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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.

Flood prediction in hilly regions, characterized by rapid flow rates and high destructive potential, remains a significant challenge. This study addresses this problem by introducing a novel machine learning-based approach to enhance flood forecast accuracy and lead time in small watersheds within hilly terrain. The study area encompasses small watersheds of approximately 600 km2. The proposed method analyzes spatiotemporal characteristics in rainfall dynamics to identify historical rainfall–flood events that closely resemble current patterns, effectively “learning from the past to predict the present”. The approach demonstrates notable precision, with an average error of 8.33% for peak flow prediction, 14.27% for total volume prediction, and a lead time error of just 1 h for peak occurrence. These results meet the stringent accuracy requirements for flood forecasting, offering a targeted and effective solution for flood forecasting in challenging hilly terrains. This innovative methodology deviates from conventional techniques by adopting a holistic view of rainfall trends, representing a significant advancement in addressing the complexities of flood prediction in these regions.

Groundwater in the McMurdo Dry Valleys of Antarctica is commonly enriched in calcium and chloride, in contrast to surface and groundwater in temperate regions, where calcium chemistry is largely controlled by the dissolution of carbonates and sulfates. These Antarctic Ca-Cl brines have extremely low freezing points, which leads to moist soil conditions that persist unfrozen and resist evaporation, even in cold, arid conditions. Several hypotheses exist to explain these unusual excess-calcium solutions, including salt deliquescence and differential salt mobility and cation exchange. Although the cation exchange mechanism was shown to explain the chemistry of pore waters in permafrost cores from several meters depth, it has not been evaluated for near-surface groundwater and wetland features (water tracks) in which excess-calcium pore-water solutions are common. Here, we use soluble salt and exchangeable cation concentrations to determine whether excess calcium is present in water-track brines and if cation exchange could be responsible for calcium enrichment in these cold desert groundwaters. We show that calcium enrichment by cation exchange is not occurring universally across the McMurdo Dry Valleys. Instead, evidence of the present-day formation of Ca-Cl–rich brines by cation exchange is focused in a geographically specific location in Taylor Valley, with hydrological position, microclimate, soil depth, and organic matter influencing the spatial extent of cation exchange reactions. Up-valley sites may be too cold and dry for widespread exchange, and warm and wet coastal sites are interpreted to host sediments whose exchange reactions have already gone to completion. We argue that exchangeable cation ratios can be used as a signature of past freeze-concentration of brines and exchange reactions, and thus could be considered a geochemical proxy for past groundwater presence in planetary permafrost settings. Correlations between water-track organic matter, fine sediment concentration, and cation exchange capacity suggest that water tracks may be sites of enhanced biogeochemical cycling in cold desert soils and serve as a model for predicting how active layers in the Antarctic will participate in biogeochemical cycling during periods of future thaw. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infection by Klebsiella pneumoniae (Kp) and drug resistance of Kp among neonates is a major concern. Hypervirulent K. pneumoniae (hvKp) infections are gradually increasing worldwide. Carbapenem-resistant hvKp infection has brought challenges to clinical treatment.Aim: To evaluate the changes in drug resistance trends of Kp strains in neonatal intensive care unit (NICU) nosocomial infections, to analyse drug resistance genes and virulence genes of carbapenem-resistant K. pneumoniae (CRKP) and to identify whether these CRKP strains are hvKp.Methods: A total of 80 neonates with Kp nosocomial infections from 2013 to 2018 were retrospectively studied. Drug susceptibility testing was performed on 80 Kp strains, among which the 12 CRKP strains were further studied.Findings: Kp accounted for 26.9% of nosocomial infections in the NICU. CRKP strains accounted for 15.0%. Among the 80 nosocomial infection Kp strains, CRKP strains accounted for 33.3% and 53.3% in 2017 and 2018 respectively. One of the 12 CRKP strains was positive in the drawing test. The 12 CRKP strains were divided into four complete genome sequence types: cgST1 (N = 2), cgST2 (N = 1), cgST3 (N = 1), and cgST4 (N = 8). Among genes that mediated carbapenem resistance, strains of cgST4 carried NDM-5, strains of cgST2 and cgST3 carried NDM-1, and strains of cgST1 carried IMP-4. None of the 12 CRKP strains carried rmpA/rmpA2 (highly related with hvKp).Conclusion: Nosocomial infections of CRKP among neonates are becoming common, but no hvKp was found among the CRKP strains in this study. [ABSTRACT FROM AUTHOR]

Abstract Background Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry. Methods Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship. Results Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China. Conclusions This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30–79 years recruited from ten diverse areas during 2004–2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history. In a random subset (n = 69,898) we further assessed the association of 18 single nucleotide polymorphisms (SNPs) previously shown to be associated with HBsAg positivity and development of chronic liver disease (CLD) (1600 cases). Several factors showed strong associations with HBsAg positivity, particularly younger age (

Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions.We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk.These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans.

The effect of topographic correction (TOC) has a profound influence on the quantitative application of remote sensing image. With regard to the invalid evaluation of the TOC model with such a single topographic correction assessment (TCA) method, we have selected five TCA indexes from five different perspectives: the difference in mean radiance radiometry between sunlit and shaded slopes, the cosine empirical relationship, stability, heterogeneity, and outlier ratio. The entropy weight method was used to assign weight to each TCA indexes, and the comprehensive evaluation value (CEV) of TOC for each band of remote sensing image was obtained by weighted superposition. After that, the weight of each band of the remote sensing image is determined by the entropy weight method, and the CEV of the TOC of the remote sensing image is obtained by weighting and superposition, so as to realize the effect evaluation of the six TOC models of C, SCS + C, VECA, Teillet, Minnaert, and Minnaert + SCS. The results indicate that the proposed method can effectively evaluate the correction effect of the TOC model. Results indicate that the SCS + C model has the best correction effect, while the Minnaert model performs the worst. The results generated from the Minnaert + SCS, Teillet, and Minnaert models typically show inferior quality. The SCS + C, VECA, and C models are better suited for generating images with high spectral fidelity, and these three correction models are recommended for TOCs over mountainous areas.

Summary: Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.

Purpose: Pegylated liposomal doxorubicin (PLD) is highly effective for treating multiple myeloma (MM). Hand-foot syndrome (HFS) is a dose-limiting adverse event of PLD that may reduce a patient’s quality of life or prevent certain patients from receiving PLD. Several researchers have discovered that pyridoxine, an activated form of vitamin B6, may prevent PLD-associated HFS. We designed a prospective randomized trial to examine whether prophylactic pyridoxine might prevent the incidence or delay the occurrence of PLD-induced HFS in patients with MM. Methods: Patients who met the trial’s eligibility requirements were randomized and then administered either pyridoxine 100 mg twice daily or no pyridoxine, in both cases accompanied by their PLD-containing chemotherapeutic agent. Follow-up of patients was performed until the completion of induction therapy, the development of HFS or disease progression. Results: Between January 1, 2017, and January 1, 2019, 105 patients were randomly assigned to the pyridoxine group (n = 52) or the no pyridoxine group (n = 53). In the pyridoxine and no pyridoxine groups, HFS developed after a median of 4 (range, 1-8 cycles) and 3 (range, 1-7 cycles) chemotherapeutic cycles, respectively. There were no grade 3 incidents recorded. Overall, 13.3% of patients experienced HFS. A 11 of 53 (20.8%) patients in the no pyridoxine group experienced HFS, compared to 3 of 52 (5.8%) patients in the pyridoxine group ( P = .042); there was no difference in HFS grades ( P = .725). Conclusions: The findings of benefit from prophylactic pyridoxine in this open-label trial have suggested its promise as a treatment for reducing HFS in MM patients. Further research with a placebo-controlled design is recommended. Clinical Trial Registration: ChiCTR2100050294.

Protein based adhesive is limited by poor mechanical properties and water resistance. Inspired by the structure of muscle tissue, a complex structure of layered double hydroxide (LDH) anchored chicken feather fiber (CFF) and tannic acid (TA) was constructed by self-assembly process, forming a novel organic–inorganic hybrid reinforcement structure (CFF-LDH-TA). CFF-LDH-TA was closely combined with soybean meal (SM) through covalent and hydrogen bond multiple interactions. TA simulated the function of connective tissue around fibers, significantly improving the cohesion of SM based adhesive through effective energy dissipation and load transfer. Due to the increased crosslinking density, the dry and wet shear strengths of SM/CFF-LDH-TA reached 2.12 and 1.60 MPa, respectively, which were 50 % and 214 % higher than original SM adhesive, and significantly exceeded the strength of several commercialized formaldehyde adhesives. The existence of bridging effect and sacrificial structure improved toughness of the adhesive, the work of adhesion increased by 802 %, reached 830 mJ. In addition, the SM/CFF-LDH-TA adhesive had better anti-mold and flame retardant ability. More importantly, the cost was lower than the commercial SM based adhesive. This simple and green preparation method provided a new strategy for the production of high-performance, multifunctional and economically effective SM based adhesive.

The polarizations of optical fields, besides field intensities, provide more degrees of freedom to manipulate coherent light–matter interactions. Here, we propose how to achieve a coherent switch of optomechanical entanglement in a polarized-light-driven cavity system. We show that by tuning the polarizations of the driving field, the effective optomechanical coupling can be well controlled and, as a result, quantum entanglement between the mechanical oscillator and the optical transverse electric mode can be coherently and reversibly switched to that between the same phonon mode and the optical transverse magnetic mode. This ability to switch optomechanical entanglement with such a vectorial device can be important for building a quantum network being capable of efficient quantum information interchanges between processing nodes and flying photons.

Abstract Background Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction. Methods We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors. Results A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072. Conclusions We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.