Publications by authors named "Hai Fang"

158 Publications

Integration of genomic and transcriptomic markers improves the prognosis prediction of acute promyelocytic leukemia.

Clin Cancer Res 2021 Apr 23. Epub 2021 Apr 23.

Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from ATRA-chemotherapy to ATRA-ATO-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed.

Patients And Methods: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator (LASSO) algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score).

Results: Through combining NRAS mutations, APL9 score with WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset.

Conclusions: We have proposed a two-category system improving prognosis in APL patients. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4375DOI Listing
April 2021

Transcriptomic Analysis of Inflammatory Cardiomyopathy Identifies Molecular Signatures of Disease and Informs Prediction of a Network-Based Rationale for Therapy.

Front Immunol 2021 5;12:640837. Epub 2021 Mar 5.

RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom.

Inflammatory cardiomyopathy covers a group of diseases characterized by inflammation and dysfunction of the heart muscle. The immunosuppressive agents such as prednisolone, azathioprine and cyclosporine are modestly effective treatments, but a molecular rationale underpinning such therapy or the development of new therapeutic strategies is lacking. We aimed to develop a network-based approach to identify therapeutic targets for inflammatory cardiomyopathy from the evolving myocardial transcriptome in a mouse model of the disease. We performed bulk RNA sequencing of hearts at early, mid and late time points from mice with experimental autoimmune myocarditis. We identified a cascade of pathway-level events involving early activation of cytokine and chemokine-signaling pathways that precede leucocyte infiltration and are followed by innate immune, antigen-presentation, complement and cell-adhesion pathway activation. We integrated these pathway events into a network-like representation from which we further identified a 50-gene subnetwork that is predominantly induced during the course of autoimmune myocardial inflammation. We developed a combinatorial attack strategy where we quantify network tolerance to combinatorial node removal to determine target-specific therapeutic potential. We find that combinatorial attack of , and disconnects 80% of nodes from the largest network component. Two of these nodes, and , are directly targeted by prednisolone and azathioprine respectively, supporting the idea that the methodology developed here can identify valid therapeutic targets. Whereas and removal disconnects 56% of nodes, we show that additional removal of and causes 72% node disconnection. In conclusion, transcriptome profiling, pathway integration, and network identification of autoimmune myocardial inflammation provide a molecular signature applicable to the diagnosis of inflammatory cardiomyopathy. Combinatorial attack provides a rationale for immunosuppressive therapy of inflammatory cardiomyopathy and provides an prediction that the approved therapeutics, ibrutinib and idelalisib targeting and respectively, could potentially be re-purposed as adjuncts to immunosuppression.
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http://dx.doi.org/10.3389/fimmu.2021.640837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973371PMC
March 2021

Genetic Interaction Network Interpretation: A Tidy Data Science Perspective.

Authors:
Lulu Jiang Hai Fang

Methods Mol Biol 2021 ;2212:347-376

National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

As practitioners, we aim to provide a consolidated introduction of tidy data science along with routine packages for relational data representation and interpretation, with the focus on analytics related to human genetic interactions. We describe three showcases (also made available at https://23verse.github.io/gini ), all done so via the R one-liner, in this chapter defined as a sequential pipeline of elementary functions chained together achieving a complex task. We guide the readers through step-by-step instructions on (case 1) performing network module analysis of genetic interactions, followed by visualization and interpretation; (case 2) implementing a practical strategy of how to identify and interpret tissue-specific genetic interactions; and (case 3) carrying out interaction-based tissue clustering and differential interaction analysis. All showcases demonstrate simplistic beauty and efficient nature of this analytics. We anticipate that mastering a dozen of one-liners to efficiently interpret genetic interactions is very timely now; opportunities for computational translational research are arising for data scientists to harness therapeutic potential of human genetic interaction data that are ever-increasingly available.
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http://dx.doi.org/10.1007/978-1-0716-0947-7_22DOI Listing
April 2021

Willingness to pay and financing preferences for COVID-19 vaccination in China.

Vaccine 2021 04 27;39(14):1968-1976. Epub 2021 Feb 27.

China Center for Health Development Studies, Peking University, Beijing 100083, China; Peking University Health Science Center-Chinese Center for Disease Control and Prevention Joint Center for Vaccine Economics, Beijing 100083, China; Key Laboratory of Reproductive Health National Health Commission of the People's Republic of China, Beijing 100083, China. Electronic address:

Background: The COVID-19 pandemic has caused significant diseases and economic burdens in the world. Vaccines are often considered as a cost-effective way to prevent and control infectious diseases, and the research and development of COVID-19 vaccines have been progressing unprecedently. It is needed to understand individuals' willingness to pay (WTP) among general population, which provides information about social demand, access and financing for future COVID-19 vaccination.

Objective: To investigate individuals' WTP and financing mechanism preference for COVID-19 vaccination during the pandemic period in China.

Methods: During March 1-18, 2020, we conducted a network stratified random sampling survey with 2058 respondents in China. The survey questionnaires included out-of-pocket WTP, financing mechanism preference as well as basic characteristics of the respondents; risk perception and impact of the COVID-19 pandemic; attitude for future COVID-19 vaccination. Multivariable Tobit regression was used to determine impact factors for respondents' out-of-pocket WTP.

Results: The individuals' mean WTP for full COVID-19 vaccination was CNY 254 (USD 36.8) with median of CNY 100 (USD 14.5). Most respondents believed that governments (90.9%) and health insurance (78.0%) needed to pay for some or full portions of COVID-19 vaccination, although 84.3% stated that individuals needed to pay. Annual family income, employee size in the workplace, and whether considering the COVID-19 pandemic in China in a declining trend affected respondents' WTP significantly.

Conclusion: The findings demonstrated the individuals' WTP for COVID-19 vaccination in China and their preferences for financing sources from individuals, governments and health insurance. And to suggest an effective and optimal financing strategy, the public health perspective with equal access to COVID-19 vaccination should be prioritized to ensure a high vaccination rate.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914003PMC
April 2021

The Association Between Panel Size and Health Outcomes of Patients with Hypertension in Urban China: a Population-Based Retrospective Cohort Study.

J Gen Intern Med 2021 Mar 10. Epub 2021 Mar 10.

China Center for Health Development Studies, Peking University, Beijing, China.

Background: There is a paucity of evidence regarding the association between family physicians' panel size and health outcomes of patients with hypertension in China.

Objective: To examine the association between family physicians' panel size and health outcomes of patients with hypertension in urban China.

Design: This retrospective cohort study during 1 contract year from July 1, 2018, to June 31, 2019, was set in four community health centers (CHCs) in Xiamen City, China.

Participants: A total of 18,119 adult patients (18+) diagnosed with hypertension and their 61 family physicians were included.

Main Measures: Family physicians' panel size was measured by the number of registered patients in the preceding 6 months. The outcome measures included blood pressure (BP) control rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) measured at each follow-up visit.

Key Results: Every additional 100 patients to the panel size were associated with an average of 17% increase in BP control rate (95% confidence interval [CI] = 1.15 to 1.19), and decrease in SBP (- 0.3 mmHg, 95% CI: - 0.38 to - 0.30), DBP (- 0.4 mmHg, 95% CI: - 0.39 to - 0.34), and MAP (- 0.4 mmHg, 95% CI: - 0.38 to - 0.33). After entering the quadratic term of panel size in the model, the panel size was negatively associated with BP control rate and positively associated with SBP, DBP, and MAP, while for the quadratic term, the odds ratio for BP control rate was positive and the coefficients for SBP, DBP, and MAP were negative. A U-shape association was found between panel size and health outcomes of patients with hypertension, and the turning point was about 600 patients.

Conclusions: The panel size of family physicians was curvilinearly associated with health outcomes of patients with hypertension in urban China.
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http://dx.doi.org/10.1007/s11606-021-06681-0DOI Listing
March 2021

The Changing Acceptance of COVID-19 Vaccination in Different Epidemic Phases in China: A Longitudinal Study.

Vaccines (Basel) 2021 Feb 25;9(3). Epub 2021 Feb 25.

China Center for Health Development Studies, Peking University, Beijing 100083, China.

COVID-19 vaccines have been conditionally used in a few countries, including China since December 2020. The present study aimed to examine whether the acceptance of COVID-19 vaccination changed in different COVID-19 epidemic phases in China. Two consecutive surveys were conducted among Chinese adults in March ( = 2058) (severe epidemic phase) and November-December ( = 2013) (well-contained phase, right before the COVID-19 vaccine was conditionally approved) 2020, and 791 respondents were longitudinally followed-up. The attitude, acceptance, and preferences for future COVID-19 vaccination were compared between two epidemic phases. Multivariate logistic regression was used to identify influencing factors of acceptance. Among the 791 respondents longitudinally followed, 91.9% in March and 88.6% of them in November-December 2020 would like to get COVID-19 vaccination in China. In March 58.3% wished to get vaccinated immediately, but the proportion declined to 23.0% in November-December 2020, because more respondents wanted to delay vaccination until the vaccine's safety was confirmed. Similar results were found by comparing all respondents from the two cross-sectional surveys in different epidemic phases. The risk perception, attitude for the importance of vaccination against COVID-19, vaccination history, valuing doctor's recommendations, vaccination convenience, or vaccine price in decision-making had impacts on respondents' intention for immediate vaccination. The public acceptance for COVID-19 vaccination in China sustained at a high level in different COVID-19 epidemic phases. However, the intention of immediate vaccination declined substantially due to concerns about the vaccine's safety. Information about vaccination safety from authoritative sources, doctor's recommendations, and vaccination convenience were important in addressing vaccine hesitancy and promoting successful herd immunity for the general population in China.
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http://dx.doi.org/10.3390/vaccines9030191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996493PMC
February 2021

Phase 4 Safety and Efficacy Study of Antihemophilic Factor (Recombinant) in Previously Treated Chinese Patients With Severe/Moderately Severe Hemophilia A.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029621989811

Baxalta Innovations GmbH, a Takeda Company, Vienna, Austria.

Antihemophilic factor (recombinant) (rAHF; ADVATE; Baxalta US Inc., a Takeda company, Lexington, MA, USA) is indicated for the treatment and prevention of bleeding in patients with hemophilia A. We aimed to assess the safety and efficacy of standard prophylaxis versus on-demand treatment with rAHF in previously treated Chinese patients with severe/moderately severe hemophilia A. This open-label, sequential, interventional, postapproval study (NCT02170402) conducted in China included patients of any age with hemophilia A with factor VIII (FVIII) level ≤2%. Patients received 6 months' on-demand rAHF then 6 months' rAHF prophylaxis (20-40 IU/kg every 48 ± 6 hours). The primary objective was percentage reduction in annualized bleeding rate (ABR) in the per-protocol analysis set (PPAS); secondary objectives included ABR by bleeding subtype, hemostatic efficacy, immunogenicity, and safety. Of 72 patients who received ≥1 rAHF dose, 61 were included in the PPAS. Total ABR was lower during prophylaxis (mean 2.5, 95% CI 1.5-3.7; median 0) versus on-demand treatment (mean 58.3, 95% CI 52.5-64.7; median 53.9), representing a 95.9% risk reduction. Similar findings in favor of prophylaxis were observed for all types of bleeding event by cause and location. rAHF hemostatic efficacy was rated as "excellent"/"good" in 96.1% of treated bleeding events. Transient FVIII inhibitors (0.6-1.7 BU) in 4 patients resolved before study end; no unexpected safety issues were observed. rAHF prophylaxis in this study of previously treated Chinese patients with severe/moderately severe hemophilia A resulted in a clear reduction in bleeding events versus rAHF on-demand treatment, with no change in safety profile.
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http://dx.doi.org/10.1177/1076029621989811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890741PMC
February 2021

Parental Vaccine Preferences for Their Children in China: A Discrete Choice Experiment.

Vaccines (Basel) 2020 Nov 16;8(4). Epub 2020 Nov 16.

Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

Vaccination is one of the most cost-effective health investments to prevent and control communicable diseases. Improving the vaccination rate of children is important for all nations, and for China in particular since the advent of the two-child policy. This study aims to elicit the stated preference of parents for vaccination following recent vaccine-related incidents in China. Potential preference heterogeneity was also explored among respondents. A discrete choice experiment was developed to elicit parental preferences regarding the key features of vaccines in 2019. The study recruited a national sample of parents from 10 provinces who had at least one child aged between 6 months and 5 years old. A conditional logit model and a mixed logit model were used to estimate parental preference. A total of 598 parents completed the questionnaire; among them, 428 respondents who passed the rational tests were analyzed. All attributes except for the severity of diseases prevented by vaccines were statistically significant. The risk of severe side effects and protection rates were the two most important factors explaining parents' decisions about vaccination. The results of the mixed logit model with interactions indicate that fathers or rural parents were more likely to vaccinate their children, and children whose health was not good were also more likely to be vaccinated. In addition, parents who were not more than 30 years old had a stronger preference for efficiency, and well-educated parents preferred imported vaccines with the lowest risk of severe side effects. When deciding about vaccinations for their children, parents in China are mostly driven by vaccination safety and vaccine effectiveness and were not affected by the severity of diseases. These findings will be useful for increasing the acceptability of vaccination in China.
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http://dx.doi.org/10.3390/vaccines8040687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712304PMC
November 2020

How Can One Strengthen a Tiered Healthcare System through Health System Reform? Lessons Learnt from Beijing, China.

Int J Environ Res Public Health 2020 10 31;17(21). Epub 2020 Oct 31.

School of Public Health, Peking University, Beijing 100191, China.

How one can reshape the current healthcare sector into a tiered healthcare system with clarified division of functions between primary care facilities and hospitals, and improve the utilization of primary care, is a worldwide problem, especially for the low and middle-income countries (LMICs). This paper aimed to evaluate the impact of the Beijing Reform on healthcare-seeking behavior and tried to explain the mechanism of the change of patient flow. In this before and after study, we evaluated the changes of outpatient visits and inpatient visits among different levels of health facilities. Using the monitored and statistical data of 373 healthcare institutions 1-year before and 1-year after the Beijing Reform, interrupted time series analysis was applied to evaluate the impact of the reform on healthcare-seeking behavior. Semi-structured interviews were used to further explore the mechanisms of the changes. One year after the reform, the flow of outpatients changed from tertiary hospitals to community health centers with an 11.90% decrease of outpatients in tertiary hospitals compared to a 15.01% increase in primary healthcare facilities. The number of ambulatory care visits in primary healthcare (PHC) showed a significant upward trend ( < 0.10), and the reform had a significant impact on the average number of ambulatory care visits per institution in Beijing's tertiary hospitals ( < 0.10). We concluded that the Beijing Reform has attracted a substantial number of ambulatory care visits from hospitals to primary healthcare facilities in the short-term. Comprehensive reform policies were necessary to align incentives among relative stakeholders, which was a critical lesson for other provinces in China and other LMICs.
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http://dx.doi.org/10.3390/ijerph17218040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663312PMC
October 2020

Longitudinal Association Between Sleep Duration and Depressive Symptoms in Chinese Elderly.

Nat Sci Sleep 2020 13;12:737-747. Epub 2020 Oct 13.

China Center for Health Development Studies, Peking University, Beijing 100083, People's Republic of China.

Aim: This study aimed to evaluate the longitudinal association between sleep duration and depressive symptoms among the elderly in China.

Methods: A data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013 and 2015 was adopted with a total of 22,847 respondents aged ≥60-years-old. A linear regression analysis with generalized estimating equations was employed to examine the longitudinal associations between duration of total sleep, nighttime sleep and daytime nap, and depressive symptoms.

Results: An extra hour of total sleep including nighttime sleep and daytime nap was associated with lower incidence of depressive symptoms among the elderly after adjusting all confounders (OR=0.83, 95% CI: 0.82-0.84). In addition, an extra hour of nighttime sleep (OR=0.82, 95% CI: 0.80-0.83) or daytime nap (OR=0.93, 95% CI: 0.89-0.97) was also negatively associated with depressive symptoms among the elderly. After controlling the total sleep time, an extra hour of nighttime sleep was negatively associated with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92), while an extra hour of daytime nap displayed a positive association with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92). Compared with the moderate nappers, only extended nappers had significantly higher incidence of depressive symptoms (OR=1.32, 95% CI: 1.19 to 1.45).

Conclusion: For the elderly in China, increasing their total sleep, nighttime sleep, and/or daytime nap duration would reduce the incidence of depressive symptoms. Moreover, after fixing the total sleep time, increasing nighttime sleep was more beneficial to the decrease of the incidence of depressive symptoms than daytime nap.
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http://dx.doi.org/10.2147/NSS.S269992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569072PMC
October 2020

Prediction of V̇O2max based on a 3-kilometer running test for water sports athletes.

J Sports Med Phys Fitness 2021 Apr 22;61(4):542-550. Epub 2020 Oct 22.

Zhejiang Institute of Sports Science, Hangzhou, China -

Background: No studies have reported the 3-kilometer running test (3KRT) intending to predict V̇O2max for water sports athletes. Therefore, the purpose of this study was to develop a new model to predict the maximal aerobic capacity (V̇O2max) for water sports athletes based on 3KRT.

Methods: One hundred and two water sports athletes completed two sessions of experiments consisting of a maximal graded exercise test (GXT) and a 3KRT. Multiple linear regression was applied to predict V̇O2max value based on the performance and physiological responses of 3KRT, along with participants' anthropometric and demographic variables. The predicted residual error sum of square (PRESS) and error terms (constant error and total error) were calculated to further evaluate the predictive accuracy.

Results: Two significant prediction models based on elapsed exercise time (T3KRT), post-exercise heart rate (PHR3KRT), body mass, and gender were proposed. One model including PHR3KRT was identified (V̇O2max=120.77-0.028×T3KRT [second]-0.11×PHR3KRT [bpm]-0.334×body mass [kg]+8.70×gender [1: male, 0: female]), with an adjusted R2 of 0.723. Another model excluding PHR3KRT was also identified (V̇O2max=103.65-0.034×T3KRT [second]-0.317×Body mass [kg] + 7.89×gender [1: male, 0: female]), with an adjusted R of 0.713. Both models were further validated by the result of PRESS statistics.

Conclusions: This endurance 3-kilometer running test accurately predicted V̇O2max value for water sports athletes (rowers, canoeists, and kayakers), and the model excluding PHR3KRT would be easier to use.
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http://dx.doi.org/10.23736/S0022-4707.20.11440-3DOI Listing
April 2021

Group-based intervention to improve developmental status among children age 6-18 months in rural Shanxi province, China: a study protocol for a cluster randomised controlled trial.

BMJ Open 2020 10 19;10(10):e037156. Epub 2020 Oct 19.

Department of Integrated Early Childhood Development, Capital Institute of Pediatrics, Beijing, China

Introduction: Early childhood development (ECD) is a critical component for building the foundation of future physical and emotional health and subsequent academic success. The quality of the home environment to promote development is an important factor in ECD. Since large rural-urban disparities in the home environment exist in China, there is a critical need to develop and evaluate interventions to promote ECD in rural areas. Individual center-based or home-based interventions dominate the current ECD programmes in rural China. However, group-based interventions offer potential advantages in terms of both effectiveness and cost. Thus, we aim to: (1) evaluate the effectiveness of an integrated group-based intervention, the Care Group Intervention, in enhancing ECD among children age 6-18 months and (2) conduct a cost-effectiveness analysis.

Methods And Analysis: The Care Group Intervention uses a cluster (by township) randomised controlled trial conducted in Fenxi county, Shanxi province, China, from July 2019, for 1 year. The intervention focuses on five key components of nurturing care including good health, adequate nutrition, responsive caregiving, security and safety, and opportunities for early learning. The intervention comprises small groups of 3-10 children within a certain age range and their primary caregivers that are led by well-trained local facilitators. Outcomes includes infants' developmental quotient (Bayley Scales of Infant Development III, Ages & Stages Questionnaire: Social-Emotional, second edition); anaemia (HemoCue Hb 301+); nurturing environment (Infant/Toddler Home Observation for Measurement of the Environment), parent-child interaction (Teaching Scale) and caregiver depression (Center for Epidemiological Studies Depression). Cost data are collected throughout the entire study to carry out a cost-effectiveness analysis.

Ethics And Dissemination: This study was approved by the Ethical Committee of Capital Institute of Pediatrics, Beijing, China on 10 July 2018 (SHERLL2018014). Findings and results from this project will be disseminated via publications and presentations.

Trial Registration Number: Chinese Clinical Trials Registry: ChiCTR1900022894. Registered on 30 April 2019.
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http://dx.doi.org/10.1136/bmjopen-2020-037156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574939PMC
October 2020

Association of Sensory Impairments With Cognitive Decline and Depression Among Older Adults in China.

JAMA Netw Open 2020 09 1;3(9):e2014186. Epub 2020 Sep 1.

Department of Family Medicine, University of Michigan, Ann Arbor.

Importance: Sensory impairments may heighten the risk of premature brain aging. Little is known regarding the association of sensory impairments with cognitive function and depression in China.

Objective: To examine the association of visual and/or hearing impairments with cognitive decline and depression.

Design, Setting, And Participants: This cross-sectional study used the data from 18 038 respondents to the 2015 survey of the China Health and Retirement Longitudinal Study, a nationally representative survey of adults aged 45 years or older and their spouses.

Exposures: The presence of sensory impairments was identified by self-reported assessment of visual and/or hearing functions.

Main Outcomes And Measures: Overall, 3 composite measures were used to assess the respondents' cognitive performance, including episodic memory, mental intactness, and global cognitive function. Depression was examined using the 10-item Center for Epidemiological Studies-Depression scale score. Multiple generalized linear regression models, adjusting for self-reported sociodemographic characteristics, health behaviors, chronic conditions, and participants' overall health, were used.

Results: Of 18 038 respondents, 9244 (51.2%) were women. The mean (SD) age was 59.9 (9.7) years. Respondents with visual impairment had poorer episodic memory (β = -0.12; 95% CI, -0.19 to -0.05) and global cognition (β = -0.16; 95% CI, -0.31 to -0.02) and a greater risk of depression (odds ratio, 1.78; 95% CI, 1.59 to 1.99) than those without visual impairment. Respondents with hearing impairment had poorer episodic memory (β = -0.24; 95% CI, -0.30 to -0.18), mental intactness (β = -0.19; 95% CI, -0.28 to -0.10), and global cognition (β = -0.43; 95% CI, -0.55 to -0.31) as well as a greater risk of depression (odds ratio, 1.57; 95% CI, 1.44 to 1.70) than those without hearing impairment. People who reported dual sensory impairment performed worse on all of the aforementioned outcome measures (episodic memory: β = -0.23; 95% CI, -0.31 to -0.14; mental intactness: β = -0.13; 95% CI, -0.27 to -0.0003; global cognition: β = -0.37; 95% CI, -0.55 to -0.19; depression: odds ratio, 2.19; 95% CI, 1.90 to 2.52).

Conclusions And Relevance: In this study, visual and hearing impairments were independently and together associated with poorer cognitive and depression outcomes. A more comprehensive and integrated system of care, covering vision, hearing, and cognition, is needed in China's health care system to address age-related sensory impairments.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.14186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525357PMC
September 2020

Acceptance of COVID-19 Vaccination during the COVID-19 Pandemic in China.

Vaccines (Basel) 2020 Aug 27;8(3). Epub 2020 Aug 27.

China Center for Health Development Studies, Peking University, Beijing 100083, China.

Background: Faced with the coronavirus disease 2019 (COVID-19) pandemic, the development of COVID-19 vaccines has been progressing at an unprecedented rate. This study aimed to evaluate the acceptance of COVID-19 vaccination in China and give suggestions for vaccination strategies and immunization programs accordingly.

Methods: In March 2020, an anonymous cross-sectional survey was conducted online among Chinese adults. The questionnaire collected socio-demographic characteristics, risk perception, the impact of COVID-19, attitudes, acceptance and attribute preferences of vaccines against COVID-19 during the pandemic. Multivariate logistic regression was performed to identify the influencing factors of vaccination acceptance.

Results: Of the 2058 participants surveyed, 1879 (91.3%) stated that they would accept COVID-19 vaccination after the vaccine becomes available, among whom 980 (52.2%) wanted to get vaccinated as soon as possible, while others (47.8%) would delay the vaccination until the vaccine's safety was confirmed. Participants preferred a routine immunization schedule (49.4%) to emergency vaccination (9.0%) or either of them (41.6%). Logistic regression showed that being male, being married, perceiving a high risk of infection, being vaccinated against influenza in the past season, believing in the efficacy of COVID-19 vaccination or valuing doctor's recommendations could increase the probability of accepting COVID-19 vaccination as soon as possible, while having confirmed or suspected cases in local areas, valuing vaccination convenience or vaccine price in decision-making could hinder participants from immediate vaccination.

Conclusion: During the pandemic period, a strong demand for and high acceptance of COVID-19 vaccination has been shown among the Chinese population, while concerns about vaccine safety may hinder the promotion of vaccine uptake. To expand vaccination coverage, immunization programs should be designed to remove barriers in terms of vaccine price and vaccination convenience, and health education and communication from authoritative sources are important ways to alleviate public concerns about vaccine safety.
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http://dx.doi.org/10.3390/vaccines8030482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565574PMC
August 2020

Exposure to Chinese famine in early life and the risk of sensory impairment in adulthood.

J Epidemiol Community Health 2021 01 28;75(1):16-21. Epub 2020 Aug 28.

China Center for Health Development Studies, Peking University, Beijing, China

Background: Studies have shown that malnutrition in early life has a negative effect on midlife cognitive functions. Little is known, however, about the relationship between early-life malnutrition and visual, hearing or dual sensory impairments in adulthood. This study aims to investigate the association between exposure to the 1959-1961 Chinese famine in early life and sensory impairments in adulthood.

Methods: A total of 6347 adults born between 1952 and 1964 surveyed in the 2015 China Health and Retirement Longitudinal Study were included in this study. The presence of sensory impairments was identified by self-reported assessment of visual and hearing functions. The associations between multi-stage early-life famine exposure and sensory functions were estimated using the multiple generalised linear model.

Results: Compared with the unexposed group, respondents exposed to famine in the fetal period and late childhood had a significantly higher risk of hearing impairment (OR 1.54, 95% CI 1.06 to 2.24; OR 1.75, 95% CI 1.23 to 2.50) and dual sensory impairments (OR 1.45, 95% CI 1.00 to 2.11; OR 1.55, 95% CI 1.09 to 2.21), respectively. Furthermore, in severely famine-affected areas, the early, mid and late childhood-exposed groups were more likely to have hearing and dual sensory impairments than the unexposed group. Those associations were not observed in less famine-affected areas. However, no significant association was found between famine exposure and visual impairment in early-life famine-exposed group.

Conclusion: Exposure to Chinese famine in the fetal period and late childhood was linked to hearing and dual sensory impairments in adulthood.
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http://dx.doi.org/10.1136/jech-2020-213775DOI Listing
January 2021

A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia.

Blood 2021 Mar;137(11):1503-1516

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Transcriptional deregulation initiated by oncogenic fusion proteins plays a vital role in leukemia. The prevailing view is that the oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor-α (PML/RARα), generated by the chromosome translocation t(15;17), functions as a transcriptional repressor in acute promyelocytic leukemia (APL). Here, we provide rich evidence of how PML/RARα drives oncogenesis through both repressive and activating functions, particularly the importance of the newly identified activation role for the leukemogenesis of APL. The activating function of PML/RARα is achieved by recruiting both abundant P300 and HDAC1 and by the formation of super-enhancers. All-trans retinoic acid and arsenic trioxide, 2 widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARα-regulated targets in APL cells. We use a series of in vitro and in vivo experiments to demonstrate that PML/RARα-activated target gene GFI1 is necessary for the maintenance of APL cells and that PML/RARα, likely oligomerized, transactivates GFI1 through chromatin conformation at the super-enhancer region. Finally, we profile GFI1 targets and reveal the interplay between GFI1 and PML/RARα on chromatin in coregulating target genes. Our study provides genomic insight into the dual role of fusion transcription factors in transcriptional deregulation to drive leukemia development, highlighting the importance of globally dissecting regulatory circuits.
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http://dx.doi.org/10.1182/blood.2020005698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976511PMC
March 2021

Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP/EP300.

Proc Natl Acad Sci U S A 2020 08 5;117(34):20753-20763. Epub 2020 Aug 5.

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford OX3 7FY, United Kingdom;

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, and Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.
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http://dx.doi.org/10.1073/pnas.2004281117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456151PMC
August 2020

Willingness to Pay for Seasonal Influenza Vaccination among Children, Chronic Disease Patients, and the Elderly in China: A National Cross-Sectional Survey.

Vaccines (Basel) 2020 Jul 22;8(3). Epub 2020 Jul 22.

China Center for Health Development Studies, Peking University, Beijing 100083, China.

: The disease burden of seasonal influenza is substantial in China, while the vaccination rate is extremely low, and most people have to pay 100% for vaccination. This study aims to examine willingness to pay (WTP) and recommended financing sources for influenza vaccination among children, chronic disease patients, and the elderly in China and determine feasible measures to expand vaccination coverage. : From August to October 2019, 6668 children's caregivers, 1735 chronic disease patients, and 3849 elderly people were recruited from 10 provinces in China. An on-site survey was conducted via a especially designed PAD system. Tobit regression was adopted to predict the influencing factors of WTP. : The average WTP was 127.5 yuan (USD18.0) for children, 96.5 yuan (USD13.7) for chronic disease patients, and 88.1 yuan (USD12.5) for the elderly. Most participants in the three groups thought government subsidies (94.8%, 95.8%, and 95.5%) or health insurance (94.3%, 95.3%, and 94.5%) should cover part of the cost, and nearly four-fifths (80.1%, 79.5%, and 76.8%) believed that individuals should also pay for part. Tobit regression showed that a higher perceived importance of vaccination, knowing about priority groups, and considering that individuals should co-pay were promoters of WTP, while considering price as a hindrance lowered WTP. : The WTP for influenza vaccination among children, chronic disease patients, and the elderly in China is fairly high, suggesting that price is not the primary hindrance and there is room to expand immunization. Most participants expected the government and/or health insurance to pay part of the cost, and such supportive funding could act as a promotive policy "signal" to improve vaccine uptake. Influenza-related health education is also needed to expand vaccine coverage.
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http://dx.doi.org/10.3390/vaccines8030405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563663PMC
July 2020

Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.

Am Heart J 2020 08 30;226:198-205. Epub 2020 May 30.

Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China; Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China. Electronic address:

Background: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed.

Methods: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death.

Current Status: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018.

Conclusion: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.
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http://dx.doi.org/10.1016/j.ahj.2020.05.013DOI Listing
August 2020

Seasonal Influenza Vaccination and Recommendation: The Difference between General Practitioners and Public Health Workers in China.

Vaccines (Basel) 2020 May 31;8(2). Epub 2020 May 31.

China Center for Health Development Studies, Peking University, Beijing 100083, China.

Seasonal influenza vaccination for healthcare workers (HCWs) is critical to the protection of HCWs and their patients. This study examined whether the separation of public health workers and general practitioners could affect the influenza vaccine uptake and recommendation behaviors among HCWs in China. A survey was conducted from August to October 2019, and HCWs from 10 provinces in China were recruited. A self-administered and anonymous questionnaire was used to assess HCWs' demographic information, knowledge, and attitudes toward influenza vaccination, as well as vaccine uptake and recommendation behaviors. The primary outcome was HCWs' vaccination and recommendation status of seasonal influenza vaccine. Multivariate logistic regression models were used to identify the influence factors of influenza vaccine uptake and recommendation among HCWs. Of the 1159 HCWs in this study, 25.3% were vaccinated against influenza in the previous season. "No need to get vaccinated" was the primary reason for both unvaccinated public health workers and general practitioners. Multivariate logistic regression showed that public health workers were more likely to get vaccinated against influenza (OR = 2.20, 95% CI 1.59-3.05) and recommend influenza vaccination to children (OR = 2.10, 95% CI 1.57-2.80) and the elderly (OR = 1.69, 95% CI 1.26-2.25) than general practitioners. Besides, the knowledge and perceived risk of influenza can give rise to HCWs' vaccination and recommendation behaviors, and HCWs who got vaccinated in the past year were more likely to recommend it to children and the elderly in their work. The influenza vaccine coverage and recommendation among HCWs are still relatively low in China, especially for general practitioners. Further efforts are needed to improve the knowledge and attitudes toward influenza and influenza vaccination among HCWs, and coherent training on immunization for both public health workers and general practitioners might be effective in the face of separated public health and clinical services in China.
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http://dx.doi.org/10.3390/vaccines8020265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350002PMC
May 2020

The Effectiveness and Cost-effectiveness of a Parenting Intervention Integrated with Primary Health Care on Early Childhood Development: a Cluster-Randomized Controlled Trial.

Prev Sci 2020 07;21(5):661-671

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Developing countries require interventions that can sustainably improve early childhood development (ECD) at scale because hundreds of millions of children are at risk of poor development. This study examined the effectiveness and cost-effectiveness of a parenting intervention integrated with primary health care in terms of ECD. A cluster-randomized controlled trial was conducted in 20 urban communities in China, with 82 and 86 children aged 1-2 months enrolled in the intervention and control groups, respectively, and 71 and 69 children, respectively, followed to 14 months of age. All children in both groups received routine primary health care services. Intervention caregivers received a parenting pamphlet and two parenting training sessions during well-child clinic visits; those with children with suspected developmental delay received additional parenting guidance by telephone. Compared with controls, children receiving the intervention had similar developmental outcomes, measured with the Chinese version of the Ages & Stages Questionnaires third edition (ASQ-C), at baseline, but had significantly higher communication (adjusted mean difference = 0.26; 95% CI 0.03, 0.51), fine motor (adjusted mean difference = 0.19; 95% CI 0.01, 0.37), and overall (adjusted mean difference = 0.25; 95% CI 0.10, 0.41) ASQ-C z-scores after 12 months of the intervention. The intervention cost per child was $50.87, and the costs for increasing the communication, fine motor, and overall ASQ-C scores by one SD were $195.65, $267.74, and $203.48, respectively. Our findings indicate that the integration of a parenting intervention with existing primary health care is a cost-effective way to improve ECD.
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http://dx.doi.org/10.1007/s11121-020-01126-2DOI Listing
July 2020

Peripheral CD8 T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma.

Nat Med 2020 02 10;26(2):193-199. Epub 2020 Feb 10.

Department of Oncology, University of Oxford & Oxford Cancer Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples, we characterized CD8 T cell gene expression across a cohort of patients with MM receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8 transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over fourfold greater, with preferential induction of mitosis- and interferon-related genes. Early samples from patients with durable clinical benefit demonstrated overexpression of T cell receptor-encoding genes. By mapping T cell receptor clonality, we find that responding patients have more large clones (those occupying >0.5% of repertoire) post-treatment than non-responding patients or controls, and this correlates with effector memory T cell percentage. Single-cell RNA-sequencing of eight post-treatment samples demonstrates that large clones overexpress genes implicated in cytotoxicity and characteristic of effector memory T cells, including CCL4, GNLY and NKG7. The 6-month clinical response to ICB in patients with MM is associated with the large CD8 T cell clone count 21 d after treatment and agnostic to clonal specificity, suggesting that post-ICB peripheral CD8 clonality can provide information regarding long-term treatment response and, potentially, facilitate treatment stratification.
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http://dx.doi.org/10.1038/s41591-019-0734-6DOI Listing
February 2020

Ascorbate and Iron Are Required for the Specification and Long-Term Self-Renewal of Human Skeletal Mesenchymal Stromal Cells.

Stem Cell Reports 2020 02 30;14(2):210-225. Epub 2020 Jan 30.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China; Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:

The effects of ascorbate on adult cell fate specification remain largely unknown. Using our stepwise and chemically defined system to derive lateral mesoderm progenitors from human pluripotent stem cells (hPSCs), we found that ascorbate increased the expression of mesenchymal stromal cell (MSC) markers, purity of MSCs, the long-term self-renewal and osteochondrogenic capacity of hPSC-MSCs in vitro. Moreover, ascorbate promoted MSC specification in an iron-dependent fashion, but not in a redox-dependent manner. Further studies revealed that iron synergized with ascorbate to regulate hPSC-MSC histone methylation, promote their long-term self-renewal, and increase their osteochondrogenic capacity. We found that one of the histone demethylases affected by ascorbate, KDM4B, was necessary to promote the specification of hPSC-MSCs. This mechanistic understanding led to the metabolic optimization of hPSC-MSCs with an extended lifespan in vitro and the ability to fully repair cartilage defects upon transplantation in vivo. Our results highlight the importance of ascorbate and iron metabolism in adult human cell fate specification.
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http://dx.doi.org/10.1016/j.stemcr.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013236PMC
February 2020

Changes in sleep duration associated with retirement transitions: The role of naps.

J Sleep Res 2020 12 27;29(6):e12975. Epub 2019 Dec 27.

China Center for Health Development Studies, Peking University, Beijing, China.

This study examined the changes in sleep duration (total sleep time, night-time sleep and daytime naps) after retirement transitions in China using a panel dataset of the China Health and Retirement Longitudinal Study in 2011, 2013 and 2015 with a total of 48,458 respondents. Linear regression analysis with generalized estimating equations was employed to examine the changes in sleep duration after transitions between different types of employment status. After controlling for the confounders, the results showed that the retired population and the population working in agricultural sectors slept 8.02 (p < .01) and 5.19 (p < .01) minutes longer than the population working in non-agricultural sectors, respectively. Employment transition also had significant effects on sleep duration. Transition from non-agricultural sectors to retirement increased total sleep time by 13.58 (p < .01) minutes and also raised the probability of daytime naps by 18% (OR = 1.18, p < .01). Transition from agricultural employment to retirement did not significantly affect the total sleep time, but significantly increased the probability of daytime naps (OR = 1.12, p = .02). Reentering the non-agricultural sectors for the retirees did not significantly affect night-time sleep, but decreased the probability of daytime naps (OR = 0.73, p < .01) and daytime nap duration (by 5.26 min, p = .01). In conclusion, people in China increased their sleep duration after transitions to retirement, but the magnitudes were much smaller than those in Western countries. Differences may be attributed to an abundant amount of Chinese people working in agricultural sectors, the high volume of retired people reentering the work force and the large proportion of people in China that had daytime naps at baseline.
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http://dx.doi.org/10.1111/jsr.12975DOI Listing
December 2020

Technical Efficiency of Public and Private Hospitals in Beijing, China: A Comparative Study.

Int J Environ Res Public Health 2019 12 20;17(1). Epub 2019 Dec 20.

China Center for Health Development Studies, Peking University, Beijing 100083, China.

With the participation of private hospitals in the health system, improving hospital efficiency becomes more important. This study aimed to evaluate the technical efficiency of public and private hospitals in Beijing, China, and analyze the influencing factors of hospitals' technical efficiency, and thus provide policy implications to improve the efficiency of public and private hospitals. This study used a data set of 154-232 hospitals from "Beijing's Health and Family Planning Statistical Yearbooks" in 2012-2017. The data envelopment analysis (DEA) model was employed to measure technical efficiency. The propensity score matching (PSM) method was used for matching "post-randomization" to directly compare the efficiency of public and private hospitals, and the Tobit regression was conducted to analyze the influencing factors of technical efficiency in public and private hospitals. The technical efficiency, pure technical efficiency and scale efficiency of public hospitals were higher than those of private hospitals during 2012-2017. After matching propensity scores, although the scale efficiency of public hospitals remained higher than that of their private counterparts, the pure technical efficiency of public hospitals was lower than that of private hospitals. Panel Tobit regression indicated that many hospital characteristics such as service type, level, and governance body affected public hospitals' efficiency, while only the geographical location had an impact on private hospitals' efficiency. For public hospitals in Beijing, those with lower average outpatient and inpatient costs per capita had better performance in technical efficiency, and bed occupancy rate, annual visits per doctor, and the ratio of doctors to nurses also showed a positive sign with technical efficiency. For private hospitals, the average length of stay was negatively associated with technical efficiency, but the bed occupancy rate, annual visits per doctor, and average outpatient cost were positively associated with technical efficiency. To improve technical efficiency, public hospitals should focus on improving the management standards, including the rational structure of doctors and nurses as well as appropriate reduction of hospitalization expenses. Private hospitals should expand their scale with proper restructuring, mergers, and acquisitions, and pay special attention to shortening the average length of stay and increasing the bed occupancy rate.
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http://dx.doi.org/10.3390/ijerph17010082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981764PMC
December 2019

I3: A Self-organising Learning Workflow for Intuitive Integrative Interpretation of Complex Genetic Data.

Genomics Proteomics Bioinformatics 2019 10 23;17(5):503-510. Epub 2019 Nov 23.

State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. Electronic address:

We propose a computational workflow (I3) for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle. We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes, particularly in conjunction with information from human population genetics and/or evolutionary history of human genes. We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains, and if highly expressed, have broad effects on the protein phenotypes studied. We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation. I3 is available at http://suprahex.r-forge.r-project.org/I3.html.
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http://dx.doi.org/10.1016/j.gpb.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056857PMC
October 2019

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens.

Genome Biol 2019 11 19;20(1):244. Epub 2019 Nov 19.

Departments of Bioengineering and Mechanical Engineering, Berkeley, CA, USA.

Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.

Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.

Conclusion: We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.
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http://dx.doi.org/10.1186/s13059-019-1835-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864930PMC
November 2019

A school-based, multi-faceted health promotion programme to prevent obesity among children: protocol of a cluster-randomised controlled trial (the DECIDE-Children study).

BMJ Open 2019 11 2;9(11):e027902. Epub 2019 Nov 2.

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China

Introduction: Obesity is a public health concern that is becoming increasingly more serious worldwide. Effective and sustainable childhood obesity prevention strategies may help to reduce the prevalence of obesity and may have an impact on lifelong health. However, few such strategies have been rigorously evaluated for Chinese children in different regions of China.

Methods And Analysis: The Diet, ExerCIse and CarDiovascular hEalth-Children is a cluster-randomised controlled trial that aims to assess the effectiveness and sustainability of a school-based, multi-faceted intervention to prevent obesity among Grade 4 primary school students (8-10 years old) in China. Twenty-four schools (approximately 1200 students) from above average, average and below average developed regions in China will be randomised to an intervention (12 schools) or usual practice (12 schools) group. The intervention will last for one school year (9 months) and consists of activities towards students, parents and school environment. A smartphone application will be used to assist in providing information on, monitoring and providing feedback on the behaviours and body weight of the students. Data will be collected at baseline, 4 months, 9 months and 21 months. The primary outcome will be the difference between groups in the change in students' body mass index at 9 months after the baseline investigation. The secondary outcomes will include the differences between groups in the changes in anthropometric measures, diet, physical activity levels and other measures at the follow-up visits. A variety of process evaluation methods will be used to evaluate the implementation process of the complex intervention.

Ethics And Dissemination: This study was approved by the Peking University Institution Review Board (IRB00001052-18021). The results will be disseminated through publication in peer-reviewed journals, presentations at conferences and in lay summaries provided to school staff and participants.

Trial Registration Number: NCT03665857.
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http://dx.doi.org/10.1136/bmjopen-2018-027902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830599PMC
November 2019

The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis.

Hum Reprod Update 2019 07;25(4):486-503

Oxford Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Background: Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet abnormalities in the immune system have been suggested to explain the origin of ectopic endometrial tissues, and an association between endometriosis and autoimmune diseases has been proposed. Evaluation of current evidence investigating the association between endometriosis and autoimmune diseases from population-based studies will facilitate our understanding of the causes and consequences of endometriosis and provide a reference for better healthcare practices population-wide.

Objective And Rationale: The aim of this study was to systematically review the literature on population-based studies investigating an association between endometriosis and autoimmune diseases and to conduct a meta-analysis of combinable results to investigate the extent and robustness of evidence.

Search Methods: Four electronic databases were searched (MEDLINE, Embase, Web of Science, and CINAHL) from each database inception date until 7 April 2018. Search terms included a combination of database-specific controlled vocabulary terms and free-text terms relating to 'endometriosis' and 'autoimmune diseases'. Study inclusion criteria focused on peer-reviewed published articles that reported an association between endometriosis and autoimmune diseases, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. Quality assessment of included studies was performed based on GRADE criteria. Key information of eligible studies was abstracted into a standard form. Meta-analysis was performed for autoimmune diseases with combinable study results from at least three studies investigating an association with endometriosis. For cross-sectional studies and case-control studies, raw data from each study were documented to calculate a Mantel-Haenszel odds ratio with 95% CIs. For cohort studies, an inverse variance probability weighted model was used to pool study results to calculate a rate ratio (a hazard ratio or a standardized incidence rate) with 95% CIs.

Outcomes: A total of 26 published population-based cross-sectional, case-control, and cohort studies that investigated the association between endometriosis and autoimmune diseases met all eligible criteria and were included in the review. The studies quantified an association between endometriosis and several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison's disease. However, the quality of the evidence was generally poor due to the high risk of bias in the majority of the chosen study designs and statistical analyses. Only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease: SLE, SS, RA, CLD, MS, or IBD.

Wider Implications: The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed. Scientists interested in research studies on endometriosis or autoimmune diseases should consider the likelihood of comorbidity when studying these two types of health conditions. Well-designed large prospective cohort studies with confounding control and mediation quantification, as well as genetic and biological studies, are needed to generate further insights into whether endometriosis is a risk factor for, or a consequence of, autoimmune diseases, and whether these two types of disorders share pathophysiological mechanisms even if they arise independently. Such insights may offer opportunities for the development of novel non-hormonal medications such as immuno-modulators or repurposing of existing immunomodulatory therapies for endometriosis.
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http://dx.doi.org/10.1093/humupd/dmz014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601386PMC
July 2019

A genetics-led approach defines the drug target landscape of 30 immune-related traits.

Nat Genet 2019 07 28;51(7):1082-1091. Epub 2019 Jun 28.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Most candidate drugs currently fail later-stage clinical trials, largely due to poor prediction of efficacy on early target selection. Drug targets with genetic support are more likely to be therapeutically valid, but the translational use of genome-scale data such as from genome-wide association studies for drug target discovery in complex diseases remains challenging. Here, we show that integration of functional genomic and immune-related annotations, together with knowledge of network connectivity, maximizes the informativeness of genetics for target validation, defining the target prioritization landscape for 30 immune traits at the gene and pathway level. We demonstrate how our genetics-led drug target prioritization approach (the priority index) successfully identifies current therapeutics, predicts activity in high-throughput cellular screens (including L1000, CRISPR, mutagenesis and patient-derived cell assays), enables prioritization of under-explored targets and allows for determination of target-level trait relationships. The priority index is an open-access, scalable system accelerating early-stage drug target selection for immune-mediated disease.
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http://dx.doi.org/10.1038/s41588-019-0456-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124888PMC
July 2019