Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

The rapid progress in cancer immunology and immunotherapy has transformed the paradigm of surgical treatment for hepatobiliary malignancies. Comprehensive treatment strategies based on immunotherapy have been applied for downstaging and conversion treatment, allowing more advanced-stage patients to undergo radical or curative surgery; it has also become a new approach for neoadjuvant and adjuvant therapy. The following points deserve attention: (1) The “dual nature” of surgical treatment：it can “cure” primary malignancies, but also induce perioperative immune suppression through various mechanisms and promote postoperative metastatic recurrence. Minimizing surgical stress is the theoretical basis and advantage of the minimally invasive concept in surgical oncology. (2) Targeting the “surgical immune suppression” is a novel way to combat postoperative metastatic recurrence: the combination of neoadjuvant and adjuvant immunotherapy is a new trend. (3) Traditional lymph node dissection may impair immune responses and immunotherapy outcomes; selective preservation of regional lymph nodes can be a promising approach. For certain subgroups of patients, preoperative therapy leading to complete remission (immunological ablation) raises the possibility of organ-sparing and de-escalation of surgery.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

The rapid progress in cancer immunology and immunotherapy has transformed the paradigm of surgical treatment for hepatobiliary malignancies. Comprehensive treatment strategies based on immunotherapy have been applied for downstaging and conversion treatment, allowing more advanced-stage patients to undergo radical or curative surgery; it has also become a new approach for neoadjuvant and adjuvant therapy. The following points deserve attention: (1) The “dual nature” of surgical treatment：it can “cure” primary malignancies, but also induce perioperative immune suppression through various mechanisms and promote postoperative metastatic recurrence. Minimizing surgical stress is the theoretical basis and advantage of the minimally invasive concept in surgical oncology. (2) Targeting the “surgical immune suppression” is a novel way to combat postoperative metastatic recurrence: the combination of neoadjuvant and adjuvant immunotherapy is a new trend. (3) Traditional lymph node dissection may impair immune responses and immunotherapy outcomes; selective preservation of regional lymph nodes can be a promising approach. For certain subgroups of patients, preoperative therapy leading to complete remission (immunological ablation) raises the possibility of organ-sparing and de-escalation of surgery.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective To investigate the effects of Jianpi Huatan Fang on lipid metabolism and expression levels of FOXO1 and PDK4 in rats with polycystic ovary syndrome(PCOS)and insulin resistance(IR).Methods Forty female rats were divided randomly into a blank control group(n=10)and a model group(n=30).A PCOS-IR rat model was established using a high-fat diet(8 weeks)combined with letrozole(added at weeks 4～8).Thirty successfully modeled rats were then divided randomly into a model control group,a Jianpi Huatan Fang group(11.07 g/kg),and a metformin group(0.2 g/kg)(n=10 rats per group).Drug intervention was given for 4 weeks.The general status,Traditional Chinese medicine syndrome score,and weight changes were observed in each group.Histopathological changes in the ovary were detected by hematoxylin and eosin staining.Fasting blood glucose and blood lipids were measured using a blood biochemical analyzer.Levels of sex hormones including follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),estradiol(E2),and insulin were determined by enzyme linked immunosorbent assay and changes in the expression of FOXO1 and PDK4 in the ovaries were determined by Western Blot and real-time fluorescence quantitative polymerase chain reaction.Results Rats in the model control group exhibited symptoms of spleen deficiency and phlegm-dampness and showed significant weight gain,sex hormone disorders,polycystic ovarian changes,and dysregulation of glucose and lipid metabolism,compared with rats in the blank control group(P＜0.01).In addition,weight increase was slower in rats in the Jianpi Huatan Fang group and the metformin group compared with that in the model control group,and follicle development was improved.Serum LH,T,LH/FSH,fasting blood glucose,insulin,homeostatic model assessment for IR,cholesterol,triglycerides,and low-density lipoprotein cholesterol decreased,estradiol and FSH increased,and ovarian FOXO1 and PDK4 mRNA and protein expression levels were down regulated in the Jianpi Huatan Fang group compared with the findings in the model control group(P＜0.05,P＜0.01).Serum high-density lipoprotein cholesterol content was also increased,but the difference was not significant(P＞0.05).Conclusions Jianpi Huatan Fang can effectively regulate sex hormone secretion,improve ovarian reproductive function,and regulate glucose and lipid metabolism in obese PCOS-IR rats,possibly via inhibiting the FOXO1/PDK4 pathway.

Objective:To investigate the effects of Jianpi Huatan Prescription on a rat model of polycystic ovary syndrome (PCOS) with insulin resistance (IR) induced by letrozole combined with high fat diet based on the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) signaling pathway; To discuss its mechanism.Methods:A total of 40 SD female rats were divided into model group (30 rats) and blank group (10 rats). The model group rats were fed with high-fat feed from the first week of modeling for 8 consecutive weeks, and from the fourth week onwards, were given a daily gavage of letrozole solution for 5 consecutive weeks; the blank group was fed normally, and from the 4th week onwards, an equal amount of sodium carboxymethyl cellulose solution was administered. After the completion of modeling, the modeling group was divided into Jianpi Huatan Prescription group, Metformin group, and model group according to random number table method. The Jianpi Huatan Prescription group and the metformin group were given corresponding drug interventions, while the other two groups were simultaneously administered an equal amount of physiological saline for a total of 4 weeks. Ovarian morphological changes were observed using HE staining; intraperitoneal glucose tolerance test (IPGTT) was used to detect glucose tolerance in rats; Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E 2), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (FINS) in rats; Real time fluorescence quantitative PCR and Western blot techniques were used to detect changes in LKB1, AMPK mRNA and protein expression in the LKB1/AMPK signaling pathway of rat ovarian tissue. Results:Compared with the model group, the polycystic changes in the ovaries of rats in the Jianpi Huatan Prescription group were improved, and the growth rate of body weight decreased. The levels of FBG, FINS, HOMA-IR, and IPGTT decreased ( P<0.05 or P<0.01), while serum FSH and HDL-C levels were significantly up-regulated ( P<0.05 or P<0.01). The levels of T, LH, LH/FSH, TC, TG, and LDL-C decreased ( P<0.05 or P<0.01); The mRNA and protein expression levels of LKB1 and AMPK in ovarian tissue increased ( P<0.05). Conclusion:Jianpi Huatan Prescription can improve PCOS-IR in rats caused by the combination of letrozole and high-fat diet, regulate various levels of sex hormones, and improve glucose and lipid metabolism disorders by regulating the LKB1/AMPK signaling pathway, which has a repairing effect on polycystic ovary disease in rats.