Indoleamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme which catalyses the metabolism of L-tryptophan(L-Trp) in the kynurenine pathway.It is overexpressed in many tumor cells and antigen presenting cells.This enzyme inhibits local immune response and supports tumor cells to evade immune surveillance by depleting L-Trp and producing kynurenine metabolites,thus,it is an important target for cancer immunotherapy.There are several IDO1 inhibitors with different scarfold under investigation,three of which have already entered clinical stage.The role of IDO1 in tumor immune tolerance and the research progress on IDO1 inhibitors in recent years are summarized in this paper.

Objective To establish the method for determination of bromate in drinking water by eluent generator suppressed conductivity ion chromatography.Methods Used application of American Dionex ICS-2100 ion chromatograph and EGC-III eluent automatic generator for ion chromatography gradient elution method to do determination of bromate in drinking water [IonPac AS19 (4×250 mm)].Eluent generator produced KOH online,gradient elution,Flow rate:1.0 ml/min.Results The method was linear in the range of Y =-0.000 609 7+0.000 873 1X,r =0.999 9,high precision (CV% < 1.5).The samples average of recovery was 99.5%~100.8%.The lowest detection limit was 0.50 μg/L.Conclusion Ion chromatog-raphy gradient elution method for the determination of bromate in drinking water was simple,rapid,and sensitive.It can be suitable for determination of bromate in drinking water.

Objective:To evaluate the role of mitochondrial calcium homeostasis in hyperoxia-induced injury to alveolar epithelial cells typeⅡ(AECⅡ) in rats.Methods:Rat AECⅡcell lines (RLE-6TN) were randomly divided into 3 groups ( n=18 each) using a random number table method: nomoxia group (group C), hyperoxia group (group H), and hyperoxia plus ruthenium red group (group HR). The cell lines were cultured in a conventional incubator for 4 h in group C. The cell lines were incubated in an incubator with 90% O 2 for 4 h in group H. In group HR, ruthenium red 2 μmol/L was added first, and then the cell lines were incubated in an incubator with 90% O 2 for 4 h. After the treatment, the Ca 2+ concentrations in mitochondria were measured using the mitochondrial Ca 2+ specific fluorescent probe Rhod-2-AM, the ROS level was measured using the fluorescent probe DCFH-DA, and the cell morphology and mitochondrial ultrastructure were observed. Results:Compared with group C, the Ca 2+ concentrations in mitochondria and ROS level were significantly increased in H and HR groups ( P<0.05). Compared with group H, the Ca 2+ concentrations in mitochondria and ROS level were significantly decreased in group HR ( P<0.05). Compared group C, the cell volume was reduced, the morphology was shrunken round, the cell arrangement was loose, the mitochondrial double-layer membrane structure was broken, and the mitochondrial cristal fragments were observed in group H. Compared with group H, the cell morphology was significantly improved, and the slight damage to mitochondrial double-layer membrane structure was found, and the structure of mitochondrial cristae was normal in group HR. Conclusion:Mitochondrial calcium homeostasis is involved in the pathophysiological process of hyperoxia-induced injury to AECⅡ in rats.

Objective To investigate the effects of high-fat diet induced insulin resistance on fibroblast growth factor-21 (FGF-21) and its receptors expression in ApoE~(-/-) mice. Method Male ApoE~(-/-) mice were randomly divided into normal-chow group(NF,n=20)and high-fat fed group(HF,n=20) and fed for 16 weeks. The insulin sensitivity and glucose-lipid metabolism in awake mice were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3-[~3H]-glucose as a tracer. The Mrna expressions of FGF-21,β-klotho, and FGFR1-4 were measured by quantitative real-time PCR. FGF-21 protein levels were determined by Western blot. Results Fasting blood glucose, plasma insulin and free fatty acids, triglycerides, free fatty acids, and cholesterols were significantly elevated in HF group compared with NF group(all P<0.01). During the steady-state of clamp, plasma insulin was significantly higher in HF group than that in NF group(P<0.01), and glucose infusion rate was also significantly decreased(P<0.01). At the end of insulin clamp, glucose disappearance rate was significantly lower in HF group than that in NF groups(P<0.01). Hepatic glucose production in NF group was suppressed by 70% ,while in HF group it was suppressed by 51%. The FGF-21 Mrna expressions of hepatic and adipose tissues in HF group were significantly increased compared with NF group(both P<0.01), and β-klotho Mrna expressions increased(P<0. 05). In hepatic and adipose tissues, FGFRI, Mrna expressions were higher in HF group than those in NF group(both P<0.01) ,and FGFR3 Mrna increased(P<0.01 and P<0.05, respectively). In hepatic tissue,FGFR4 Mrna levels were significantly up-regulated in HF group(P<0. 05). Plasma FGF-21 levels were elevated in HF group compared with NF group(P<0.01) ,and FGF-21 protein expressions of hepatic and adipose tissues were also increased(both P<0.05). Conclusion FGF-21, β-klotho, FGFR1, and FGFR3 were significantly up-regulated in ApoE~(-/-) mice fed by high-fat diet, and they might be the targets in regulating glucose-lipid metabolism by FGF-21.

Objective To study the epidemiological status of reproductive health related behaviors of out of school adolescents in Kunming and Shenzhen City,and to explore the social-psychological influencing factors of the behaviors.Methods A cross-sectional study was conducted in 410 out of school adolescents aged 15-24 years who were recruited with accidental sampling.All the subjects were required to complete a self-administrated questionnaire.Single factor Chi-square analysis and multi-factor Logistic method were used for data analysis.Results The correct respondent rate of the questions on reproductive health knowledge among the adolescents was low.The sexual intercourse rate was 42.9％ (176/410).Nearly 44.9％ (79/176) of the adolescents who had sexual experience did not use condom in the latest sexual intercourse,and those who had no less than one sexual partner accounted for 48.9％ (86/176).The prevalence of genital discomfort and sexual transmitted disease was 48.8％ (200/410) and 2.9％ (12/ 410),respectively.Chi-square test showed that marriage,living statue,behaviors of holding hands,kiss,caress the body,sexual intercourse and having no less than one sexual partner influenced the prevalence of genital discomfort(x2 values were 4.667,10.862,10.032,15.619,17.423,28.239,17.817 and 21.369,respectively ; all P ＜ 0.05).In binary Logistic analysis,living in a dormitory or with other people,behaviors of caress the body,sexual intercourse and having no less than one sexual partner influenced the prevalence of genital discomfort (odds ratio (OR) was 0.449 (95％ CI:0.216-0.933),0.377 (95％ CI:0.147-0.967),4.364 (95％ CI:1.594-11.949),0.312 (95％ CI:0.111-0.877) and2.646 (95％ CI:1.417-4.941),respectively ; all P ＜ 0.05).Conclusions The status of reproductive health was poor among out of school girls in kunming and Shenzhen,and living status,behaviors of caress the body,sexual intercourse and having no less than one sexual partner could influence the prevalence of genital discomfort.Comprehensive measures should be taken to strengthen the reproductive health management in this population.

c-Met receptor tyrosine kinase plays an important role in signaling pathways including cell proliferation, metabolism as well as tumorigenic growth, migration and angiogenesis. c-Met has emerged as an attractive target for cancer therapy. Moreover, the interactive cross-talk between c-Met signaling and several other signaling pathways underlies a key effect for resistance of anti-cancer drugs. Thus, multi-target inhibitors become a new approach to cancer therapy. This paper introduces the c-Met signaling pathway and the resistance of kinase inhibitors caused by the cross-talk between c-Met and other membrane receptors and then will reviews the progress of single-target and multi-target c-Met inhibitors.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure.Methods Thirty patients undergoing cardiac transcathe-ter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to com-pare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and mus-cle ARNT-1 like protein-1(BMAL1),cryptochrome1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score be-fore and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery.Results The postoperative mRNA level of CLOCK was higher[1.38±1.23 vs.1.90±1.47;MD(95％CI):0.52(0.20-0.84),t=3.327,P=0.002]and the postoperative mRNA levels of CRY1[1.56±1.50 vs.1.13±0.98;MD(95％CI):-0.43(-0.81--0.05),t=-2.319,P=0.028]and PER2[0.82±0.63 vs.0.50±0.31;MD(95％CI):-0.33(-0.53--0.12),t=-3.202,P=0.003]were lower than the preoperative levels.One week after surgery,the pa-tients presented advanced sleep chronotype[3:03±0:59 vs.2:42±0:37;MD(95％CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency[(67±64)min vs.(37±21)min;MD(95％CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration[(436±83)min vs.(499±83)min;MD(95％CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency[(87.59±10.35)％vs.(92.98±4.27)％;MD(95％CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score[1.13±0.78 vs.0.80±0.71;MD(95％CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score[6.60±3.17 vs.4.03±2.58;MD(95％CI):-2.57(-3.87--1.27),t=-4.039,P＜0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery.Conclusions Total intravenous anesthe-sia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

This article introduces the health management service specification for a chronic patient population. The concept of this specification comes from the whole process of people-centered and integrated health management of the chronic patient population. It is also based on the World Health Organization′s integrated chronic patient population management model. The completion of the specification has gone through several rounds of expert discussion in related fields in China. The contents include seven key links: suspect selection, clinical diagnosis, health assessment, intervention plan development, intervention plan implementation, follow-up, and health reassessment. It also includes establishing a professional team and developing a support system and mechanism of financing, compensation, and incentives. The specification aims at integrating regional health resources through standardizing service technology and scientific management concepts. It would help to improve the efficiency and quality of health management of chronic patient population in China, thereby reducing the economic burden of chronic diseases for patients and their families, and achieving the goal of improving residents′ health.

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.