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 observe the detection and drug resistance of carbapenem-resistant Klebsiella pneumoni-ae(CRKP)strains causing hospital-acquired infections(HAI)and community-acquired infections(CAI)in recent years so as to provide bases for prevention and control of CRKP infection and reasonable clinical use of antibiotics.METHODS A total of 3444 patients who were diagnosed with Klebsiella pneumonia infection and were hospitalized in the 2nd Affiliated Hospital of Fujian Medical University from Jan.1,2017 to Dec.31,2023 were recruited as the research subjects.Totally 230 patients with CRKP infection were chosen based on the result of drug susceptibility testing,73 of whom had HAI,and 157 had CAI.The isolation rate of CRKP strains,popula-tion distribution,specimens sources and drug resistance rates were observed and compared between the patients with HAI and the patients with CAI.RESULTS The total isolation rate of CRKP strains was 6.68％(230/3444).There was no difference in the sex of the patients with CRKP infection between the HAI patients and the CAI patients,however,the isolation rate of the CRKP strains from the patients aged between 18 and 45 years old was higher in the HAI group than in the CAI group(P＜0.05).The isolation rates of CRKP strains causing the two types of infections increased year by year,showing a remarkable increasing amplitude in 2022-2023,with the HAI increasing from 9.33％to 20.67％,the CAI increasing from 5.54％to 15.03％.The lower respiratory tract,urinary tract and bacteremia were the most common infection sites,the detection rate of soft tissue infec-tions was higher among the patients with HAI than among the patients with CAI(P=0.047).CRKP strains cau-sing HAI showed the highest isolation rate(33.33％)in catheter specimens,and the isolation rate of CRKP strains in pus specimens was higher among the HAI patients than among the CAI patients(P=0.011).The isola-tion rate of CRKP strains in sputum specimens of the CAI patients raised four times in 2023 as compared with that in 2022.The drug resistance rates of the CRKP strains to 25 types of antibiotics were relatively high and showed upward trends;the drug resistance rate of the HAI-KPN strains to imipenem was 48.78％,higher than 7.09％of the CAI-KPN strains(P＜0.001),and there were no significant differences in the drug resistance rates to other carbapenems between the CAI-KPN strains and the HAI-KPN strains.CONCLUSIONS The isolation rates of the CRKP strains causing the HAI and CAI are increasing year by year.The clinical invasive procedures and community-acquired respiratory tract infections are the key points for prevention and control.It is necessary to in-tensify the hospital-community cooperative prevention and control system based on the isolation rates and drug re-sistance rates of the CRKP strains,and take comprehensive prevention and control measures so as to curb the transmission of the drug-resistant strains.

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 observe the detection and drug resistance of carbapenem-resistant Klebsiella pneumoni-ae(CRKP)strains causing hospital-acquired infections(HAI)and community-acquired infections(CAI)in recent years so as to provide bases for prevention and control of CRKP infection and reasonable clinical use of antibiotics.METHODS A total of 3444 patients who were diagnosed with Klebsiella pneumonia infection and were hospitalized in the 2nd Affiliated Hospital of Fujian Medical University from Jan.1,2017 to Dec.31,2023 were recruited as the research subjects.Totally 230 patients with CRKP infection were chosen based on the result of drug susceptibility testing,73 of whom had HAI,and 157 had CAI.The isolation rate of CRKP strains,popula-tion distribution,specimens sources and drug resistance rates were observed and compared between the patients with HAI and the patients with CAI.RESULTS The total isolation rate of CRKP strains was 6.68％(230/3444).There was no difference in the sex of the patients with CRKP infection between the HAI patients and the CAI patients,however,the isolation rate of the CRKP strains from the patients aged between 18 and 45 years old was higher in the HAI group than in the CAI group(P＜0.05).The isolation rates of CRKP strains causing the two types of infections increased year by year,showing a remarkable increasing amplitude in 2022-2023,with the HAI increasing from 9.33％to 20.67％,the CAI increasing from 5.54％to 15.03％.The lower respiratory tract,urinary tract and bacteremia were the most common infection sites,the detection rate of soft tissue infec-tions was higher among the patients with HAI than among the patients with CAI(P=0.047).CRKP strains cau-sing HAI showed the highest isolation rate(33.33％)in catheter specimens,and the isolation rate of CRKP strains in pus specimens was higher among the HAI patients than among the CAI patients(P=0.011).The isola-tion rate of CRKP strains in sputum specimens of the CAI patients raised four times in 2023 as compared with that in 2022.The drug resistance rates of the CRKP strains to 25 types of antibiotics were relatively high and showed upward trends;the drug resistance rate of the HAI-KPN strains to imipenem was 48.78％,higher than 7.09％of the CAI-KPN strains(P＜0.001),and there were no significant differences in the drug resistance rates to other carbapenems between the CAI-KPN strains and the HAI-KPN strains.CONCLUSIONS The isolation rates of the CRKP strains causing the HAI and CAI are increasing year by year.The clinical invasive procedures and community-acquired respiratory tract infections are the key points for prevention and control.It is necessary to in-tensify the hospital-community cooperative prevention and control system based on the isolation rates and drug re-sistance rates of the CRKP strains,and take comprehensive prevention and control measures so as to curb the transmission of the drug-resistant strains.

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 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.

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.