OBJECTIVE：To optimi ze the optimal composition proportion of 4 ingredients （Panax ginseng ，Astragalus membranaceus，Polygonatum sibiricum ，Lycium chinensis ）in Compound ginseng immune-enhancing formula （CGIF），and to study immune activity and acute toxicity of the extracts with the optimal ratio. METHODS ：The cell activity test was used to screen the crude drug concentration range of 4 ingredients. After treated with different crude drug concentrations of each medicinal material，using the contents of NO ，IL-6 and TNF-α as indexes，uniform design was used to determine the optimal ratio of each ingredient in CGIF. Totally 240 mice were taken and randomly divided into 4 batches，with 60 mice in each batch. Each batch of mice was randomly divided into blank group （normal saline ），model group （normal saline ），positive drug group [levamisole ，4 mg/（kg·d）]，and optimal proportion extract of CGIF low-dose ，medium-dose and high-dose groups [ 0.952 8，1.905 6，3.811 2 g/（kg·d）]，with 10 mice in each group ；they were given medicine intragastrically ，qd，for consecutive 30 d. Except for blank group，mice in the other groups were intraperitoneally injected with cyclophosphamide [ 40 mg/（kg·d）] on the 24th day after first administration，qd，for consecutive 3 d to induce immunocompromised model. The immune activity of the optimal proportion extract was evaluated by determining visceral coefficients ，spleen lymphocyte transformation capacity ，serum contents of hemolysin，IL-2，IgM，IgG and IgA ，phagocytosis function of peritoneal macrophages. Another 20 mice were collected and given the optimal proportion extract 20 mL/kg intragastrically ，twice；acute toxicity of the formula was investigated with oral maximum tolerated dose （MTD）. RESULTS ：The optimal ratio of CGIF was that crude drug mass ratio of P. ginseng ， membranaceus，P. sibiricum ，L. chinensis was 1 ∶ 2 ∶ 2 ∶ 4. The immunological activity experiment showed that theoptimal proportion extract can significantly improve visceral indexes of mice ， spleen lymphocyte proliferation ability serum contents of hemolysin ，IL-2，IgM，IgG and IgA as well as macrophage phagocy tosis ability （P＜0.05 or P＜ 0.01）. The acute toxicity test indicated that oral MTD was over 15 g/kg，which was non-toxic. CONCLUSIONS ：The optimal proportion extract of CGIF can significantly enhance the immune function of mice and are non-toxic.

Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.

Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P<0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P<0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P<0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P<0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P<0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality (HR(95%CI):4.739(2.272-9.885), P<0.01), cardiovascular mortality (HR(95%CI):7.258(2.237-23.548), P=0.001) and MACCE (OR(95%CI):4.143(2.031-8.453), P<0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality (HR(95%CI): 6.387(2.533-16.104), P<0.01), cardiovascular mortality (HR(95%CI): 10.848(2.586-45.506), P=0.001) and MACCE (OR(95%CI): 4.081(1.299-12.816), P=0.016), while not for re-hospitalization for HF (OR(95%CI):1.010(0.700-1.457), P=0.957). Conclusions: Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.
China ; Female ; Heart Failure ; Humans ; Mental Status and Dementia Tests ; Prognosis ; Prospective Studies

Objective::To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11 (KCNJ11) with gestational diabetes mellitus (GDM).Methods::Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018, in which 241 pregnant women were identified as GDM, and 391 were non-GDM. All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn, and DNA in the blood was extracted. rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses.Results::After adjusting age and body mass index, the variant genotypes of rs5210 in genotype models were as follows: P for dominant model was 0.945, (odd ratio: 0.987, 95% confidence intervals ( CI): 0.681-1.430); P for recessive model: 0.556, (odd ratio: 1.217, 95% CI: 0.633-2.343) and P for addictive model was 0.098 (genotype AA vs. GG), (odds ratio: 1.435, 95% CI: 0.936-2.201). Weight-gain during pregnancy and total cholesterol were significantly different in recessive model ( P= 0.015, P= 0.022, respectively) of all participants. Conclusion::No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women. But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels. However, more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.

Objective::To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK) /extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin.Methods::The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot.Results::Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated ( P < 0.05). Conversely, GW9662 downregulated the mRNA levels of AKT2 and MAPK1 ( P < 0.05). Rosiglitazone and GW1929 increased the protein levels of PPARγ, chemerin, CMKLR1 and GPR1 ( P < 0.05). Rosiglitazone and GW1929 had no effect on the expression of PI3K p110β and phospho-AKT2 without CMKLR1 ( P > 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 ( P > 0.05). Conclusion::Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.

Objective::To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11 (KCNJ11) with gestational diabetes mellitus (GDM).Methods::Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018, in which 241 pregnant women were identified as GDM, and 391 were non-GDM. All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn, and DNA in the blood was extracted. rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses.Results::After adjusting age and body mass index, the variant genotypes of rs5210 in genotype models were as follows: P for dominant model was 0.945, (odd ratio: 0.987, 95% confidence intervals ( CI): 0.681-1.430); P for recessive model: 0.556, (odd ratio: 1.217, 95% CI: 0.633-2.343) and P for addictive model was 0.098 (genotype AA vs. GG), (odds ratio: 1.435, 95% CI: 0.936-2.201). Weight-gain during pregnancy and total cholesterol were significantly different in recessive model ( P= 0.015, P= 0.022, respectively) of all participants. Conclusion::No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women. But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels. However, more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.

Objective::To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK) /extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin.Methods::The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot.Results::Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated ( P < 0.05). Conversely, GW9662 downregulated the mRNA levels of AKT2 and MAPK1 ( P < 0.05). Rosiglitazone and GW1929 increased the protein levels of PPARγ, chemerin, CMKLR1 and GPR1 ( P < 0.05). Rosiglitazone and GW1929 had no effect on the expression of PI3K p110β and phospho-AKT2 without CMKLR1 ( P > 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 ( P > 0.05). Conclusion::Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.

Objective: To investigate the incidence rate of parastomal hernia(PH) among patients who have received laparoscope radical cystectomy and ileal conduit diversion and to discover the risk factors for PH. Methods: Data of 162 patients who underwent surgery of laparoscope radical cystectomy and ileal conduit diversion for bladder cancer between Jan 2012 and Dec 2017 were studied. The patients who had suffered other tumors before surgery or without follow-up data were excluded. At last, 148 patients were enrolled in this retrospective study. According to the occurrence of PH, the patients were divided into two groups: PH group and non-PH group. There were 21 patients (12 males and 9 females) in PH group. The mean age was (66.5±8.6) years old, and mean body mass index (BMI) was (33.4±5.2) kg/m². 11 patients with synchronous disease and 10 patients without synchronous disease before operation in PH group. Postoperative T stage 3 in 17 cases, ≥T₃ in 4 cases. 4 Cases received neoadjuvant chemotherapy and 5 cases received adjuvant chemotherapy. Tumor recurrence was found in 6 cases. 16 cases had hypoproteinemia. Ileal conduit was made through abdominal incision in 9 cases, and 12 cases was made with laparoscopy. After the surgery, there was severe cough in 7 cases and abdominal distension in 7 cases. 3 cases had previous abdominal operation, and 5 cases had history of glucocorticoid use. The mean size of the stoma was (3.0±0.6) cm. The mean length of the outflow tract was (11.2 ±1.3) cm. We did trans-rectus stoma in 4 cases, and para-rectus stoma in 17 cases. There were 127 patients (82 males and 45 females) in non-PH group. The mean age was (71.4 ±7.4) years, and the mean BMI was (28.8±4.1)kg/m². 60 patients with synchronous disease and 67 patients without. Postoperative T stage 3 in 96 cases, ≥T₃ in 31 cases. 29 patients received neoadjuvant chemotherapy and 39 cases received adjuvant chemotherapy. Tumor recurrence was found in 38 cases. 66 cases had hypoproteinemia. Ileal conduit was made through abdominal incision in 55 cases, under laparoscopy in 72 cases. There was severe cough in 34 cases and abdominal distension in 38 cases. 21 cases had previous abdominal operation, and 35 cases had history of glucocorticoid use. The mean size of the stoma was (2.3±0.4) cm. The mean length of the outflow tract was (12.2±1.6) cm. 4 cases had trans-rectus stoma, and 17 cases had para-rectus stoma. Postoperative rate of PH was estimated using the Kaplan-Meier methods. Chi-square test were used for the univariate analysis between group of PH and the normal one. Multivariate Logistic regression analysis was used to judge the independent risk factors of PH. Results: Patients were followed up for 24 months. PH occurred in 21 cases, the 1, 2, 5 year cumulative incidence of PH was 9.9%, 5.4% and 16.7% respectively. Clinical characteristics, including age at surgery(χ²=4.018, P=0.045), obesity(χ²=3.949, P=0.047), perioperative hypoproteinemia(χ²=4.279, P=0.039), chronic constipation(χ²=5.416, P=0.020), stoma location(χ²=6.464, P=0.011), stoma size(χ²=3.915, P=0.048), were significantly different between the PH group and the normal group(P<0.05). Multivariate Logistic regression analysis shows that obesity(OR=1.326, 95%CI=1.102-1.548, P=0.043), stoma location(OR=0.892, 95%CI=0.854-0.931, P=0.028), stoma size(OR=1.365, 95%CI=1.089-1.631, P=0.028) were the independent risk factors for PH. Conclusion We demonstrated that most of PH usually develop in 2 years after undergoing radical cystectomy with ileal conduit diversion. Obesity, stoma location and stoma size are independent risk factors. Preoperative counseling and preventative measures regarding PH formation should be emphasized, particularly in those patients with risk factors.

OBJECTIVE: To observe the in vivo metabolism and distribution characteristics of nano-cerium oxide( nanoCeO_2) in rats,and to explore the radio-protective effect of nano-CeO_2. METHODS: i) A total of 18 specific pathogen free( SPF) SD rats were randomly divided into 3 groups. Rats of experiment group and CeO_2 blood group were gavaged with1. 0 g/kg body weight( bw) nano-CeO_2 suspension. Rats of control group were gavaged with double distilled water( DDW)in equal volume. At different time-points after treatment,venous blood was collected from the rats' eye socket in CeO_2 blood group,meanwhile urine and excrement of rats of experiment group were also collected. Organ and tissue samples of experiment group and control group were collected 24. 0 hours after treatment. The concentrations of cerium in biological samples were detected by inductively coupled plasma mass spectrometry. ii) A total of 72 SPF BALB/c mice were randomly divided into 6 groups. Mice of low-,medium-and high-dose groups were gavaged with 100,300 and 900 mg/kg bw nano-CeO_2 suspension respectively. Mice of negative control group,irradiation control group and drug positive control group were gavaged with DDW in equal volume once daily. After 14 days,mice of the other 5 groups were exposed by60Coγ-rays once with 3. 5 Gy( 1 Gy/min) except the negative control group. Mice of drug positive control group were given intraperitoneal injection with 200 mg/kg bw amifostine half an hour before irradiation. After exposure,mice were treated by the above gavages once daily. After 3 and 8 days,6 mice were randomly selected to collect the peripheral blood for the count of white blood cell( WBC) and lymph cell measuring. RESULTS: i) The cerium concentration in blood reached peak value in 4. 0 hours after exposure of nano-CeO_2,and the cerium concentration of urine and excrement reached maximum in8. 0 hours after exposure. After 24. 0 hours of exposure,the cerium concentration of brain in experiment group was higher than that of control group( P < 0. 05). Among the experiment group,the cerium concentrations of sternum,duodenum and brain were higher than that of kidney and heart( P < 0. 05),meanwhile the cerium concentrations of thymus and lung were higher than that of kidney( P < 0. 05). ii) There was no statistical difference in interactive effect of WBC count and lymph cell counts between nano-CeO_2 exposure ways and time( P > 0. 05). The WBC counts of the low-and medium-dose groups were lower than those of the negative control group and the drug positive control group( P < 0. 05). The WBC count of high-dose group was lower than those of irradiation control group,drug positive control group and medium-dose group( P <0. 05). The lymph cell counts of the 3 dose groups were lower than that of drug positive control group( P < 0. 05).CONCLUSION: The nano-CeO_2 is mainly cumulated in organs such as sternum,duodenum,brain,thymus and lung. After induced by radiation,nano-CeO_2 has a certain degree of promotion role in increasing the WBC counts.

Objective To observe the effect and the mechanisms of ferulic acid on radiationinduced damage of mice peripheral blood and bone marrow hematopoietic function.Methods Ninety-six mice were randomly divided into sham irradiation group,irradiation group,positive drug group and 10,30,90 mg·kg-1 ·d-1 ferulic acid group,16 mice per group.Mice were exposed to 3.5 Gy γ-rays 24 h after first drug taken.Then,mice were given drugs for 7 d after irradiation.White blood cells in peripheral blood of 10 mice per group were counted 2 d before irradiation and 3,7,10,15 and 22 days after irradiation.The bone narrow of the other six mice was taken to detect the micronuclei frequency of polychromatic erythrocyte,the hematopoietic progenitor cell colony formation capacity,Thbd and HMGB1 protein expressions in mice bone marrow on the seventh day after irradiation.Results Compared with the irradiation alone group,the treatment of mice with ferulic acid 90 mg· kg-1 · d-1 increased the number of white blood cells in peripheral blood at 3,10,15 and 22 d after irradiation (t =2.267,2.399,1.945,2.828,P ＜ 0.05).Treatment with mice with ferulic acid 90 mg· kg-1 · d 1 decreased the micronuclei rate of erythrocytes in irradiated bone marrow (t =4.013,P ＜ 0.05),increased the clone numbers of CFU-E,BFU-E and CFU-GM of hematopoietic progenitor cells (t =2.366,2.953,3.115,P ＜0.05),improved the relative expression of the Thbd protein in bone marrow and the HMGB1 protein in nuclear (t =17.75,23.39,P ＜ 0.01).Conclusions Ferulilc acid could protect the bone marrow hematopoietic of mice exposed to irradiation by regulating the expressions of Thbd and HMGB1 protein,and then accelerate the peripheral cells recovery.