China guideline for liver cancer screening (2022, Beijing) / 临床肝胆病杂志

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous exploration. To address this pressing issue, the Bureau of Disease Control and Prevention of the National Health Commission commissioned this guideline. The National Cancer Center of China initiated the guideline development and convened a multidisciplinary expert panel and working groups. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China's national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help standardize the practice of liver cancer screening in China.

China guideline for liver cancer screening (2022, Beijing) / 中华消化外科杂志

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous explora-tion. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated the guideline develop-ment and convened a multidisciplinary expert panel and working group. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China′s national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help to standardize the practice of liver cancer screening in China.

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma / 医学前沿

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

China guideline for the screening and early detection of lung cancer(2021, Beijing) / 中国综合临床

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 / 中华预防医学杂志

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.

No association between circulating levels of testosterone and sex hormone-binding globulin and risk of COVID-19 mortality in UK biobank

Background: Sex-disaggregated data suggest that men with coronavirus disease 2019 (COVID-19) are more likely to die than women. Whether circulating testosterone or sex hormone-binding globulin (SHBG) contributes to such sex differences remains unknown. Objective: To evaluate the associations of circulating total testosterone (TT), free testosterone (FT), and SHBG with COVID-19 mortality. Design: Prospective analysis. Setting: UK Biobank. Participants: We included 1306 COVID-19 patients (678 men and 628 women) who had serum TT and SHBG measurements and were free of cardiovascular disease or cancer at baseline (2006-2010). Main outcome measures: The death cases of COVID-19 were identified from National Health Service death records updated at 31 July 2020. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CI) for mortality. Results: We documented 315 deaths of COVID-19 (194 men and 121 women). After adjusting for potential confounders, we did not find any statistically significant associations for TT (OR per 1-SD increase = 1.03, 95% CI: 0.85-1.25), FT (OR per 1-SD increase = 0.95, 95% CI: 0.77-1.17), or SHBG (OR per 1-SD increase = 1.09, 95% CI: 0.87-1.37) with COVID-19 mortality in men. Similar null results were observed in women (TT: OR per 1-SD increase = 1.10, 95% CI: 0.85-1.42; FT: OR per 1-SD increase = 1.10, 95% CI: 0.82-1.46; SHBG: OR per 1-SD increase = 1.16, 95% CI: 0.89-1.53). Conclusions: Our findings do not support a significant role of circulating testosterone or SHBG in COVID-19 prognosis.

Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank

BackgroundCoronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. ObjectiveTo investigate the association between circulating IGF-1 concentrations and mortality risk among COVID-19 patients. DesignProspective analysis. SettingUK Biobank. Participants1425 COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010). Main outcome measuresCOVID-19 mortality (available death data updated to 22 May 2020). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality across the IGF-1 quartiles. ResultsAmong 1425 COVID-19 patients, 365 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 37% lower risk of mortality (OR: 0.63, 95% CI: 0.43-0.93, P-trend=0.03). The association was stronger in women and nonsmokers (both P-interaction=0.01). ConclusionsHigher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.

A systematic review and meta-analysis reveals long and dispersive incubation period of COVID-19

BackgroundThe incubation period of SARS-CoV-2 remains uncertain, which has important implications for estimating transmission potential, forecasting epidemic trends, and decision-making in prevention and control. PurposeTo estimate the central tendency and dispersion for incubation period of COVID-19 and, in turn, assess the effect of a certain length of quarantine for close contacts in active monitoring. Data SourcesPubMed, Embase, medRxiv, bioRxiv, and arXiv, searched up to April 26, 2020 Study SelectionCOVID-19 studies that described either individual-level incubation period data or summarized statistics for central tendency and dispersion measures of incubation period were recruited. Data ExtractionFrom each recruited study, either individual-level incubation period data or summarized statistics for central tendency and dispersion measures were extracted, as well as population characteristics including sample size, average age, and male proportion. Data SynthesisFifty-six studies encompassing 4 095 cases were included in this meta-analysis. The estimated median incubation period for general transmissions was 5.8 days [95% confidence interval (95%CI), 5.3 to 6.2 d]. Median and dispersion were higher for SARS-CoV-2 incubation compared to other viral respiratory infections. Furthermore, about 20 in 10 000 contacts in active monitoring would develop symptoms after 14 days, or below 1 in 10 000 for young-age infections or asymptomatic transmissions. LimitationSmall sample sizes for subgroups; some data were possibly used repeatedly in different studies; limited studies for outside mainland China; non-negligible intra-study heterogeneity. ConclusionThe long, dispersive incubation period of SARS-CoV-2 contributes to the global spread of COVID-19. Yet, a 14-day quarantine period is sufficient to trace and identify symptomatic infections, which while could be justified according to a better understanding of the crucial parameters.

Isolating multiple formats of human monoclonal neutralizing antibodies against SARS-CoV-2 by in vitro site-directed antibody screening

Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19.

Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China

BackgroundPrevious studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. MethodsEpidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. FindingsNone of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. InterpretationThe asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.

Principles of dynamics model and its application in forecasting the epidemics and evaluation the efforts of prevention and control interventions / 中华预防医学杂志

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 evaluation the efforts of prevention and control strategies.

Prediction modeling with data fusion and prevention strategy analysis for the COVID-19 outbreak / 中华流行病学杂志

Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.

Study on genetic structure differences and adjustment strategies in different areas of China / 中华流行病学杂志

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 fast 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.

Study on genetic structure differences and adjustment strategies in different areas of China / 中华流行病学杂志

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 fast 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.

Application of polygenic risk scores in risk prediction and precision prevention of complex diseases: opportunities and challenges / 中华流行病学杂志

Along with the rapid progress in the field of human genomics, genome-wide association studies have successfully identified numerous risk loci for complex diseases. Polygenic risk scores can predict disease risk by integrating the effects of multiple susceptibility loci, and begin to show good performance for improving risk prediction, screening strategy and precision prevention. This paper briefly reviews the recent progress of polygenic risk scores in disease prevention, and summarizes the opportunities and challenges of its application.

Integrated case teaching based on clinical competency in Nanjing Medical University / 中华医学教育探索杂志

Curriculum integration and problem based learning (PBL) is the development trend of medical education all over the world,and it is an effective mode to train high-quality medical talents to meet the needs of the times and national medical and health services.However,PBL is difficult to popularize in an all-round way at present due to the large enrollment of clinical medicine major in medical colleges and universities in China.Aiming at integrating knowledge and focusing on ability,Nanjing Medical University implemented a problem-based two-way integrated case teaching after top-level design,careful trial and steady promotion and has achieved initial results and improved the clinical competency of medical students.

Low-dose CT for lung cancer screening: opportunities and challenges / 医学前沿

Lung cancer is among the most frequently diagnosed cancers worldwide and the leading cause of cancer death in both males and females. Screening for lung cancer coupled with earlier intervention has long been studied as an approach to mortality reduction. However, minimal progress was achieved until recently, when lowdose spiral computed tomography (LDCT) screening demonstrated a 20% reduction in mortality from lung cancer in a randomized controlled trial (RCT), the National Lung Screening Trial, from the United States. On the basis of this finding, LDCT has been recommended for lung cancer screening in high-risk populations by several clinical guidelines. However, results from the following independent RCTs in Europe failed to show consistent conclusions. In addition, intractable problems gradually emerged with the progress of LDCTscreening. This paper summarizes and discusses the main observations and challenges of LDCT screening for lung cancer. Before spreading implementation of LDCTscreening, challenges, including high false-positive rates, overdiagnosis, enormous costs, and radiation risk, must be addressed. Complementary biomarkers and technical improvement are expected in the field of lung cancer screening in the near future.

Data management and quality control strategies for population based cohort study / 中华预防医学杂志

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.

Family History and Stroke Risk in China: Evidence from a Large Cohort Study / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 0.5 million Chinese adults. METHODS: Information about FHS was self-reported. The median follow-up time was 7.16 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system. Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests. RESULTS: Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number of first degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively, P(trend) <0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for sibling history and parental history, respectively. Similar associations with offspring stroke risk were observed between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49, 95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking). CONCLUSIONS: FHS is an independent risk factor for stroke in Chinese. The more first degree relatives are affected by stroke, the higher are individuals’ risk of suffering from stroke. The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS.

Analysis of projects of infectious disease epidemiology sponsored by Nation-al Natural Science Foundation of China / 中国血吸虫病防治杂志

Objective To analyze the projects on the infectious disease epidemiology sponsored by the National Natural Sci?ence Foundation of China(NSFC),explore the hotspot and development trend,and offer a reference for researchers in this field. Methods Based on the NSFC database,the projects on the infectious disease epidemiology(H2609)sponsored from 1987 to 2014 were analyzed. The changes of fund numbers,amounts and research fields were described. Results During the study period,NSFC sponsored 373 projects,including 228 general projects(61.1%),78 youth projects(20.9%)and 67 other projects(18.0%). The average amount of the grant was 358.2 thousand Yuan(20 thousand?8 million). The main sponsored re?search fields were mechanisms of pathogen and immunity(36.2%)and population?based epidemiological studies(33.0%). The top three diseases were hepatitis,HIV/AIDS and tuberculosis. Conclusion The amount of funding on researches of infectious disease epidemiology has increased continuously,which has played an important role in training scientific talents in the field of prevention and control of infectious diseases.