Objective: To explore the effect of vaginal micro-environment alterations and HPV16 infection and their interaction in the progression of cervical intraepithelial neoplasia. Methods: The participants of this study came from the cervical lesions study cohort in Shanxi province, including 623 women with normal cervical (NC), 303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CINⅠ) and 93 patients with pathogenically diagnosed high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ). The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected, and HPV16 infection were detected by using flow-through hybridization technology and H(2)O(2), β-glucuronidase, clotting enzyme, neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis. pH value and vaginal cleanliness were also detected at the same time. The database was established and analyzed by SPSS statistical software (version 22.0). Results: The HPV16 infection rate (trend χ(2)=55.45, P<0.001) and the abnormal rates of H(2)O(2) (trend χ(2)=26.19, P<0.001), pH (trend χ(2)=5.06, P=0.024), vaginal cleanliness (trend χ(2)=19.55, P<0.001), β-glucuronidase (trend χ(2)=17.52, P<0.001) and neuraminidase (trend χ(2)=14.90, P<0.001) increased gradually along with the severity of cervical intraepithelial neoplasia, but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend. The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H(2)O(2), β-glucuronidase, clotting enzyme and neuraminidase in CINⅠ group, and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness, H(2)O(2), β-glucuronidase and neuraminidase in CIN Ⅱ/Ⅲ group. Conclusion: Our findings indicated that the vaginal micro-environment alterations and HPV16 infection could increase the risk of cervical intraepithelial neoplasia, and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.
Female ; Human papillomavirus 16/isolation & purification* ; Humans ; Hydrogen Peroxide ; Papillomavirus Infections/virology* ; Uterine Cervical Neoplasms/virology* ; Uterine Cervical Dysplasia/virology*

Atomic force microscopy (AFM), as a sophisticated imaging tool with nanoscale resolution, is widely used in virus research and the application of functional viral particles. To investigate single viruses by AFM in a physiologically relevant environment (liquid), an appropriate surface treatment to properly adhere the viruses to the substrate is essential. Here we discuss hydrophobic treated glass coverslips as a suitable substrate for the adhesion of single adenovirus particle (Adenovirus type 5 F35, Ad5F35) when studied with AFM in liquid. From the high resolution AFM images, the orientation of the adhered virus particles can be distinguished. Furthermore, the particles exhibit the expected height of -90 nm. This illustrates that the viruses adhere to the substrate firmly without large deformations. Hence, the described method works well on (fragile) viruses. The described experimental approach can be widely used for AFM studies in liquid of virus structure and mechanics as well as for investigating the interaction of viruses with cellular receptors.
Adenoviridae ; chemistry ; Imaging, Three-Dimensional ; Microscopy, Atomic Force ; methods ; Virion ; chemistry

The era of medical big data, translational medicine and precision medicine brings new opportunities for the study of etiology of chronic complex diseases. How to implement evidence-based medicine, translational medicine and precision medicine are the challenges we are facing. Systems epidemiology, a new field of epidemiology, combines medical big data with system biology and examines the statistical model of disease risk, the future risk simulation and prediction using the data at molecular, cellular, population, social and ecological levels. Due to the diversity and complexity of big data sources, the development of study design and analytic methods of systems epidemiology face new challenges and opportunities. This paper summarizes the theoretical basis, concept, objectives, significances, research design and analytic methods of systems epidemiology and its application in the field of public health.
Epidemiology ; Forecasting ; Humans ; Precision Medicine ; Translational Research, Biomedical

As a national strategy, the goal of Build a Healthy China is of significant importance on forming a well-off society, in which Public Health endeavor always stands an epi-center role. In developing the Healthy China strategy, we need to prioritize the people's health and recognize that Healthy China requires both brilliant health guidance and the belief of One Health. In addition, we must adhere to public welfare of health and health development. We should also take continuous reforming process and innovation as the fundamental motive force for promoting the construction of healthy China, with building up strong professional teams as one of the core elements. The development of Healthy China should adhere to the following strategies as Prevention First, Improving people's health, Strengthening control and prevention on chronic diseases, Improving health education, Building self-awareness on healthy behavior, Improving physical quality of the people, Increasing the accessibility on public health service, promoting the fully use of unique advantages provided by traditional Chinese medicine, Strengthening the health service of the key crowd, etc. We should also carry out the Patriotic Health Campaign and improve the governance of environmental problems that affecting health status of the people. In the process of building up Healthy China, the following points should stick to at all times, which are: leadership of the government and Prevention first policy' should be emphasized and adhere to the basic functions of the public health concept and providing health for all in the nation, practising the mass ecological health model which would promote the integrated development of medicine. We should also adhere to the talent strategy in improving the capacity building of the public health team, recognizing research as essential importance. The strategy should also scientifically and orderly adhere to the routine public health practices to ensure the coordination between routine and emergency services and adhere to the evidence-based decision-making models to make sure the equalization of public health services provided at an early date. Both Healthy China and Healthy life need healthy environment as well. We should work together to tackle the global public health problems. In the new era of Healthy China development, we should provide Chinese people with comprehensive and full life-cycle health services. We will make all efforts to step out the development of health-related endeavor under China's own characteristics, to contribute to the great practice of socialism in the new era.
China ; Delivery of Health Care ; Humans ; Public Health

Large cohort study gained its popularity in biomedical research and demonstrated its application in exploring disease etiology and pathogenesis, improving the prognosis of disease, as well as reducing the burden of diseases. Data science is an interdisciplinary field that uses scientific methods from computer science and statistics to extract insights or knowledge from data in a specific domain. The results from the combination of the two would provide new evidence for developing the strategies and measures on disease prevention and control. This review included a brief introduction of data science, descriptions on characteristics of large cohort data according to the development of the study design, and application of data science at each stage of a large cohort study, as well as prospected the application of data science in the future large cohort studies.
Cohort Studies ; Data Science ; Interdisciplinary Studies

Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females (χ(2)=3.630, P=0.057), and the differences in intestinal parasite infection rate among different age groups had significance (χ(2)=124.783, P=0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis. Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people (χ(2)=70.969, P=0.000 1), the differences had significance (χ(2)=120.118, P=0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children (χ(2)=15.765, P=0.000 1) and drinking well water (χ(2)=45.589, P=0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.
Animals ; Child ; Child, Preschool ; Clonorchiasis/epidemiology* ; Farmers ; Feces/parasitology* ; Female ; Helminthiasis/epidemiology* ; Helminths ; Humans ; Intestinal Diseases, Parasitic/parasitology* ; Male ; Prevalence ; Protective Factors ; Risk Factors ; Rural Population ; Soil Microbiology ; Surveys and Questionnaires ; Taeniasis/epidemiology* ; Trematode Infections/parasitology* ; Urban Population ; Water Wells

Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.
Case-Control Studies ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; Human papillomavirus 16 ; Humans ; Papillomavirus Infections ; Uterine Cervical Neoplasms/virology* ; Uterine Cervical Dysplasia/virology*

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.
Acid Anhydride Hydrolases/metabolism* ; Carcinoma, Squamous Cell/pathology* ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Neoplasm Proteins/metabolism* ; Polymerase Chain Reaction/methods* ; RNA, Messenger ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology*

Objective: To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia. Methods: A total of 486 patients, including 208 women with normal cervix (NC), 154 patients with low-grade cervical intraepithelial neoplasm (CINⅠ), 124 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ), were selected from the cervical lesions cohort from June to December, 2014. HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography. By using software SPSS 22.0, the χ(2) test, trend χ(2) test, Kruskal-Wallis H test, Nemenyi rank test and Spearman rank correlation analysis were performed. And the interaction effects were evaluated by additive model. Results: The HR-HPV infection rates in NC, CINⅠ and CINⅡ/Ⅲ groups were 27.9%, 37.0% and 58.9%, respectively. The urine concentrations of 1-OHP (μmol/molCr) were 0.07±0.09, 0.11±0.10 and 0.17±0.15, respectively. With increasing severity of the cervical lesions, the HR-HPV infection rate gradually increased (trend χ(2)=29.89, P<0.001) and the high exposure rate of PAHs gradually increased (trend χ(2)=27.94, P<0.001). HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680, P<0.001). There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group, but it was not found in CIN Ⅰ group. Conclusion: Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm, and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.
Case-Control Studies ; Cohort Studies ; Disease Progression ; Female ; Humans ; Papillomaviridae/isolation & purification* ; Papillomavirus Infections/virology* ; Polycyclic Aromatic Hydrocarbons/pharmacology* ; Pyrenes/urine* ; Severity of Illness Index ; Uterine Cervical Dysplasia/virology* ; Uterine Cervical Neoplasms/virology*

Objective: To analyze the relationship between medication taken during pregnancy and congenital heart disease of the newborns. Methods: A large cross-sectional survey was conducted between August and November 2013. A questionnaire survey was conducted among the childbearing aged women, selected through multistage stratified random sampling in Shaanxi from 2010 to 2013. All of the childbearing aged women under study were in pregnancy and with definite pregnancy outcomes. Multivariable Poisson regression was conducted for data analyses. Results: A total of 28 680 cases were included in this study. The proportion of medication taken at any time during pregnancy was 16.0%, and the prevalence of congenital heart disease among the newborns was 67.9/10 000. After adjustment for factors as general demographic characteristic, history of heart disease and drug allergy and the situation of disease during pregnancy of these women, results from the multivariable Poisson regression showed that, factors as taking drugs (RR=1.95, 95%CI: 1.42- 2.68), cold medicine (RR=1.68, 95%CI: 1.07-2.64), antibiotics (RR=1.90, 95%CI: 1.25-2.90), salicylates (RR=5.01, 95%CI: 1.84-13.64) and antifungal drugs (RR=10.22, 95%CI: 3.25-32.19) during pregnancy were all related to congenital heart disease, and with the history of taking cold medicine (RR=1.90, 95%CI: 1.01-3.61), antibiotics (RR=2.18, 95%CI: 1.17-4.06), salicylates (RR=6.07, 95%CI: 1.45-25.41), antifungal drugs (RR=21.01, 95%CI: 4.17-105.87) and other drugs (RR=2.31, 95%CI: 1.19-4.47) during early pregnancy. These factors were with higher risks for congenital heart disease. Conclusion: Women of childbearing age who took cold medicine, antibiotics, salicylic acid drugs, antifungal drugs and other drugs during early pregnancy would increase the risks related to congenital heart diseases.
Adult ; Cross-Sectional Studies ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Heart Diseases/epidemiology* ; Humans ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome ; Prevalence ; Surveys and Questionnaires