Metabolic disorders and hepatitis: Insights from a Mendelian randomization study.

BACKGROUND: Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study. AIM: To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes. METHODS: A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections). RESULTS: The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035). CONCLUSION: The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated.

Evaluation of the star family doctors training program: an observational cohort study of a novel continuing medical education program for general practitioners within a compact medical consortium: a quantitative analysis.

INTRODUCTION: To determine the effectiveness of the Star Family Doctors Training Program, a comprehensive Continuing professional development (CPD) program for general practitioners (GPs) in a compact medical consortium. PATIENTS AND METHODS: Observational cohort study with a quantitative analyses in primary health care institutions in Sichuan Province. The interventions were as following: (1) The Star Family Doctors Training Program is a full-time, local government allocation program certified by the Health Department of Sichuan Province, emphasizing small group learning and practice, and using standard patients and medical patient simulators; 30 participants were selected by their institutions. (2) The control group underwent a self-financed after-work CPD program using conventional lectures; 50 participants were self-selected. Short-term effectiveness assessed using immediate post-training tests and self-evaluations; long-term (1 year) effectiveness evaluated using self-reported surveys. RESULTS: The study involved 80 GPs (28.75% men; mean age: 38.2 ± 9.2 years). The average post-training total score was higher in the STAR group than in the control group (72.83 ± 5.73 vs. 68.18 ± 7.64; p = 0.005). Compared to the controls, STAR participants reported seeing more patients (all p < 0.05), and had more patients who signed family-doctor contracts (p = 0.001) as well as increased patient satisfaction (p = 0.03), respectively. STAR-group trainees appraised the program higher and were more willing to recommend it to colleagues (90% vs. 64%, p = 0.011). CONCLUSION: The Star Family Doctors Training Program achieved good responses and provides a reference for future CPD programs.

[Effect of Social Support on Multimorbidity and Related Outcomes of Middle-Aged and Older Adults in China].

Objective: To analyze the current status of social support for middle-aged and older adults with multimorbidity and to explore the correlation between different dimensions of social support and multimorbidity and the related outcomes on the basis of China Health and Retirement Longitudinal Study (CHARLS) 2015 survey data so as to reveal the complex social background of multimorbidity and the impact of social support on multimorbidity. Methods: A total of 9168 valid samples, with an average age of 59.60 years, were included in the study. Using the social support-related variables of the respondents, we conducted factor analysis and constructed regression models of common factors of social support and multimorbidity-related outcomes, intending to analyze the impact of common factors of social support on multimorbidity in the middle-aged and older adults. Results: The multimorbidity of middle-aged and older adults in China was related to multiple factors of social support, and the differences were statistically significant. Logistic regression showed that social support in the form of activity/recreational facilities and medical resources was a protective factor of multimorbidity, that family emotional support and economic support had a positive effect on life satisfaction of comorbid patients, and that social support in the form of education, social life and housing conditions was negatively correlated with catastrophic medical expenditure of the comorbid population ( P<0.05). Conclusion: Social support for middle-aged and older adults in China is unevenly distributed. Social support in the form of activity/recreational facilities and medical resources may reduce the risks of multimorbidity among middle-aged and older adults. Good family economic and emotional support can improve the life satisfaction of middle-aged and older adults with multimorbidity. Social support in the form of education, social life and housing conditions may reduce the risk of catastrophic medical expenditure in middle-aged and older adults with multimorbidity.

[Exploration and Practice of Specialty Training Program in General Practice].

Innovation is the lifeline of medical education reform in the new era. Based on the strategic goals of the Healthy China Initiative, we presented in this paper the practical experience of the Department of General Practice, West China Hospital, Sichuan University. We proposed the construction of an integrated model of general practitioner (GP) core competency training program consisting of 4 components, medical service, management, education, and academic ability. The integration of "generalist-specialist" and "hospital-community health service center" forms the basis of the coordinated training rotation plans. This model of training promotes collaboration among the GPs. Furthermore, GP with special interests (GPwSI) training is organically incorporated into the content of the program. In addition, we discussed the diversified approaches to evaluation incorporating formative and summative evaluation measures adopted for the training program. We summarized the innovative implementation plan of GPwSI, which is an efficient, replicable, and generalizable standardized specialty training program compatible with the Healthy China Initiative, intending to contribute constructive information and references to the education reform of the GP standardized training under the new circumstances.

[Risk factors associated with chronic obstructive pulmonary disease: a comparison between urban and rural populations in Chengdu].

OBJECTIVE: To determine risk factors associated with the prevalence of chronic obstructive pulmonary disease (COPD) in urban and rural populations in Chengdu. METHODS: A multistage random cluster sampling method was adopted to select participants from four communities in Chengdu. All residents aged 40-70 yr. were eligible to participate in this study, which involved a questionnaire survey, physical examination and portable spirometry. Those with airflow limitations were also given post-bronchodilator testing 15 min after inhalation of a dose of 200 microg salbutamol. We defined a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than 70% as COPD. Logistic regression models were performed to identify risk factors of COPD. RESULTS: Of a total of 1931 eligible participants, 1579 (81.77%) completed the questionnaire and spirometry. About 8.35% were identified with COPD: 7.69% in urban vs. 12.37% in rural (P<0.05). The prevalence of COPD increased with age (P<0.05) in the male and total populations. Rural COPD patients had a higher level of smoking rate and use of coal as fuel for cooking than their urban counterparts (P<0.05). But rural COPD patients had a lower level of BMI, waist circumference, literacy, and average household income per capita than their urban counterparts (P<0.05). The multivariate analysis showed that tobacco smoking index (pack-year), education, age and BMI were predictors of COPD for male patients; whereas, coal fuel usage, income and BMI were predictors of COPD for female patients. CONCLUSION: COPD prevalence is higher in rural areas than in urban Chengdu. Major risk factors of COPD include smoking, coal fuels and BMI.

Effects of MicroRNA-10b on lung cancer cell proliferation and invasive metastasis and the underlying mechanism.

OBJECTIVE: To study the influence of MicroRNA-10b on proliferation and invasion of human low metastatic lung cancer cell 95-C and its mechanism. METHODS: Lipofectamine MicroRNA-10b eukaryotic expression plasmid was transfected into 95-C. The experiment group was divided into blank control group, empty vector transfected group and MicroRNA-10b transfected group. Real time quantitative RT-PCR was used to detect the expression of MicroRNA-10b and KLF4mRNA expression. Proliferations of cells were detected by cell proliferation assay, invasion of the detected the cell Transwell experiments, the expression of KLF4 protein was detected in Western blotting cells. RESULTS: The proliferation rate of MicroRNA-10b plasmid transfection group increased significantly after transfection, invasion and migration ability enhancement, by comparison, there are statistically significant differences in the blank control group and negative control group (P<0.05); the expression of MicroRNA-10b plasmid transfection group KLF4 protein decreased, the difference was statistically significant (P<0.05); reduce the expression of MicroRNA-10b plasmid transfection group KLF4mRNA, but no significant differences (P>0.05). CONCLUSIONS: MicroRNA-10b may promote proliferation and invasion of 95-C cells by down regulating the expression of KLF4 protein.

[Effect of fractalkine on proliferation of pulmonary artery smooth muscle cells].

AIM: To investigate the effect of fractalkine on cell proliferation of cultured rat pulmonary artery smooth muscle cells (PASMCs) in vitro. METHODS: Rat PASMCs were cultured in vitro, and treated with different concentrations (10(-10), 10(-9), 10(-8) mol/L) of fractalkine for 12 h, 24 h and 48 h. The cell proliferation was quantified by MTT assay. The cell cycle of PASMCs was measured by flow cytometric(FCM) analysis. RESULTS: MTT assay showed that fractalkine promoted significantly the proliferation of PASMCs, and the effect was concentration-dependent. FCM analysis indicated that fractalkine increased the percentage of S phase and proliferative index (PI). The percentage of S phase and PI of PASMCs were increased after treated with fractalkine for 12 hours, which reached a maximal level at 24 hours. CONCLUSION: Fractalkine promotes rat PASMCs proliferation in a concentration-dependent manner.

[The effect of breviscapine on the pulmonary arterial pressure and the expression of Rho-kinase in pulmonary arterioles of hypoxic rats].

OBJECTIVE: To observe the effect of breviscapine on the pulmonary artery pressure and the Rho-kinase and Rho-kinase mRNA in pulmonary arterioles of rats treated with hypoxia, and therefore to explore the mechanisms of breviscapine on hypoxic pulmonary hypertension. METHODS: Eighteen adult male SD rats were randomly divided into 3 groups. One group was exposed to air (normal group), the second group was exposed to isobaric hypoxia for 3 weeks (hypoxic group), and the third group was exposed to hypoxia for 3 weeks and treated with breviscapine (preventive group). Cardiac catheterization was used to measure the mean pulmonary arterial pressure (mPAP). The heart was isolated, and the right ventricle (RV), left ventricle plus ventricular septum (LV + S) were weighed to calculate the ratio RV/(LV + S). The ratio of vascular wall thickness/vascular external diameter (WT%) and the ratio of vascular wall area/total vascular area (WA%) were measured by image analysis. The quantity of Rho-kinase and Rho-kinase mRNA in rat pulmonary arterioles were determined by immunohistochemistry and in situ hybridization respectively. RESULTS: The mPAP in the preventive group [(19.83 +/- 1.47) mm Hg, 1 mm Hg = 0.133 kPa] was significantly lower than that of the hypoxic group [(27.3 +/- 5.0) mm Hg], t = 4.28, P < 0.05. The RV/(LV + S) in the preventive group (0.29 +/- 0.03) was significantly lower than that in the hypoxic group (0.34 +/- 0.05, t = 2.39, P < 0.05). The WT% and WA% in the preventive group (25 +/- 5 and 45 +/- 5, respectively) were significantly lower than those in the hypoxic group (36 +/- 12 and 59 +/- 13, respectively, t = 4.89, 5.89, P < 0.05). The positive staining of ROCKI and ROCKII on pulmonary arterioles in the preventive group (1.18 +/- 0.10 and 1.30 +/- 0.12, respectively) were significantly lower than those in the hypoxic group (1.29 +/- 0.08 and 1.63 +/- 0.24, respectively, t = 3.90, 5.82, P < 0.05). The positive staining of ROCKI mRNA and ROCKII mRNA in the preventive group (1.23 +/- 0.13 and 1.22 +/- 0.06, respectively) were significantly lower than those in the hypoxic group (1.37 +/- 0.13 and 1.59 +/- 0.31, respectively, t = 3.94, 5.83, P < 0.05). CONCLUSION: Breviscapine was shown to prevent hypoxic pulmonary hypertension and decrease Rho-kinase and Rho-kinase mRNA.

[The change of fractalkine in lung tissue of rat with hypoxic pulmonary hypertension].

OBJECTIVE: To evaluate the role of fractalkine in the pathogenesis of hypoxic pulmonary hypertension. METHODS: Twenty male SD rats were randomly divided into control group and hypoxic group. Rats in hypoxic group were exposed to hypoxia for 3 weeks. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured with a computerized image analyzer. The rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated. The fractalkine level in lung tissue were measured by enzyme-linked immunosorbent assay. Fractalkine mRNA expression in lung were observed by reverse transcriptase-polymerase chain reaction. RESULTS: The rat mPAP of hypoxic group was higher than that of the control group [(28.7 +/- 3.8) mmHg vs (16.3 +/- 2.1) mmHg, P < 0.01]. The WT% and WA% were increased significantly in hypoxic group than in control group (WT%: (21.28 +/- 4.60)% vs (10.20 +/- 1.56)%, WA%: (67.08 +/- 9.44)% vs (38.11 +/- 42.30)%, P < 0.01, respectively]. In hypoxic group, the expression of fractalkine mRNA in the lung was significantly up-regulated [(0.49 +/- 0.05) vs (0.29 +/- 0.02), P < 0.01], the expression level of fractalkine in lung tissue was higher than that in control group [(7622.6 +/- 938.4) pg/mL vs (4168.5 +/- 403.5) pg/mL, P < 0.01. Linear correlation analyses showed that fractalkine mRNA and protein were positively associated with WA% and WT% (P < 0.05). CONCLUSION: The synthesis and release of fractalkine are increase in the lung tissue of chronic hypoxic rats, and fractalkine may play an important role in hypoxic pulmonary hypertension.

[Effect of simvastatin on endothelin-1 expression in endothelial cell cultured hypoxically].

OBJECTIVE: To observe the role of simvasatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in synthesis and excretion of endothelin-1 (ET-1) in endothelial cell cultured hypoxically. METHODS: Human umbilical vein endothelial cells were hypoxically cultured and treated with simvastatin by different concentrations (0, 1.0, 2.5, 5.0, 10.0 micromol/L) and different times (12, 24, 48 h). Mevalonate was used to intervent the effect of simvastatin. Reverse transcription-polymerase chain reaction (RT-PCR)and enzyme-linked immunoadsorbent assay (ELISA) were adopted to measure ET-1 mRNA and ET-1 in supernatant fluid of endothelial cell culture. RESULTS: (1) There were no changes of ET-1 mRNA and ET-1 expression after the hypoxically cultured endothelial cell were incubated with 1 MICROmol/L simvastatin, but ET-1 expression decreased without significant difference compared to control (0 micromol/L simvastatin) when interfered with 2.5 micromol/L simvastatin. The decreases of ET-1 mRNA and ET-1 expression became more obvious when expression were interfered by 5 micromol/Land 10 micromol/L simvastatin (P < 0.01). (2) ET-1 mRNA and ET-1 expression decreased at 12 h after the endothelial cells were incubated with 10 micromol/L simvastatin, which became more fewer at 24 h and reached the minimum expression at 48 h (P < 0.01). (3) The inhibition effect of simvastatin on ET-1 mRNA and ET-1 expression of endothelial cells could be prevented by mevalonate with concentration of 100 micromol/L. CONCLUSION: Simvastatin can inhibit ET-1 expression in endothelial cell cultured hypoxically.

[The change of nuclear factor-kappa B expression in the lung tissues of chronic hypoxic rats].

OBJECTIVE: To investigate the change of nuclear factor-kappa B (NF-kappaB) expression in the lung tissues from chronic hypoxic rats and the role of NF-kappaB in the pathogenesis of hypoxic pulmonary hypertension. METHODS: Twenty male SD rats were randomly divided into two groups: control group and hypoxic group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for three weeks. The mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The indices of wall thickness of pulmonary arteriole (WT% and WA%) were measured by a computerized image analyzer. NF-kappaB expression in lung tissues were observed by using immunohistochemistry. RESULTS: (1) The mPAP of hypoxic rats was (29.1 +/- 4.5) mmHg,and it was (16.8 +/- 2.6) mmHg in normal rats, there was significant difference between two groups (P < 0.001). (2) In hypoxic group, the WT% was (22.36 +/- 2.99)% and WA% was (69.14 +/- 5.38)%; in normal group, WT% was (15.36 +/- 3.08)% and WA% was (46.75 +/- 6.54)%, the differences were significant (P < 0.01). (3) Both normal and hypoxic group, there were positive cells for NF-kappaB nuclear staining in lung tissues of rats. The percentage of positive cells for NF-kappaB nuclear staining in bronchiolar epithelial cells was significantly increased in the hypoxic group [(29.11 +/- 1.12)%] than that in the control group [(12.23 +/- 1.08)%], P < 0.001. CONCLUSION: NF-kappaB expression is increased in the lung tissue of rats with chronic hypoxia. It may play a role in the pathogenic process of hypoxic pulmonary hypertension.

[The effects of losartan on pulmonary arterial collagen and AT1 in chronic hypoxic rats].

OBJECTIVE: To investigate the effects of losartan on pulmonary arterial collagen and AT1 in chronic hypoxic rats. METHODS: Thirty male SD rats were randomly divided into three groups: control group, hypoxic group and therapeutic group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for three weeks. Then, the therapeutic group was given losartan for two weeks. We measured the expression of Collagen I, III and AT1 in arterioles by means of immunohistochemistry. RESULTS: The positive degree of Collagen I in pulmonary arterioles in the hypoxic group was higher than that in the control group [(1.5202+/-0.069) vs (1.1324+/-0.071), P<0.01]; but in the therapeutic group it was lower than that in the hypoxic group [(1.1637+/-0.062) vs (1.5202+/-0.069), P<0.01]. There was no significant difference in collagen III and AT1 among the three groups (P>0.05). CONCLUSION: Losartan could reduce pulmonary arterial collagen I expression, it may be one of the therapeutic mechanisms on hypoxic pulmonary hypertension of losartan.