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 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 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 effects of oral probiotics on gut microbiota diversity,colony structure,and intergroup differences in mice with subcutaneous colon cancer tumors,based on 16S rRNA sequencing technology.Methods Twenty-four 6-week-old male BALB/c mice were divided randomly into normal control group(NC group,n = 8),model group(M group,n = 8),and probiotic + model group(PM group,n = 8)after adaptive feeding for 1 week.Mice in the PM group were given 200 μL probiotic mixed solution(Bifidobacterium longum and Lactobacillus delbrueckii subsp.bulgaricus mixed lyophilized powder,2×108 colony-forming units)by gavage three times/week for 7 weeks,while the M group and PM group received 200 μL normal saline.At 10 weeks old,0.2 mL CT26.WT cell suspension(1×107/mL)was inoculated subcutaneously into the left hind limbs of M group and PM group,while NC group were inoculated with 0.2 mL normal saline.The general state of mice was observed,the growth of subcutaneous tumor was monitored,and the changes of intestinal flora structure were detected by 16S rRNA sequencing.Results The subcutaneous tumors of the M group were prominent,and the subcutaneous tumor volume and weight of the PM group were significantly reduced(P<0.05).Compared with NC group,Alpha diversity index was lower in the M group,and a significant difference of Beta diversity inter groups(P<0.01).And supplementation of probiotics had a certain effect on gut microbiota diversity in the M group.Compared with M group,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Bacteroides were higher in the PM group,while the relative abundance of Firmicutes,Desulfobacterota,Lachnospiraceae_NK4A136_group,Alistipes were lower in the PM group.LEfSe analysis showed that Muribaculaceae and Bacteroides in the PM group were different species with high abundance(LDA values>4).Conclusions Oral probiotics may improve the gut microbiota by increasing the relative abundance of beneficial Muribaculaceae and Bacteroides in subcutaneous tumors in mice with colon cancer.

Objective    To evaluate the safety and efficacy of peripheral cannulation for cardiopulmonary bypass (CPB) in patients with reoperation of congenital heart disease. Methods    The perioperative data of patients with congenital heart disease who underwent reoperation in Fuwai Hospital from 2019 to 2020 were retrospectively collected. They were divided into two groups according to the cannulation methods: a central group and a peripheral group. The prognosis of the patients was analyzed. Results     A total of 80 patients were collected, including 43 patients in the central group, and 37 pateints in the peripheral group. In the central group, the median age was 18 (14, 32) years, and 21 patients were male. The median age of the peripheral group was 16 (10, 27 ) years, and 18 patients were male. The CPB time in the peripheral group was 201 (164, 230) min, which was longer than that in the central group [143 (97, 188 ) min, P<0.001]. The lactate after CPB in the peripheral group was statistically higher than that in the central group [2 (1, 2 ) mmol/L vs. 1 (1, 1) mmol/L, P=0.002]. The dosage of albumin use during CPB in the peripheral group was statistically higher than that in the central group [10 (0, 20) g vs. 0 (0, 0) g, P=0.004]. There was no statistical difference in the postoperative dosage of red blood cells use [0 (0, 2) U vs. 0 (0, 0) U, P=0.117], mechanical ventilation time [14 (11, 19) h vs. 13 (10, 15) h, P=0.296], ICU stay time [43 (23, 80) h vs. 40 (20, 67) h, P=0.237] or postoperative hospital stay time [10 (7, 12) d vs. 8 (7, 10) d, P=778] between the two groups. Conclusion    It’s safe and efficient to establish CPB through peripheral cannulation in patients with complex congenital heart disease undergoing reoperation.

Homeostatic synaptic plasticity is an important negative feedback regulation mechanism that maintains the functional stability of the nervous system, acting by regulating the release of presynaptic neurotransmitters or interfering with the synthesis of postsynaptic receptors. A series of studies have demonstrated strong links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric disorders, including autism spectrum disorder, intellectual disability, schizophrenia, fragile X syndrome, etc. In-depth understanding of homeostatic synaptic plasticity at cellular and molecular levels may help finding new targets and therapies for treatment of these related diseases. In this review, we explore the possible mechanisms of synaptic homeostasis regulatory system in neurological diseases as follows.

[Objective]To investigate the effect of simvastatin on the osteoclast and the focal resorptin of calvaria bone.[Method]Animal model of calvaria bone resorption was induced by parathyroid hormone-related peptide in mice.[Result]Simvastatin on the dose of 10,20 mg/kg/d could inhibit the resorption of calvaria bone and the formation of osteoclast,while,no significant inhibition was observed on the low dose(0,5 mg/kd/d).[Conclusion]Simvastation can effectively inhibit the resorption of focal bone in mice.It may provide an important strategy in treatment of diseases involved focal bone resorption.

[Objective]To study the effect of simvastatin in the osteoclastic resorption stimulated by PTHrP and murine bone anabolism in vitro.[Method]The bone resorption activities of the osteoclast stimulated by PTHrP were evaluated after treatment with simvastatin for 8 days in vitro;the concentration of Ca~(2+) in the supernatant was also detected by atomic absorption spectrometer.The concentration of ALP and Ca~(2+) of the supematant in murine calvarial organ culture were detected.The histology of calvaria was observed.[Result]Simvastatin greatly inhibited the osteoclastic bone resorption stimulated by PTHrP in vitro and reduced the release of Ca~(2+).Simvastatin increased the ALP activities and bone mineralization of murines calvarial organ culture in vitro.[Conclusion]Simvastatin may inhibit the osteoclasric resorption stimulated by PTHrP and promote osteoblast differentiation and bone mineralization in vitro,thus play an important role in the prevention and treatment of osteoporosis.

Objective:To study the effect of simvastatin on PTHrP stimulated osteoclastic resorption of murine calvarium and bone anabolism in vitro. Methods:Osteoclasts were isolated from bone marrow of Balb/C mice,cultured and identified.Calvaria of the new born Balb/C mice were cultured with PTHrP at 45 ng/ml and/or simvastatin at 10~ -7 -10~ -5 mol/L for 8 d.Ca~ 2+ and ALP in the culture supernatent were measured by atom spectrophotometer and automatic biochemical analyzer respectively.The bones were examined histologically.Results:Simvastatin at 10~ -7 -10~ -5 mol/L inhibited osteoclast formation and the osteoclastic bone resorption stimulated by PTHrP in vitro and reduced the release of Ca~ 2+ from the cultured osteoclasts in a dose-dependent manner. Simvastatin increased the ALP activities and bone mineralization of murines calvaria cultured in vitro. Conclusions:Simvastatin may inhibit the osteoclasric resorption stimulated by PTHrP and promote bone mineralization in vitro.