyu) than in counties (Zhuji, Shengzhou and Xinchang) (0.58/105 vs. 1.96/105; χ2=326.880, P<0.001). Conclusion The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022, and the incidence was high in late spring, early summer and winter. The HFRS cases were mainly males, young and middle-aged people, and farmers, and predominantly distributed in counties. Targeted control measures are needed.

Objective:To investigate the birth weight (BW) of infants born to pregnant women living with human immunodeficiency virus (HIV) and its associated factors, and to provide more evidence for the prevention of mother-to-child transmission (PMTCT) in China.Methods:This study was a retrospective cohort study. Between January 2004 and December 2021, pregnant women living with HIV and their infants in Hubei Province were recruited and followed up, and clinical data were collected through hospital medical records and HIV/acquired immunodeficiency syndrome comprehensive response information management system. The multivariable linear regression was performed on the collected data to investigate associated influencing factors of BW.Results:In total, 531 pregnant women living with HIV (581 pregnancies) and 581 infants were enrolled. Of the 581 infants, 36 were HIV-positive, with a PMTCT rate of 6.2%. The mean BW of the infants was (3 075.0±470.2) gram. Protease inhibitor (PI) based-anti-retroviral therapy (ART) ( β=-0.1, 95% confidence interval ( CI)-188.2 to -37.1, P=0.004), ART in the first trimester( β=-0.1, 95% CI -201.9 to -65.5, P<0.001), infant HIV infection ( β=-0.1, 95% CI -310.4 to -68.2, P=0.002), hepatitis C virus infection ( β=0.1, 95% CI 71.2 to 410.4, P=0.005) and gestational age ( β=0.6, 95% CI 155.9 to 191.5, P<0.001) were associated with decreased BW. Conclusions:While improving the effectiveness of PMTCT for HIV, more attention should be paid to pregnant women who received ART in the first trimester and PI-based ART for preventing lower BW and improving maternal and infantile health.

Objective:To investigate the common diseases and the Constitution of Traditional Chinese Medicine of plateau-related soldiers, and explore the correlation between them.Methods:A total of 271 plateau-related soldiers in our sanatorium from January 1, 2020 to December 31, 2020 were selected as the subjects. All of them were assessed by the TCM constitution scale and the self-designed disease questionnaire and Sociodemographic information.Results:Eighty two percent of 271 plateau-related soldiers were regarded as paranoid constitution and 17.7% were gentleness type. There 73.1% of plateau-related soldiers had one or more diseases, and 90.9% of them were paranoid constitution. There were 47 cases of respiratory diseases, including 2 cases of gentleness type (4.3%) and 45 cases of paranoid constitution (95.7%); 53 cases of digestive system diseases, including 1 case of gentleness type (1.9%) and 52 cases of paranoid constitution (98.1%); 27 cases of skin diseases, including 1 case of gentleness type (3.7%) and 26 cases of paranoid constitution (96.3%); 148 cases of musculoskeletal diseases, including 15 cases of gentleness type (10.1%) and 133 cases of paranoid constitution (89.9%). The digestive system diseases with the highest proportion of paranoid constitution were selected for TCM Constitution correlation analysis, suggesting that there was a correlation between them( χ2=11.32, P<0.01). People including Qi deficiency and phlegm-dampness were more prone to digestive system diseases ( P<0.01). There was a significant negative correlation between gentleness type and digestive system diseases [ OR=0.17, 95% CI(0.040-0.726); P=0.017], as well as Qi deficiency [ OR=4.98, 95% CI(2.717-9.120)] and phlegm-dampness [ OR=12.00, 95% CI(5.269-27.332)]were risk factors for them ( P<0.01). Conclusions:The overall health level of plateau-related soldiers was not optimistic. The digestive system diseases of them were positively correlated with Qi deficiency and phlegm-dampness.