Objective To investigate the effect of asperuloside(ASP)on the malignant progression and chemotherapy resistance of hepatocellular carcinoma(HCC)cells by regulating the supersonic hedgehog(SHH)/glioma-associated oncogene homolog 1(GLI1)signaling pathway.Methods The expression of SHH and GLI1 protein in human hepatocellular carcinoma cell line(SMMC-7721)/adriamycin(ADM)and SMMC-7721 cell line were detected by Western blot(WB).The HCC drug-resistant cell line SMMC-7721/ADM were divided into Control group,ADM group,L-ASP group(1 mmol/L ASP),M-ASP group(2 mmol/L ASP),H-ASP group(3 mmol/L ASP),ASP+PM group(1 μmol/L SHH/GLI1 signaling pathway activator PM).Ex-cept for Control group,5 μg/mL ADM was added to each group.The effect of ASP on the proliferation of SMMC-7721/ADM cells was detected by cell counting kit-8(CCK8)assay and plate cloning assay.The effect of ASP on the invasion and migration of SMMC-7721/ADM cells were detected by Transwell assay.The effect of ASP on the apoptosis of SMMC-7721/ADM cells was detected by flow cytometry.The expression of SHH,GLI1,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-9(MMP-9)and B cell lymphoma-2 associated X protein(Bax)in SMMC-7721/ADM cells were detected by WB.Animal experiments verified the effect of ASP on the growth of HCC xenografts and the expression of SHH/GLI1 signaling pathway proteins.Results The expression of SHH and GLI1 in SMMC-7721/ADM cells were higher than those in SMMC-7721 cells(P＜0.05).L-ASP group,M-ASP group and H-ASP group decreased the proliferation,migration and in-vasion of SMMC-7721/ADM cells in a dose-dependent manner,decreased the expression of SHH,GLI1,PCNA and MMP-9,and promoted cell apoptosis and Bax expression(P＜0.05).SHH/GLI1 signaling pathway acti-vator PM could reverse the inhibitory effect of H-ASP treatment on malignant progression and chemotherapy resistance of SMMC-7721/ADM cells(P＜0.05).ASP could inhibit the growth of HCC transplanted tumor and the expression of SHH and GLI1(P＜0.05).Conclusion ASP can inhibit the malignant progression of HCC cells and enhance the sensitivity of chemotherapy,which may be achieved by inhibiting the SHH/GLI1 signaling pathway.

BackgroundIn schizophrenia， a subset of patients may progress to treatment-resistant schizophrenia owing to inadequate response to standard antipsychotic therapies， resulting in profound impairments in cognitive and social functioning alongside a cumulative burden of adverse drug reactions during the prolonged treatment. Currently， evidence supporting the use of blonanserin for treatment-resistant schizophrenia remains limited. ObjectiveTo investigate the efficacy and safety of blonanserin in the treatment of treatment-resistant schizophrenia， so as to provide references for clinical management of this condition. MethodsA total of 43 inpatients fulfilling the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria for treatment-resistant schizophrenia were consecutively recruited from Taiyuan Psychiatric Hospital from September 2024 to January 2025. Subjects were assigned to either the study group （n=21） or the control group （n=22） using the random number table method. The study group received blonanserin at a daily dosage ranging from 8 to 24 mg， while the control group was administered amisulpride at a daily dosage from 400 to 1 200 mg. At baseline and at the end of the 4^th and 8^th week of treatment， the Positive and Negative Symptom Scale （PANSS） and the Personal and Social Performance scale （PSP） were used to access patients' psychotic symptoms and social functioning， respectively. Cognitive function was evaluated using the Hopkins Verbal Learning Test （HVLT）， the Stroop Color-Word Test （SCWT）， the Trail Making Test （TMT）， the Digit Span Test （DST）， and the Digit Symbol Substitution Test （DSST）. During the treatment process， treatment-related adverse reactions were recorded between two groups. ResultsSignificant time effects were found in PANSS total scores， as well as its positive symptom， negative symptom， and general psychopathological subscale scores （F=186.505， 149.318， 135.671， 416.744， P<0.01）. The group-by-time interaction effect was significant in PANSS total scores and general psychopathological subscale scores （F=3.483， 4.318， P<0.05）. At the end of the 8^th week， the study group exhibited lower general psychopathological subscale scores and the PANSS total scores compared to the control group， with statistically significant differences （t=-2.106， -2.429， P<0.05）. Significant group effects were detected in HVLT scores， Stroop word scores and Stroop color scores （F=6.720， 7.921， 11.383， P<0.05 or 0.01）. The group-by-time interaction effect for Stroop word scores， Stroop interference scores， TMT scores and DSST scores were statistically significant （F=3.571， 4.095， 3.463， 37.000， P<0.05 or 0.01）. At the end of the 8^th week， the DSST score of the study group was higher than that of the control group （t=2.074， P<0.05）. For PSP scores， significant time effect， group effect and group-by-time interaction effect were all observed （F=433.710， 4.463， 10.491， P<0.05 or 0.01）. At the end of the 8^th week， the study group reported higher PSP score compared to the control group， with a statistically significant difference （t=3.451， P<0.05）. No significant difference in the incidence of adverse reactions was exhibited between the two groups （P>0.05）. ConclusionBlonanserin demonstrates efficacy comparable to amisulpride in ameliorating positive and negative symptoms in patients with treatment-resistant schizophrenia. Notably， blonanserin exhibits a superior efficacy to amisulpride in improving general psychopathological symptoms， cognitive and social functioning， while both agents show comparable safety profiles. （www.chictr.org.cn number： ChiCTR2400094222）

ObjectiveTo observe the clinical efficacy of Tongfu Kuanzhong decoction （TFKZ） in the treatment of constipation-predominant irritable bowel syndrome （IBS-C） with spleen deficiency and Qi stagnation and its effects on anorectal manometry and colonic electrical activity parameters. MethodsSixty-four patients with IBS-C of the spleen deficiency and Qi stagnation type were included as research subjects and were randomized into the observation group （thirty-two cases） and control group （thirty-two cases）. The control group was orally administered mosapride citrate tablets， and the observation group was orally administered TFKZ. Both groups were treated for 4 weeks. The traditional Chinese medicine （TCM） syndrome scores， patient assessment of constipation symptoms （PAC-SYM） score， general anxiety disorder-7 （GAD-7） score， patient health questionnaire-9（PHQ-9）score， anorectal manometry， and colonic electrical activity parameters were observed before and after treatment in the two groups. ResultsThe total points of TCM syndromes were significantly lower in both groups after treatment （P<0.01） and lower in the observation group （P<0.05）. The fecal symptoms， rectal symptoms， abdominal symptoms， and total symptom scores of the patients in both groups were significantly decreased after treatment （P<0.01）， and the rectal symptoms， abdominal symptoms， and total symptom scores of the observation group were lower （P<0.05，P<0.01）. In both groups， the forced anal residual pressure and the initial rectal sensation threshold decreased after treatment （P<0.05，P<0.01）， and forced anal residual pressure in the control group was lower （P<0.01）. After treatment， the GAD-7 and PHQ-9 scores of patients in both groups decreased significantly （P<0.01）， and the GAD-7 score of the observation group was significantly lower （P<0.01）. After treatment， the average wave amplitude at different time points of each lead increased significantly in both groups， compared with that before treatment （P<0.01）. The average wave amplitude of each lead of the ascending colon， descending colon， sigmoid colon， and rectum in the observation group at 5 min before the meal and 10 min after the meal， as well as that of the ascending colon and rectum at 20 min and 30 min after the meal， was higher than that of the control group （P<0.05）. ConclusionTFKZ is effective in the treatment of IBS-C. Its mechanism may be related to the regulation of colonic function by down-regulating the forced anal residual pressure and the initial rectal sensation threshold and up-regulating the amplitude and frequency of intestinal electrical activity in each intestinal segment of the colon.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Objective:To explore the clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective To explore the effect of aerobic exercise on sarcopenia in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism.Methods Forty-eight SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group(group NC,n=12),a normal control+aerobic exercise group(group NA,n=12),a CT26 tumor-associated sarco-penia group(group TS,n=12)and a CT26 tumor-associated sarcopenia+aerobic exercise group(group TSA,n=12).After a 2-week adaptive exercise period,CT26 cell suspension(0.2 mL,1×107 cells/mL)was subcutaneously injected into the dorsal region of mice in group TS and group TSA,while group NC and group NA were inoculated with 0.2 mL normal saline.One day later,group NA and group TSA underwent a 4-week aerobic treadmill running intervention(14 m/min,60 min/day,6 days/week).If a mouse failed to complete the target intensity on a given day,its running speed was reduced by 20%the following day.Moreover,group NA and group TSA received no exercise interven-tion.General health status of all groups was monitored throughout the study.The forelimb gripping force,rotarod walking time and the cross-sectional area of gastrocnemius muscle fibers were measured.Moreover,the ultrastructural changes of gastrocnemius were observed by transmission electron micro-scope,while the cecum contents were observed by 16S rRNA sequencing.Meanwhile,the pathological morphological changes of small intestine wall were observed using HE,while the contents of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and lipopoly saccharide(LPS)of serum and gastrocnemius muscle were determined by using ELISA.Moreover,small intestine zonula occludens-1(ZO-1),Occludin and muscle ring finger 1(MuRF1),muscle atrophy F-box(MAF-bx),Toll-like receptor 4(TLR4)/myeloid differentiation factor 8(MyD88)/nuclear transcription factor-κB(NF-κB)signal pathway related proteins expression levels of gastrocnemius muscle,as well as muscle ring finger 1(MuRF1)and muscle atrophy F-box(MAF-bx)were detected using Western blot.Results(1)Subcutaneous tumors were prominent in group TS.The forelimb gripforce,wet weight and cross-sectional area of gastrocnemius,and rotarod walking time in group TS at the 5th and 6th weekends were significantly lower than group NC(P<0.01),while the relative expression levels of MuRF1 and MAF-bx proteins in the gastrocnemius muscle in group TS were significantly higher than the latter group(P<0.05,P<0.01).Moreover,transmission electron microscopy revealed sparse and dis-organized muscle fiber arrangement in group TS,with visible Z-lines but indistinct M-lines,as well as shortened,poorly defined,and thin sarcomeres.(2)The group TSA exhibited significantly higher α-diversity indices(Shannon,Chao1,and Observed species)in gut microbiota compared to group TS(P<0.05,P<0.01,P<0.05),while the β-diversity differed to some extent between the two groups.At phylum level,the F/B ratio was lower in group NA than that group NC,with that of group TSA low-er than group TS.At genus level,the relative abundances of Muribaculaceae,Bacteroides,Roseburia,and Alistipes in group NA were higher than group NC,and those of Alloprevotellaand Helicobacter were significantly lower,while those of Muribaculaceae,Lachnospiraceae_NK4A136_group,Roseburia,Bacteroides,Lachnospiraceae_UCG-001 of group TSA were significantly higher than group TS.Nota-bly,Roseburia and Alistipes were the most significantly enriched genera in group TSA and group TS(LDA score>4 for both).(3)The inflammatory cells of the small intestine wall in group TSA signifi-cantly reduced than those in group TS(P<0.05).Moreover,the expression level of ZO-1 proteins in the small intestine wall were significantly higher in group NA than group NC,and that of ZO-1 and Occludin proteins in the small intestine wall was significantly higher in group TSA than those in group TS(P<0.05).(4)The group NA exhibited significantly lower LPS concentrations in the gastrocne-mius muscle compared to group NC(P<0.05).Similarly,the group TSA showed reduced LPS levels in both serum and gastrocnemius compared to group TS(P<0.05).The relative protein expression of p-IκBα and p-NF-κB p65 significantly decreased in group TSA compared to group TS(P<0.05).The group TS displayed elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-1β)in serum and gastrocnemius compared to group NC(P<0.01,P<0.05).The group TSA demonstrated significantly lower levels of TNF-α and IL-6 in these tissues in comparison with group TS(P<0.05,P<0.01).Conclusion Aerobic exercise can improve gut microbiota α diversity,adjusting its composition,improv-ing intestinal mucosal barrier function,reducing the LPS-induced pro-inflammatory response,and delay-ing skeletal muscle atrophy.The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle,which has a positive effect on Gut-Muscle Axis.

Objective To explore the effect of aerobic exercise on sarcopenia in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism.Methods Forty-eight SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group(group NC,n=12),a normal control+aerobic exercise group(group NA,n=12),a CT26 tumor-associated sarco-penia group(group TS,n=12)and a CT26 tumor-associated sarcopenia+aerobic exercise group(group TSA,n=12).After a 2-week adaptive exercise period,CT26 cell suspension(0.2 mL,1×107 cells/mL)was subcutaneously injected into the dorsal region of mice in group TS and group TSA,while group NC and group NA were inoculated with 0.2 mL normal saline.One day later,group NA and group TSA underwent a 4-week aerobic treadmill running intervention(14 m/min,60 min/day,6 days/week).If a mouse failed to complete the target intensity on a given day,its running speed was reduced by 20%the following day.Moreover,group NA and group TSA received no exercise interven-tion.General health status of all groups was monitored throughout the study.The forelimb gripping force,rotarod walking time and the cross-sectional area of gastrocnemius muscle fibers were measured.Moreover,the ultrastructural changes of gastrocnemius were observed by transmission electron micro-scope,while the cecum contents were observed by 16S rRNA sequencing.Meanwhile,the pathological morphological changes of small intestine wall were observed using HE,while the contents of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and lipopoly saccharide(LPS)of serum and gastrocnemius muscle were determined by using ELISA.Moreover,small intestine zonula occludens-1(ZO-1),Occludin and muscle ring finger 1(MuRF1),muscle atrophy F-box(MAF-bx),Toll-like receptor 4(TLR4)/myeloid differentiation factor 8(MyD88)/nuclear transcription factor-κB(NF-κB)signal pathway related proteins expression levels of gastrocnemius muscle,as well as muscle ring finger 1(MuRF1)and muscle atrophy F-box(MAF-bx)were detected using Western blot.Results(1)Subcutaneous tumors were prominent in group TS.The forelimb gripforce,wet weight and cross-sectional area of gastrocnemius,and rotarod walking time in group TS at the 5th and 6th weekends were significantly lower than group NC(P<0.01),while the relative expression levels of MuRF1 and MAF-bx proteins in the gastrocnemius muscle in group TS were significantly higher than the latter group(P<0.05,P<0.01).Moreover,transmission electron microscopy revealed sparse and dis-organized muscle fiber arrangement in group TS,with visible Z-lines but indistinct M-lines,as well as shortened,poorly defined,and thin sarcomeres.(2)The group TSA exhibited significantly higher α-diversity indices(Shannon,Chao1,and Observed species)in gut microbiota compared to group TS(P<0.05,P<0.01,P<0.05),while the β-diversity differed to some extent between the two groups.At phylum level,the F/B ratio was lower in group NA than that group NC,with that of group TSA low-er than group TS.At genus level,the relative abundances of Muribaculaceae,Bacteroides,Roseburia,and Alistipes in group NA were higher than group NC,and those of Alloprevotellaand Helicobacter were significantly lower,while those of Muribaculaceae,Lachnospiraceae_NK4A136_group,Roseburia,Bacteroides,Lachnospiraceae_UCG-001 of group TSA were significantly higher than group TS.Nota-bly,Roseburia and Alistipes were the most significantly enriched genera in group TSA and group TS(LDA score>4 for both).(3)The inflammatory cells of the small intestine wall in group TSA signifi-cantly reduced than those in group TS(P<0.05).Moreover,the expression level of ZO-1 proteins in the small intestine wall were significantly higher in group NA than group NC,and that of ZO-1 and Occludin proteins in the small intestine wall was significantly higher in group TSA than those in group TS(P<0.05).(4)The group NA exhibited significantly lower LPS concentrations in the gastrocne-mius muscle compared to group NC(P<0.05).Similarly,the group TSA showed reduced LPS levels in both serum and gastrocnemius compared to group TS(P<0.05).The relative protein expression of p-IκBα and p-NF-κB p65 significantly decreased in group TSA compared to group TS(P<0.05).The group TS displayed elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-1β)in serum and gastrocnemius compared to group NC(P<0.01,P<0.05).The group TSA demonstrated significantly lower levels of TNF-α and IL-6 in these tissues in comparison with group TS(P<0.05,P<0.01).Conclusion Aerobic exercise can improve gut microbiota α diversity,adjusting its composition,improv-ing intestinal mucosal barrier function,reducing the LPS-induced pro-inflammatory response,and delay-ing skeletal muscle atrophy.The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle,which has a positive effect on Gut-Muscle Axis.