AIM:This study aims to investigate the effects of aerobic exercise on hypothalamic autophagy and central leptin resistance in obese mice,and to explore the potential mechanisms.METHODS:Forty male C57BL/6J mice,aged 7 to 8 weeks,were randomly assigned to 5 groups:normal control(CON)group,high-fat diet(HFD)group,HFD+exercise(HFD+Exe)group,HFD+phosphate-buffered saline(PBS)group,and HFD+rilmenidine(autophagy ago-nist)group,with 8 mice in each group.Additionally,twelve fibronectin type Ⅲ domain-containing protein 5(Fndc5)gene(encoding irisin precursor protein)knockout(Fndc5 KO)mice were randomly allocated to Fndc5 KO+HFD group and Fndc5 KO+HFD+Exe group,with 6 mice in each group.All mice were fed for 28 weeks.The mice in CON group re-ceived a normal diet,while those in the remaining groups were provided with an HFD.The mice in HFD+Exe and Fndc5 KO+HFD+Exe groups engaged in aerobic treadmill exercise while continuing an HFD from weeks 17 to 28.The mice in HFD+PBS group received intraperitoneal injections of PBS as a control,while those in HFD+rilmenidine group received in-traperitoneal injections of rilmenidine(10 mg?kg-1?d-1),4 times a week over a total duration of 12 weeks(weeks 17 to 28).Following the intervention,serum metabolite levels,as well as concentrations of leptin and irisin,were quantified by ELISA.Morphological alterations in the liver and white adipose tissues were evaluated through oil red O staining and he-matoxylin-eosin(HE)staining.Western blot was utilized to assess the hypothalamic protein levels of autophagy markers,autophagy-related protein 7(ATG7),beclin-1,microtubule-associated protein 1 light chain 3(LC3)and p62,and leptin resistance markers,suppressor of cytokine signaling 3(SOCS3)and protein tyrosine phosphatase 1B(PTP1B).RE-SULTS:Observations of mouse phenotypes indicated that HFD feeding significantly increased body weight,blood lipid content and serum leptin level(P<0.05).The results of HE and oil red O staining demonstrated that HFD feeding marked-ly promoted lipid accumulation in the liver and caused ballooning of white adipocytes.Western blot analyses revealed that HFD feeding significantly down-regulated the protein levels of ATG7,beclin-1 and LC3-Ⅱ/LC3-I,but up-regulated the pro-tein level of p62(P<0.05),thus reducing cellular autophagy capacity.Furthermore,HFD feeding elevated the protein levels of leptin resistance markers SOCS3 and PTP1B(P<0.05).Aerobic exercise and autophagy agonist were found to partially reverse these changes,enhancing cellular autophagy capacity and alleviating leptin resistance.However,these effects were diminished after knockout of Fndc5 gene,further substantiating the role of irisin in exercise-mediated en-hancement of cellular autophagy and attenuation of leptin resistance.CONCLUSION:Aerobic exercise alleviates hypo-thalamic autophagy defect and central leptin resistance in obese mice,which may be associated with exercise-induced irisin.

Objective:To explore the trajectory and predictors of depressive symptoms in disabled middle-aged and elderly adults in China.Methods:Survey data from the 2013-2020 China Health and Retirement Longitudinal Study (CHARLS) data of disabled middle-aged and elderly adults were selected to analyze the trajectory categories of depressive symptom in disabled middle-aged and elderly adults and to explore their predictors.Results:A total of 1 844 disabled middle-aged and elderly adults were analyzed for survey data. The trajectory of depressive symptoms in disabled middle-aged and elderly adults was categorized into four groups, including a low-level depression group, a depression remission group, a high-level depression group, and a depression worsening group. Logistic regression analyses revealed that gender, age, place of residence, chronic disease, self-rated health, social participation, cognition, and hearing ability were predictors of trajectories of depressive symptoms in disabled middle-aged and elderly adults.Conclusions:There is group heterogeneity in the trajectory of depressive symptoms among disabled middle-aged and elderly adults. Healthcare professionals can carry out targeted health management according to the characteristics of different categories of people.

AIM:This study aims to investigate the effects of aerobic exercise on hypothalamic autophagy and central leptin resistance in obese mice,and to explore the potential mechanisms.METHODS:Forty male C57BL/6J mice,aged 7 to 8 weeks,were randomly assigned to 5 groups:normal control(CON)group,high-fat diet(HFD)group,HFD+exercise(HFD+Exe)group,HFD+phosphate-buffered saline(PBS)group,and HFD+rilmenidine(autophagy ago-nist)group,with 8 mice in each group.Additionally,twelve fibronectin type Ⅲ domain-containing protein 5(Fndc5)gene(encoding irisin precursor protein)knockout(Fndc5 KO)mice were randomly allocated to Fndc5 KO+HFD group and Fndc5 KO+HFD+Exe group,with 6 mice in each group.All mice were fed for 28 weeks.The mice in CON group re-ceived a normal diet,while those in the remaining groups were provided with an HFD.The mice in HFD+Exe and Fndc5 KO+HFD+Exe groups engaged in aerobic treadmill exercise while continuing an HFD from weeks 17 to 28.The mice in HFD+PBS group received intraperitoneal injections of PBS as a control,while those in HFD+rilmenidine group received in-traperitoneal injections of rilmenidine(10 mg?kg-1?d-1),4 times a week over a total duration of 12 weeks(weeks 17 to 28).Following the intervention,serum metabolite levels,as well as concentrations of leptin and irisin,were quantified by ELISA.Morphological alterations in the liver and white adipose tissues were evaluated through oil red O staining and he-matoxylin-eosin(HE)staining.Western blot was utilized to assess the hypothalamic protein levels of autophagy markers,autophagy-related protein 7(ATG7),beclin-1,microtubule-associated protein 1 light chain 3(LC3)and p62,and leptin resistance markers,suppressor of cytokine signaling 3(SOCS3)and protein tyrosine phosphatase 1B(PTP1B).RE-SULTS:Observations of mouse phenotypes indicated that HFD feeding significantly increased body weight,blood lipid content and serum leptin level(P<0.05).The results of HE and oil red O staining demonstrated that HFD feeding marked-ly promoted lipid accumulation in the liver and caused ballooning of white adipocytes.Western blot analyses revealed that HFD feeding significantly down-regulated the protein levels of ATG7,beclin-1 and LC3-Ⅱ/LC3-I,but up-regulated the pro-tein level of p62(P<0.05),thus reducing cellular autophagy capacity.Furthermore,HFD feeding elevated the protein levels of leptin resistance markers SOCS3 and PTP1B(P<0.05).Aerobic exercise and autophagy agonist were found to partially reverse these changes,enhancing cellular autophagy capacity and alleviating leptin resistance.However,these effects were diminished after knockout of Fndc5 gene,further substantiating the role of irisin in exercise-mediated en-hancement of cellular autophagy and attenuation of leptin resistance.CONCLUSION:Aerobic exercise alleviates hypo-thalamic autophagy defect and central leptin resistance in obese mice,which may be associated with exercise-induced irisin.

Objective:To explore the trajectory and predictors of depressive symptoms in disabled middle-aged and elderly adults in China.Methods:Survey data from the 2013-2020 China Health and Retirement Longitudinal Study (CHARLS) data of disabled middle-aged and elderly adults were selected to analyze the trajectory categories of depressive symptom in disabled middle-aged and elderly adults and to explore their predictors.Results:A total of 1 844 disabled middle-aged and elderly adults were analyzed for survey data. The trajectory of depressive symptoms in disabled middle-aged and elderly adults was categorized into four groups, including a low-level depression group, a depression remission group, a high-level depression group, and a depression worsening group. Logistic regression analyses revealed that gender, age, place of residence, chronic disease, self-rated health, social participation, cognition, and hearing ability were predictors of trajectories of depressive symptoms in disabled middle-aged and elderly adults.Conclusions:There is group heterogeneity in the trajectory of depressive symptoms among disabled middle-aged and elderly adults. Healthcare professionals can carry out targeted health management according to the characteristics of different categories of people.

BACKGROUND:Muscle weakness is a common symptom after coronavirus disease 2019(COVID-19)infection and affects the ability to perform daily activities in humans during recovery.Low-frequency pulsed magnetic field stimulation at a strength of 1.5 mT and a frequency of 3 300 Hz can enhance the maximal voluntary contraction and strength endurance of human skeletal muscle by inducing and activating classical transient receptor potential channel 1(TRPC1),which produces a series of pathological support effects on muscle tissue.It has not been studied whether this means will improve muscle weakness in patients recovering from COVID-19. OBJECTIVE:To select the low-frequency pulsed magnetic field for magnetic stimulation of lower limb muscle groups in patients with COVID-19,in order to observe the effect of this stimulation on the improvement of muscle weakness of lower limb muscle groups in patients with COVID-19 during the recovery period. METHODS:Fourteen patients infected with COVID-19(Omicron strain)positive for Innovita COVID-19 Ab Test(Colloidal Gold)and accompanied by muscle weakness were recruited and randomly divided into two groups:a test group receiving magnetic field stimulation and a control group receiving sham treatment,respectively.The total duration of the trial was 3 weeks.The test group was given low-frequency pulsed magnetic stimulation of the lower limbs every 48 hours and the control group was given the same intervention procedure as the test group but with sham stimulation.Patients in both groups were not informed whether the magnetic stimulation apparatus was running or not.Nine sessions were performed in both groups and the changes in the maximum voluntary contraction,explosive leg force and strength endurance of the local muscle groups of the lower limbs were subsequently observed in both groups. RESULTS AND CONCLUSION:Among the eight local muscle groups collected,seven local muscle groups in the test group showed an increase in the maximum voluntary contraction value after 3 weeks of low-frequency pulsed magnetic field stimulation.In the control group,there were only three muscle groups with improvement in the maximum voluntary contraction.The rate of improvement in the anterior and posterior muscle groups of the left leg in the test group was significantly higher than that in the control group.The longitudinal jump height and peak angular velocity of the knee joint in both groups were improved compared with the pre-test measurement,and the elevation rate of jumping height in the test group was higher than that in the control group.Under the fatigue condition,the decline rates of peak angular velocity of the knee joint and jumping height in the test group decreased significantly,while those in the control group did not change significantly.The above data confirmed that the low-frequency pulsed magnetic field stimulation with the intensity of 1.5 mT and frequency of 3 300 Hz could improve the muscle strength of more local muscle groups in the lower limbs of patients with COVID-19 during the recovery period compared with the human self-healing process,and the whole-body coordination ability and functional status based on explosive leg force of the legs could be significantly improved.Therefore,low-frequency pulsed magnetic field stimulation can be used as an effective,non-exercise rehabilitation tool to improve muscle weakness in the lower limbs of patients with COVID-19.

Serious diseases and other negative events bring serious physical and mental damage to individuals, but there are still some individuals can construct positive meaning of life from adversity, which is closely related to the role of benefit finding. According to the theory of stress system, if negative events such as disease are taken as stressors, benefit finding can be regarded as a good manifestation of individual psychological stress response. At present, most of the studies on benefit finding are cross-sectional studies, ignoring the characteristics of its dynamic development and the predictive role of individual advantages and disadvantages on benefit finding. This paper reviews the predictive factors in the longitudinal study of benefit finding from protective factors and risk factors, in order to reduce the adverse effects of risk factors on the basis of exploring individual protective factors and provide a starting point for the research design of positive psychological cognitive intervention.

Objective:To explore the clinical features of recurrence after choledocholithotomy and to analyze the risk factors.Methods:The clinical data of 730 patients with choledocholithiasis who were treated in our hospital from January 2005 to July 2016 were analyzed retrospectively,550 cases who were received choledocholithotomy were defined as laparotomy group,30 cases with laparoscopic common bile duct exploration (LCBDE) were defined as the LCBDE group,and 150 cases with endoscopic sphincterotomy (EST) were defined as EST group.The recurrence rate of the three groups were compared.The patients of three groups were divided into recurrence group (n=227) and non recurrence group (n=503) according to the recurrent situation,then the clinical features and risk factors of recurrent patients were analyzed by univariate and multivariate Logistic regression analysis.Results:The recurrence rate of EST group was 38.67％,which was significantly higher than that of LCBDE group with 26.67％ and the laparotomy group with 29.27％,and there was statistical difference (P＜0.05).The results of univariate analysis showed that there were statistically significant differences in age,history of HBV infection,jaundice,abnormal total bilirubin,peripapillary diverticulum,biliary infection,biliary stricture,papillary stenosis,sphincter of Oddis dysfunction,history of biliary surgery,cholecystectomy,bile duct diameter ≥ 15 mm,bile duct angle ≤120°,operation type,stone quantity ≥ 2 grains,stone diameter ≥ 10 mm,with or without gallstones (P＜0.05).The results of Logistic multivariate regression analysis showed that age,having peripapillary diverticulum,having history of biliary surgery,bile duct diameter ≥ 15 mm,stone quantity ≥ 2grains and EST operation type were the independent risk factors of the recurrence after choledocholithotomy (P＜0.05).Conclusion:There are many risk factors of recurrence after choledocholithotomy,and operation method should be based on the size and the number of the stones,and the constitution of patients.Preventive measures should be strengthened to control the recurrence after choledocholithotomy.

Objective To study the postoperative nutritional effects of early orogastric feeding compared with nasoenteric tube enteral nutrition within postoperative 24-48 h in pancreaticoduodenectomy (PD) patients.Methods The clinical data of 87 PD patients from June 2013 to January 2015 in Huaxi Hospital was analyzed retrospectively.Patients were divided into orogastric enteral nutrition group and nasoenteric tube enteral nutrition group.Patients' tolerance,hospital stay,mortality,and major complications associated with PD were compared.Results The average time of bowel function recovery (P ＜0.001) and average hospital stay (P=0.017) in the nasoenteric tube enteral nutrition group were significantly shorter than those in the orogastric enteral nutrition group.The differences of patients' tolerance were not statistically different (P =0.089).The differences of major complications and mortality were not statistically different (P =0.745,P =1.00).Conclusions Nasoenteric tube enteral nutrition in after PD patients improves nitrogen balance,promotes bowel function recovery and makes hospital stay shorter.

Pancreatic neuroendocrine tumors (P-NETs) are a group of heterogeneous tumors,including functional and nonfunctional ones.With the enhancement of clinicians' awareness about this disease and the improvement of imaging diagnostic techniques,the incidence of P-NETs has obviously increased in the past years.Based on the mitotic counting and Ki-67 positive index,the grading classification is of great value for the diagnosis,treatment and even prognosis of P-NETs.P-NETs are a group of malignant tumors with inert biological behaviors,whose surgical resection rate and long-term survival is much better than those of pancreatic ductal adenocarcinoma.P-NETs have different malignant potentials.Clinicians need to develop a comprehensive treatment plan in combination with the patient's symptoms,tumor grading classification and TNM staging information.Surgery is the only curable way to cure P-NETs.Even if radical resection is not suitable,palliative surgery may alleviate the patients,symptoms,and even prolong their survival time.According to the tumor location,size,quantity,degree of grading,local invasion and distant metastasis,different surgical procedures should be selected.

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet.The lack of a suitable animal model,however,remains a considerable challenge in obesity studies.In the current study,we provided high-fat diet (HFD) to dams during lactation and to pups after weaning.We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity.Results showed that feeding with HFD induces fat deposition and obesity in pups.Furthermore,HFD more potently increased the body weight (BW) of male than female pups.HFD-fed female pups were obese,underwent precocious puberty,and showed increased kisspeptin expression in the hypothalamus.However,parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups.Interestingly,some HFD-fed litters with normal BW also exhibited precocious puberty.This finding suggested that diet composition but not BW triggers puberty onset.Our model suggests good construction validity of obesity and precocious puberty.Furthermore,our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.