OBJECTIVE: To investigate the effect of Echinococcus multilocularis infection on Tim3 expression and its co-expression with immune checkpoint molecules 2B4 and LAG3 in spleen natural killer (NK) cells of mice. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were randomly divided into a high-dose infection group (15 mice), a low-dose infection group (13 mice), and a control group (11 mice). Mice in the high- and low-dose infection groups were inoculated with 2 000 and 50 Echinococcus multilocularis protoscolices via the hepatic portal vein, while animals in the control group was injected with an equivalent amount of physiological saline via the hepatic portal vein. Mouse spleen cells were harvested 12 and 24 weeks post-infection, and Tim3 expression and its co-expression with 2B4 and LAG3 in NK cells were detected using flow cytometry. RESULTS: There were significant differences in the proportions of Tim3 expression (F = 13.559, P < 0.001) and Tim3 and 2B4 co-expression (F = 12.465, P < 0.001) in mouse spleen NK cells among groups 12 weeks post-infection with E. multilocularis, and the proportion of Tim3 expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(23.84 ± 2.28)%] than in the high-dose infection group [(15.72 ± 3.67)%] and the control group [(16.14 ± 3.83)%] (both P values < 0.01), while the proportion of Tim3 and 2B4 co-expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(22.20 ± 2.13)%] than in the high-dose infection group [(14.17 ± 3.81)%] and the control group [(15.20 ± 3.77)%] (both P values < 0.01). There were significant differences in the proportions of Tim3 expression (F = 5.243, P < 0.05) and Tim3 and 2B4 co-expression (F = 4.659, P < 0.05) in mouse spleen NK cells among groups 24 weeks post-infection with E. multilocularis infection, and the proportions of Tim3 expression and Tim3 and 2B4 co-expression were significantly lower in mouse spleen NK cells in the high-dose infection group [(20.55 ± 7.04)% and (20.98 ± 7.12)%] than in the control group [(31.38 ± 3.19)% and (31.25 ± 3.06)%] (both P values < 0.05), and there were no significantly difference between the proportions of Tim3 expression and Tim3 and 2B4 co-expression in splenic NK cells in the low-dose infection group [(26.80 ± 6.47)% and (26.48 ± 6.48)%] and the control group (both P > 0.05). There were no significant differences in the proportions of Tim3 and LAG3 co-expression in mouse spleen NK cells among groups 12 (F = 2.283, P > 0.05) and 24 weeks post-infection (F = 0.375, P > 0.05). In the low-dose infection group, there were no significant differences in the proportions of Tim3 expression or Tim3 and 2B4 co-expression in mouse spleen NK cells 12 (t = -1.137, P > 0.05) or 24 weeks post-infection (t = -1.658, P > 0.05), and the proportion of Tim3 and LAG3 co-expression increased in mouse spleen NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -5.261, P < 0.01). In the highdose infection group, there was no significant difference in the proportion of Tim3 expression in mouse spleen NK cells 12 and 24 weeks post-infection (t = -1.546, P > 0.05); however, the proportions of Tim3 co-expression with 2B4 and LAG3 increased in mouse splenic NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -2.425 and -4.745, both P values < 0.05). CONCLUSIONS The Tim3 expression and Tim3 co-expression with LAG3 and 2B4 on spleen NK cells is affected by doses of E. multilocularis infection and disease stages, and present different phenotypes during the course of alveolar echinococcosis. NK cells tend to form an immunosuppressive phenotype with the progression of E. multilocularis infection, which facilitates immune escape and chronic parasitism of E. multilocularis.
Animals ; Mice ; Hepatitis A Virus Cellular Receptor 2/genetics* ; Killer Cells, Natural ; Mice, Inbred C57BL ; Spleen

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective: From the economic point of view, this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs, in China. Methods: PubMed, EMbase, The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide, from the inception of studies to June 30(th), 2018. Basic characteristics, methods and main results were extracted. Quality of studies was assessed. Cost were converted to Chinese Yuan under the exchange rates from the World Bank. The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated. Results: A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted. 22 studies were from the developed countries. Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program. Smoking history was widely applied for the selection of criteria on target populations (18). Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness. Annual (17) and once-life time (7) screening were more common frequencies. 22 studies reported ICERs for LDCT screening, compared to no screening, of which 17 were less than 3 times local GDP per capita, and were considered as cost-effectiveness, according to the WHO's recommendation. 15 and 7 studies reported ICERs for annual and once-life time screening, of which 12 and 7 studies were in favor the results of their cost-effectiveness, respectively. Additionally, the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening. Differences of cost-effectiveness among the subgroups, by starting age or by the smoking history, might exist. Conclusions: Based on the studies, evidence from the developed countries demonstrated that LDCT screening programs on lung cancer, implemented among populations selected by age and smoking history, generally appeared more cost-effective. Combined with the local situation of health resource, the findings could provide direction for less developed regions/countries lacking of local evidence. Low frequency of LDCT screening for lung cancer could be adopted when budget was limited. Data on starting ages, smoking history and other important components related to the strategy of screening programs, needs to be precisely evaluated under the situation of local population.
China ; Cost-Benefit Analysis ; Early Detection of Cancer/methods* ; Humans ; Lung Neoplasms/prevention & control* ; Middle Aged ; Quality-Adjusted Life Years ; Randomized Controlled Trials as Topic

Heavy metal is one of pollutants existed widely in the environment, its relationship with cardiovascular disease has attracted more and more attention. In this review, the concentrations of heavy metals, including lead, cadium and asenic, in the body from several national surveillance networks and the epidemiological studies on the effects of the exposure of three heavy metals on cardiovascular system were summarized. It is suggested to strengthen nationwide surveillance for body concentrations of heavy metals in general population in order to provide baseline data for quantitative evaluation of the risk of heavy metal exposure on cardiovascular disease.
Cadmium ; Cardiovascular Diseases/chemically induced* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Epidemiologic Studies ; Humans ; Lead/toxicity* ; Metals, Heavy/toxicity* ; Neoplasms ; Research/trends*

It is reported that depression has caused heavy disease burden across the world, with an possible association between ambient air pollution and depressive symptoms. In this paper, we reviewed relative literature in this field and summarized the research events on association between ambient air pollution and depression, both in China and abroad and found that the results of the existed studies were inconsistent, with most studies showing that there existed a positive correlation between the exposure of air pollution and depression, but few studies showing the negative correlation or no correlation between the two.
Air Pollutants/analysis* ; Air Pollution/statistics & numerical data* ; China ; Depression/epidemiology* ; Depressive Disorder ; Environmental Exposure/statistics & numerical data* ; Female ; Humans ; Particulate Matter/analysis* ; Research/trends* ; Residence Characteristics

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.
Adult ; Asian People ; China/epidemiology* ; Cholesterol/blood* ; Cohort Studies ; Humans ; Incidence ; Lipids ; Lung Neoplasms/ethnology* ; Male ; Proportional Hazards Models ; Prospective Studies ; Risk Factors

Objective: To estimate the prevalence of HIV/HCV co-infection and explore the influence factors and their interaction on HIV/HCV co-infection of patient's access to methadone maintenance treatment (MMT). Methods: A face to face interviews were conducted among 750 patients at two MMT clinics in Guangxi Zhuang Autonomous Region. The questionnaires information included demographic characteristics, HIV and HCV infection status, history of drug abuse, urine test for morphine, high risk sex behaviors, needle sharing, dropped out etc. Methods of χ(2) test one-way, multivariate logistic regression and interactions were used to analyze the related factors of HIV/HCV co-infection. Results: The study subjects included 750 participants, 18.31% (127/691) of patients were co-infected with HIV and HCV. The HIV/HCV co-infection rate in patients who shared needles with others or dropped out of treatment was 35.84% (81/226) and 19.88% (64/322) respectively, which were higher than those who have never shared needles or dropped out (9.89%, 46/465 and 17.07%, 63/369). Logistic regression analysis results showed that after adjusted for confounding factors, patients who shared needles (OR=4.50, 95%CI: 2.72-7.43) and dropped out of treatment (OR=1.71, 95%CI: 1.04-2.80) were more likely to be infected with HIV/HCV. Interaction analysis showed that sharing needles and dropping out of treatment exist additive effect on co-infection of HIV and HCV (RERI=4.21, AP=0.44, SI=1.95). Conclusions: Needle sharing and dropping out of treatment are associated with HIV/HCV co-infection. Health education, psychological counseling and other measures should be taken to reduce needle sharing and dropping out of MMT.
China/epidemiology* ; Coinfection/epidemiology* ; Female ; HIV Infections/epidemiology* ; Hepatitis C/diagnosis* ; Humans ; Logistic Models ; Male ; Methadone/therapeutic use* ; Morphine ; Needle Sharing ; Opiate Substitution Treatment ; Prevalence ; Risk Factors ; Sexual Behavior ; Substance Abuse, Intravenous/drug therapy* ; Substance-Related Disorders

Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.
Adult ; Alcohol Drinking/epidemiology* ; China/epidemiology* ; Cohort Studies ; Humans ; Lung Neoplasms/epidemiology* ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Risk Factors

Objective: To identify related factors associated with unprotected anal intercourse (UAI) among HIV-positive men who have sex with men (MSM) in the context of knowing their HIV infection status. Methods: HIV positive MSM who known that they had been infected with HIV for more than 6 months and accepted follow up services were recruited by convenience sampling method in Chengdu 2015. Semi-structured questionnaire was used to collect their information, such as demographic characteristics, antiviral therapy and sexual behavior characteristics etc. Logistic regression model was used for univariate and multivariate analyses. Results: A total of 330 HIV- positive MSM were recruited, 201 eligible MSM were interviewed. The prevalence of UAI in recent six months was 18.41% (37/201). The results of multivariate logistic regression analysis revealed that the number of anal intercourse with male ≥3 in last month (OR=6.22, 95%CI: 1.88-20.56), low education level (OR=7.29, 95%CI: 1.36-39.16), married, divorced or widowed status (OR=4.65, 95%CI: 1.13-19.17), homosexual cohabitation (OR=3.32, 95%CI: 1.01-10.95) were the risk factors related with UAI among the HIV-positive MSM. Conclusion: Frequent homosexual anal intercourse, low education level, married, divorced or widowed status and homosexual cohabitation might be the risk factors related with UAI in HIV-positive MSM in Chengdu.
HIV ; HIV Infections/transmission* ; Homosexuality, Male ; Humans ; Male ; Risk-Taking ; Sexual Behavior ; Sexual Partners ; Sexual and Gender Minorities ; Unsafe Sex

Objective: To establish a classified evaluation system for recognizing the levels of influenza epidemics and to explore the new reporting system on influenza epidemics. Methods: The following 3 indicators, including 1) the number of influenza-like illness, 2) positive rate of detection on influenza virus nucleic acids, and 3) the number of influenza outbreaks were chosen to calculate the synthetic index and to classify the grades of evaluation. Results: 209 weeks during 2013-2017 were classified into 5 grades: Grade 1 were 110 weeks (52.63%), Grade 2 were 47 weeks (22.49%), Grade 3 were 44 weeks (21.05%), Grade 4 were 8 weeks (3.83%), and Grade 5 were 0 week. Conclusion: This classified evaluation system provided simple, comprehensive and comparable reference indicators and used for the evaluation on influenza epidemics, also providing suggestions for influenza prevention and control accordingly.
Beijing/epidemiology* ; Disease Outbreaks ; Epidemics ; Humans ; Influenza, Human/epidemiology* ; Population Surveillance ; Virus Diseases