AIM:To observe the effect of the extract of Ginkgo biloba(EGB)on pituitary-testicular axis and the mRNA expressions of luteinizing hormone receptor(LHR)and steroidogenic acute regulatory protein(StAR).METHODS:Thirty male Sprague-Dauley rats were divided into three groups randomly:normal control group,type II diabetic group and EGB treatment group.After fed with high-fat diet for 4 weeks,the later two groups were injected with strepozotocin intraperitoneally to induce type II diabetes mellitus.The EGB treatment group was given EGB at the dose of 50 mg/kg once a day for 12 weeks by intragastric administration.The normal control and diabetic group were given normal saline of equal volume per day for 12 weeks.The indices of blood glucose,insulin and low-density lipoprotein-cholesterol(LDL-c)were measured.The morphologic change of testicular tissue was observed under light microscopy(LM)and transmission electron microscopy(TEM)respectively.The concentrations of blood luteinizing hormone(LH)and testosterone(T)were assayed by the technique of enzyme linked immunosorbent assay(ELISA).The mRNA expressions of LHR and StAR from Leydig cells were detected by RT-PCR.RESULTS:The concentrations of blood glucose,insulin and LDL-c increased obviously,and the testis weights lessened obviously in type II diabetic groups compared to those in normal control groups.Rare spermatogenic cells of seminiferous tubule and germinal arrest were observed in diabetic group under LM.Ultrastructural analysis of testicular tissue by TEM showed dilation of the endoplasmic reticulum and mitochondrial swelling in Leydig cell and sertoli cell in diabetic group.The level of blood LH and T decreased in typeⅡ diabetic groups in comparison with that in the normal control group.Compared to normal groups,the mRNA expression of StAR in type Ⅱ diabetic groups decreased,while the mRNA expression of LHR increased.After the treatment of EGB,the pathological change of testis was relieved,the concentrations of blood glucose,insulin and LDL-c were decreased,the level of blood LH and T,and the mRNA expression of StAR were increased,and the mRNA expression of LHR descended compared to type Ⅱ diabetic groups.CONCLUSION:EGB may increase the LH-induced testosterone production by correcting metabolic disorder of glucose and lipid,improving the function of pituitary-testicular axis and regulating the expression of LHR and StAR mRNA.

AIM:To study the effect of gossypol on the cognitive function of type 2 diabetic rats,and to explore its mechanism. METHODS:Thirty male Sprague-Dawley rats were divided into three groups randomly:normal group,type 2 diabetic group and gossypol treated group. After fed with high-fat diet for 4 weeks,the later two groups were injected with streptozotocin intraperitoneally to establish type 2 diabetic rat model. The animals in gossypol treated group were given gossypol at dosage of 15 mg/kg once per day for 4 weeks by gavage. Since 5th week,the times of gavages were changed into once per week at the same dosage and lasted to 12th week. Learning and memory abilities of rats were assayed with Morris water maze test. The concentration of blood glucose was measured by biochemical method. The levels of serum corticosterone and insulin were detected by enzyme-linked immunosorbent assay and radioimmunoassay,respectively. The protein expressions of 11?-HSD1 and GR in cerebral cortex and hippocampus were determined by Western blotting. The morphological changes of cerebral cortex and hippocampus were observed under light microscope and transmission electronic microscope,respectively. RESULTS:Compared to normal group,the karyopyknosis,dilation of golgiosome and mitochondria swelling of neuron from cerebral cortex and hippocampus were prominent in diabetic group. The concentrations of blood glucose,serum corticosterone and insulin increased significantly (P

Objective To assess the value of passive leg raising (PLR) combined with echocardiography in predicting volume responsiveness in patients with septic shock. Methods Thirty septic shock patients with spontaneous respiration admitted to intensive care unit (ICU) of Tianjin First Center Hospital from July 2016 to August 2018 were enrolled. PLR and volume expansion (VE) were performed successively. The hemodynamic parameters including left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV) and left ventricular ejection fraction (LVEF) before PLR (baseline level), after PLR, immediately after VE were examined by echocardiography, and the central venous pressure (CVP) was monitored. The patients with increase in SV after VE (ΔSV) ≥ 15% were served as reaction group, while ΔSV < 15% were served as non-reaction group. The changes in LVEDV, LVESV, SV, LVEF and CVP at baseline level, after PLR and after VE were compared between the two groups. Pearson correlation method was used to analyze the correlation between ΔSV, increase in LVEF (ΔLVEF) after PLR and ΔSV, and ΔLVEF after VE. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of ΔSV and ΔLVEF after PLR for volume responsiveness. Results PLR and VE were successfully performed in 30 patients, of which 23 patients (76.7%) were enrolled in the reaction group, and 7 patients (23.3%) in the non-reaction group. Compared with baseline levels, LVEDV, SV, and LVEF in the reaction group were significantly increased after PLR [LVEDV (mL): 83.5±9.6 vs. 77.1±6.2, SV (mL): 48.5±5.6 vs. 43.2±4.9, LVEF: 0.58±0.04 vs. 0.56±0.06, all P < 0.05], and CVP was significantly increased after VE [cmH2O (1 cmH2O = 0.098 kPa): 7.4±3.3 vs. 4.6±0.7, P < 0.01], however, there was no significant change in LVESV. In the non-reaction group, SV and LVEF were significantly increased after PLR as compared with those at baseline levels [SV (mL): 42.7±3.7 vs. 40.6±3.1, LVEF: 0.52±0.05 vs. 0.50±0.05, both P < 0.05], while LVEDV and CVP were significantly increased after VE as compared with those at baseline levels [LVEDV (mL): 84.4±4.1 vs. 80.6±5.9, CVP (cmH2O): 10.6±3.5 vs. 7.6±0.5, both P < 0.05], however, there was no significant change in LVESV. Pearson correlation analysis showed that ΔSV and ΔLVEF after PLR were positively correlated with ΔSV and ΔLVEF after VE (r1 = 0.86, r2 = 0.65, both P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of PLR-induced ΔSV and ΔLVEF for predicting volume responsiveness was 0.85 and 0.66 respectively. When the cut-off value of ΔSV after PLR was 10.6%, the sensitivity was 78.2%, the specificity was 82.3%; when the cut-off value of ΔLVEF after PLR was 3.6%, the sensitivity was 78.2%, and the specificity was 73.2%. Conclusion ΔSV and ΔLVEF measured by PLR combined with echocardiography can be used to evaluate the volume responsiveness in patients with septic shock and can guide fluid therapy.

Objective:To analysis the construction of the world's top PhaseⅠclinical trial registration agencies, compare their size, composition, operation and funding, to provide further reference for the construction of clinical trial agency in China.Methods:Search for PhaseⅠclinical trial research agencies by region on clinicaltrials.gov. Collecting information about the agency’s management, staffing, implementation in Asia, America and Europe. Descriptive analysis was carried out to explore the type, proportion and operation among different regions, the organizational structure, operational management and effectiveness of each agency from different regions were compared.Results:The United States, Europe and East Asia are dense areas of PhaseⅠclinical research around the world. The types of agencies in the United States, Britain, France, Germany, South Korea, Japan, and Israel are mainly enterprises. Among other types of agencies, the organizational models are diversified. The agencies have different spatial distances from medical institutions, but possess relatively consistent scale and institutional operation. All the agencies have a stable source of funding.Conclusions:In order to strengthen the construction of clinical trial agencies in China, we should speed up the establishment of a close connection mechanism to promote deep cooperation in clinical trials. Control the construction scale and maintain stable input of the agency. Meanwhile, establish and strengthen international exchanges and cooperation.