1.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
2.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
3.Renal Protective Mechanism of Danggui Shaoyaosan in db/db Mice Based on RhoA/ROCK/NF-κB Signaling Pathway
Luyu HOU ; Yuanyuan ZHANG ; Wenjing SHI ; Shilong GUO ; Zixuan WANG ; Linlin ZHENG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):30-38
ObjectiveTo investigate whether Danggui Shaoyaosan (DSS) inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway, thereby delaying the progression of diabetic kidney disease (DKD) and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group, and forty 8-week-old db/db mice were randomly divided into the model group, DSS low-dose group (8.39 g·kg-1), DSS medium-dose group (16.77 g·kg-1), DSS high-dose group (33.54 g·kg-1), and irbesartan group (0.025 g·kg-1), with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration, changes in body weight, fasting blood glucose (FBG), and 24 hour urinary protein (24 h UTP) were observed. After 12 consecutive weeks of administration, hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species (ROS) in renal tissue were detected using the dihydroethidium (DHE) method. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were determined. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of RhoA, ROCK1, and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of fibronectin (FN), Collagen Ⅳ(Col Ⅳ), transforming growth factor-β1 (TGF-β1), RhoA, ROCK, and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed significantly increased body weight, FBG, and 24 h UTP levels (P<0.01), elevated serum IL-1β and IL-6 levels, enlarged glomerular volume, diffuse mesangial expansion, increased mesangial matrix, and marked collagen fiber proliferation in renal tissues. SOD activity was decreased, while MDA, ROS, RhoA, ROCK1, and NF-κB p65 mRNA expression levels were increased (P<0.01), and the protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 were also elevated (P<0.01). Compared with the model group, the DSS low-, medium-, and high-dose groups and the irbesartan group showed reductions in body weight, FBG, and 24 h UTP, decreased serum IL-1β and IL-6 levels, varying degrees of improvement in renal histopathology, increased SOD activity, decreased MDA levels, reduced ROS expression, and significantly downregulated RhoA, ROCK1, and NF-κB p65 mRNA expression (P<0.05, P<0.01), as well as reduced protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 (P<0.05, P<0.01). ConclusionDSS can alleviate oxidative stress and inflammation, reduce extracellular matrix deposition, and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway, thereby exerting a therapeutic effect on DKD.
4.Effects of aerobic exercise on skeletal muscle mass and function in colon cancer-loaded mice
Hongli LI ; Luyu ZUO ; Shiliang HU ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):353-364
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.
5.Ultrasonic gallbladder morphology analysis in 711 children with biliary atresia
Luyu LIU ; Yedi WANG ; Zijian ZHANG ; Zelong JIN ; Zhimin QIU ; Ya MA
Chinese Journal of Hepatobiliary Surgery 2025;31(7):519-523
Objective:To analyze the gallbladder morphology in ultrasound examinations of children with biliary atresia, classify them accordingly, and compare the gallbladder size of different types of patients and healthy infants.Methods:Clinical data of 711 cases with biliary atresia treated at the Department of General Surgery at the Capital Center for Children's Health, Capital Medical University from January 2017 to July 2022 were retrospectively analyzed, including 407 males and 304 females, aged (46.5±26.9) days. Additionally, 106 healthy infants recruited from the same hospital between January 2024 and March 2024 were included in the control group, including 60 males and 46 females, aged (48.5±23.9) days. The gallbladder morphology was classified into four types (A, B, C and D) based on its size and shape on ultrasonography. The long diameter of the gallbladder gradually increased, with its shape gradually approaching normal. The proportions of gender, time of jaundice onset (calculated from birth), total bilirubin, direct bilirubin, γ-glutamyl transferase (γ-GT), gallbladder contraction rate, hepatic portal cyst, and cholangiography were compared among different types. The gallbladder length and width of type D were also compared with those of the healthy control group.Resluts:Among the 711 patients, 123(17.3%) were of type A, 330 (46.4%) were of type B, 112 (15.8%) were of type C, and 146 (20.5%) were of type D. There were no statistically significant differences in the male ratio, the timing of jaundice onset, total bilirubin levels, direct bilirubin levels, or γ-GT levels among the four types of patients (all P>0.05). However, the incidences of combined hepatic portal cysts in type C and D were higher than those in type A and B (all P<0.01). Notably, 68.5% (100/146) of type D patients had a gallbladder contraction rate of ≤25%, lower than the 91.8% (303/330) of type B and 95.5% (107/112) of type C ( χ2=42.41, 29.22, both P<0.001). The success rates of cholangiography for type C and D patients were 75.0% (84/112) and 76.7% (112/146), respectively, both higher than the 11.4% (14/123) for type A and 45.2% (149/330) for type B (all P<0.001). In the healthy control group, the length and width of gallbladder were larger than those in type D patients ( t=10.64, 11.62, both P<0.001). Conclusion:The ultrasonic gallbladder morphology in biliary atresia patients is diverse, and there are no significant clinical differences among the four types. However, there are differences in gallbladder contraction rates and the success rates of gallbladder imaging. The gallbladder length and width of type D patients, with a nearly normal gallbladder morphology, are smaller than those of healthy infants at the same age.
6.Effects of aerobic exercise preconditioning on cardiac protein metabolism and cardiac function in mice with subcutaneously transplanted tumors
Shiliang HU ; Luyu ZUO ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Chinese Journal of Sports Medicine 2025;44(7):560-569
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.
7.Effects of aerobic exercise on skeletal muscle mass and function in colon cancer-loaded mice
Hongli LI ; Luyu ZUO ; Shiliang HU ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):353-364
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.
8.Effects of aerobic exercise preconditioning on cardiac protein metabolism and cardiac function in mice with subcutaneously transplanted tumors
Shiliang HU ; Luyu ZUO ; Yequn LIU ; Min YANG ; Jianjun YANG ; Huangyan LI ; Shuling ZHANG ; Junzhi SUN
Chinese Journal of Sports Medicine 2025;44(7):560-569
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.
9.Ultrasonic gallbladder morphology analysis in 711 children with biliary atresia
Luyu LIU ; Yedi WANG ; Zijian ZHANG ; Zelong JIN ; Zhimin QIU ; Ya MA
Chinese Journal of Hepatobiliary Surgery 2025;31(7):519-523
Objective:To analyze the gallbladder morphology in ultrasound examinations of children with biliary atresia, classify them accordingly, and compare the gallbladder size of different types of patients and healthy infants.Methods:Clinical data of 711 cases with biliary atresia treated at the Department of General Surgery at the Capital Center for Children's Health, Capital Medical University from January 2017 to July 2022 were retrospectively analyzed, including 407 males and 304 females, aged (46.5±26.9) days. Additionally, 106 healthy infants recruited from the same hospital between January 2024 and March 2024 were included in the control group, including 60 males and 46 females, aged (48.5±23.9) days. The gallbladder morphology was classified into four types (A, B, C and D) based on its size and shape on ultrasonography. The long diameter of the gallbladder gradually increased, with its shape gradually approaching normal. The proportions of gender, time of jaundice onset (calculated from birth), total bilirubin, direct bilirubin, γ-glutamyl transferase (γ-GT), gallbladder contraction rate, hepatic portal cyst, and cholangiography were compared among different types. The gallbladder length and width of type D were also compared with those of the healthy control group.Resluts:Among the 711 patients, 123(17.3%) were of type A, 330 (46.4%) were of type B, 112 (15.8%) were of type C, and 146 (20.5%) were of type D. There were no statistically significant differences in the male ratio, the timing of jaundice onset, total bilirubin levels, direct bilirubin levels, or γ-GT levels among the four types of patients (all P>0.05). However, the incidences of combined hepatic portal cysts in type C and D were higher than those in type A and B (all P<0.01). Notably, 68.5% (100/146) of type D patients had a gallbladder contraction rate of ≤25%, lower than the 91.8% (303/330) of type B and 95.5% (107/112) of type C ( χ2=42.41, 29.22, both P<0.001). The success rates of cholangiography for type C and D patients were 75.0% (84/112) and 76.7% (112/146), respectively, both higher than the 11.4% (14/123) for type A and 45.2% (149/330) for type B (all P<0.001). In the healthy control group, the length and width of gallbladder were larger than those in type D patients ( t=10.64, 11.62, both P<0.001). Conclusion:The ultrasonic gallbladder morphology in biliary atresia patients is diverse, and there are no significant clinical differences among the four types. However, there are differences in gallbladder contraction rates and the success rates of gallbladder imaging. The gallbladder length and width of type D patients, with a nearly normal gallbladder morphology, are smaller than those of healthy infants at the same age.
10.Effect of intrathecal morphine on myocardial injury in elderly patients undergoing thoracoscopic surgery
Jianyou ZHANG ; Luyu SUN ; Suhong TANG ; Suhong BAO
The Journal of Clinical Anesthesiology 2024;40(11):1139-1144
Objective To investigate the myocardial injury effects of intrathecal morphine injection in elderly patients undergoing thoracoscopic lobectomy.Methods Fifty-five elderly patients undergoing elective thoracoscopic lobectomy,28 males and 27 females,aged 65-85 years,BMI 18.5-27.9 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using the digital random allocation method:the control group(group C,n=28)and intrathecal morphine group(group M,n=27).Group M was given a single injection of morphine 4 pig/kg in the L2-3 space before surgery.General anesthesia was used in both groups,and single-lung ventilation was performed with double-lumen endotracheal intubation.Venous blood was collected before induction,24 and 48 hours after the operation to measure the levels of N-terminal brain natriuretic peptide precursor(NT-proBNP),creatine kinase isoenzyme(CK-MB),high-sensitivity troponin T(hs-TnT)and C-reactive protein(CRP).The incidence of myocardial injury after noncardiac surgery(MINS)was recorded.The intraoperative remifentanil dosage was recorded and the VAS pain scores at rest and during activity at 6,12,24,and 48 hours postoperatively were evaluated.The number of effective pa-tient-controlled intravenous analgesia(PCIA)compressions,the total number of PCIA compressions,the times of remedial analgesia in the postoperative period of 48 hours,as well as the incidence of postoperative adverse reactions(respiratory depression,nausea and vomiting,urinary retention,and pruritus)were re-corded.Postoperative 30-day major adverse cardiovascular and cerebrovascular events were recorded.Results Compared with preoperative,the levels of serum NT-proBNP,CK-MB,hs-TnT,and CRP were significantly higher in both groups at 24 and 48 hours postoperatively(P<0.05).Compared with group C,the elevated levels of serum NT-proBNP,CK-MB,hs-TnT,CRP,and absolute hsTnT changes were signifi-cantly lower in group M 24 and 48 hours after operation(P<0.05),the incidence of MINS was signifi-cantly lower in group M(P<0.05).Compared with group C,the VAS pain scores of patients in group M were decreased significantly 6,12 and 24 hours during activity and 12 and 24 hours at rest after surgery(P<0.05),the dosage of intraoperative remifentanil,the number of effective and total postoperative PCIA compressions,and the incidence of need for postoperative remedial analgesia were significantly reduced in group M(P<0.05).There was no significantly difference in the incidence of postoperative adiverse reca-tions between the two groups.Conclusion Intrathecal morphine can reduce the levels of markers of myo-cardial injury in elderly patients undergoing thoracoscopic lobectomy,which plays a partial role in myocardial protection.

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