OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

Objective:To compare the efficacy and safety of Tonghua Dongbao′s insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes.Methods:A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment.Results:For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P=0.320). Ratios of negative to positive were 7.43% and 10.61% ( P=0.360), and ratios of positive to negative were 10.40% and 7.58% ( P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P=0.371), and the incidence of adverse events was 76.60% and 77.70% ( P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions:Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Objective:To understand the health status of young and middle-aged residents in Tianjin based on the intelligent health monitoring system to explore influencing factors of residents suffering from chronic diseases, so as to provide suggestions for development of intervention measures for the community.Methods:From April to June 2019, a total of 512 young and middle-aged residents in Tianjin were selected as research objects, and data on demographic characteristics, living habits and health conditions were collected with the help of an intelligent health monitoring system. Descriptive analysis was used to summarize the health characteristics of residents, χ 2 test and rank sum test were used for univariate analysis, and Logistic regression was used to explore influencing factors of chronic diseases among young and middle-aged residents. Results:The age of 512 young and middle-aged residents was (35.13±12.59) years old, and 163 (31.8%) suffered from chronic diseases. Multivariate analysis showed that age ( OR=1.668, P=0.002) , education level ( OR=0.779, P=0.039) , moderate exercise in the past week ( OR=2.064, P=0.018) , BMI ( OR=2.339, P<0.001) , the frequency of blood pressure monitoring ( OR=2.560, P=0.003) , and the frequency of uric acid monitoring ( OR=2.742, P=0.001) entered the regression equation, which were the influencing factors of chronic diseases among young and middle-aged residents. Conclusions:Medical staff need to pay more attention to the health status of young and middle-aged residents in Tianjin. Increasing age, lack of moderate exercise in the past week, obesity, frequent monitoring of blood pressure and uric acid are positively correlated with the incidence of chronic diseases in young and middle-aged residents. Medical staff can refer to the survey results to propose health intervention measures.

Objective: To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC). Methods: The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected, including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University, 32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University, 21 in the First Hospital Affiliated to Army Medical University, 20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College, 19 in the West China Hospital of Sichuan University, 18 in the Second Hospital Affiliated to Zhejiang University School of Medicine, 18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 16 in the Beijing Friendship Hospital Affiliated to Capital Medical University, 10 in the Xuanwu Hospital Affiliated to Capital Medical University, 7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, 5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University, and 3 in the Affiliated Hospital of North Sichuan Medical College. There were 281 males and 167 females, aged from 22 to 80 years, with a median age of 57 years. Of the 448 patients, 143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group, respectively. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after matching; (2) intraoperative and postoperative situations; (3) follow-up; (4) survival analysis. Patients were followed up by outpatient examination, telephone interview and email to detect survival of patients and tumor recurrence up to October 31, 2018 or death. Follow-up was conducted once every 3 months within postoperative 1-2 years, once every 6 months within postoperative 2-5 years, and once a year after 5 years. The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates and draw survival curve, and Log-rank test was used to perform survival analysis. Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model, respectively. Results: (1) The propensity score matching conditions and comparison of general data between the two groups after matching: 286 of 448 patients had successful matching, including 143 in each group. The number of males and females, cases with hepatitis, cases with grade A and B of Child-Pugh classification, cases with distance from margin to tumor <1 cm and ≥1 cm, cases with highly, moderately, and poorly differentiated tumor, cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 204, 101, 121, 165, 140, 207, 98, 251, 54, 124, 181 in the control group, respectively, showing significant differences in the above indices between the two groups (χ²=7.079, 11.885, 7.098, 14.763, 5.184, 8.362, P<0.05). After propensity score matching, the above indices were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 79, 64, 29, 88, 55, 71, 72, 112, 31, 74, 69 in the control group, respectively, showing no significant difference in the above indices between the two groups (χ²=0.056, 0.329, 2.158, 0.014, 0.936, 1.400, P>0.05). (2) Intraoperative and postoperative situations: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with postoperative complications, and duration of postoperative hospital stay were 265 minutes (range, 160-371 minutes), 300 mL (range, 200-500 mL), 37, 46, 12 days (range, 9-17 days) for the LND group, and 59 minutes (range, 46-250 minutes), 200 mL (range, 100-400 mL), 24, 25, 9 days (range, 7-11 days) for the control group, respectively. There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z=1.700, χ²=3.520, P>0.05). There were significant differences in the operation time, cases with postoperative complications, and duration of postoperative hospital stay (Z=6.520, χ²=8.260, Z=4.270, P<0.05). (3) Follow-up: 143 patients in the LND group was followed up for 18-26 months. The 1-, 3-, 5-year survival rates were 66.9%, 32.8%, 25.0%, and the median survival time was 22.0 months (range, 18.0-26.0 months). In the control group, 143 patients were followed up for 11-32 months. The 1-, 3-, 5-year survival rates were 71.7%, 38.0%, 31.0%, and the median survival time was 22.0 months (range, 11.0-32.0 months). There was no significant difference in the overall survival between the two groups (χ²=0.466, P>0.05). (4) Survival analysis: results of univariate analysis showed that distance from margin to tumor, tumor diameter, the number of tumors, microvascular tumor thrombus, and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (χ²=10.662, 9.477, 16.944, 6.520, 11.633, P<0.05). Results of multivariate analysis showed that distance from margin to tumor<1 cm, tumor diameter>5 cm, multiple tumors, microvascular tumor thrombus, positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio=0.600, 1.571, 1.601, 1.750, 1.723, 95% confidence interval: 0.430-0.837, 1.106-2.232, 1.115-2.299, 1.083-2.829, 1.207-2.460, P<0.05). Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients, and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.

Objective To investigate the effects and mechanisms of shRNA interfered with expression of leucine-rich repeat containing G-protein coupled receptor 5 (Lgr5) on the malignant behaviors of colorectal cancer stem cells (CSCs).Methods The experimental study was conducted.The CSCs expressing Lgr5+ were sorted by fluorescence activated cell sorting.Lgr5+ cells that were transfected with Lgr5-shRNA lentiviral vector and nontarget shRNA lentiviral vector were respectively allocated into the experimental group and control group.The percentage of Lgr5+ cells was analyzed by flow cytometery.The relative expression of Lgr5 mRNA was detected by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR).The capacity of self-renewal was detected by sphere forming assay.The tumorigenesis in vitro and in vivo were respectively measured by colony formation assay and xenografting experiment.The mRNA expressions of stem cells related genes (Oct4,Sox2,Nanog,KLF4),CSCs genes (CD133,CD44,ALDH) and Wnt/β-catenin pathway key genes (Axin2,Wnt5a,Wnt3a,Fzd3,c-myc,VEGF,Ascl2,claudin-1) were detected by qRT-PCR.Measurement data with normal distribution were represented as-x±s.Comparison between groups was analyzed using the t test.Results (1)Transfection efficiency of shRNA lentiviral vector induced Lgr5 by flow cytometery was respectively 6.8％± 1.0％ in the experimental group and 92.7％±3.3％ in the control group,with a statistically significant difference (t =43.148,P＜0.05).The relative expression of Lgr5 mRNA measured by qPT-PCR was respectively 0.168±0.057 in the experimental group and 1.148±0.004 in the control group,with a statistically significant difference (t=28.778,P＜0.05).(2) The capacity of self-renewal was detected by sphere forming assay.The results of sphere forming assay:the number of spheres was 29±6 in the experimental group and 410± 10 in the control group,with a statistically significant difference (t =41.070,P＜0.05).The results of colony formation assay:the numbers of colonies in the experimental group and control group were respectively 72±4 and 412± 19,showing a statistically significant difference (t =31.433,P＜ 0.05).The results of tumorigenesis:the volumes of tumors in the experimental group and control group were respectively (81± 15)mm3 and (328±24)mm3,with a statistically significant difference (t=11.304,P＜0.05).(3) The effects of Lgr5 down-regulation on related genes,results of qRT-PCR detection:① The mRNA relative expressions of Oct4,Sox2,Nanog and KLF4 (stem cells related genes) were 0.377±0.093,0.662±0.104,3.591±0.300,0.425±0.091 in the experimental group and 1.957± 0.026,2.137±0.015,5.831±0.165,1.536±0.014 in the control group,with statistically significant differences (t=23.079,22.261,8.446,19.186,P＜0.05).② The mRNA relative expressions of CD133,CD44 and ALDH (CSCs genes) were 1.490±0.155,5.535±0.487,1.640±0.039 in the experimental group and 2.488± 0.061,9.908±0.332,5.718±0.292 in the control group,with statistically significant differences (t =8.170,9.667,27.849,P＜0.05).③The mRNA relative expressions of Axin2,Wnt5a,Wnt3a,Fzd3,c-myc,VEGF,Ascl2 and claudin-1 genes in the Wnt/β-catenin pathway were respectively 1.592±0.267,0.528±0.138,2.153±0.078,1.480±0.064,0.248±0.128,1.492±0.025,0.658±0.095,1.647±0.087 in the experimental group and 3.651±0.224,2.570±0.093,2.301±0.157,1.636±0.058,1.415±0.080,2.610±0.159,2.480±0.123,3.432±0.273 in the control group.There were statistically significant differences in the mRNA relative expressions of Axin2,Wnt5a,c-myc,VEGF,Ascl2 and claudin-1 genes between the 2 groups (t =7.316,15.332,12.649,12.320,14.831,9.063,P＜0.05),and no statistically significant difference in the mRNA relative expressions of Wnt3a and Fzd3 between the 2 groups (t =2.887,2.242,P＞0.05).Conclusion The malignant behaviors of colorectal CSCs are suppressed after shRNA lentivirus interfered with expression of Lrg5,and its mechanism is related to inhibiting activity of Wnt/β-catenin pathway.

Objective To evaluate the effect of Eucommia on hyperlipidemia and related indexes in rats, and provide animal data useful for the clinical experimental studies on hyperlipidemia.Methods Seventy-two healthy male SD rats were used in this study.One group of 12 rats fed with normal diet was chosen as normal control group, and other 60 rats were fed with high fat diet for two weeks to generate rat models of hyperlipidemia.48 of the hyperlipidemic model rats were taken and divided randomly into 4 groups, including model group, high dose Eucommia, moderate dose Eucommia, and low dose Eucommia groups.The last three groups were gavaged different dose of Eucommia, respectively.Druing this period, the other groups except the normal control group were fed with high fat diet continuously.The levels of serum TC, TG, LDL-C, and HDL-C of rats were measured on day 30 and 45.Results The serum levels of TC and LDL-C of the rats in the model group were obviously higher than those in the normal control group.The rat models of hyperlipidemia were established successfully.The three dose groups had a tendency of lowing blood lipid after 30 days.At 45 days, the levels of serum TC and LDL-C in the low and high dose groups were lower than those in the model group (P<0.01, P<0.05), (P<0.01, P<0.01).TG in the high, moderate and low dose groups were lower than that in the model group (P<0.01, P<0.01, P<0.01), but the level of the serum HDL-C was not significantly lower than that in the model group (P>0.05, P>0.05, P>0.05).Conclusions Eucommia in a dose of 0.43 g/kg, 0.86 g/kg and 1.71 g/kg administered for 30 days have a tendency to reduce the level of serum TC, TG, and LDL-C.When Eucommia is administered in a dose of 0.43 g/kg, 1.71g/kg and 3.42 g/kg for 45 days, it shows an adjuvant hypolipidemic effect.

ObjectiveTo investigate the immunological improvement effects of different doses of ursodeoxycholic acid (UDCA) on patients with different stages of primary biliary cirrhosis (PBC) and enhance the understanding of the roles of the immune system in the disease, and to provide evidence for the standardized clinical treatment of PBC. MethodsOne hundred and eighty patients with PBC who were admitted to our hospital from March 2012 to Janurary 2014 were enrolled and equally divided into three classes according to the stage of PBC: early stage, cirrhotic stage, and poor biochemical response stage. Patients in each class were equally divided into three groups according to the dose of UDCA: 8-10, 13-15, and 20-25 mg·kg-1·d-1. The general information, clinical symptoms, biochemical indices, and changes in T lymphocyte subsets and cytokines in peripheral blood after the treatment with different doses of UDCA were analyzed. Comparison of continuous data was performed by t test, and comparison of categorical data was performed by χ2 test. ResultsIn patients with early-stage PBC who were treated with 13-15 mg·kg-1·d-1 UDCA, the percentage of CD3+CD4+ T cells, CD4+/CD8+ ratio, and expression of interferon-gamma were significantly reduced after treatment (54.8%±11.6% vs 34.7%±7.7 %, t=6.5, P＜0.05; 2.3±1.0 vs 1.6±0.6, t=2.7, P＜0.05; 33.0±12.3 vs 23.7±7.2 ng/L, t=2.9, P＜0.05), while the secretion of interleukin-4 was significantly increased after treatment (29.0±4.6 vs 38.5±7.1 ng/L, t=5.0, P＜0.05). ConclusionThe UDCA with a dose of 13-15 mg·kg-1·d-1 can substantially improve the immune status in patients with early-stage PBC. The application of UDCA should be standardized in order to achieve the desired response.

Extended liver resection may provide longterm survival in selected patients with hilar cholangiocarcinoma.In May 2013,a patient with hilar cholangiocarcinoma received right hemihepatectomy combined with caudate lobectomy under the guidance of precision hepatectomy technique.The porta hepatis was clamped in the operation for 3 times intermittently.The operation time was 8 hours,and the volume of intraoperative blood loss was 600 mL.The patient was discharged at postoperative day 14.The results of pathological examination confirmed that the patient had moderately-highly differentiated adenocarcinoma with full-thickness infiltration of the bile duct and tumorfree margins.No tumor recurrence was detected during the followup which was lasted for 6 months.The operation was carried out based on the three dimensional reconstruction,liver reserve function evaluation,intraoperative controlled low central venous pressure and precision hepatectomy technique,and the results were satisfactory.

Objective Basing on overall survival(OS)of HBsAg-positive hepatocellular carcinoma(HCC)patients we evaluate several currently used HCC staging systems for OS predictivity.Methods This retrospective study included 775 patients with HBsAg-positive HCC treated in our department during 11-year period from Jan.2000 to Feb.2010.Clinicopathologic factors were evaluated for their possible association with OS in univariate and multivariate analysis using Cox proportional hazard model.Receiver operating characteristics(ROC)analysis with calculation of the area under the curve (AUC),sensitivity,and specificity was applied to define cutoff point values where appropriated and to assess HCC staging systems for their predictive ability of OS.Results The 1-,2-,3-and 5-year OS rates were 21.3％(165/775),9.4％(73/775),4.9％(38/775)and 1.7％(13/775),respectively.Multivariate analysis identified that severity of concomitant liver cirrhosis(B =4.519),treatment modality (B =4.888),ALT≥2N(B =4.068),portal vein tumor thrombi(B =0.537),spontaneous rupture(B =5.033)and inferior vena cava tumor thrombi(B =7.049)as independent risk factors influencing OS.NSMCS(North Sichuan Medical College Score)exhibited best performance predicting OS with AUC 0.801 (95％ CI 0.761-0.840),sensitivity of 78.8％,specificity of 69.3％ at NSMCS ≥-2.Median survival time reached statistically significant difference(13.6 mons,3.4 mons vs.1.3 mons,x2 =467.636,P =0.000).Conclusions Multiple factors determine OS in patients with HBsAg-positive HCC.NSMCS staging system demonstrates better predictability for the survival of HBsAg positive HCC patients.

ObjectiveTo evaluate the impact of anatomic and non-anatomic liver resection on prognosisofpatientswithsmallhepatocellularcarcinoma( HCC ) usingaMeta-analysis.MethodsLiterature on anatomic versus non-anatomic liver resection for the treatment of small HCC ( ≤5 cm) was retrieved. ResultsFour nonrandomized controlled trials were included consisting of 776 patients:484 undergoing anatomic liver resection and 292 non-anatomic resection.The age ranged from 53.4 to 63.0 years.Male ∶ female ratio was 3.56 ∶ 1.87.1％ patients were Child-Pugh class A.Most patients (94.5％ ) had a single tumor.No significant differences were found conceming the 1,3,and 5 year disease-free survival rate between the two groups.There was no significant difference in overall survival and disease-free survival between the two groups at 1,3,and 5 years.Sensitivity analysis found anatomic resection was superior to non-anatomic resection in 3 year disease free survival rate (OR =0.72,95％ CI:0.52 - 0.99,P =0.04). ConclusionsAnatomic liver resection elevated the 3 year disease free survival rate of patients with small hepatocellular carcinoma when compared with non-anatomic hepatectomy but failed to further elevate long-term disease free survival and overall survival.