Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. Methods: By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. Results: There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). Conclusions: There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

Objective: To evaluate the association of educational level with anthropometric measurements at different adult stages and their long-term changes in adults who participated in the second re-survey of China Kadoorie Biobank (CKB). Methods: The present study excluded participants who were aged >65 years, with incomplete or extreme measurement values, or with major chronic diseases at baseline survey or re-survey. The weight at age 25 years was self-reported. Body height, body weight and waist circumference at baseline survey (2004-2008) and re-survey (2013-2014) were analyzed. Results: The present study included 3 427 men and 6 320 women. Both body weight and waist circumference (WC) increased with age. From age 25 years to baseline survey (mean age 45.2±6.5), the mean weight change per 5-year was (1.70±2.63) kg for men and (1.27±2.10) kg for women. From baseline survey to re-survey (53.2±6.5), the mean changes per 5-year for body weight were (1.12±2.61) kg for men and (0.90±2.54) kg for women; and that for WC was (3.20±3.79) cm for men and (3.83±3.85) cm for women. Among women, low educational level was consistently associated with higher body mass index (BMI) and WC at age 25 years, baseline survey and re-survey. Among men, low educational level was associated with higher BMI at age 25 years. At baseline survey and re-survey, the educational level in men was not statistically associated with BMI; but men who completed junior or senior high school showed slight higher WC and increase of WC from baseline survey to re-survey than other male participants. Conclusions: Body weight and WC increased with age for both men and women. The associations of educational level with BMI and WC were different between men and women.
Adult ; Asian People/statistics & numerical data* ; Body Height ; Body Mass Index ; Body Weight ; China/epidemiology* ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Obesity/ethnology* ; Risk Factors ; Sex Distribution ; Waist Circumference/ethnology*

Objective: To examine the prevalence of 'healthy lifestyle' from data extracted from the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. Methods: After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at second survey (2013- 2014), were included for analysis. 'Healthy lifestyle' was defined as haing the following characteristics: a) never smoking or having stopped smoking for reasons other than illness; b) alcohol drinking <25 g/day (men)/<15 g/day (women); c) diet rich in vegetables, fruits, legumes and fish, but low in red meat; d) upper quarter of the physical activity level; e) body mass index of 18.5-23.9 kg/m(2) and waist circumstance <85 cm (men)/80 cm (women). We calculated the healthy lifestyle scores (HLS) by counting the number of all the healthy lifestyle factors, with a range from 0 to 6. Results: At baseline, prevalence rates of the above five healthy lifestyles (except physical activity) were 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively, with the mean HLS being 3.1±1.2. Most participants (81.4%) had2-4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of all the participants had all six healthy lifestyles. Participants who were women, at younger age, with more schooling and rural residents, were more likely to adhere to the healthy lifestyle. After ten years, the mean HLS showed a slight decrease. Conclusion: The prevalence of optimal lifestyles in Chinese adults appeared extremely low. Levels of 'healthy lifestyle' varied greatly among those populations with different socio-demographic characteristics across the ten areas in China.
Adult ; Asian People/statistics & numerical data* ; China ; Female ; Healthy Lifestyle ; Humans ; Life Style ; Male ; Prevalence ; Risk Factors

Objective: To analyze the pathogenic surveillance programs and related factors on bacillary dysentery in Beijing, 2008-2017, to provide evidence for the practices of diagnosis, treatment and prevention of the disease. Methods: Analysis was conducted on surveillance data of bacillary dysentery, collected from the surveillance areas of national bacillary dysentery in Beijing. Shigella positive rate of stool samples were used as the gold standard while detection rate of Shigella, diagnostic accordance rate and resistance were computed on data from the surveillance programs. Chi-square test was used to compare the rates and unconditional logistic regression was used to analyze the related factors of Shigella infection. Results: Both the reported incidence rate on bacillary dysentery and detection rate of Shigella in diarrhea patients showed significantly decreasing trend, from 2008 to 2017. The accordance rate of bacillary dysentery was only 7.80% (111/1 423). Shigella sonnei was the most frequently isolated strain (73.95%, 159/215) followed by Shigella flexnery. Results from the multivariate logistic regression of Shigella positive rate revealed that among those patients who were routine test of stool positive vs. routine test of stool positive (OR=1.863, 95%CI: 1.402-2.475), onset from July to October vs. other months'time (OR=7.271, 95%CI: 4.514-11.709) temperature ≥38 ℃vs. temperature <38 ℃(OR=4.516, 95%CI: 3.369-6.053) and age from 6 to 59 years old vs. other ages (OR=1.617, 95%CI: 1.085-2.410), presenting higher positive detection rates of Shigella from the stool tests. The resistant rates on ampicillin and nalidixic acid were 97.57% (201/206) and 94.90% (186/196), both higher than on other antibiotics. The resistant rates on ciprofloxacin (16.33%, 32/196), ofloxacin (9.57%, 11/115) and on amoxilin (15.05%, 31/206) were relatively low. The resistant rate appeared higher on Shigella flexnery than on Shigella sonnei. The proportion of strains with resistance on 3 more drugs, was 30.00%(21/70). Conclusions: The diagnostic accordance rate of bacillary dysentery in Beijing was low, with severe resistance of Shigella. Our findings suggested that clinicians should take multiple factors into account in their practices about epidemiological history, clinical symptom and testing results for diarrhea patients.
Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use* ; Beijing/epidemiology* ; Child ; China/epidemiology* ; Dysentery, Bacillary/prevention & control* ; Feces/microbiology* ; Humans ; Middle Aged ; Population Surveillance/methods* ; Sentinel Surveillance ; Shigella/isolation & purification* ; Shigella flexneri/isolation & purification* ; Shigella sonnei/isolation & purification* ; Young Adult

Objective: To evaluate the association of family history with risk of major coronary events (MCE) and ischemic heart disease (IHD). Methods: After excluding participants with heart disease, stroke or cancer at baseline survey, a total of 485 784 participants from the China Kadoorie Biobank, who had no missing data on critical variables, were included in the analysis. Cox regression analysis was used to estimate the hazard ratios (HR) and 95% CI. Subgroup analyses were performed according to the baseline characteristics. Results: During a median of 7.2 years of follow-up, we documented 3 934 incident cases of MCE and 24 537 cases of IHD. In multivariable-adjusted models, family history was significantly associated with risk of MCE and IHD. The adjusted HRs (95%CI) were 1.41 (1.19-1.65) and 1.25 (1.18-1.33), respectively. History of disease among siblings was more strongly associated with early-onset MCE than parental history (HR=2.97, 95%CI: 1.80-4.88). Moreover, the association of family history with MCE and IHD was stronger in persons who were overweight or obesive, and the association between family history and MEC was stronger in smokers. Conclusion: This large-scale, prospective study indicated that family history was an independent risk factor for MCE and IHD in China. The intervention targeting major known lifestyle risk factors and the management of chronic diseases should be strengthened for Chinese population, especially for the individuals with family history were at high risk.
Asian People/statistics & numerical data* ; China/epidemiology* ; Coronary Disease/genetics* ; Humans ; Incidence ; Myocardial Ischemia/genetics* ; Overweight/ethnology* ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Risk Factors ; Smoking/ethnology*

Objective: To describe the regional and population-related differences in calcaneus bone mineral density (BMD) across ten regions of China. Methods: Based on the results: from the second Re-survey of China Kadoorie Biobank project, in which 5% of the surviving participants were interviewed during 2013-2014 and 24 677 participants aged 38-87 years were included in the study. We excluded those people with missing data for BMD and important variables. Calcaneus BMD was measured using the quantitative ultrasound bone densitometer. We analyzed four indexes, including broadband ultrasound attenuation (BUA), speed of sound (SOS), stiffness index (SI), and T score. Results The average calcaneus BMDs of the present population were: BUA (109.7±12.6) dB/MHz, SOS (1 554.7±45.6) m/s, SI (88.3±18.8), T score (-0.74±1.28). Urban residents showed higher calcaneus BMD, so as in men. The calcaneus BMD decreased by age, with a larger decline seen in women. Current smokers and postmenopausal women presented lower calcaneus BMD, while in those who frequently drank milk or yogurt or being physically more active, had higher calcaneus BMD. Conclusion: Calcaneus BMD varied greatly among people from the ten regions of CKB study and among participants having different demographic characteristics, lifestyle behaviors or health conditions.
Absorptiometry, Photon/methods* ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Density/physiology* ; Calcaneus/diagnostic imaging* ; China ; Female ; Humans ; Male ; Middle Aged ; Residence Characteristics ; Rural Population ; Sex Factors ; Ultrasonography ; Urban Population

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
Adolescent ; Bayes Theorem ; Beijing ; Body Weight ; Child ; DNA Methylation/genetics* ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study ; Humans ; Male ; Obesity/genetics* ; Twins, Monozygotic ; Waist Circumference

Objective: To study the characteristics of social relations and relative factors among MSM in Guangzhou. Methods: Data was collected through a cross-sectional study in Guangzhou from November 2016 to May 2017. Sample size was estimated and participants were recruited from the voluntary counseling and testing services (VCT) which were set for MSM population, by nongovernmental organizations (NGOs) and the Centers for Disease Control and Prevention (CDC). Social ties and demographic characteristics of the respondents and their sexual partners were analyzed through both Chi square test and generalized estimating equations (GEE). Results: A total of 1 073 MSM, together with their nominated 4 301 partners were successfully recruited and involved in this study. Age (OR=1.2, P=0.01) and non-internet based intercourse (OR=1.65, P<0.01) were easy to form close relation with strong ties. Compared with MSM traditional venues (chess and cards room, tea room bathhouse, club), general public venue (bars, KTV, parks, shopping malls, schools, restaurants) (OR=1.46-3.12, P<0.01) showed close relation with strong ties. Our finding showed that MSM at the age of 18-25 preferred to build weak ties with the older MSM, while the 26-30-year-olds and 31-40-year-olds prefer to establish weak ties with younger partners but the 41-50-year-olds preferred to develop weak ties with one that were ten years younger. Conclusions: Clusters were noticed in the MSM populations when grouping and making friends with ones at different age. Characteristics regarding the relationship between sexual partners in choosing venues and ways of dating were different. Targeted intervention programs need to be explored innovatively.
Coitus ; Cross-Sectional Studies ; Homosexuality, Male/psychology* ; Humans ; Interpersonal Relations ; Male ; Middle Aged ; Recreation ; Risk-Taking ; Schools ; Sexual Behavior ; Sexual Partners ; Social Behavior ; Surveys and Questionnaires