Search

Chenyu Zhang,1,2,* Yalan Li,1,* Wo Wang,1 Zhenghao Jiang,1 Chuan Liu,1 Yiting Kong,2 Daqi Li,1 Liuyi Ran,1 Li Kuang1,2 1Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, People’s Republic of China; 2Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liuyi Ran; Li Kuang, Mental Health Center, University-Town Hospital of Chongqing Medical University, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel/Fax +86-023-65714061, Email ranliuyi@163.com; kuangli0308@163.comPurpose: The aim of our study was to explore the relation between serum levels of non-enzymatic antioxidants, thyroid function with the risk of non-suicidal self-injury (NSSI) in depressed adolescents.Patients and Methods: We retrospected the electronic records of 454 hospitalized patients aged 13– 17 years old with a diagnosis of major depressive disorder (239 patients with NSSI and 215 subjects without NSSI), and collected their demographic and clinical information, including serum levels of total bilirubin (Tbil), uric acid (UA), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH).Results: The incidence of NSSI was 52.6% among depressed adolescents aged 13– 17, 57.1% in female and 38.5% in male. After using the propensity scoring method to exclude the influence of age between the two groups, it was found that patients with NSSI showed lower levels of Tbil (P=0.046) and UA (P=0.015) compared with those without NSSI. Logistic regression results showed that serum UA was associated with NSSI behavior in female patients (OR=0.995, 95% CI: 0.991– 0.999, P=0.014), and TSH was associated with NSSI in male participants (OR=0.499, 95% CI: 0.267– 0.932, P=0.029).Conclusion: Female and male may have different pathological mechanisms of NSSI. NSSI is more likely to be related to antioxidant reaction in female adolescent patients, while more likely to be related to thyroid function in male depressed adolescent patients.Keywords: antioxidant system, depressed adolescents, incidence, non-suicidal self-injury, thyroid function

Wenjing Wu,1,2 Yongmei Jiang,1,2 Wei Zhou,1,2 Linghan Kuang1,2 1Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Linghan Kuang, Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-8550-1201, Email hanhan840106@163.comObjective: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is spreading worldwide, becoming a serious threat to public health. The present study aimed to analyze the molecular epidemiology and drug resistance mechanism of CRKP isolated from neonatal patients in Sichuan, Southwest China.Methods: CRKP isolates were collected from neonatal patients of West China Second University Hospital from June 2017 to June 2021. Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing of all isolates were performed to determine the antimicrobial resistance genes, sequence typing, phylogenetic relationships.Results: In total, 41 nonduplicate CRKP isolates were collected. All isolates were highly resistant to the cephalosporins and carbapenems, however, they were all susceptible to amikacin, tigecycline, ciprofloxacin, and colistin. Various resistance genes were detected, blaNDM-5 (n = 35, 85.4%) was the predominant carbapenemase genes. The most common replicon type was IncX3, which was harbored by 36 (87.8%) isolates, followed by IncFIB (n = 34, 82.9%), and IncFII (n = 32, 78.0%). The 41 CRKP isolates belonged to 8 sequence types (STs) and ST789 (n = 29, all had blaNDM-5) was the dominant sequence type.Conclusion: The study revealed that blaNDM was the most dominant carbapenemase resistance gene. ST789 CRKP strains carrying blaNDM-5 were a tremendous menace to neonates in this hospital. Therefore, effectively implement prevention and control measures need to be taken for the prevention and treatment of CRKP infection in the neonatal ward.Keywords: Klebsiella pneumoniae, carbapenemase, NDM-5, ST789, neonates

Lisha Kuang,1,&ast; Cheng Ren,2,&ast; Xiuqing Liao,2 Xiaobin Zhang,2 Xuegang Zhou2 1Department of Health Management Center, Chongqing University Fuling Hospital, Chongqing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Chongqing University Fuling Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuqing Liao, Department of Respiratory and Critical Care Medicine, Chongqing University Fuling Hospital, Chongqing, People’s Republic of China, Tel +86 23-72250973, Email 98116lxq@163.comBackground: Previous studies indicate that the percent recovery index (PRI: the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation), one of the indexes of methacholine bronchial provocation, may predict acute asthma exacerbations in childhood and elderly asthmatics. It is known that childhood (< 12) and elder (> 60) asthmatics may be different to adult patients in many aspect including prognosis. However, in adults, a research for predicting value of PRI to exacerbation is still absence. Besides exacerbation, predicting value of PRI to poor asthma control is also unknown. We try to detect whether PRI can predict poor asthma control and exacerbation in adults in this research. Meanwhile, we try to detect whether treatment can influence PRI.Methods: In 61 adults with asthma, baseline PRI was measured during enrollment. And then baseline PRI was evaluated as a predictor of exacerbation or poor asthma control at an upcoming 3-month follow-up. The covariates included age, sex, BMI, previous exacerbation, smoking status and baseline lung function. After treatment for 3 months, PRI was measured again and compared with baseline PRI.Results: After the 3-month follow-up, we found that baseline PRI was significantly related to asthma exacerbation (P = 0.023), poor asthma control (ACT at 3 months, P = 0.014), decreased quality of life (decrease of MiniAQLQ, P = 0.010) and cumulative number of EDHO at 3 months (P = 0.039). Meanwhile, no significant correlation was observed between baseline PRI and inflammation factors (FENO, CaNO, and EOS). Finally, PRI was dramatically reduced after standard treatment for 3 months.Conclusion: PRI is efficient in the prediction of poor asthma control and exacerbation in adults. The predictive value of PRI may rely on the inherent property of asthmatic airway smooth muscle (ASM) independent of inflammation factors. Effective treatment can alleviate PRI dramatically and that indicate PRI may also be valuable in evaluation of curative effect.Keywords: asthma, exacerbation, poor control, percent recovery index, bronchodilator reversibility

Liwen Kuang,1,&ast; Chenchen Zhang,1,&ast; Binghui Li,1 Haibo Deng,1 Ran Chen,1 Gongchi Li2 1Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China; 2Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gongchi Li, Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Road, Wuhan, Hubei, 430022, People’s Republic of China, Tel +8613618615209, Email ligongchi@foxmail.comPurpose: Diabetic wound is a highly prevalent and refractory disease. Extensive studies have confirmed that keratinocytes and macrophages play an important role in the process of wound healing. Additionally, exosomes are regarded as a vital intercellular communication tool. This study aimed to investigate the role of human keratinocyte-derived exosomal MALAT1 in the treatment of diabetic wound by influencing the biological function of macrophages.Methods: We mainly assessed the function of MALAT1 on the biological changes of macrophages, and the expression of MALAT1 in the keratinocyte-exosomes analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The downstream interaction between RNAs or proteins was assessed by mechanistic experiments. Besides, we evaluated the effects of human keratinocyte-derived exosomal MALAT1 on diabetic wound healing in vivo to verify in vitro results.Results: We demonstrated that human keratinocyte-derived exosomal MALAT1 enhanced the biological functions of high glucose-injured macrophages, including phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. Mechanistically, MALAT1 accelerated the expression of MFGE8 by competitively binding to miR-1914-3p, thereby affecting the function of macrophages and the signal axis of TGFB1/SMAD3, and finally promoting the healing of diabetic wounds. Human keratinocyte-derived exosomal MALAT1 might promote collagen deposition, ECM remodeling, and expression of MFGE8, VEGF, and CD31 but reduce the expression of TGFB and SMAD3 in an in vivo model of diabetic mice wounds, which accelerated diabetic wound healing and restored its function.Conclusion: The current study revealed that human keratinocyte-derived exosomal MALAT1 would suppress miR-1914-3p to activate MFGE8 and eventually promote wound healing by enhancing macrophage phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. It proposed that keratinocyte-derived exosomes might have the capacity to serve as a new method for the clinical treatment of diabetic wound.Graphical Abstract: Keywords: exosomes, keratinocytes, macrophages, MALAT1, diabetic wound healing

Yiting Kong,1,&ast; Chuan Liu,2,&ast; Chenyu Zhang,1 Wo Wang,2 Yalan Li,2 Haitang Qiu,1 Gaomao Wang,2 Daqi Li,2 Xiaorong Chen,2 Zhen Lv,2 Dongdong Zhou,2 Liyang Wan,2 Ming Ai,1 Jianmei Chen,1 Liuyi Ran,2,&ast; Li Kuang1,2,&ast; 1Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liuyi Ran, Mental Health Center, University-Town Hospital of Chongqing Medical University, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel/Fax +86-023-65714061, Email ranliuyi@163.com Li Kuang, Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-023-89012696, Email kuangli0308@163.comPurpose: Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD).Patients and Methods: We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out.Results: Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993∼ 0.999, P < 0.01) when controlling for possible confounding variables.Conclusion: This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.Keywords: suicide, MDD, uric acid, antioxidant, oxidative stress, biomarker

Ming Ai,1 Jun Wang,1 Jianmei Chen,1 Wo Wang,2 Xiaoming Xu,1 Yao Gan,1 Xuemei Li,1 Xinyuan Gou,1 Jun Cao,1 Zhen Lv,1 Xiaorong Chen,1 Hengguang Wang,1 Qing Ma,2,3 Li Kuang1,21Department of Psychiatry, First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USAPurpose: The relationship was investigated between brain-derived neurotrophic factor (BDNF) concentrations, a BDNF polymorphism (196G>A), and the response to selective serotonin reuptake inhibitors (SSRIs) among Chinese patients with major depressive disorder (MDD).Patients and methods: A total of 125 patients and 91 healthy controls were enrolled. The disease progression and treatment responses were evaluated using the Hamilton depression rating scale (HAMD24), the Hamilton anxiety scale, the Beck depression index, and BDNF concentrations at the baseline, 4, 8, and 12 weeks after treatment. Responders were defined as patients with at least a 50% decrease in the HAMD24.Results: The BDNF concentrations were significantly lower in MDD (947±297 vs 1187±236 pg/mL, p=0.019), in MDD with attempted suicide than those without (779±231 vs 993±298, p=0.024) at the baseline. The BDNF concentrations remarkably increased in response to SSRI treatment. Significant correlations were noted between the BDNF concentrations and suicide ideation or attempted suicide (pA correlated with neither suicide ideation nor treatment responses.Conclusion: BDNF concentrations were significantly lower in patients with attempted suicide/ideation. BDNF concentrations could serve as a response marker for antidepressant treatment in MDD.Keywords: brain-derived neurotrophic factor, depression, polymorphism, attempted suicide, SSRI

Yi Liang,1 Ying Shen,2 Liangjian Kuang,1 Guang Zhou,1 Longju Zhang,1 Xiaoning Zhong,1 Jianquan Zhang,1 Jifeng Liu1 1Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, 2Division of General Practice, General Practice School of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China Purpose: This study aimed to investigate the impact of cigarette smoke exposure upon CD40–CD40L ligation between bone marrow-derived dendritic cells (BMDCs)and CD4+T cells, and to examine the effects of cigarette smoke exposure upon differentiation of CD4+T cells toward Th17 cells through blockade of CD40-CD40L pathway in mice.Methods: The study was processed in vivo and in vitro. In vivo, Th17 cells, CD40, interleukin (IL)-17A, and IL-27 in the lung tissues were quantified and compared between mice with and without cigarette smoke exposure. In vitro, Th17 cells, IL-17A, and IL-27 yielded by multiple cell cultivations in which BMDCs from mice with or without cigarette smoke exposure were fostered with CD4+ T cells from healthy mice spleens in the presence of antagonistic CD40 antibody and/or cigarette smoke extract (CSE) were quantified and compared. The flow cytometry was used to detect expressions of Th17 cells and CD40, and the liquid chip was used to detect levels of IL-17A and IL-27.Results: Both in vivo exposed to cigarette smoke and in vitro to CSE, CD40 expressions noticeably escalated on the surfaces of BMDCs. The presence of Th17 cells, IL-17A, and IL-27 in the lung tissues prominently increased in mice exposed to cigarette smoke. The in vitro culture of CD4+ T cells and BMDCs significantly enhanced the differentiation of CD4+ T cells toward Th17 cells and secretions of IL-17A and IL-27 in the case that BMDCs were produced from mice exposed to cigarette smoke or the culture occurred in the presence of CSE. Usage of antagonistic CD40 antibody evidently reduced the number of Th17 cells, IL-17A, and IL-27 that increased due to cigarette smoke exposure.Conclusion: The CD40–CD40L ligation is associated with the quantities of Th17 cells and relevant cytokines in the context of cigarette smoke exposure. Reducing the number of Th17 cells via the usage of antagonistic CD40 antibody can be an inspiration for pursuing a novel therapeutic target for immune inflammation in COPD. Keywords: cigarette smoke extract, BMDC, CD4+IL-17+ T cell, CD40–CD40L pathway, IL-17A, IL-27

Abstract Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

Abstract Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.

The oedometer tests of remoulded deep clay in East China subjected to consolidation stresses ranging from 0.2 to 15.0 MPa were carried out. Both the measured compression curves and the curves of logarithmic permeability versus void ratio consist of two linear segments, among which the bilinear shape of the compression curves is less noticeable. The consolidation stress and void ratio at the intersection of two lines are around 2 MPa and 0.565 [+ or -] 0.015, respectively, and the corresponding saturated water content is very close to the reported saturated adsorbed water content. Lastly, but most importantly, the calculated microscopic pore size corresponding to the intersection point agrees well with the transitional range of the distance between two clay surfaces within which water molecules transform from bulk-liquid-like water into confined water. This is confirmed by experimental results available in the literature. Key words: clay, high consolidation stress, compressibility, microscopic mechanism. Des essais redometriques sur de l'argile profonde remaniee provenant de l'est de la Chine et soumise a des contraintes de consolidation variant de 0,2 a 15,0 MPa ont ete realises. Les courbes de compression mesurees de meme que les courbes de la permeabilite en logarithme versus l'indice des vides consistent en deux segments lineaires, dans lesquels la forme bilineaire des courbes de compression est moins apparente. La contrainte de consolidation et l'indice des vides a l'intersection de deux lignes sont d'environ 2 MPa et 0,565 [+ or -] 0,015, respectivement, et la teneur en eau a saturation correspondante est tres pres de la teneur en eau adsorbee saturee rapportee. Enfin, le plus important resultat est que la taille des pores microscopiques calculee correspondant au point d'intersection correspond bien avec les distances de transition entre deux surfaces d'argile dans lesquelles les molecules d'eau se transforment d'eau de type liquide a de l'eau confinee. Ceci est confirme par les resultats experimentaux disponibles dans la litterature. [Traduit par la Redaction] Mots-cles: argile, contrainte de consolidation elevee, compressibilite, mecanisme microscopique., Introduction There are over 100 deeply penetrating vertical shafts in East China. Most of them penetrate the Quaternary-age overburden layer, with an average thickness of over 200 m and a [...]

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Abstract Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.

IntroductionThe rise in global temperatures due to climate change has escalated the frequency and intensity of wildfires worldwide. Beyond their direct impact on physical health, these wildfires can significantly impact mental health. Conventional mental health studies predominantly rely on surveys, often constrained by limited sample sizes, high costs, and time constraints. As a result, there is an increasing interest in accessing social media data to study the effects of wildfires on mental health.MethodsIn this study, we focused on Twitter users affected by the California Tubbs Fire in 2017 to extract data signals related to emotional well-being and mental health. Our analysis aimed to investigate tweets posted during the Tubbs Fire disaster to gain deeper insights into their impact on individuals. Data were collected from October 8 to October 31, 2017, encompassing the peak activity period. Various analytical methods were employed to explore word usage, sentiment, temporal patterns of word occurrence, and emerging topics associated with the unfolding crisis.ResultsThe findings show increased user engagement on wildfire-related Tweets, particularly during nighttime and early morning, especially at the onset of wildfire incidents. Subsequent exploration of emotional categories using Linguistic Inquiry and Word Count (LIWC) revealed a substantial presence of negative emotions at 43.0%, juxtaposed with simultaneous positivity in 23.1% of tweets. This dual emotional expression suggests a nuanced and complex landscape, unveiling concerns and community support within conversations. Stress concerns were notably expressed in 36.3% of the tweets. The main discussion topics were air quality, emotional exhaustion, and criticism of the president's response to the wildfire emergency.DiscussionSocial media data, particularly the data collected from Twitter during wildfires, provides an opportunity to evaluate the psychological impact on affected communities immediately. This data can be used by public health authorities to launch targeted media campaigns in areas and hours where users are more active. Such campaigns can raise awareness about mental health during disasters and connect individuals with relevant resources. The effectiveness of these campaigns can be enhanced by tailoring outreach efforts based on prevalent issues highlighted by users. This ensures that individuals receive prompt support and mitigates the psychological impacts of wildfire disasters.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Abstract Background Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited. Methods We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake. Results We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). Conclusion This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.