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 clinical characteristics of neonatal necrotizing enterocolitis（NEC）and analyze the risk factors for early-onset NEC.Methods:A total of 220 children with NEC admitted to the Department of Pediatrics，Tianjin Medical University General Hospital from January 1st，2018 to February 29th，2024 were retrospectively selected as the research objects. According to the time of onset，the early-onset group（ n=120）and the late-onset group（ n=100）were established，and the clinical characteristics of the two groups were compared. Another 150 cases of normal healthy newborns born in this hospital in the same period were selected as the control group，and the clinical data of the control group were collected. The clinical characteristics of the early-onset group and the control group were compared，and the risk factors of early-onset NEC were analyzed by multivariate Logistic regression. Results:Compared with the late-onset group，the early-onset group had fever［50.0%（60/120）vs. 40%（40/100）， χ2=7.333， P=0.007］，apnea［39.17%（47/120）vs. 28%（28/100）， χ2=7.568， P=0.006］，no rise in body temperature［56.67%（68/120）vs. 39%（39/100）， χ2=6.815， P=0.009］，abdominal distension［25%（30/120）vs. 40%（40/100）， χ2=13.200， P<0.001］，vomiting［30.83%（37/120）vs. 45%（45/100）， χ2=12.797， P<0.001］was significantly different（all P<0.05）；Multivariate Logistic regression analysis：weight<1 500 g（ OR=5.871，95% CI：3.153～9.673， P<0.001），gestational age<30 weeks（ OR=4.256，95% CI：2.641～7.896， P=0.007），hemodynamically significant patent ductus arteriosus（hs-PDA）（ OR=3.113，95% CI：1.865～5.133， P=0.033），severe anemia（ OR=3.057，95% CI：2.165～4.802， P=0.001），feeding intolerance（ OR=4.215，95% CI：1.579～10.802， P=0.005），amniotic fluid pollution（ OR=2.452，95% CI：1.579～3.111， P<0.001）were the independent risk factors for early-onset NEC（all P<0.05）. Conclusion:Weight<1 500 g，gestational age<30 weeks，hs-PDA，severe anemia，feeding intolerance，and amniotic fluid contamination are independent risk factors for early-onset NEC. In clinical practice，more attention should be paid to these factors for disease prevention，early identification，and timely intervention in newborns to reduce the occurrence of NEC.

Objective: To explore the effectiveness of a comprehensive sexuality education (CSE) curriculum on university students hostile and benevolent sexism, so as to provide a reference for evaluating the effects of CSE on reducing ambivalent sexism. Methods: From September 2018 to January 2019, 165 university students from a university in Beijing were recruited using convenience sampling for a 5 month of CSE curriculum (36 sessions, 2 sessions per week, 45 min per session), including CSE and gender studies, sexual physiology and health, gender and gender roles, gender bias, intimate relationships and gender bias, gender based violence and gender bias, culture and gender bias, and gender and power. Students who took CSE curriculum were included in the intervention group ( n =97) and students from the same university who had not taken CSE curriculum were included in the control group ( n =68). Using the Ambivalent Sexism Inventory, both groups of university students were surveyed before and after the curriculum to analyze the effectiveness of the CSE curriculum. Chi -square test, ANOVA，cluster analysis and Kruskal Wallis test were used for statistical analysis. Results: After the CSE curriculum, both hostile and benevolent sexism scores were lower in the intervention group (2.21±0.76, 2.36±0.68) than in the control group (2.81±0.61, 3.03±0.60) ( F =17.24, 33.26), and pre test scores were higher in the intervention group (2.64±0.67, 2.88±0.68) ( F =45.62, 66.93) ( P <0.01). On both hostile and benevolent sexism, female students scores (2.46±0.72, 2.65±0.70) were lower than male students scores (2.86±0.59, 3.09± 0.69 ) ( F=11.02, 14.20, P <0.01). Comparison of the curriculum effectiveness of hostile and benevolent sexism among clustered groups showed that the difference in hostile sexism scores was higher in the inconsistent type [0.63(0.25, 1.25)]than in the more consistent type [0.38(-0.16, 0.88)] and the lower consistent type [0.38(0.06, 0.63)] ( H=8.71, P <0.05); and the difference in benevolent sexism scores was higher in the more consistent type [0.75(0.53, 1.22)] than in the less consistent type [0.38(0.09, 0.88 )] and inconsistent type [0.38(-0.13,0.63)] ( H=10.82, P <0.05). Conclusions CSE can improve hostile and benevolent sexism in university students with sex and type differences. Attention should be paid to CSE curriculum to improve ambivalent sexism among university students with a view to fostering their awareness of gender equality.

Objective To evaluate the effectiveness and safety of acupuncture in patients with Major Depressive Disorders.Methods Search the database for relevant literature published before April 15,2023.Select randomized controlled trial that meeting the enrollment criteria,evaluate the quality of the literature and classify before meta-analysis systematic evaluation.Results 15 RCTs are included in this study,with a total of 1077 patients.The results showed that acupuncture treatment,compared with antidepressants alone,The score of Hamilton Depression Scale(HAMD)in patients with liver-qi depression disorder[MD=-0.73,95%CI(-1.22,-0.24),P<0.05],the score of TCM Syndrome Scale[MD=-1.89,95%CI(-2.35,-1.44),P<0.001],effective rate[RR=1.09,95%CI(1.03,1.153),P=0.001]and TESS score[MD=-2.76,95%CI(-3.68,-1.85),P<0.001]were statistically significant.Compared with fluoxetine hydrochloride,the effective rate of HAMD scale score was statistically significant[RR=1.07,95%CI(1.01,1.14),P<0.05].Conclusion Compared with antidepressants alone,acupuncture therapy has the advantages for the improvement of HAMD score in patients,the improvement of Traditional Chinese medicine symptoms,and significantly less adverse effects than those in the control group.Through this study,it is considered that acupuncture can be a safe and effective treatment modality.However,due to the quantity and quality of the included literature,the above conclusions still need to be verified by more high-quality clinical trials.

Objective To evaluate the efficacy of transcatheter aortic valve replacement(TAVR)in patients with severe aortic valve stenosis.Methods This study included 46 patients with severe aortic valve stenosis who underwent TAVR and completed a six-month follow-up at the Heart Center of the First Hospital of Hebei Medical University between May 2020 and May 2023.All patients underwent a preoperative examination,mini-mental state examination(MMSE),the Montreal cognitive assessment scale(MOCA),and the following safety indicators of surgery,including immediate success rate of valve implantation,valve displacement,death,heart conduction block,perivalve leakage,coronary occlusion,stroke,approach vessel rupture,cardiac tamponade,aortic dissection,and massive bleeding.Effec-tiveness indicators included clinical symptoms,BNP,sST2,and cardiac color Doppler ultrasound preoperatively and one day,seven days,three months,and six months postoperatively.Cognitive function indicators(MMSE and MOCA),were used preoperatively and three and six months postoperatively.The efficacy of transcatheter aortic was evaluated using these indicators.Results The immediate success rate of valve implantation was 100％,with one case of valve displacement,four cases of new bundle branch block,two cases of perivalve leakage,two cases of stroke,one case of inlet vessel rupture,one case of major bleeding,and no deaths,coronary artery occlusion,car-diac tamponade,or aortic dissection.Clinical symptoms improved significantly postoperatively,with 30 cases of NYHA grades Ⅰ to Ⅱbeing significantly higher than the 18 cases preoperatively.The indicators of cardiac function,BNP,and sST2 significantly decreased,and the maximum aortic valve cross-valve flow velocity,aortic valve systolic cross-valve pressure difference,average aortic valve cross-valve pressure difference,and left ventricular end-diastolic diameter significantly improved.The MMSE and MOCA showed significant improve-ments three and six months postoperatively.Conclusion TAVR is a safe and effective method to improve cognitive function in patients with severe aortic stenosis.

Objective:To investigate the splanchnic vessel diameter changes following splenectomy in cirrhotic portal hypertension.Methods:The retrospective cohort study was con-ducted. The clinical data of 149 patients with cirrhotic portal hypertension who underwent splenec-tomy in the People′s Hospital of Ningxia Hui Autonomous Region from January 2012 to June 2022 were collected. There were 115 males and 34 females, aged 46(range, 17-68)years. The patients underwent abdominal computed tomography (CT) before surgery and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, 5 years after surgery. The blood vessel diameters in the portal vein system and abdominal visceral artery system were measured after three-dimensional image reconstruction. Measurement data with skewed distribution were represented as M(range). The repeated measured data were analyzed using the generalized linear mixed model, and the marginal mean of the estimated target was expressed as Mean± SE. Simple effects were used to analyze the differences in vascular diameter between pre-surgery and different time points after surgery, and sequential Bonferroni adjusted significance was used for multiple comparisons of marginal means. Results:(1) Changes in diameters of common hepatic artery (CHA), proper hepatic artery (PHA), gastroduodenal artery (GDA) before and after splenectomy. There were significant differences in the diameter change of CHA, PHA and GDA before and after splenectomy ( F=28.66, 29.46, 8.12, P<0.05). The diameter of CHA was thicker at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, and 5 years after splenectomy than pre-surgery ( P<0.05). It reached a peak at 1 week after surgery, and then declined slowly and fluctuated. The diameters of PHA and GDA were thicker at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, and 5 years after splenectomy ( P<0.05). They reached a peak at 1 month after surgery, and then declined slowly and fluctuated. (2) Changes in diameters of splenic artery (SA), celiac artery (CA), and left gastric artery (LGA) before and after splenectomy. There were significant differences in the diameter change of SA and CA before and after splenectomy ( F=155.33, 66.40, P<0.05). The diameters of SA and CA at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, and 5 years after splenectomy were thinner than those before operation ( P<0.05), the changes of which were obvious within 3 months after splenectomy, and then tended to be stable. There was no significant difference in the diameter of the LGA before and after splenectomy ( F=1.07, P>0.05). (3) Changes in diameters of superior mesenteric artery (SMA), right renal artery (RRA), left renal artery (LRA) before and after splenectomy. There were significant differences in the diameter change of SMA, RRA and LRA before and after splenectomy ( F=8.22, 13.21, 10.27, P<0.05). The diameter of SMA at 1 month, 3 months, 6 months, 1 year, and 3 years after splenectomy was thicker than those before operation ( P<0.05). The diameters of both RRA and LRA were thicker at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, and 5 years after splenectomy than those before operation ( P<0.05). (4) Changes in diameters of portal vein (PV) and superior mesenteric vein (SMV) before and after splenectomy. There were significant differences in the diameter change of PV and SMV before and after splenectomy ( F=31.74, 2.01, P<0.05). The diameter of PV at 1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year, 3 years, and 5 years after splenectomy was thinner than that before operation ( P<0.05), and there was no significant difference in the diameter of SMV at above time points compared with that before operation ( P>0.05). Conclusions:After splenectomy in patients with cirrhotic portal hypertension, the diameters of PV, SA and CA were reduced, and the diameters of CHA, PHA, GDA and renal artery, superior mesenteric artery were enlarged. These postoperative vessel diameter changes maintain as long as five years.