Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

This study aims to screen the diagnostic biomarkers for fecal antigen of Echinococcus granulosus(E.granulosus)in dogs with high specificity and sensitivity.The sheep-derived EgPSC artificially infected dogs were collected,and the negative and positive fecal samples of dogs with E.granulosus were prepared by arecoline hydrobromide leakage method.Polyclonal antibody,negative fecal antigen-polyclonal antibody conjugates and positive fecal antigen-polyclonal antibody conju-gates were purified by ammonium sulfate precipitation and affinity chromatography,three groups of samples were detected by ELISA and Western blot,LC-MS/MS and bioinformatics analysis were performed on the three groups of samples.The positive fecal antigen-polyclonal antibody con-jugate was used as the treatment group,the polyclonal antibody and the negative fecal antigen-polyclonal antibody conjugates were used as the control groups to screen the unique peptides of the treatment group.ELISA and Western blot showed that only the positive fecal antigen-polyclonal antibody conjugates were positive.According to LC-MS/MS and bioinformatics analysis,11 unique peptides were screened out only in the treatment group.Among them,3 proteins were related to E.granulosus,namely dysferlin,integrator complex 9 and diagnostic antigen gp50,which were mem-brane-associated proteins,INT complex components and diagnostic antigens.This study has pre-liminarily screened out three candidate canine E.granulosus fecal antigen diagnostic markers,pro-viding a reference for further exploration of diagnostic standards for E.granulosus,screening of echinococcosis target genes,and vaccine development.

BACKGROUND:At present,there is a main kind of operation,which is represented by the proximal femoral nail antirotation,to treat femoral intertrochanteric fractures,but some sequelae still occur such as internal fixation loosening,failure,and nail withdrawal.We designed a new femoral neck spiral blade system to solve this problem,so we analyze the mechanical structure by the finite element method that can be regard as the theoretical basis for the system.OBJECTIVE:To compare the mechanical properties of the new femoral neck spiral blade system and the proximal femoral nail antirotation in the treatment of femoral intertrochanteric fracture by the finite element method.METHODS:Based on the finite element model of the femur,the A1.2 and A2.2 femoral intertrochanteric fracture models were established according to the AO fracture classification principle of 2018 edition.The models were fixed with the proximal femoral nail antirotation and the new internal fixation system,applying an axial load of 700,1 400,and 2 100 N above the femoral head.The mechanical characteristics of the two internal fixation methods were respectively compared and analyzed by observing the maximum equivalent stress and the maximum deformation of each group.RESULTS AND CONCLUSION:(1)The maximum equivalent stress of the new internal fixation group under different compressive loads was smaller than that of the proximal femoral nail antirotation group.(2)In the A1.2 fracture model,under different compression loads,the deformation of the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.113 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 2.017 mm between the two.(3)In the A1.2 fracture model,under different compressive loads,the maximum deformation of the spiral blade fixed by the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.062 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 1.891 mm between the two.(4)The results indicate that the new femoral neck spiral blade system has a lower internal fixation stress value compared to the proximal femoral nail antirotation,and a smaller displacement value of the femur after fixation and internal fixation.It can more effectively fix fractures and prevent the spiral blade from retracting or cutting out in the femoral neck.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Objective:To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors in the treatment of acute severe ulcerative colitis (ASUC).Methods:A retrospective cohort study was conducted. Patients with ASUC treated with JAK inhibitors at the First Affiliated Hospital of Air Force Medical University between January 2021 and March 2024 were enrolled. The primary endpoints were clinical response rate at 1 week and colectomy rate at 90 days. The secondary endpoints were clinical response rate and clinical remission rate at 8 weeks, and adverse events rate at 90 days.Results:A total of 15 patients with ASUC (7 men, 8 women; mean age, 42.47±9.92 years) were included. Eight patients were treated with upadacitinib, and 7 with tofacitinib. The clinical response rate at 1 week was 53.3% (8/15), the colectomy rate at 90 days was 20.0% (3/15), the clinical response rate at 8 weeks was 60.0% (9/15), and the clinical remission rate at 8 weeks was 33.3% (5/15). During the 90-day follow-up, only 1 patient (6.7%) treated with tofacitinib experienced a mild leukopenia.Conclusion:JAK inhibitors are effective for ASUC with the high safety.

BACKGROUND:Degenerative diseases caused by bone and muscle degeneration are major reasons for the decline in physical function and mobility,increased fragility fractures,and high mortality rates in the elderly,significantly affecting their health and quality of life.OBJECTIVE:To review the research progress in the mechanisms of muscle-bone interaction and the etiology,prevention,and treatment of related diseases.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature published from 2014 to 2024.The search terms were"muscle-bone crosstalk,musculoskeletal system,inter-tissue communication,myokines,osteokines,osteosarcopenia,sarcopenia,osteoporosis,bone regeneration,fibro-adipogenic progenitors"in Chinese and English.By reading the articles,we eliminated irrelevant,outdated,and poorly focused literature,and finally 94 articles were included for review.RESULTS AND CONCLUSION:Mechanical interaction,secretion factor interaction,and stem cell interaction between muscle and bone are crucial for the metabolism and regeneration regulation of the musculoskeletal system.Systemic interventions targeting biochemical signals of muscle factors(such as myostatin and irisin)and bone factors(such as nuclear factor-κB receptor-activating factor ligand and sclerostin)can improve the quality and function of skeletal muscle and bone,and have positive effects on fracture healing.In recent years,it has been found that related stem cells in the musculoskeletal system can interact,with the activation of muscle progenitor cells(such as fibro-adipogenic progenitors)having a significant impact on bone growth,repair,and regeneration.Research on the mechanisms of muscle-bone interaction can provide insights into the etiology,prevention,and treatment of related diseases.However,there are currently no effective clinical treatments for muscle-bone comorbidities,with most research still at the cellular and animal experiment stage.Therefore,extensive research is needed in the future to gradually move from experiments to clinical applications,developing more targeted therapies and drugs to better serve clinical needs.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.