ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus （T2DM）， and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were randomly assigned to the model group， metformin group， and low-， medium-， and high-dose Jiangtang No. 3 prescription groups， and a normal group was also set. Daily gavage was administered for 8 weeks as follows： metformin at 0.1 g·kg^-1·d^-1， Jiangtang No. 3 prescription granules at 1.62， 3.24， 6.48 g·kg^-1·d^-1 for the respective dose groups， and sterile water for the normal and model groups. Rat body weight， fasting blood glucose （FBG）， oral glucose tolerance test （OGTT）， and insulin tolerance test （ITT） were measured. After drug intervention， enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL）， high-density lipoprotein cholesterol （HDL）， non-esterified fatty acids （NEFA）， interleukin （IL）-1β， IL-18， and insulin （INS）. Hematoxylin-eosin （HE） staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， NOD-like receptor protein 3 （NLRP3）， Caspase-1， IL-1β， IL-18， and gasdermin D （GSDMD） in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group， Jiangtang No. 3 prescription groups exhibited significantly increased body weight （P<0.05， P<0.01）， significantly reduced FBG （P<0.05， P<0.01）， significant reductions in TC， TG， NEFA， and LDL （P<0.05， P<0.01）， and a significant increase in HDL （P<0.01）. Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased （P<0.01）， the homeostatic model assessment of insulin resistance （HOMA-IR） index was significantly reduced （P<0.05， P<0.01）， and adipose tissue pathology was improved. The protein expression levels of TLR4， NF-κB， NLRP3， Caspase-1， IL-1β， IL-18， and GSDMD were markedly decreased （P<0.05， P<0.01）， and the mRNA expression levels of these indicators were also significantly downregulated （P<0.05， P<0.01）. Some effects were superior to those of the positive control drug metformin， and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses， disordered glucose and lipid metabolism， and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators， improves glucose and lipid metabolism and insulin resistance， and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue， thereby influencing downstream inflammatory mediators.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Antimicrobial resistance(AMR)has become a global public health crisis,posing a serious threat to the achievement of sustainable development goals(SDGs)of the United Nations.This article explores the potential con-sequences and far-reaching impacts of AMR on the global health system,economic development,and social well-being from the perspective of SDGs.This article analyzes the current situation and challenges of AMR prevention and control globally and domestically,proposes comprehensive response suggestions,such as establishing a global collaborative governance mechanism for AMR,deepening the"One Health"practice framework,perfecting survei-llance as well as infection prevention and control system on AMR,accelerating the development of new vaccines,ex-ploring AMR innovative response technologies,and strengthening AMR literacy education for all people.The re-search findings can provide reference globally,especially for developing countries to comprehensively respond to the threat of AMR and promote the SDGs process.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

BACKGROUND:At present,there are many clinical studies on dysphagia,but little is known about the stress of bones and hyoid muscles caused by dysphagia.OBJECTIVE:To establish a three-dimensional model of swallowing musculoskeletal system to investigate the stress changes of hyoid and suprahyoid muscles during swallowing.METHODS:A healthy adult male was selected for head and neck CT scanning.A three-dimensional model was constructed by image extraction method.According to hyoid motion,the lowest and highest positions of hyoid were set,and the muscle strength of suprahyoid muscles was successively loaded to observe the stress influence of suprahyoid muscles on hyoid under physiological state.By changing the material properties of muscles,we simulated different degrees of dysphagia and observed the stress changes of suprahyoid muscle group under the condition of dysphagia.RESULTS AND CONCLUSION:(1)The finite element models including C2-C4 vertebrae,partial temporal bone,mandible,hyoid,and mylohyoid-geniohyoid muscle were established,which could reflect the displacement of hyoid and stress changes during swallowing.(2)Under physiological conditions,among suprahyoid muscles,mylohyoid muscle had the greatest influence on hyoid stress,followed by digastric muscle,geniohyoid muscle,and stylohyoid muscle.(3)By simulating different degrees of dysphagia,it was found that with the increase of the severity of dysphagia,the stress of suprahyoid muscles gradually increased.(4)These findings conclude that among suprahyoid muscles,mylohyoid muscle and digastric muscle have the greatest influence on hyoid stress,which suggests the importance of specific muscle stimulation.The aggravation of dysphagia was positively correlated with the stress change of suprahyoid muscles,which could provide a biomechanical reference for the mechanism study and clinical diagnosis and treatment of dysphagia.

Objective To evaluate the application value of fascial platform versus commercial platform in transumbilical single-port laparoscopic transabdominal preperitoneal repair(TAPP)for inguinal hernia.Methods One hundred patients with inguinal hernia admitted between January and December 2024 were prospectively enrolled and randomly assigned to either the fascial platform group(n=50)or the commercial platform group(n=50)by using a random number table.The following parameters were compared between the two groups:platform establishment time,operative time,intraoperative blood loss,incision suture time,operative difficulty score,camera manipulation difficulty score,postoperative 24-hour Visual Analogue Scale(VAS)score of pain,postoperative hospital stay,total hospitalization cost,comprehensive satisfaction score,and postoperative complications.Results The fascial platform group demonstrated significantly superior outcomes compared to the commercial platform group in platform establishment time[(3.4±1.0)min vs.(8.1±1.5)min,t=-18.389,P＜0.001],operative time[(67.5±7.9)min vs.(72.2±11.5)min,t=-2.380,P=0.019],intraoperative blood loss[(8.3±4.3)ml vs.(11.1±5.7)ml,t=-2.798,P=0.006],incision suture time[(7.0±1.4)min vs.(11.8±2.7)min,t=-11.212,P＜0.001],operative difficulty score(14.4±3.6 vs.23.1±4.1,t=-11.215,P＜0.001),camera manipulation difficulty score(11.4±2.6 vs.18.3±2.5,t=-13.370,P＜0.001),VAS score of postoperative 24-hour pain(2.4±1.0 vs.3.7±1.1,t=-6.139,P＜0.001),total hospitalization cost[(15.8±1.6)thousand yuan vs.(18.3±1.6)thousand yuan,t=-7.841,P＜0.001],and comprehensive satisfaction score(7.3±1.1 vs.6.3±1.0,t=5.271,P＜0.001).However,there were no statistically significant differences in postoperative hospital stay or postoperative complication between the two groups(P＞0.05).All the patients were followed up for 1-12 months postoperatively[(5.3±1.8)months vs.(5.7±2.0)months,t=-0.945,P=0.347],with no recurrence observed in either group.Conclusions Both fascial platform and commercial platform can be used for transumbilical single-port TAPP.The fascial platform offers advantages including shorter platform establishment time,reduced incision suture time,lower operative and camera manipulation difficulty,decreased cost,less postoperative pain,and higher patient satisfaction.

Objective To explore the change trend and related mechanism of resting metabolic rate induced by corticosterone in mice,and observe the intervention effects of Zhibai Dihuang Pill and Jinkui Shenqi pill.Methods Sixty-four mice were randomly divided into short-term and long-term groups,and each group was randomly divided into four groups.Mice in CORT group,ZBDH group and JKSQ group were given sterile drinking water containing corticosterone,and mice in Ctrl group were given sterile drinking water containing 1%anhydrous ethanol.Mice in ZBDH group and JKSQ group were given Chinese medicine by gavage.RMR of mice in each group was dynamically monitored during modeling and Chinese medicine intervention.The morphology of mitochondria in liver and muscle were observed by transmission electron microscope.The TR expression level in liver and muscle tissues of each group was observed by immunofluorescence,and MDA and ATP levels were detected in liver and muscle tissues of each group.levels of ACTH,TSH,INS,T3,T4,FT3,FT4,8-OHdG,FGF-21,GDF-15,L-lactic acid and pyruvic acid in serum were also detected.Results Compared with Ctrl group,the mitochondrial morphology of liver and muscle tissues in CORT group was damaged,and the expression of TR was decreased.In short-term(Day 8),RMR,ATP in liver,serum T4,ACTH and INS levels were significantly increased in the CORT group,while serum FGF-21,TSH levels and MDA in liver were significantly decreased.In long term(Day 56),RMR,serum 8-OhdG,INS,and ATP in liver and muscle were significantly decreased in the CORT group,serum FGF-21,GDF-15,T3,T4,FT3,FT4,MDA in liver and muscle were significantly increased.Compared with CORT group,in short term,RMR,serum L(+)-lactate in ZBDH group were significantly decreased,while serum 8-OHdG and the expression of TRα in muscle were significantly increased.In JKSQ group,the mitochondrial morphology of muscle tissue was improved,the expression of TRα and serum FGF-21 were significantly increased,while serum L(+)-lactic acid,FT4 and ATP in liver were significantly decreased.In long term,serum FGF-21 was significantly lower in ZBDH group,and in JKSQ group,RMR,ATP in liver tissue and TRα expression in muscle were significantly increased,while the levels of FGF-21,GDF-15,T3,FT4 in serum and MDA in muscle tissue were significantly decreased.Conclusion CORT induced RMR to increase first and then decrease with the intervention time.In the short term,Zhibai Dihuang Pill significantly decreased RMR in mice,while in the long term,Jinkui Shenqi Pill significantly increased RMR.The mechanism may be related to mitochondrial injury,thyroxine secretion and thyroxine receptor expression.

BACKGROUND:At present,there are many clinical studies on dysphagia,but little is known about the stress of bones and hyoid muscles caused by dysphagia.OBJECTIVE:To establish a three-dimensional model of swallowing musculoskeletal system to investigate the stress changes of hyoid and suprahyoid muscles during swallowing.METHODS:A healthy adult male was selected for head and neck CT scanning.A three-dimensional model was constructed by image extraction method.According to hyoid motion,the lowest and highest positions of hyoid were set,and the muscle strength of suprahyoid muscles was successively loaded to observe the stress influence of suprahyoid muscles on hyoid under physiological state.By changing the material properties of muscles,we simulated different degrees of dysphagia and observed the stress changes of suprahyoid muscle group under the condition of dysphagia.RESULTS AND CONCLUSION:(1)The finite element models including C2-C4 vertebrae,partial temporal bone,mandible,hyoid,and mylohyoid-geniohyoid muscle were established,which could reflect the displacement of hyoid and stress changes during swallowing.(2)Under physiological conditions,among suprahyoid muscles,mylohyoid muscle had the greatest influence on hyoid stress,followed by digastric muscle,geniohyoid muscle,and stylohyoid muscle.(3)By simulating different degrees of dysphagia,it was found that with the increase of the severity of dysphagia,the stress of suprahyoid muscles gradually increased.(4)These findings conclude that among suprahyoid muscles,mylohyoid muscle and digastric muscle have the greatest influence on hyoid stress,which suggests the importance of specific muscle stimulation.The aggravation of dysphagia was positively correlated with the stress change of suprahyoid muscles,which could provide a biomechanical reference for the mechanism study and clinical diagnosis and treatment of dysphagia.