Prenatal exposure to PM2.5 components and the risk of different types of preterm birth and the mediating effect of pregnancy complications: a cohort study.

OBJECTIVES: This study aims to reveal the single and mixed associations of PM2.5 and its components with very, moderately, and late preterm births and to explore the potential mediating role of pregnancy complications in PM2.5-induced preterm birth. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 168,852 mothers and matched the concentrations of PM2.5 and its five components (OM, SO42-, BC, NO3-, and NH4+) based on their geographical location. Next, we used generalized linear models, quantile g-computation, and mediation analysis to evaluate the associations of PM2.5 and its components with very, moderately, and late preterm births and the mediating role of pregnancy complications. RESULTS: Prenatal exposure to PM2.5 and its components was associated with preterm birth, and the association was strongest in the third trimester. Preterm birth was associated with co-exposure to a mixture of PM2.5 components in the third trimester, and the contributions of NO3-, NH4+, and BC to the risk of preterm birth were positive. Meanwhile, pregnancy complications mediated PM2.5-induced preterm birth. Moreover, very and moderately preterm births were associated with PM2.5 and its components in the second and third trimesters, and very and late preterm births were associated with co-exposure to a mixture of PM2.5 components in the third trimester. CONCLUSIONS: Later exposure to PM2.5 during pregnancy will cause earlier preterm birth. Targeted and positive interventions for anthropogenic sources of specific PM2.5 components and pregnancy complications are helpful for preterm birth prevention.

[Evaluation of the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province-based on interrupted time series].

Objective: To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province. Methods: Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design. Results: The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 (t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 (t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 (ß1+ß3=0.071). Conclusions: The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

[Incidence of chronic obstructive pulmonary disease and pneumoconiosis in different occupational positions among populations from jinchang cohort].

Objective: To investigate the incidence and rank of chronic obstructive pulmonary disease and pneumoconiosis to the workers in different occupational positions in Jinchang Cohort. Methods: In January 2014, a cohort of follow-up population in jinchang city was taken as the research object, 17843 individuals among follow-up populations in Jinchang Cohort Study, removed the individuals with chronic obstructive pulmonary disease and pneumoconiosis before 2013, and counted the new incidence individuals diagnosed by the A-Class hospital in Grade III in Jinchang City, Gansu Province, as the investigation objects to investigate the incidence rate & rank of chronic obstructive pulmonary disease and pneumoconiosis. The statistical significance was tested by chi-square test. Results: The 2-year incidence rate of Chronic Obstructive Pulmonary Disease and Pneumoconiosis in the population of Jinchang Cohort Study were 11.60‰, 13.51‰ for male and 8.46‰ for female. the ranks of 2-year incidence rates of chronic bronchitis, emphysema, pneumoconiosis and other phenotypes of chronic obstructive pulmonary disease were 7.06‰ã€3.42‰ã€0.84‰ã€0.34‰, respectively. Incidence rate of chronic bronchitis among administrators and executive staffs were 10.45‰; incidence rate of chronic bronchitis among service staffs were 10.45‰; incidence rate of pneumoconiosis among mining staffs were 3.44‰. Conclusion: The first incidence rank of chronic obstructive pulmonary disease and pneumoconiosis in Jinchang cohort is chronic bronchitis, and the risk factors are smoking and occupational exposure.

[Detection of preoperative chemoradiotherapy sensitivity molecular characteristics of rectal cancer by transcriptome second generation sequencing].

OBJECTIVE: To detect the preoperative chemoradiotherapy sensitivity molecular characteristics of rectal cancer by transcriptome second generation sequencing. METHODS: The clinicopathological data of 30 patients with locally advanced rectal cancer were collected prospectively, including 9 indicators (general conditions, imaging data before radiotherapy and chemotherapy, pathological data of biopsy before radiotherapy and chemotherapy, and tumor differentiation degree, etc.), in order to analyze the correlation between them and tumor regression grading (TRG) after radiotherapy and chemotherapy for rectal cancer. At the same time, frozen specimens of colonoscopy biopsy before neoadjuvant therapy were collected from these 30 patients, and transcriptome second-generation sequencing was performed for bioinformatics analysis to screen out the genes that might drive the radio chemotherapy sensitivity of rectal cancer. RESULTS: Among the 30 patients with rectal cancer, 9 had complete pathological remission, 12 had partial remission, and 9 had poor remission. The degree of pathological TRG remission after radiotherapy and chemotherapy for rectal cancer was negatively correlated with the preoperative MRI T stage (P=0.046), and positively correlated with preoperative MRI rectal cancer extravascular invasion (EMVI) (P=0.003). Transcriptome second-generation sequencing of the obtained 217 transcripts (P<0.05) for signal pathway enrichment analysis, and multiple cell signal transduction pathways related to antigen presentation could be found. The high expression of HSPA1A, HSPA1B and EXOSC2 was positively correlated with postoperative pathological remission (P<0.05). The high expression of DNMBP, WASH8P, FAM57A, and SGSM2 was positively correlated with postoperative pathological remission (P<0.05). CONCLUSION: Preoperative NMR detection of extra-tumoral vascular invasion (EMVI-positive) in patients with rectal cancer was significantly better than that of EMVI-negative patients after chemoradiotherapy. Patients with high expressions of HSPA1A, HSPA1B and EXOSC2 had poor postoperative pathological remission, while patients with high expressions of genes, such as DMNMB, WASH8P, FAM57A, and SGSM2 had good postoperative pathological remission. Based on the molecular characteristics of rectal cancer radiotherapy and chemotherapy, attempts to block or enhance the molecular pathways associated with chemosensitivity of rectal cancer, are to be made to further explore new candidate therapeutic targets that can increase the sensitivity of radiotherapy and chemotherapy for rectal cancer.

[Study on the classification of dominant pathogens related to febrile respiratory syndrome, based on the method of Bayes discriminant analysis].

Objective: To understand the dominant pathogens of febrile respiratory syndrome (FRS) patients in Gansu province and to establish the Bayes discriminant function in order to identify the patients infected with the dominant pathogens. Methods: FRS patients were collected in various sentinel hospitals of Gansu province from 2009 to 2015 and the dominant pathogens were determined by describing the composition of pathogenic profile. Significant clinical variables were selected by stepwise discriminant analysis to establish the Bayes discriminant function. Results: In the detection of pathogens for FRS, both influenza virus and rhinovirus showed higher positive rates than those caused by other viruses (13.79%, 8.63%), that accounting for 54.38%, 13.73% of total viral positive patients. Most frequently detected bacteria would include Streptococcus pneumoniae, and haemophilus influenza (44.41%, 18.07%) that accounting for 66.21% and 24.55% among the bacterial positive patients. The original-validated rate of discriminant function, established by 11 clinical variables, was 73.1%, with the cross-validated rate as 70.6%. Conclusion: Influenza virus, Rhinovirus, Streptococcus pneumoniae and Haemophilus influenzae were the dominant pathogens of FRS in Gansu province. Results from the Bayes discriminant analysis showed both higher accuracy in the classification of dominant pathogens, and applicative value for FRS.

[Risk factors of gout in Jinchang cohort: a Cox regression analysis].

Objective: To explore the incidence and risk factors of gout in Jinchang cohort and provide scientific evidence for the prevention and control of gout. Methods: People without gout detected by baseline survey in Jinchang cohort were selected as study subjects. All the subjects were followed up through questionnaire interview, physical examination as well as laboratory test from January 24, 2013 to November 24, 2015. Cox regression model was used to analyze the risk factors for gout in Jinchang cohort. In addition, log-linear model was used to analyze the interaction between risk factors. Results: A total of 33 153 subjects were followed up, and there were 277 newly diagnosed gout cases in the cohort. The overall incidence of gout was 0.8%. The incidence of gout in males was higher than that in the females, but the incidence of gout in males and females was similar after the age of 60 years. Cox regression analysis showed that age >40 years (at age 40 to 59 years: HR=2.982, 95%CI: 1.503-5.981; at age 60 to 91 years: HR=2.588, 95%CI: 1.107-6.049), alcohol abuse (HR=2.234, 95% CI: 1.128-4.427), obesity (HR=2.204, 95% CI: 1.216-3.997), diabetes (HR=2.725, 95% CI: 1.500-4.950) and high uric acid (HR=5.963, 95%CI: 3.577-9.943) were risk factors for gout, while weekly beans intake ≥0.25 kg (HR=0.528, 95%CI: 0.345-0.808) and regular physical exercise (HR=0.499, 95% CI: 0.286-0.869) were protective factors for gout. The analysis with log-linear model showed that there were two order effects between the risk factors. Conclusions: Age, beans intake, alcohol abuse, physical exercises, obesity, diabetes and high uric acid were important factors influencing the incidence of gout. It is important to have healthy lifestyle and dietary habits, receive regular health examination to prevent and control the incidence of gout in this cohort.

[Evaluation of estimation of prevalence ratio using bayesian log-binomial regression model].

To evaluate the estimation of prevalence ratio (PR) by using bayesian log-binomial regression model and its application, we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software. The results showed that caregivers' recognition of infant' s risk signs of diarrhea was associated significantly with a 13% increase of medical care-seeking. Meanwhile, we compared the differences in PR's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1: not adjusting for the covariates; model 2: adjusting for duration of caregivers' education, model 3: adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model. The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95%CI: 1.005-1.265), 1.128(95%CI: 1.001-1.264) and 1.132(95%CI: 1.004-1.267), respectively. Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95% CI: 1.055-1.206) and 1.126(95% CI: 1.051-1.203), respectively, but the model 3 was misconvergence, so COPY method was used to estimate PR, which was 1.125 (95%CI: 1.051-1.200). In addition, the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model, but they had a good consistency in estimating PR. Therefore, bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

[Effect of combination model on fitting cancer mortality and prediction].

Objective: To reduce the cancer burden in the Jinchang cohort and provide evidence for developing cancer prevention strategies and performing effectiveness evaluation in the Jinchang cohort. We are fitting thirteen years of cancer mortality data from the Jinchang cohort by using six kinds of predicting methods to compare relative fitness and to select good predicting methods for the prediction of cancer mortality trends. Methods: The mortality data of cancer in Jinchnag cohort from 2001-2013 were fitted using six kinds of predicting methods: dynamic series, linear regression, exponential smoothing, autoregressive integrated moving average (ARIMA) model, grey model (GM), and Joinpoint regression. Weight coefficients of combination models were calculated by four methods: the arithmetic average method, the variance inverse method, the mean square error inverse method, and the simple weighted average method. Results: The cancer mortality was fitted and compared by using six kinds of forecasting methods; the fitting precision of the Joinpoint linear regression had the highest accuracy (87.64%), followed by linear regression (87.32%), the dynamic series (86.99%), GM (1, 1) (86.25%), exponential smoothing (85.72%) and ARIMA (1, 0, 0) (81.98%), respectively. Prediction accuracy of the combination model derived from GM (1, 1) and linear regression (>99%) was higher than that of the combination model derived from ARIMA (1, 0, 0) and GM (1, 1). The combination model derived from the GM (1, 1) and linear regression, with weight coefficients based on the arithmetic average method and the mean square error inverse method, had the best prediction effect of the four weight calculation methods. Conclusion: Prediction accuracy of the combination model, with accuracy >95%, was higher than that of the single prediction methods.

Simvastatin-induced myopathy with concomitant use of cyclosporine: case report.

OBJECTIVE: Simvastatin has been shown to play an important role in reducing the risk of cardiovascular events caused by atherosclerosis. To promote the understanding of the potential toxicity of simvastatin and individualized treatment in genetic factors, we report a case of a renal transplant in a female patient who had developed acute myopathy after taking simvastatin. METHODS: By PCR restriction fragment length polymorphism (PCR-RFLP) and allele-specificity polymerase chain reaction (AS-PCR) and direct sequencing. The genotypes of CYP3AP1, CYP3A5, CYP3A4 and SLCO1B1 were analyzed. RESULTS AND DISCUSSION: The patient was identified to have mutant genotypes of CYP3AP1*3/*3 (-44G > A), CYP3A5*3/*3 (6986A > G) and wild genotype of CYP3A4*1/*1 and SLCO1B1*1/*1, which finally led to the elevation of her cyclosporine level except the SLCO1B1*1/*1 genotype and the acceleration of simvastatin-induced acute myopathy. CONCLUSION: Genetic factors have partly contributed to the development of simvastatin-induced myopathy with concomitant use of cyclosporine, and provided information on the adverse reactions of statins. What is different from other studies is that the SNP of SLCO1B1*5 does not take part in this adverse reaction.

A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellular carcinoma.

We constructed a novel hepatocellular carcinoma-specific conditionally replicative adenovirus (CRAd). This adenovirus, designated Ad.HS4.AFP.E1A/TRAIL, expresses E1A to mediate viral replication and TRAIL to enhance HCC-killing efficacy under the control of a modified AFP promoter. An insulator HS-4 was placed in front of the AFP promoter to enhance the fidelity of the heterologous promoter. This virus was shown to have specific cytolytic activity in AFP-expressing HCC cells in vitro. Furthermore, the replication efficiency of Ad.HS4.AFP.E1A/TRAIL correlated well with AFP expression of the host cells, showing a 100-fold and 1 000 000-fold decrease in the low-and non-AFP-expressing HCC cells, respectively, compared to the high AFP-expressing HCC cells. An increase in mRNA of TRAIL and the elevated Caspase-3 activity were also observed in Ad.HS4.AFP.E1A/TRAIL-infected HCC cells. These results indicated that TRAIL expression from the viral vector activated the Caspase-3 enzymatic capacity and the HCC cells were sensitive to TRAIL. In vivo, Ad.HS4.AFP.E1A/TRAIL effectively prevented the growth of low AFP-expressing BEL-7404 xenografts. These results indicate that Ad.HS4.AFP.E1A/TRAIL could provide a new strategy of gene therapy for HCC.