Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective To investigate the effect and mechanism of curculigoside(CUR)on hippocampal neuron injury in epileptic rats.Methods Forty-eight rats were selected,and the epileptic rat models were established by induction with 35 mg/kg pentylenetetrazol.The epileptic rats were randomly divided into the epilepsy group,the epilepsy+low-dose CUR group(the epilepsy+CUR-L group),the epilepsy+high-dose CUR group(the epilepsy+CUR-H group),and the epilepsy+CUR-H+PI3K activator 740Y-P group(the epilepsy+CUR-H+740Y-P group),with 12 rats in each group.Another 12 rats that were intraperitoneally injected with the same amount of normal saline were taken as the control group.Four weeks after administration,the behavioral changes of rats in each group were observed.Nissl staining was applied to determine the neuronal changes in hippocampal tissue.Immunohistochemistry was applied to detect the number of microglia in hippocampal tissue.ELISA was applied to detect the levels of interleukin-6(IL-6),IL-1β,and gamma-aminobutyric acid(GABA)in hippocampal tissue.TUNEL staining was applied to analyze the level of neuronal apoptosis in hippocampal tissue.Western blot was applied to detect the phosphorylation levels of PI3K,Akt and mTOR in hippocampal tissue.Results Compared with the control group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy group were obviously increased(P<0.05),while the level of GABA in hippocampal tissue was obviously reduced(P<0.05),and the arrangement of neurons in hippocampal tissue was disordered,with neuronal loss.Compared with the epilepsy group,the Racine score,and the frequency of epileptic seizures in rats,and the number of microglia,levels of IL-6,levels of IL-1β,the apoptosis rates of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-L group and the epilepsy+CUR-H group were significantly decreased(P<0.05),while the levels of GABA in hippocampus tissue were significantly increased(P<0.05),the loss and necrosis of neurons in hippocampus tissue were decreased,and the disorder of cell arrangement was improved.Compared with the epilepsy+CUR-H group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-H+740Y-P group were significantly increased(P<0.05),while the level of GABA in hippocampus tissue was significantly decreased(P<0.05),the loss and necrosis of hippocampal neurons increased,and the cell arrangement was disordered.Conclusion CUR may reduce hippocampal neuron damage in epileptic rats by downregulating the PI3K/Akt/mTOR signaling pathway.

Articular cartilage is a crucial tissue structure in humans.With ongoing exploration of joint tissue structure and the emergence of innovative biotechnological organoids,various sources of stem cells can be selected for induction to differentiate into articular cartilaginous organoids based on the articular cartilage tissue structure,which can be applied to the treatment of cartilage defects,drug testing,and precision medicine and biological development.This article presents a review of the research progress concerning articular cartilaginous organoids,in order to provide a reference for clinical practice.

Objective To investigate the differences in physical fitness and physiological indexes of male soldiers stationed at different altitudes and to analyze the determinants of physical fitness of these soldiers.Methods A total of 13 648 male soldiers at different altitudes were included,whose results of annual military physical assessment and physiological indexes in 2023 were collected and comparatively analyzed.Results The 3000-meter running performance,30-meter × 2 serpentine running performance and resting blood oxygen saturation of high-altitude soldiers gradually declined with the increase of altitudes.The pull-up performance dropped significantly when the altitude＞2000 m.Soldiers ≥30 years old demonstrated a marked decline in physical fitness across different training programs.Moderate altitude acclimatization was conduciveto the recovery of physical fitness of soldiers,while exposure to high-altitude environment ≥5 years led to overall deterioration.Conclusion The high-altitude environment significantly impacts the aerobic endurance,speed,agility,and strength of soldiers.Altitude ≥4000 m,age ≥30 years,and prolonged exposure ≥5 years may contribute to the decline in physical fitness of soldiers.

Systems theory emphasizes the multidimensional interactions among elements within a system and their dynamic changes over time， to provide a crucial theoretical framework and analytical tools for investigating the onset and evolution of mental disorders. From a complex systems perspective， this review examines the influence of multi-factor interaction networks on the development of depressive and anxiety disorders， and reviews research progress on early-warning signals based on dynamical systems theory for symptom prediction. This study specifically examines two system-oriented psychological interventions： acceptance and commitment therapy （ACT） and mindfulness-based intervention for emotional distress （MIED）. Building upon their respective psychopathological models， this review elucidates the multifactorial interaction of depressive and anxiety disorders at a transdiagnostic level， and further analyzes the mechanism through which core intervention strategies adjust the key factors to achieve clinical improvement. ［Funded by General Projects of National Natural Science Foundation of China （number， 32371138）］

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Objective To explore the characteristics of military training injuries in high-altitude troops and determine the possible impact of daily diet on these training injuries in order to provide theoretical reference for scientific training and medical service support for high-altitude troops.Methods A cross-sectional scheme was adopted in this study.A self-designed Military Training Injury Questionnaire for Plateau Troops was used to survey the officers and soldiers from resident high-altitude troops in July 2024 for their training injuries,daily diet,and other situations.The obtained data were statistically analyzed.Results Among the 3 655 participants,the incidence of military training injuries was 17.87%.The subject with highest incidence was physical training(45.94%),the most common season was winter(31.39%).The most common sites of injury were waist(28.48%),knees(22.21%),and ankles(18.07%),and the most common types were sprains(28.48%),chronic fatigue injuries(18.38%)and strains(12.25%).The intake amounts of coarse grains and potatoes,bean products,aquatic products and nuts were relatively low in the daily diet of high-altitude troops.Multivariate logistic regression analysis found intake of fruit(OR=0.625,95%CI:0.508～0.768,P<0.001)and of nut(OR=0.759,95%CI:0.654～0.879,P<0.001)were correlated with the occurrence of training injury.Conclusion The occurrence pattern of military training injuries in high-altitude troops in this survey is basically consistent with that of previous reports,but the incidence rate is slightly decreased.Regular consumption of fruit and nut may be protective factors for the occurrence of training injuries.

Objective To investigate the effect and mechanism of curculigoside(CUR)on hippocampal neuron injury in epileptic rats.Methods Forty-eight rats were selected,and the epileptic rat models were established by induction with 35 mg/kg pentylenetetrazol.The epileptic rats were randomly divided into the epilepsy group,the epilepsy+low-dose CUR group(the epilepsy+CUR-L group),the epilepsy+high-dose CUR group(the epilepsy+CUR-H group),and the epilepsy+CUR-H+PI3K activator 740Y-P group(the epilepsy+CUR-H+740Y-P group),with 12 rats in each group.Another 12 rats that were intraperitoneally injected with the same amount of normal saline were taken as the control group.Four weeks after administration,the behavioral changes of rats in each group were observed.Nissl staining was applied to determine the neuronal changes in hippocampal tissue.Immunohistochemistry was applied to detect the number of microglia in hippocampal tissue.ELISA was applied to detect the levels of interleukin-6(IL-6),IL-1β,and gamma-aminobutyric acid(GABA)in hippocampal tissue.TUNEL staining was applied to analyze the level of neuronal apoptosis in hippocampal tissue.Western blot was applied to detect the phosphorylation levels of PI3K,Akt and mTOR in hippocampal tissue.Results Compared with the control group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy group were obviously increased(P<0.05),while the level of GABA in hippocampal tissue was obviously reduced(P<0.05),and the arrangement of neurons in hippocampal tissue was disordered,with neuronal loss.Compared with the epilepsy group,the Racine score,and the frequency of epileptic seizures in rats,and the number of microglia,levels of IL-6,levels of IL-1β,the apoptosis rates of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-L group and the epilepsy+CUR-H group were significantly decreased(P<0.05),while the levels of GABA in hippocampus tissue were significantly increased(P<0.05),the loss and necrosis of neurons in hippocampus tissue were decreased,and the disorder of cell arrangement was improved.Compared with the epilepsy+CUR-H group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-H+740Y-P group were significantly increased(P<0.05),while the level of GABA in hippocampus tissue was significantly decreased(P<0.05),the loss and necrosis of hippocampal neurons increased,and the cell arrangement was disordered.Conclusion CUR may reduce hippocampal neuron damage in epileptic rats by downregulating the PI3K/Akt/mTOR signaling pathway.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.