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Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Societal Impact Statement Crop wild relatives represent precious genetic resources for crop improvement. Investigating their local adaptation to marginal environments is important for the utilization of wild genetic resources. Oryza officinalis and Oryza granulata are wild relatives of cultivated rice and possess genes that convey resistance to insects, disease, and tolerance to shade and drought. The northern edge for the distribution of these two lies in China where populations are facing habitat destruction. This study found that the northern marginal populations of both species have adapted to local conditions, with specific implications for the conservation and utilization of wild rice. Summary O. officinalis and O. granulata, wild relatives of cultivated rice, represent important gene reservoirs with the potential to improve rice with respect to insect resistance and stress tolerance. However, the northern marginal populations of these two species in China are facing habitat destruction. Here, we investigated the genetic diversity and divergence of northern marginal populations of O. officinalis and O. granulata. The genomic variation of two species was examined by whole‐genome sequencing on 357 individuals. Generalized dissimilarity modeling was applied to investigate the effects of geographic and environmental isolation on population differentiation. Genetic‐environment association analysis and genome‐wide FST outlier scans were used to identify environmentally driven signals of selection. The marginal populations of both species exhibited low genetic diversity and obvious genetic differentiation stemmed from the joint effects of isolation by geographic distance and the environment. Both genomes exhibited specific signals of adaptation to cold environments in the north. Investigation of the divergence and adaptation of marginal populations of O. officinalis and O. granulata will help us to determine how wild rice can adapt to local environments, thus allowing for the development of scientific conservation policies and the identification of new genetic resources for rice with improved resistance.

Abstract Background Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. Methods Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan–Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. Results The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17–609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. Conclusions We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

Abstract BackgroundCardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. ObjectiveWe aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life’s Essential 8 construct. MethodsThis study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. ResultsAmong 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. ConclusionsLow education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

Abstract Background For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). Methods The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). Results Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). Conclusions For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

Abstract Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486). Tissue- and cell type-specific effects of FADS1/FADS2 expression on cognitive function were estimated using brain tissue cis-expression quantitative trait loci (cis-eQTL) datasets (GTEx, N ≤ 209; MetaBrain, N ≤ 8,613) and single cell cis-eQTL data (N = 373), respectively. These causal effects were further evaluated in whole blood cis-eQTL data (N ≤ 31,684). A series of sensitivity analyses were conducted to validate MR assumptions. Leave-one-out MR showed a FADS gene-specific effect of omega-3 fatty acids on cognitive function [β = −1.3 × 10−2, 95% confidence interval (CI) (−2.2 × 10−2, −5 × 10−3), P = 2 × 10−3]. Tissue-specific MR showed an effect of increased FADS1 expression in cerebellar hemisphere and FADS2 expression in nucleus accumbens basal ganglia on maintaining cognitive function, while decreased FADS1 expression in nine brain tissues on maintaining cognitive function [colocalization probability (PP.H4) ranged from 71.7% to 100.0%]. Cell type-specific MR showed decreased FADS1/FADS2 expression in oligodendrocyte was associated with maintaining cognitive function (PP.H4 = 82.3%, respectively). Increased FADS1/FADS2 expression in whole blood showed an effect on cognitive function maintenance (PP.H4 = 86.6% and 88.4%, respectively). This study revealed putative causal effect of FADS1/FADS2 expression in brain tissues and blood on cognitive function. These findings provided evidence to prioritize FADS gene as potential target gene for maintenance of cognitive function.

Background/Aims: Necrotizing pancreatitis (NP) presents a more severe clinical trajectory and increased mortality compared to edematous pancreatitis. Prompt identification of NP is vital for patient prognosis. A risk prediction model for NP among Chinese patients has been developed and validated to aid in early detection. Methods: A retrospective analysis was performed on 218 patients with acute pancreatitis (AP) to examine the association of various clinical variables with NP. The least absolute shrinkage and selection operator (LASSO) regression was utilized to refine variables and select predictors. Subsequently, a multivariate logistic regression was employed to construct a predictive nomogram. The model's accuracy was validated using bootstrap resampling (n=500) and its calibration assessed via a calibration curve. The model's clinical utility was evaluated through decision curve analysis. Results: Of the 28 potential predictors analyzed in 218 AP patients, the incidence of NP was 25.2%. LASSO regression identified 14 variables, with procalcitonin, triglyceride, white blood cell count at 48 hours post-admission, calcium at 48 hours post-admission, and hematocrit at 48 hours post-admission emerging as independent risk factors for NP. The resulting nomogram accurately predicted NP risk with an area under the curve of 0.822, sensitivity of 82.8%, and specificity of 76.4%. The bootstrap-validated area under the curve remained at 0.822 (95% confidence interval, 0.737 to 0.892). This model exhibited excellent calibration and demonstrated greater predictive efficacy and clinical utility for NP than APACHE II, Ranson, and BISAP. Conclusions: We have developed a prediction nomogram of NP that is of great value in guiding clinical decision.

Abstract Background Mitochondrial outer membrane permeabilisation (MOMP) plays a pivotal role in cellular death and immune activation. A deeper understanding of the impact of tumour MOMP on immunity will aid in guiding more effective immunotherapeutic strategies. Methods A comprehensive pan‐cancer dataset comprising 30 cancer‐type transcriptomic cohorts, 20 immunotherapy transcriptomic cohorts and three immunotherapy scRNA‐seq datasets was collected and analysed to determine the influence of tumour MOMP activity on clinical prognosis, immune infiltration and immunotherapy effectiveness. Leveraging 65 scRNA‐Seq datasets, the MOMP signature (MOMP.Sig) was developed to accurately reflect tumour MOMP activity. The clinical predictive value of MOMP.Sig was explored through machine learning models. Integration of the MOMP.Sig model and a pan‐cancer immunotherapy CRISPR screen further investigated potential targets to overcome immunotherapy resistance, which subsequently underwent clinical validation. Results Our research revealed that elevated MOMP activity reduces mortality risk in cancer patients, drives the formation of an anti‐tumour immune environment and enhances the response to immunotherapy. This finding emphasises the potential clinical application value of MOMP activity in immunotherapy. MOMP.Sig, offering a more precise indicator of tumour cell MOMP activity, demonstrated outstanding predictive efficacy in machine‐learning models. Moreover, with the assistance of the MOMP.Sig model, FOXO1 was identified as a core modulator that promotes immune resistance. Finally, these findings were successfully validated in clinical immunotherapy cohorts of skin cutaneous melanoma and triple‐negative breast cancer patients. Conclusions This study enhances our understanding of MOMP activity in immune modulation, providing valuable insights for more effective immunotherapeutic strategies across diverse tumours.

Abstract Plateau pikas, small mammals native to the Qinghai‐Tibet Plateau (QTP), create bare patches through burrowing. No previous assessment exists on their impact on permafrost. This study fills this gap by simulating hypothetical scenarios in the Three Rivers Headwaters Region of the QTP using the Noah‐MP model for the plant growing seasons during 2015–2018. Our findings reveal a significant increase in soil temperature in the active layer due to pika‐induced bare patches, particularly during July–August. The average temperature rise at 2.5 cm depth was 0.36°C in permafrost regions and 0.29°C in seasonally frozen ground regions during August. Minimal impact on unfrozen water content was observed, with a slight increase in deep soil layers in permafrost regions, and negligible in seasonally frozen areas. These findings underscore the previously unexplored influence of pika burrowing on permafrost temperature, suggesting a potential risk of accelerating permafrost degradation, especially in permafrost‐dominated regions.

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Abstract Background Previous observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways. Methods We performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight. Results Genetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22–1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16–1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association. Conclusions Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Abstract Background The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by “Life’s Essential 8” has not been characterized. We aim to examine the associations of early adulthood weight change and midlife “Life’s Essential 8” CVH status with cardiometabolic outcomes in a Chinese cohort. Methods The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in “Life’s Essential 8” was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

Abstract Background Patient–ventilator asynchrony is common during mechanical ventilation (MV) in intensive care unit (ICU), leading to worse MV care outcome. Identification of asynchrony is critical for optimizing MV settings to reduce or eliminate asynchrony, whilst current clinical visual inspection of all typical types of asynchronous breaths is difficult and inefficient. Patient asynchronies create a unique pattern of distortions in hysteresis respiratory behaviours presented in pressure–volume (PV) loop. Methods Identification method based on hysteretic lung mechanics and hysteresis loop analysis is proposed to delineate the resulted changes of lung mechanics in PV loop during asynchronous breathing, offering detection of both its incidence and 7 major types. Performance is tested against clinical patient data with comparison to visual inspection conducted by clinical doctors. Results The identification sensitivity and specificity of 11 patients with 500 breaths for each patient are above 89.5% and 96.8% for all 7 types, respectively. The average sensitivity and specificity across all cases are 94.6% and 99.3%, indicating a very good accuracy. The comparison of statistical analysis between identification and human inspection yields the essential same clinical judgement on patient asynchrony status for each patient, potentially leading to the same clinical decision for setting adjustment. Conclusions The overall results validate the accuracy and robustness of the identification method for a bedside monitoring, as well as its ability to provide a quantified metric for clinical decision of ventilator setting. Hence, the method shows its potential to assist a more consistent and objective assessment of asynchrony without undermining the efficacy of the current clinical practice.

Abstract Background Low‐density lipoprotein cholesterol (LDL‐C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL‐C levels confer a risk for diabetes remains unclear. Objective We aimed to examine the association between serum LDL‐C concentrations at baseline and the risk of developing diabetes at follow‐up in the general population of Chinese adults. Methods This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.4 years. A standard 75‐g oral glucose tolerance test was conducted at baseline and follow‐up visits to diagnose diabetes. Logistic regression models and a restricted cubic spline were used to examine the association between baseline serum LDL‐C levels and the risk of diabetes development. Subgroup analyses were conducted stratifying on age, sex, body mass index, hypertension, family history of diabetes, and LDL‐C levels. Results A total of 652 participants (12%) developed diabetes during the follow‐up period. Compared to quartile 1 of serum LDL‐C, quartiles 2, 3, and 4 were associated with a 30%, 33%, and 30% significantly higher risk of diabetes, respectively after adjustment for confounders including homeostatic model assessment for insulin resistance. The linear relationship between baseline LDL‐C down to 30.1 mg/dL and incident diabetes was demonstrated by restricted cubic spline analysis, and each 1‐SD increase in LDL‐C concentration (28.5 mg/dL) was associated with a 12% increase in the risk of diabetes (odds ratio 1.12, 95% confidence interval 1.03–1.22). Conclusion In this community‐based general population, higher serum LDL‐C levels were linearly associated with an elevated risk of incident diabetes.

Background. ATP binding cassette transporter A1 (ABCA1) is a candidate gene within a POAG susceptibility locus by GWAS analysis, and it is involved in IOP modulation via the Cav1/eNOS/NO signaling pathway. We aim to examine the phenotype of ABCA1 deletion in the ABCA1 gene knockout (Abca1−/−) mice. Methods. The anterior segments of Abca1−/− eyes were imaged by slit-lamp microscopy and anterior segment OCT. IOPs were measured by rebound tonometry. By perfusing enucleated eyes at various pressures, the aqueous humor outflow facility was determined. The mRNA expressions of ABCA1, Cav1, and eNOS were measured by RT-qPCR. The protein expressions were analyzed by western blot and immunofluorescence staining. Results. There was no significant difference in the anterior segment morphology of Abca1−/− mice. IOP and aqueous humor outflow facility did not change in Abca1−/− mice compared with wild-type mice. mRNA and protein expressions of ABCA1 were significantly lower in the outflow tissue of Abca1−/− eyes. The expressions of Cav1 and eNOS were both significantly upregulated in the outflow tissue of Abca1−/− eyes. Conclusion. ABCA1 deletion does not affect IOP and aqueous humor outflow function but the Cav1/eNOS/NO pathway is changed in Abca1−/− mice. The function of ABCA1 in aqueous humor outflow still requires further research.

Abstract Aim Mindfulness has been widely used with all kinds of people, such as students, educators or patients. However, there have been no studies explicitly targeting ward nurses. The aim of this study is to explore the concept analysis of mindfulness in ward nurses. Design A concept analysis. Methods An electronic literature search of MEDLINE, Google Scholar, PubMed, Cambridge Online Dictionary and EBSCO on mindfulness was conducted over a ten‐year period of Peer‐reviewed scholarly articles published in English. The Walker and Avant's framework was used for this paper. Results Eleven articles in total were included in this study. Three attributes of mindfulness in ward nurses were identified as in the present moment, paying attention and being receptive. The consequence of mindfulness in ward nurses lead to positive changes, which included improving well‐being, decreased burnout, anxiety and depression. An exploration of mindfulness in ward nurses was developed. The findings of this paper can be used in ward nurses, research and administration.

Abstract Background Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Methods Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Results Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. Conclusions This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

Abstract Background Cataract is the primary cause of blindness globally, and surgery offers the only method by which to remove cataracts. We aimed to examine whether previous cataract surgery is associated with cognitive function. Methods Our study included 13,824 participants. Data from the baseline of the China Health and Retirement Longitudinal Study (CHARLS) were used. The participants were categorized into two groups: with and without previous cataract surgery. Weighted multiple linear regression was used to obtain the β and 95% confidence intervals (CI). Results The participants who had previous cataract surgery (n = 261) scored lower in cognition, including both memory and mental state, than those without previous cataract surgery. After adjusting for socioeconomic factors and metabolic measures, a negative association was evident between previous cataract surgery and cognition (β = −0.647, 95% CI: −1.244, − 0.049). Furthermore, the participants who were older and female demonstrated a decline in cognition, while living in cities and having higher levels education were associated with higher cognition. Conclusions Better cognitive function was associated with less previous cataract surgery or cataract occurrence. This suggests that a period of vision loss due to cataract leads to cognitive decline, however further studies are need to dissect the impact of vision loss and cataract surgery on cognitive decline.

Abstract Background Continuous renal replacement therapy (CRRT) remains a crucial treatment for critically ill patients with acute kidney injury (AKI), although the timing of its initiation is still a matter of contention. Furosemide stress testing (FST) may be a practical and beneficial prediction instrument. This research was meant to examine if FST can be used to identify high-risk patients for CRRT. Methods This study is a double-blind, prospective interventional cohort study. For patients with AKI receiving intensive care unit (ICU) income, FST was selected with furosemide 1 mg/kg intravenous (1.5 mg/kg intravenous if a loop diuretic was received within 7 days). Urinary volume more than 200 ml at 2 h after FST was FST-responsive, less than 200 ml was FST-nonresponsive. The FST results are kept strictly confidential from the clinician, who decides whether to initiate CRRT based on laboratory testing and clinical symptoms other than the FST data. The FST data are concealed from both the patients and the clinician. Results FST was delivered to 187 of 241 patients who satisfied the inclusion and exclusion criteria, with 48 patients responding to the test and 139 patients not responding. 18/48 (37.5%) of the FST-responsive patients received CRRT, while 124/139 (89.2%) of the FST-nonresponsive patients received CRRT. There was no significant difference between the CRRT and non-CRRT groups in terms of general health and medical history (P > 0.05). Urine volume after 2 h of FST was considerably lower in the CRRT group than in the non-CRRT group (35 ml, IQR5-143.75 versus 400 ml, IQR210-890; P = 0.000). FST non-responders were 2.379 times more likely to initiate CRRT than FST responders (95% CI 1.644–3.443, P = 0.000). The area under the curve (AUC) for initiating CRRT was 0.966 (cutoff of 156 ml, sensitivity of 94.85%, specificity of 98.04%, P

Objectives This study aimed to investigate the knowledge, attitudes and practical experiences of cardiac surgery nurses regarding kinesiophobia management during early mobilisation.Design Using a descriptive qualitative research method, 21 cardiac surgery nurses participated in this study from October 2022 to January 2023, and the interview data were analysed using the Colaizzi 7-step analysis method.Setting Data were collected through in-depth face-to-face or online interviews in a tertiary hospital located in Nanjing, China.Participants 21 cardiac surgery nurses were interviewed from October 2022 to January 2023.Results Two themes were summarised: knowledge, attitude and practice of nurses (high recognition and low participation; low knowledge reserve; low willingness); the promotion and essential elements of kinesiophobia management (efficient health education model; stable medical staff–family caregiver collaboration; simplified clinical protocol; specialist nursing team; clarify the multidisciplinary division of labour).Conclusion The management of kinesiophobia in patients undergoing cardiac surgery is currently in the developmental phase. It is advisable to give due consideration to emotional support and cognitive training for medical staff. In addition, a workable management plan, consistent with clinical practice, should be formulated through multidisciplinary and medical staff–family caregiver collaboration to optimise patient outcomes.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4

In this report, we present a case study of a 64-year-old female who was diagnosed with gastrointestinal stromal tumors (GISTs) and subsequently developed liver metastases despite undergoing radical resection. Next-generation sequencing (NGS) assays indicated that the tumor lacked KIT/PDGFRA/SDH/RAS-P (RAS pathways, RAS-P) mutations, thereby classifying this patient as quadruple WT GIST (qGIST). Treatment with imatinib was initiated, and after 2.5 months, recurrence of the tumor and multiple metastases around the surgical site were observed. Consequently, the patient was switched to sunitinib treatment and responded well. Although she responded well to sunitinib, the patient died of tumor dissemination within 4 months. This case study highlights the potential efficacy of imatinib and the VEGFR-TKI sunitinib in treating qGIST patients harboring a TP53 missense mutation.

Purpose: To compare the morphological characteristics of Schlemm’s canal (SC) in patients with primary open-angle glaucoma (POAG) and healthy controls, using swept-source optical coherence tomography (SS-OCT) with en face reconstruction.Methods: In this Prospective comparative study, we included 100 eyes from 50 patients diagnosed with POAG and 50 healthy controls. Three-dimensional cube and line scans of the temporal and nasal quadrants of the anterior segment of the limbus were acquired using SS-OCT. SC was identified using en face and cross-sectional images. The diameter and area of SC in cross-sectional images and the visible percentage and area of SC in en face images were measured using ImageJ.Results: SC was observed in 84% of en face images and 81% of cross-sectional images in eyes with POAG but in 92% of en face images and 86% of cross-sectional images in control eyes. Significant differences between the POAG and normal control eyes were found in the en face area (0.35 ± 0.14 mm2 vs. 0.56 ± 0.22 mm2 in the temporal quadrant and 0.36 ± 0.14 mm2 vs. 0.58 ± 0.23 mm2 in the nasal quadrant; both p < 0.001) and visible percentage of SC (85.71% vs. 94.91% and 87.10% vs. 95.52% in the temporal and nasal quadrant respectively, both p < 0.001) in en face images as well as the cross-sectional area (2790.9 ± 942.2 μm2 vs. 4138.6 ± 2027.8 μm2 in the temporal quadrant and 2805.7 ± 947.2 μm2 vs. 4224.0 ± 2002.2 μm2 in the nasal quadrant, both p < 0.001) and diameter of SC (123.1 ± 25.4 μm vs. 149.5 ± 34.7 μm in the temporal quadrant and 126.3 ± 28.9 μm vs. 155.3 ± 36.0 μm in the nasal quadrant, both p < 0.001) in cross-section images. In addition, the mean intraocular pressure (IOP) significantly correlated with the en face area, visible percentage of SC, and cross-sectional area in the temporal and nasal quadrants.Conclusion: SS-OCT can obtain high-quality en face images of SC without post-acquisition processing. Eyes with POAG had a decreased en face SC area compared with normal eyes. A correlation between SC area, visible percentage of en face images, and IOP was also observed.

The Stimulator of Interferon Genes (STING) is predominantly expressed in immune cells, including macrophages, natural killer cells, dendritic cells, and T cells, functioning as a pattern recognition receptor. STING activation upon detecting cytosolic DNA released from damaged cells initiates downstream pathways, leading to the production of inflammatory cytokines such as IFNs, IL-6, and TNF-α. Dysregulated STING activation has been implicated in inflammatory and metabolic diseases. Ischemia/reperfusion injury (I/RI) is common in stroke, acute myocardial infarction, organ transplantation, and surgeries for certain end-stage diseases. Recent studies suggest that STING could be a novel therapeutic target for I/RI treatment. In this review, we provide a concise overview of the cGAS-STING signaling pathway's general functions and summarize STING's role in I/RI across various organs, including the heart, liver, kidney, and lung. Moreover, we explore potential therapeutic approaches for I/RI by targeting STING.

Abstract Background Studies indicate lower, comparable, and higher cardiovascular risks in women vs men in normal glucose regulation (NGR), prediabetes, and diabetes, respectively. However, this sex difference is uncertain and aging might play a part. We aimed to estimate sex differences in arterial stiffness in NGR, prediabetes, or diabetes and the potential modifications by age. Methods We used baseline data of 9618 participants aged ≥40 years in a large community‐based cohort study in Shanghai. Glycemic status was determined by history of diabetes, fasting and 2‐h post‐load glucose levels, and hemoglobin A1c levels. Arterial stiffness was examined by brachial‐ankle pulse wave velocity (ba‐PWV). Multivariable linear regression analysis was conducted to examine the associations between sex and ba‐PWV levels in glycemic and age categories. Results Before adjustment for age, women had lower, comparable, and higher ba‐PWV vs men in the NGR, prediabetes, and diabetes groups, respectively. In participants aged 40–59 years, women were associated with lower ba‐PWV levels in generally all glycemic strata after adjustment for age and other confounders. In participants aged ≥60 years, women were associated with significantly higher ba‐PWV levels (β coefficient = 71.5; 95% confidence interval = 23.4, 119.7) and the sex difference was attenuated in the groups of prediabetes and diabetes with a borderline significant interaction between sex and glycemic status (p for interaction = .068). Conclusions The sex difference in cardiovascular risks in adults with NGR, prediabetes, or diabetes was dependent on age. Our findings provide new evidence for prioritizing preventive treatment against atherosclerosis in men vs women with different glycemic status.

Biofilm formation plays a crucial role in the pathogenesis of Candida albicans and is significantly associated with resistance to antifungal agents. Tea seed saponins, a class of non-ionic triterpenes, have been proven to have fungicidal effects on planktonic C. albicans. However, their anti-biofilm activity and mechanism of action against C. albicans remain unclear. In this study, the effects of three Camellia sinensis seed saponin monomers, namely, theasaponin E1 (TE1), theasaponin E2 (TE2), and assamsaponin A (ASA), on the metabolism, biofilm development, and expression of the virulence genes of C. albicans were evaluated. The results of the XTT reduction assay and crystal violet (CV) staining assay demonstrated that tea seed saponin monomers concentration-dependently suppressed the adhesion and biofilm formation of C. albicans and were able to eradicate mature biofilms. The compounds were in the following order in terms of their inhibitory effects: ASA > TE1 > TE2. The mechanisms were associated with reductions in multiple crucial virulence factors, including cell surface hydrophobicity (CSH), adhesion ability, hyphal morphology conversion, and phospholipase activity. It was further demonstrated through qRT-PCR analysis that the anti-biofilm activity of ASA and TE1 against C. albicans was attributed to the inhibition of RAS1 activation, which consequently suppressed the cAMP–PKA and MAPK signaling pathways. Conversely, TE2 appeared to regulate the morphological turnover and hyphal growth of C. albicans via a pathway that was independent of RAS1. These findings suggest that tea seed saponin monomers are promising innovative agents against C. albicans.

Sclerotinia, which is caused by Sclerotinia sclerotiorum, is a severe disease of oilseed rape, which is an important oil crop worldwide. In this study, we isolated a novel strain of Bacillus cereus, named B. cereus HF10, from the rhizosphere soil of the reed on the seaside of Yagzhou Bay, Sanya city, Hainan Province, China. HF10 exhibited a significant antagonistic effect on Sclerotinia sclerotiorum, with an inhibition rate of 79%, and to other species in Sclerotinia, but no antagonistic effect was found on various other fungi or bacteria. HF10 had an 82.3% inhibitory effect on the S. sclerotiorum infection of oilseed rape leaves and a 71.7% control effect on Sclerotinia infection in oilseed rape based on in vitro and in vivo experiments, respectively. The genomics and transcriptomics of HF10 and its loss of the antifungal function mutant Y11 were analyzed, and the results provided insight into potential antifungal substances. Our work provides a novel strain, HF10, for developing a promising biological control agent against Sclerotinia, which infects oilseed rape and other plants.

Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high apolipoprotein B (ApoB), and low low density lipoprotein (LDL) cholesterol to ApoB ratio. We investigated whether and to what extent hypertriglyceridemic hyperapoB associates with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). This prospective cohort study included 9,019 Chinese participants 40 years or older, from 2010 to 2015. Logistic regression models were used to examine the odds ratios (ORs) for the incidence and resolution of NAFLD associated with the hypertriglyceridemic hyperapoB lipoprotein phenotype and individual lipid and lipoprotein parameters. During a median 4.3 years of follow-up, compared with participants with optimal phenotype, the fully adjusted ORs (95% CIs) for participants with hypertriglyceridemic hyperapoB were 2.75 (1.91, 3.95) and 0.57 (0.33, 1.00) for incidence and resolution of NAFLD, respectively. These associations were consistent across subgroup participants with varied demographic, lifestyle, and metabolic status. Individually, each unit increase in HDL cholesterol (OR: 0.98; 95% CI: 0.97, 0.99), natural logarithm-transformed triglycerides (1.89; 1.52, 2.36), and ApoB (1.006; 1.002, 1.011) was independently associated with NAFLD incidence, and only triglycerides (0.77; 0.60, 0.99) was independently associated with NAFLD resolution. Our findings suggest that Chinese adults with hypertriglyceridemic hyperapoB have a higher risk of NAFLD incidence and a lower likelihood of NAFLD resolution. These associations were stable among adults with different demographic, lifestyle, and metabolic status, supporting hypertriglyceridemic hyperapoB as a valuable clinical marker for the prevention and control of NAFLD.

BackgroundStimulation of IFN genes (STING) is central to the production of interferon and proinflammatory cytokines in response to microbial DNA or self-DNA in the cytosol. The detrimental role of the activation of STING during sepsis has been well documented.MethodsHere, we found that gelsevirine (GS) potently inhibit interferon and inflammatory cytokine induction in macrophages exposed to STING agonists (2'3'-cGAMP, IFN stimulatory DNA (ISD), and poly(dA:dT)). I n silico docking analysis and surface plasmon resonance binding study showed that GS bonds with high affinity to the cyclic dinucleotide (CDN)-binding pocket of STING. Biotin pull-down assay also confirmed that GS competitively bonded to STING protein. Furthermore, GS inhibited 2’3’-cGAMP-induced STING dimerization and subsequent activation. In addition, GS induced K48-linked STING ubiquitination and degradation, which was likely through upregulating and recruiting TRIM21. In mice exposed to cecal ligation and puncture (CLP)-induced sepsis, post-operative administration of GS significantly extended the survival period and mitigated acute organ damage.ResultsOverall, GS inhibited STING signaling by competitively binding to the CDN-binding pocket to lock STING in an inactive open conformation, while also promoting K48-linked STING ubiquitination and degradation.ConclusionsOur findings identify a novel STING-specific inhibitor that could be applied in the treatment of sepsis.

TIPARP, an inducible poly-ADP-ribose polymerase, is identified as a novel regulator of intraocular pressure through modulation of extracellular matrix and cell cytoskeleton proteins in trabecular meshwork cells.

Abstract Background Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them. Methods Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self‐report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator. Results Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12–1.27), while college‐educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73–0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] −0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women. Conclusions In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.

Abstract Background Age has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities. Methods We analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese. Results The sex and BMI standardized prevalence of hypertension in Chinese aged 18–40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of β-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old. Conclusions The age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.

Abstract Background Previous studies reported that famine exposure had an effect on metabolic syndrome (MetS). However, there is an inadequacy of study regarding the association between famine exposure, adulthood general obesity, and the risk of MetS. Methods A total of 8883 subjects aged ≥40 years from Jiading community in Shanghai were included. We defined famine exposure subgroups as nonexposed (1963–1974), fetal exposed (1959–1962), childhood exposed (1949–1958), and adolescence exposed (1941–1948). MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATP III) criteria. Results Compared with the nonexposed group, the risks of MetS were increased in the fetal‐, childhood‐, and adolescence‐exposed groups with odds ratios (OR) and 95% confidence intervals (CI) of 1.48 (1.23–1.78), 1.89 (1.63–2.20), and 2.34 (1.99–2.74), respectively. After adjusting for sex, age, smoking status, drinking status, education, body mass index (BMI), and physical activity, the increased risk of MetS related to the fetal‐exposed and childhood‐exposed groups with OR and 95% CI of 1.42 (1.04–1.94) and 1.50 (1.02–2.21), respectively, were observed only in women. Famine exposure was significantly associated with MetS among individuals with a BMI

Abstract Background The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals. Methods This prospective study was conducted in 5751 adults with normal carotid intima‐media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow‐up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models. Results After a median follow‐up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00‐1.66) and 1.42 (95% CI, 1.11‐1.83), respectively. Restricted cubic splines demonstrated an approximately U‐shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity

Abstract Background Prediabetes is an important risk factor of cardiovascular disease (CVD) and is associated with subclinical atherosclerosis. However, the evidence of prediabetes as a cardiovascular risk factor is mainly derived from middle-aged adults. Recently, multiple studies supported that prediabetes in older adults would not lead to higher risk of CVD or mortality. We aimed to investigate the age-specific difference in the association between prediabetes and subclinical atherosclerosis in a Chinese prospective cohort study. Methods We included 4739 individuals aged ≥ 40 years and without diagnosed diabetes or CVD history, and divided them into middle-aged adults (age

Abstract Background Foods have a considerable influence on human health and were directly related to glycemic control for diabetes patients. However, little is known about the effects of biscuits, a traditional food consumed in large amounts in several countries, on diabetic retinopathy. This study aimed to explore the association between biscuit consumption and diabetic retinopathy prevalence in adults of the United States population. Methods A cross-sectional study with 1904 participants from the National Health and Nutrition Examination Survey database were included in this population-based, cross-sectional study. The association between different consumption frequencies of biscuit and diabetic retinopathy prevalence was evaluated using a binary logistic regression model. Trend test, stratified and interaction analyses were also performed. Results After possible confounders including sex, age, ethnicity, education, marital status, family poverty income ratio, smoking and alcohol consumption habit, fasting blood glucose level, hemoglobin A1c level, diagnosis of diabetes, insulin use, blood pressure, body mass index were adjusted, the participants who consumed biscuit 1–11 times a year, 1–3 times a month, and more than once a week had a 139.8% (95% confidence interval, 1.003–5.734), 182.1% (95% confidence interval, 1.106–7.191), and 236.2% (95% confidence interval, 1.335–9.844) higher risk of diabetic retinopathy prevalence, respectively, compared with those who never ate biscuit. For male, non-Hispanic, and overweight (body mass index ≥ 25 kg/m2) subgroups, the trend test demonstrated that the diabetic retinopathy prevalence significantly elevated with increased frequency of biscuit consumption (P trend = 0.021, 0.009, and 0.002, respectively). The interaction analysis suggested that no aforementioned confounders played an interactive role in the relationship between biscuit consumption and diabetic retinopathy prevalence. Conclusions The risk of diabetic retinopathy was positively associated with biscuit consumption. Moreover, for male, non-Hispanic, or overweight individuals, the risk of diabetic retinopathy significantly increased with the frequency of biscuit consumption.

Seabed soils can undergo liquefaction under cyclic loading, resulting in a rapid decrease in strength and stiffness, which may lead to the destruction of offshore structures. Therefore, the assessment of seabed soil liquefaction will become an important factor in disaster prevention and risk analysis in coastal and offshore engineering construction. In this study, the ocean ambient noise with low-frequency, long-wavelength, and wide-band characteristics was used to conduct and analysis noise based on the horizontal-to-vertical spectral ratio method. The shear wave velocity of the seabed soil was obtained by inverting the ocean ambient noise dataset. Then, we proposed a shear wave velocity threshold that can be used for liquefaction assessment of Holocene unconsolidated fine-grained soils by statistical analysis, and the liquefaction potential of the soils was evaluated according to 1-D shear wave velocity structures and 2-D shear wave velocity profiles. The results showed that the distribution of the shear wave velocity obtained by inverting ocean ambient noise was generally consistent with the measured shear wave velocity in the field, indicating that the inversion results have a certain degree of accuracy. A shear wave velocity threshold of 200 m/s was proposed for liquefaction assessment, determining that the soils within 0-10 m depth in the coastal area of Yellow River Delta have liquefaction potential. This result is in accordance with the assessment based on the critical shear wave velocity, indicating that this threshold is applicable to the assessment of seabed soil liquefaction in the Yellow River Delta. The in-situ observations of ocean ambient noise provide a more convenient, economical, and environmentally friendly method, which can help to investigate marine geology disasters and serve marine engineering construction.

Observations of the association between carbohydrate intake and hypertension are inconsistent, with mediating pathways unclear. We aimed to investigate the causal effect of relative carbohydrate intake on hypertension and the mediating roles of psychological well-being and adiposity. Using summary-level statistics of genome-wide association studies of European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate the bidirectional causal association between relative carbohydrate intake (total energy-adjusted, mean: 42–51%) and hypertension (FinnGen: 42,857 cases/162,837 controls; UK Biobank: 77,723 cases/330,366 controls) and two-step MR to assess the mediating effects of psychological well-being indicators and adiposity traits on the association. MR estimates of hypertension from FinnGen and UK Biobank were meta-analyzed using the fixed-effect model given no heterogeneity. Meta-analyses of multivariable MR estimates from FinnGen and UK Biobank indicated that each one-SD higher relative carbohydrate intake was associated with 71% (odds ratio: 0.29; 95% confidence interval: 0.11–0.79) lower risk of hypertension, independently of other dietary macronutrients. Hypertension showed no reverse effect on carbohydrate intake. Five psychological well-being indicators and four adiposity traits causally mediated the association between relative carbohydrate intake and hypertension, including body mass index (mediation proportion: 51.37%), waist circumference (40.54%), waist-to-hip ratio (35.00%), hip circumference (24.77%), major depressive disorder (23.37%), positive affect (17.08%), depressive symptoms (16.52%), life satisfaction (16.05%), and neuroticism (11.22%). Higher relative carbohydrate intake was causally associated with lower hypertension risk, substantially mediated by better psychological well-being and less adiposity. Our findings inform causal targets and pathways for the prevention and intervention of hypertension.

Abstract Background Family history of diabetes, unhealthy lifestyles, and metabolic disorders are individually associated with higher risk of diabetes, but how different combinations of the three risk categories are associated with incident diabetes remains unclear. We aimed to estimate the associations of comprehensive risk profiles of family history and lifestyle and metabolic risk factors with diabetes risk. Methods This study included 5290 participants without diabetes at baseline with a mean follow‐up of 4.4 years. Five unhealthy lifestyles and five metabolic disorders were each allocated a score, resulting in an aggregated lifestyle and metabolic risk score ranging from 0 to 5. Eight risk profiles were constructed from combinations of three risk categories: family history of diabetes (yes, no), lifestyle risk (high, low), and metabolic risk (high, low). Results Compared with the profile without any risk category, other profiles exhibited incrementally higher risks of diabetes with increasing numbers of categories: the hazard ratio (HR, 95% confidence interval [CI]) for diabetes ranged from 1.34 (1.01–1.79) to 2.33 (1.60–3.39) for profiles with one risk category, ranged from 2.42 (1.45–4.04) to 4.18 (2.42–7.21) for profiles with two risk categories, and was 4.59 (2.85–7.39) for the profile with three risk categories. The associations between the numbers of risk categories and diabetes risk were more prominent in women (pinteraction = .025) and slightly more prominent in adults

The role of gut microbiota in acute myeloid leukaemia (AML) remains unclear. Here, the authors show disordered gut microbiota and reduced butyrate cause intestinal barrier damage in AML mice, with increased plasma LPS that accelerates AML progression.

ObjectivesOur aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.MethodsWe extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.ResultsTwo taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.ConclusionsGut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.

Immunotherapy plus chemotherapy has been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC, stage IV). Recently, the 2023 version of the National Comprehensive Cancer Network Guidelines recommended immunotherapy plus chemotherapy as the neoadjuvant regimen in patients with resectable non-small cell lung cancer (NSCLC). However, it is still unclear whether the combination regimen of immunotherapy plus chemotherapy is also beneficial for SCLC in the neoadjuvant context. Here, we report the case of a patient with stage IIIB SCLC who showed long-term survival and good tolerance to the neoadjuvant chemoimmunotherapy consisting of tislelizumab (an anti–PD-1 monoclonal antibody) plus etoposide-carboplatin. The patient achieved pathological complete response after receiving two cycles of neoadjuvant tislelizumab and chemotherapy followed by surgery. Two courses of post-operative tislelizumab and etoposide-carboplatin treatment were performed. The patient has survived for more than 23 months with no recurrence or metastases after neoadjuvant therapy. Multiplexed immunofluorescence and immunohistochemistry staining showed that the post-treatment specimens had remarkable immune cells infiltration, including CD3+ T cells, CD4+ T cells, and CD8+ T cells, which contrasted with very low levels of these cells in the pre-treatment samples. This study is, to the best of our knowledge, the first attempt to present the neoadjuvant chemoimmunotherapy of tislelizumab in combination with etoposide-carboplatin in SCLC. Our study suggested that neoadjuvant tislelizumab plus chemotherapy may facilitate radical resection and benefit patients with locally advanced (stage IIB-IIIC) SCLC.

BackgroundExposure to light at night (LAN) is a potent disruptor of the circadian system. Whether LAN exposure exerts a sex- or age-specific influence on obesity needs investigation.ObjectivesTo estimate the sex- and age-specific associations of exposure to outdoor LAN and obesity based on a national and cross-sectional survey.MethodsThe study included a nationally representative sample of 98,658 adults aged ≥ 18 years who had lived in their current residence for ≥ 6 months from 162 study sites across mainland China in 2010. Outdoor LAN exposure was estimated from satellite imaging data. General obesity was defined as body-mass index (BMI) ≥ 28 kg/m2 and central obesity was defined as waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Linear and logistic regression models were used to examine the associations between LAN exposure and prevalent obesity in sex and age categories.ResultsA monotonically increasing association of outdoor LAN with BMI, waist circumference was observed in all sex and age categories, except for adults aged 18-39 years. Significant associations of LAN exposure with prevalent obesity were observed in each sex and age category, especially in men and older people. Per 1-quintile increase in LAN was associated with 14% increased odds of general obesity in men (odds ratio, OR=1.14, 95% confidence interval, CI=1.07-1.23) and 24% in adults aged ≥ 60 years (OR=1.24, 95% CI=1.14-1.35). Per 1-quintile increase in LAN was associated with 19% increased odds of central obesity in men (OR=1.19, 95% CI=1.11-1.26) and 26% in adults aged ≥ 60 years (OR=1.26, 95% CI=1.17-1.35).ConclusionsIncreased chronic outdoor LAN exposure was associated with increased prevalence of obesity in sex- and age- specific Chinese populations. Public health policies on reducing light pollution at night might be considered in obesity prevention.

Silique walls play pivotal roles in contributing photoassimilates and nutrients to fuel seed growth. However, the interaction between seeds and silique walls impacting oil biosynthesis is not clear during silique development. Changes in sugar, fatty acid and gene expression during Brassica napus silique development of L192 with high oil content and A260 with low oil content were investigated to identify key factors affecting difference of their seed oil content. During the silique development, silique walls contained more hexose and less sucrose than seeds, and glucose and fructose contents in seeds and silique walls of L192 were higher than that of A260 at 15 DAF, and sucrose content in the silique walls of L192 were lower than that of A260 at three time points. Genes related to fatty acid biosynthesis were activated over time, and differences on fatty acid content between the two genotypes occurred after 25 DAF. Genes related to photosynthesis expressed more highly in silique walls than in contemporaneous seeds, and were inhibited over time. Gene set enrichment analysis suggested photosynthesis were activated in L192 at 25 and 35 DAF in silique walls and at both 15 and 35 DAF in the seed. Expressions of sugar transporter genes in L192 was higher than that in A260, especially at 35 DAF. Expressions of genes related to fatty acid biosynthesis, such as BCCP2s, bZIP67 and LEC1s were higher in L192 than in A260, especially at 35 DAF. Meanwhile, genes related to oil body proteins were expressed at much lower levels in L192 than in A260. According to the WGCNA results, hub modules, such as ME.turquoise relative to photosynthesis, ME.green relative to embryo development and ME.yellow relative to lipid biosynthesis, were identified and synergistically regulated seed development and oil accumulation. Our results are helpful for understanding the mechanism of oil accumulation of seeds in oilseed rape for seed oil content improvement.

Abstract Background Laser peripheral iridotomy (LPI) is effective in primary angle-closure suspects (PACS); however, predictors for anterior segment alterations after LPI are limited. We aimed to evaluate the anterior segment biometric parameters before and after LPI in PACS using the recently developed, CASIA 2 device of anterior segment optical coherence tomography (AS-OCT). Methods We performed LPI in 52 PACS. Anterior segment parameters, including anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber volume (ACV), iris curvature (ICURVE), iridotrabecular contact (ITC), lens vault (LV), lens thickness (LT), radius of the lens, angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and trabecular iris angle (TIA) at different distances (i.e., 500 μm from the sclera spur), were evaluated before and after LPI using CASIA 2. Results Eyes of PACS after LPI had a greater ACV, AOD, ARA, TISA, and TIA, and a lower ITC and ICURVE (all p

Abstract Background Serum electrolytes were found to associate with type 2 diabetes. Our study aimed to stratify nondiabetes by clusters based on multiple serum electrolytes and evaluate their associations with risk of developing diabetes and longitudinal changes in glucose and lipid metabolic traits. Methods We performed a data‐driven cluster analysis in 4937 nondiabetes individuals aged ≥40 years at baseline from a cohort follow‐up for an average of 4.4 years. Cluster analysis was based on seven commonly measured serum electrolytes (iron, chlorine, magnesium, sodium, potassium, calcium, and phosphorus) by using the k‐means method. Results A total of 4937 nondiabetes individuals were classified into three distinct clusters, with 1635 (33.1%) assigned to Cluster A, 1490 (30.2%) to Cluster B, and 1812 (36.7%) to Cluster C. Individuals in Cluster A had higher serum chlorine, were older, and more were women. Individuals in Cluster B had higher serum iron and body mass index (BMI). Individuals in Cluster C had higher serum phosphorus, were younger, and had lower BMI. Cluster B had 1.41‐fold higher risk of developing diabetes and Cluster C’s risk was 1.33‐fold higher compared with Cluster A. Over an average follow‐up of 4.4 years, Cluster A showed a moderate and stable BMI, Cluster B showed an accelerated deterioration in glucose metabolism, and Cluster C showed the most sharply increased serum low‐density lipoprotein cholesterol level. Conclusions Clusters based on seven common serum electrolytes differed in diabetes risk and progression of glucose and lipid metabolic traits. Serum electrolytes clusters could provide a powerful tool to differentiate individuals into different risk stratification for developing type 2 diabetes.

Abstract Background Promoting patient participation in decision-making aims to maintain the partnership between doctors and patients, reflect the patients’ goals, values, and preferences, and achieve patient-centered care. Realizing patient-centered care, shared collaboration between doctors and patients, and the decision-making process that considers the patients’ priorities and goals are the keys to high-quality health care. Therefore, it is indispensable to analyze the patients’ willingness to participate in the decision-making process and related participation needs regarding anticoagulation treatment for patients undergoing valve replacement. Purpose To analyze the patients’ willingness to participate in the decision-making process and the participation needs of patients undergoing mechanical cardiac valve replacement in the process of anticoagulation therapy to provide a basis for promoting patients' participation in decision-making. Methods Using phenomenological research methods, data were collected through semistructured interviews. Patients were interviewed after mechanical valve replacement from June to August 2021 in a Grade A hospital in Nanjing. Data were analyzed according to the Colaizzi phenomenology method. Results Three major themes were identified from the data: strong willingness to participate but low actual participation, supportive needs, and family members’ participation. Conclusions This study guided interventions to encourage patients who underwent heart valve replacement to participate in the decision-making process. From the patient's perspective, obtaining support in the decision-making process and caregiver enthusiasm is important. This study prompted thoughts about the use of auxiliary tools and provided a reliable basis for constructing decision-making auxiliary programs to guide clinical practice.