Background: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.

Objective To explore the effect of total saponins of diaphragma juglandis fructus(DJF)on testicular function in rats and its possible mechanism.Methods Fifty SD male rats were randomly divided into NC group,MG model group(MG group),DJF low-dose group(LDJF group),DJF medium-dose group(MDJF group)and DJF high-dose group(HDJF group),with 10 rats in each group.The NC group was given daily subcutaneous injection of normal saline 500 mg/kg,and the other groups were given daily subcutaneous injection of D-galactose 500 mg/kg for 8 weeks to establish the subacute aging rat model.After 4 weeks of subcutaneous injection,rats of the LDJF group,MDJF group and HDJF group were given 100 mg/kg,200 mg/kg and 400 mg/kg DJF total saponin extract by gavage,respectively,and rats of the NC group and MG group were given 100 mg/kg normal saline by gavage,respectively,for 28 consecutive days.The body weight of rats in each group was measured,the testicular index and sperm parameters of rats in each group were analyzed,and the pathological changes of testicular tissue were observed.The serum levels of testosterone,oxidation factor superoxide dismutase(SOD)and malondialdehyde(MDA)in each group were detected.The expression of related proteins was detected by Western blot.Results Compared with the NC group,testicular weight,testicular index,serum testosterone and SOD levels,sperm density,sperm survival rate and sperm activity of rats in MG group were decreased,and MDA level of rats in MG group was increased;the protein expressions of Nrf2 and HO-1 in testicular tissue of rats in MG group were down-regulated,and the protein expressions of p53 and p21 in testicular tissue of rats in MG group were up-regulated,with statistically significant differences(P<0.05).Compared with the MG group,testicular weight,testicular index,serum testosterone and SOD levels,sperm density,sperm survival rate and sperm activity of rats in HDJF group were increased,and MDA level of rats in HDJF group was decreased;the protein expressions of Nrf2 and HO-1 in testicular tissue of rats in HDJF group were up-regulated,and the protein expressions of p53 and p21 in testicular tissue of rats in HDJF group were down-regulated,with statistically significant differences(P<0.05).There was no significant difference in the above indexes between LDJF group,MDJF group and MG group(P>0.05).Compared with the NC group,the arrangement of spermatogenic cells in testicular tissue was disordered,the number of spermatogenic cells was reduced,and the number of spermatozoa in seminiferous tubule was reduced in the MG group.Compared with the MG group,the testicular morphology was improved and the number of spermatozoa was increased after DJF total saponins intervention,and the improvement was most obvious in the HDJF group.Conclusion DJF total saponins can effectively ameliorate the decline of testicular functionin in rats,which may be related to activation of Nrf2/HO-1 pathway,enhancement of antioxidant stress level and inhibition of aging-related protein expression.

OBJECTIVE To analyze the distribution and drug resistance of pathogenic bacteria in hospital-associat-ed infections for patients after renal transplantation,and to provide a reference for the rational selection of antibac-terial drugs for anti-infective treatment in such patients.METHODS Clinical data were collected from 89 hospital-ized patients who underwent renal transplantation and developed hospital-associated infection at Beidaihe Rehabili-tation and Recuperation Center(formerly known as 281 Hospital)from 2017 to 2021.The pathogenic bacteria de-tected in different types of hospital-associated infections and the drug resistance of the main pathogenic bacteria were analyzed.RESULTS A total of 89 pathogenic bacterial strains were isolated from the 89 patients with hospi-tal-associated infection,including 74 gram-negative bacterial strains(83.15％)and 15 gram-positive bacterial strains(16.85％).The predominant pathogenic bacterial strains were Klebsiella pneumoniae,Escherichia coli and Pseudomonas aeruginosa.Respiratory tract infection was the most common.E.coli showed severe drug re-sistance,with high drug resistance rates to various antibacterial drugs(complete drug resistance to piperacillin and ampicillin).K.pneumoniae was generally drug resistant to ampicillin.Enterobacter cloacae showed high sensitivi-ty to carbapenems,amikacin and enzyme inhibitor combinations.P.aeruginosa had low drug resistance rates to imipenem and meropenem.Staphylococcus aureus was completely drug resistant to antibacterial drugs such as penicillin,erythromycin and gentamicin,and no drug-resistant strains to vancomycin and linezolid were found.CONCLUSIONS The gram-negative bacteria are dominant among the bacteria isolated from the renal trans-planted patients with postoperative hospital-associated infections,with a high detection rate of E.coli and a severe drug resistance situation.Therefore,it is necessary to strengthen the monitoring of drug resistance in renal trans-plant recipients and make rational choices of antibacterial drugs.

Objective To investigate the differences in neurite density index(NDI),neurite orientation dispersion index(ODI),and volume fraction of isotropic water molecule(Viso)of subcutaneous white matter fiber tracts in patients with cerebral small ves-sel disease(CSVD),and the effect of the glymphatic system(GS)on NDI,ODI,and Viso values of white matter fiber tracts in patients with CSVD.Methods A total of 69 CSVD patients(CSVD group)were retrospectively selected.All patients underwent conventional plain MRI scans[3D-T1,T2WI,3D-T2 fluid attenuated inversion recovery(FLAIR)],spin echo-echo planar imaging(SE-EPI),and susceptibility weighted imaging(SWI)scans.The NDI,ODI,and Viso values of 29 white matter fiber tracts in the brain were meas-ured using post-processing software.Thirty-five healthy volunteers were recruited as the control group,and the independent sample t test was used to compare the differences of NDI,ODI,and Viso values between the two groups.Multiple linear regression was used to evaluate the relationship between along the perivascular space(ALPS)index and NDI,ODI,and Viso values of 29 white matter fiber tracts in CSVD patients.Results Compared with control group,CSVD group showed a statistically significant increase in Viso values in 26 white matter fiber tracts and decrease in NDI values in 14 white matter fiber tracts(PFDR<0.05).In multiple linear regression,the decrease of ALPS index in CSVD patients was found to be statistically different from that of NDI values in certain white matter fiber tracts(PFDR<0.05)and primarily located in the frontal and temporal lobes.Conclusion Neurite orientation dispersion and density imaging(NODDI)technology is more effective in identifying the biological differences,which impact the integrity of white matter fiber tracts in patients with CSVD.Furthermore,it reflects the pathophysiological changes of the brain GS on different white matter fiber tracts in CSVD patients.This provides valuable insights for recognizing the clinical manifestations of CSVD and developing appropri-ate treatment plans.

Objective Based on the transcriptome data of Scolopendra subspinipes mutilans L.Koch,SSR primers were designed and developed to evaluate the genetic diversity and analyze the population structure of the germplasm resources of S.mutilans,which can provide a theoretical basis for the development and utilization of the germplasm resources of S.mutilans.Methods We collected 301 samples of S.mutilans from major production areas,and analyzed the population genetic diversity and population structure of the germplasm resources of S.mutilans using 18 pairs of highly polymorphic SSR primers after screening.Results A total of 142 alleles were amplified by 18 primer pairs across all samples,with an average of 7.89 alleles amplified per locus.The mean of observed heterozygosity(HO)of the 18 populations was 0.39,the mean of expected heterozygosity(HE)was 0.46,the mean of polymorphism information content(PIC)was 0.41,the mean of Nei's gene diversity index(H)was 0.46,and the mean of Shannon information index(I)was 0.81.The results showed that the wild resources of S.mutilans collected in this study had a high level of genetic diversity,Four populations in Anhui and Zhejiang had higher genetic diversity than populations in Hubei.Molecular analysis of variance(AMOVA)of the population showed that most of the genetic variation in the materials of this study mainly occurred within populations.The STRUCTURE analysis of germplasm resources showed that all germplasm could be divided into four populations.Conclusion This study showed that the natural population of S.mutilans possesses high genetic diversity with high genetic variation and is better adapted to changes in the environment.Our results provided a research basis for the rational utilization of the germplasm resources of S.mutilans and the selection and breeding of superior varieties.

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

Objectives:To analyze the clinical application effect of the preloaded snare technique in patients with risk of atrial septal occluder migration during percutaneous atrial septal defect(ASD)occlusion.Methods:The clinical data of 24 patients with secundum ASD who underwent preloaded snare-assisted transcatheter closure in Fuwai Central China Cardiovascular Hospital between December 2022 and August 2024 were retrospectively analyzed.The preprocedural echocardiography revealed that all patients presented with large secundum ASD or insufficient margins,indicating potential risk of device migration during percutaneous ASD occlusion.Consequently,preloaded snare technique was applied for ASD closure.Postprocedural evaluations were conducted to assess device stability(migration or shedding),residual shunt,pericardial effusion,and new-onset arrhythmia during the procedure,immediately after intervention,and at 1-month follow-up.Results:Among 24 patients,there were 4 males,with an average age of(37.88±13.18)years and an average weight of(59.70±10.78)kg.Twenty-two cases underwent successful interventional closure.Two cases occurred atrial septal occluder migration during the procedure,both were successfully retrieved using the preloaded snare and subsequently scheduled for surgical repair.Postprocedural electrocardiograms and echocardiograms(obtained immediately and at 1-month follow-up)demonstrated no device migration,residual shunt,occluder dislodgement,pericardial effusion,or new-onset arrhythmias.Conclusions:The preloaded snare technique can reduce the risk of atrial septal occluder migration and shedding,simplify the process of retrieving the occluder,enhance the safety of the intervention,and avoid emergency surgical intervention in high-risk populations.

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.