[Association between chronic lung diseases and the risk of lung cancer in UK Biobank: observational and Mendelian randomization analyses].

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q1, Q3)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.

[China guideline for the screening and early detection of female breast cancer(2021, Beijing)].

Breast cancer is the commonest malignant tumor among Chinese females, ranking first in terms of incidence of female cancers. Commissioned by the Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China, the National Cancer Center formulated the Guideline for Screening and Early Diagnosis and Treatment of Female Breast Cancer in China according to WHO Handbook for Guideline Development. The methods on Cochrane China were referred to for the formulation of the system evaluation procedures. The GRADE methods for assessment, formulation and evaluation were adopted for the classification of evidence quality and recommendation strength, and the items were reported according to Reporting Items for Practice Guidelines in Healthcare. Based on the results of evaluation, the guideline gives evidence-based recommendations for the appropriate population and technical procedures for breast cancer screening and early diagnosis and treatment after comprehensive consideration of China's national conditions, the advantages and disadvantages of the evidence, the quality of the evidence, the economic cost of screening, the feedback of multidisciplinary clinical research respondents, and in-person expert consensus. It is aimed at regulating the practices of female breast cancer screening and early diagnosis and treatment and enhancing the effectiveness of the prevention and control of female breast cancer in China.

[China guideline for the screening and early detection of lung cancer(2021, Beijing)].

In China, the malignant tumor with the highest incidence and motality is lung cancer (LC). As screening and early detection and treatment are effective in reducing LC mortality, formulating a guideline in line with China's national conditions for the screening and early detection and treatment of LC will greatly promote the homogeneity and accuracy of LC screening, and result in an improvement of the effectiveness of LC screening. Commissioned and directed by the Disease Prevention and Control Bureau of the National Health Commission of the People's Republic of China, the guidline was initiated by the National Cancer Center of China and formulated with joint effort by experts from different disciplines. Following the principles and methods in WHO Handbook for Guideline Development, the guidline integrates the latest development in LC screening and early diagnosis and treatment worldwide while fully considering China's national conditions and practical experience in LC screening. It provides detailed evidence-based recommendations for different aspects of LC screening, such as the targeted population, the technologies and the procedures, to regulate the practices of LC screening and early diagnosis and treatment and enhance the effectiveness of the prevention and control of LC in China.

[Advance on theoretical epidemiology models research of prevention and control of COVID-19].

COVID-19 has brought a significant impact to the global health system, and also opportunities and challenges to epidemiological researches. Theoretical epidemiological models can simulate the process of epidemic in scenarios under different conditions. Therefore, modeling researches can analyze the epidemical trend of COVID-19, predict epidemical risks, and evaluate effects of different control measures and vaccine policies. Theoretical epidemiological modeling researches provide scientific advice for the prevention and control of infectious diseases, and play a crucial role in containing COVID-19 over the past year. In this study, we review the theoretical epidemiological modeling researches on COVID-19 and summarize the role of theoretical epidemiological models in the prevention and control of COVID-19, in order to provide reference for the combination of mathematical modeling and epidemic control.

The relationship between glucose homeostasis status and prostate size in aging Chinese males with benign prostatic hyperplasia.

PURPOSE: Increasing evidence shows that many metabolic factors are involved in the progression of benign prostatic hyperplasia (BPH). We aimed to assess the relationship between the status of glucose homeostasis and prostate size in aging Chinese males undergoing transurethral resection of the prostate (TURP) for BPH. METHODS: A total of 1006 medical records of BPH patients undergoing TURP were reviewed. Prostate size was measured by transrectal ultrasound. Annual total prostate (TP) and transitional zone (TZ) growth rates were calculated. According to the American Diabetes Association criteria, the patients were categorized as normoglycemic, prediabetic, or diabetic. Levels of glucose homeostasis and other variables were considered independent variables in an effort to evaluate any potential correlations using non-adjusted and multivariate-adjusted regression models. RESULTS: A total of 659 individuals were included in the study. BPH patients < 70 years old and ≥ 70 years old in the normoglycemic group had a stable prostate growth rate. The change in prostate size in those younger than 70 years, however, was faster in the prediabetic and diabetic group. Further analysis revealed that abnormal glucose homeostasis was positively correlated with prostate size. In those younger than 70 years, compared with the normal glucose group, the adjusted odds ratio (OR) for TP and TZ enlargement in the prediabetic group was 2.27 (95%CI 1.29-4.00) and 3.19 (95%CI 1.78-5.72), respectively, and the adjusted ORs were 4.74 (95%CI 2.18-10.30) and 6.16 (95%CI 2.70-14.06), respectively, for men with diabetes. However there was no significant difference among men aged ≥ 70 years. CONCLUSIONS: Among patients undergoing TURP, the prostate volume and growth rate were affected by different status of glucose homeostasis. Hyperglycemia may play an important role in prostate growth.

[Principles of dynamics model and its application in forecasting the epidemics and evaluation the efforts of prevention and control interventions].

During the epidemics of COVID-19 in domestic China and recently continuing rapid spread worldwide, a bunch of studies fitted the epidemics by transmission dynamics model to nowcast and forecast the trend of epidemics of COVID-19. However, due to little known of the new virus in early stage and much uncertainty in the comprehensive strategies of prevention and control for epidemics, majority of models, not surprisingly, predict in less accuracy, although the dynamics model has its great value in better understanding of transmission. This comment discusses the principle assumptions and limitations of the dynamics model in forecasting the epidemic trend, as well as its great potential role in evaluating the efforts of prevention and control strategies.

[Thoughts on the reform of preventive medicine education in the context of new medicine].

Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.

[Construction of urban scale-free network model and its epidemiological significance in the prevention and control of COVID-19].

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

[Data management and quality control strategies for population based cohort study].

Large-scale cohort study has unique advantages in the field of etiology research for its large sample size a multi-time point data, but it also brings great difficulty in data management and quality control at the same time. Recently, China has initiated a number of large-scale population cohort studies, posing enormous challenges to the management and quality control of related cohort data. This paper summarizes the existing experience and consensus in the field of cohort study in China from the characteristics of the cohort data, aiming at the types and main forms of the four main sources of questionnaire data, clinical diagnosis and treatment data, biological sample detection data and observation outcome data, from the data storage, circulation and transmission work.The contents and methods of queue data management are comprehensively summarized. Corresponding data quality control strategies are advised in the questionnaire evaluation, data logic verification, survey object sampling and multi-database review, etc. The goal of this review is to provide guidance for the management of data and the formulation of quality control strategies in the cohort study in China.

[Clinical value of classified detection of circulating tumor cells in peripheral blood of NSCLC patients].

OBJECTIVE: To investigate the clinical value of detection of circulating tumor cells (CTCs) classified by epithelial cell adhesion molecule (EpCAM) in peripheral blood of patients with non-small cell lung cancer (NSCLC). METHODS: Peripheral blood samples (7.5 ml each time) were collected from 47 NSCLC patients. Among them, blood samples were collected at the end of each therapy-cycle in three patients for longitudinal monitoring of CTCs. CTCs were enriched by the depletion of leucocytes using a magnetic bead separation technique, stained with EpCAM, cytokeratin 7/8 and their isotypic control antibodies, respectively, and then identified and counted by multi-parameter flow cytometry. RESULTS: In the blood samples from 47 patients, EpCAM-positive CTCs were detected in 64.3%(9/14), 40.0%(4/10) and 43.5%(10/23) of patients in stages Ⅰ-Ⅱ, Ⅲ and Ⅳ, respectively. EpCAM-negative CTCs were detected in 78.6%(11/14), 90.0%(9/10) and 91.3%(21/23) of patients in stage Ⅰ-Ⅱ, Ⅲ, and Ⅳ, respectively. The total detection rates of EpCAM-positive and EpCAM-negative CTCs were 48.9%(23/47) and 87.2%(41/47), respectively, showing a statistically significant difference between them (P<0.001). According to the stage of the cancer, there was a significant difference between the detection rates of the two types of CTCs in patients of stage Ⅳ(P=0.001), but not in stage Ⅰ-Ⅱ and Ⅲ (P>0.05). The number of EpCAM-negative CTCs was significantly higher than that of EpCAM-positive CTCs in all stages (P<0.05). The frequency of patients with the percentage of EpCAM-negative CTCs >90% was significantly higher in stage Ⅳ patients than that in stage Ⅰ-Ⅱ cases (P=0.030), while the frequency of patients with the percentage of EpCAM-negative CTCs between 50%~90% was significantly lower in the stage Ⅳ than that in the stage Ⅰ-Ⅱ patients (P=0.001). The treatment of most patients with EpCAM-negative CTCs >50% showed to be ineffective (P=0.033). CONCLUSION: Detection of CTCs classified by EpCAM in peripheral blood is helpful in evaluating the distant metastasis and treatment effectiveness of NSCLC patients.

[DNA damage associated genetic variants contribute to lung cancer susceptibility in a Han Chinese population].

OBJECTIVE: To explore the association between DNA damage-related genetic variants and lung cancer susceptibility in a Han Chinese population. METHODS: This case-control study enrolled patients from the Cancer Hospital of Jiangsu Province and Jiangsu Province Hospital from 2003 to 2009. Controls were randomly selected from individuals who visited the same hospital or a community-based health examination program during the same time period. A 5 ml venous blood sample was obtained from each participant and epidemiological information was collected on a standard questionnaire. Illumina Infinium(®) BeadChip was used for genotyping of 35 DNA damage-related single nucleotide variations (SNVs), which were identified in our previous study. Multivariate and binary logistic regressions were used to calculate the OR and 95%CI for lung cancer risk. HaploReg V4.1 and Regulome DB were used to understand functional annotation on important SNV. RESULTS: The distributions of age (61.06±10.15) vs. (61.32±11.07) years; t=-0.72, P=0.473) and sex (χ(2)=1.81, P=0.179) were similar between cases and controls. However, the case group had a higher frequency of smokers (61.08% vs. 48.54%; χ(2)=50.04, P<0.001) and heavy smokers (42.28% vs. 24.07%; χ(2)=122.32, P<0.001). Among the 34 SNVs that passed quality control, two SNVs were significantly associated with lung cancer risk after adjustments for age, sex and cumulative smoking dose: rs9267576 C>A (CA genotype/CC genotype, OR=1.56, 95% CI: 1.01-2.40) and rs3130683 A>G (AG genotype/AA genotype, OR=1.87, 95%CI: 1.13-3.09). After step-wise logistic regression analysis, only the rs3130683 SNV was retained in the model, indicating that the association between rs9267576 and lung cancer may be due to the effect of rs3130683. Functional annotation indicated that rs3130683 was located in the promoter and enhancer regions, and was an expression quantitative trait loci of HLA. The Cancer Genome Atlas indicated that expression of HLA-C, DQB1, DRB1 and DRB5 in lung cancer tissue was significantly lower than in paired normal tumor-adjacent tissue, with down-regulation of the four respective genes in 81.3%, 88.8%, 90.7% and 90.7% of lung cancer tissues (P-values were 6.68×10(-15), 2.21×10(-13), 2.20×10(-16), 2.58×10(-13), respectively). CONCLUSIONS: The SNV rs3130683 (A>G) was associated with the risk of lung cancer in a Han Chinese population. This SNV may affect the risk of lung cancer by regulating HLA expression.

Hepatitis C virus infection and risk factors in the general population: a large community-based study in eastern China, 2011-2012.

Limited information is available on the prevalence of hepatitis C virus (HCV) in the general population in China. A community-based epidemiological study was conducted in three counties in eastern China. A total of 149 175 individuals were investigated in 60 communities in three counties in Jiangsu province, eastern China, of whom 1175 subjects [0·79%, 95% confidence interval (CI) 0·74-0·83] were HCV antibody positive. The prevalence was low in children (0·09%, 95% CI 0·04-0·17), but increased progressively from adolescents (0·20%, 95% CI 0·15-0·28) to adults aged ⩾21 years (95% CI 0·15-1·64). Women had a higher prevalence of HCV infection than men in most age groups. In a multilevel regression analysis, age, sex, education, occupation, blood transfusion [odds ratio (OR) 2·91, 95% CI 1·09-5·37], invasive testing (OR 1·28, 95% CI 1·14-1·61), and dental therapy (OR 2·27, 95% CI 1·41-3·42) were associated with HCV infection. In conclusion, although the prevalence of HCV in this population was lower than reported from national levels, the total reservoir of infection is significant and warrants public health measures, such as health education to limit the magnitude of the problem.

Effect of functional nuclear factor-kappaB genetic polymorphisms on hepatitis B virus persistence and their interactions with viral mutations on the risk of hepatocellular carcinoma.

BACKGROUND: Nonresolving inflammation and viral mutations are important in hepatitis B virus (HBV)-induced hepatocarcinogenesis. However, the effects of genetic polymorphisms affecting nuclear factor-kappaB (NF-κB) on HBV persistence and generation of hepatocellular carcinoma (HCC)-related HBV mutations remain unknown. PATIENTS AND METHODS: rs28362491 (NFKB1 -94Ins > Del), rs2233406 (NFKBIA -826C > T), rs3138053 (NFKBIA -881A > G), and rs696 (NFKBIA +2758G > A) were genotyped in 1342 healthy controls, 327 HBV-clearance subjects, and 3976 HBV-positive subjects including 1495 HCC patients, using quantitative PCR. HBV mutations were determined by sequencing. The NFKBIA promoter activity was assessed by transient transfection. Multiplicative interactions of the polymorphisms and viral mutations were assessed by multivariate logistic regression. RESULTS: Compared with HBV-clearance subjects, rs2233406 (CT versus CC) and rs3138053 (AG or AG + GG versus AA) significantly decreased HBV persistence, especially in the genotype B HBV-infected subjects. In the genotype C HBV-infected subjects, rs2233406 variant genotypes were significantly associated with an increased risk of HCC [CT versus CC: age-, gender-adjusted odds ratio (AOR), 1.33; 95% confidence interval (CI) 1.01-1.75 in training set and AOR, 1.59; 95% CI 1.01-2.52 in validation set] compared with HCC-free HBV-infected subjects and significantly increased the frequencies of HCC-related HBV mutations (A1762T/G1764A, T1753V, preS1 start codon mutation, and preS deletion); rs28362491 (Del/Del or Ins/Del + Del/Del versus Ins/Ins) significantly increased the frequency of A1762T/G1764A and reduced the frequency of preS2 start codon mutation. The variant genotypes impaired NFKBIA promoter activity in hepatic cells. The interaction of rs2233406 variant genotypes (CT + TT versus CC) with A1762T/G1764A significantly increased HCC risk in genotype C HBV-infected subjects, with AOR of 2.61 (95% CI 1.09-6.26). CONCLUSION: Genetic polymorphisms improving NF-κB activity contribute to genotype B HBV clearance. The rs2233406 variant genotypes significantly increase HCC risk, possibly via facilitating immune selection of the HBV mutations. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

High-efficiency diode-pumped actively Q-switched ceramic Nd:YAG/BaWO4 Raman laser operating at 1666 nm.

A diode-pumped actively Q-switched Raman laser employing BaWO4 as the Raman active medium and a ceramic Nd:YAG laser operating at 1444 nm as the pump source is demonstrated. The first-Stokes-Raman generation at 1666 nm is achieved. With a pump power of 20.3 W and pulse repetition frequency rate of 5 kHz, a maximum output power of 1.21 W is obtained, which is the highest output power for a 1.6 µm Raman laser. The corresponding optical-to-optical conversion efficiency is 6%; the pulse energy and peak power are 242 µJ and 8.96 kW, respectively.

High efficiency Nd:YAG ceramic eye-safe laser operating at 1442.8 nm.

We report on a diode-pumped Nd:YAG ceramic laser operating at 1442.8 nm for the first time. In our experiment, two different Nd:YAG ceramics with the Nd-doped concentrations of 1.0 and 0.6 at. % and a Nd:YAG with the Nd-doped concentration of 1.0 at. % were used as the laser gain mediums, respectively. At a pump power of 20.7 W, a maximum output power of up to 3.96 W with optical-to-optical efficiency of up to 19.1% was obtained by using the 1.0 at. % Nd-doped ceramic as the laser gain medium. To the best of our knowledge, this is the highest output power of a LD-pumped 1.44 µm Nd:YAG ceramic laser and the highest optical-to-optical efficiency of a LD-pumped 1.44 µm Nd-doped crystal laser.

[Multi-omics approaches for revealing the etiology of cancer: from genomics, exposomics, metabolomics to system epidemiology].

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.

[Rethinking of institutional reform and development of disease control and prevention system in post COVID-19 epidemic era in China].

The problems and shortcomings revealed in our response to COVID-19 epidemic have suggested us to take measures to improve the disease control and prevention system of China. For the reform and development of China's disease control and prevention institution in the new era,we need to rethink the function orientation of the disease control and prevention institution, the key and difficult points in institutional mechanism reform and the building of core competence and essential capacity of disease control and prevention system.

[Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence].

Objective: To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence. Methods: After excluding individuals with missing educational levels and cancer information at baseline, 446 772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer. Results: During a median follow-up of 7.13 years, 1 994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer (HR=0.88, 95%CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self-report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95%CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with ß coefficients (95%CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score (ß=0.042, 95%CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95%CI: 31.802%-51.659%) and 1.784% (95%CI: 0.405%-3.713%), respectively. Conclusion: Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

[Progress in metabolomics epidemiology].

In recent years, with the rapid development of metabonomic technology and analytic methods, metabolomics epidemiology, as an important branch of systems epidemiology, attracts more attention. Metabolomics epidemiology can better describe the characteristics of exposure, reflect the interaction between environmental factors and genetics, uncover the "black box" of the mechanisms underlying exposure and disease, and identify new biomarkers. This article briefly introduces the definition, methods, and progress of metabolomics epidemiology.