Melittin induces autophagy to alleviate chronic renal failure in 5/6-nephrectomized rats and angiotensin II-induced damage in podocytes.

BACKGROUND/OBJECTIVES: Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear. MATERIALS/METHODS: A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. RESULTS: In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes. CONCLUSION: Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

A hybrid effectiveness-implementation trial of application-based tiered care (Mom's Good Mood) in treating perinatal anxiety within a primary health care system in China.

INTRODUCTION: Perinatal anxiety (PNA) is a major public health concern. METHODS: A hybrid effectiveness-implementation trial was conducted in two antenatal clinics in Hefei, China, to assess the effectiveness and cost-effectiveness of application-based tiered care (Mom's Good Mood, MGM) in treating PNA and to understand how well it fits into routine practices. Pregnant women who scored at least 5 points on the 7-Item Generalised Anxiety Disorder Scale (GAD-7) scale were successively assigned to the control group or the intervention group, which were given the usual care and MGM on usual care, respectively. At 6 months post partum, anxiety, depression and life satisfaction were assessed. Intention-to-treat analysis and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework were adopted. RESULTS: A total of 214 women were assigned to the control group and 341 to the intervention group. The mean changes in GAD-7 scores (Least-squares means, LSM, -1.42, 95% CI -2.18 to -0.66) and the risk of anxiety (adjusted odds ratio, aOR 0.30, 95% CI 0.18 to 0.51) were decreased, and the anxiety remission rate (aOR 2.72, 95% CI 1.69 to 4.40) were improved in the intervention group. Similar findings were observed regarding the change in Edinburgh Postnatal Depression Scale scores (LS -1.92, 95% CI -2.85 to -0.99), depression remission rate (aOR 2.24, 95% CI 1.39 to 3.63) and the risk of depression (aOR 0.57, 95% CI 0.33 to 0.98). MGM only costs ¥1.88 (US$0.27) per pregnant woman to boost the postpartum anxiety remission rate by 1% and was revealed to have a high reach rate of 78.3%, an adoption rate of 51.3%-80.8%. CONCLUSION: MGM is a cost-effective and accessible tool in coping with PNA. TRIAL REGISTRATION NUMBER: ChiCTR2100053419.

Understanding knowledge, perception, and willingness of non-invasive prenatal testing for fetal aneuploidy: a survey among Chinese high-risk pregnant women.

Objectives: Non-invasive prenatal testing (NIPT) is utilized for screening the likelihood of fetal aneuploidy, presenting the benefits of non-invasiveness, high sensitivity, and specificity. Its application in prenatal screening has become ubiquitous. The inquiry into how pregnant women comprehend and determine NIPT screening strategies is paramount. Regrettably, there has been a dearth of research on this subject in China. Consequently, this study scrutinizes pregnant women's cognizance and perspectives concerning NIPT, furnishing a foundation for advancing its judicious implementation. Methods: From February 2021 to December 2022, a questionnaire survey was conducted among pregnant women receiving prenatal care and screening at the Women's Hospital, School of Medicine, Zhejiang University, who were randomly selected from a pool of individuals exhibiting a high risk of fetal aneuploidy on serological screening. The survey aimed to gather data on participant characteristics, knowledge, perception, and willingness concerning NIPT. The study employed chi-square and Kruskal Wallis tests to analyze subgroup differences. Results: A total of 226 valid questionnaires were obtained. 83.2% of women pregnant women identified as high risk by serological screening would opt for NIPT, with 66.4% indicating that they would prefer NIPT for fetal aneuploidy screening in future pregnancies. These findings suggest a notable willingness among pregnant women to undergo NIPT. Additionally, the results suggest that various factors, including place of residence, educational level, family income, causes of abortion, and conception method, influence pregnant women's knowledge about NIPT Accordingly, the level of NIPT knowledge varies among pregnant women. Conclusion: The survey generally revealed that pregnant women were strongly inclined to select NIPT; however, expectant Chinese mothers possess limited knowledge and perception regarding this screening method for fetal aneuploidy. Therefore, the government must implement effective measures to augment public awareness of fetal aneuploidy screening and encourage the judicious utilization of NIPT.

Shift work and menstruation: A meta-analysis study.

Background: Shift work is a potential risk factor for women's reproductive health. Evidence suggests that shift work is associated with menstrual disorders, reproductive disturbances, and adverse pregnancy outcomes. However, previous studies did not systematically examine the results of menstrual irregularities, dysmenorrhea, and early menopause at the same time. Objective: To determine the relationship between shift work and women's menstrual characteristics (e.g., irregular menstruation, dysmenorrhea, and early menopause). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched up to December 2022. The study characteristics and risk assessment values of the literature were extracted from 21 studies that met the criteria. Odds ratios (ORs), relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated to assess the relationship between shift work exposure and menstruation. The included studies were evaluated for heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Results: A total of 21 studies with 195,538 female participants, including 16 cross-sectional studies and 5 cohort studies, were included in this meta-analysis. According to the quality evaluation, the included research had high methodological quality. The overall ORs of shift work for the likelihood of irregular menstruation and dysmenorrhea were 1.30 (95% CI, 1.23-1.36) (I2 = 41.9%, P < 0.05) and 1.35 (95% CI, 1.04-1.75) (I2 = 73.0%, P < 0.05), respectively. There was a significant positive association between shift work and the risk of early menopause (HR = 1.09, 95% CI, 1.04-1.14), without significant heterogeneity (I2 = 0.0%, P > 0.05). Conclusions: This meta-analysis indicated that shift workers have significantly higher odds of menstrual disorders, dysmenorrhea, and early menopause. This study focuses on female reproductive health and has broad implications for adjusting optimal working hours and shift schedules for female workers.

[Combined effect of active smoking history and passive smoking during pregnancy on postpartum depression and anxiety].

OBJECTIVE: To explore the independent and combined effects of smoking and passive smoking during pregnancy on maternal depression, anxiety and depressive anxiety comorbidities. METHODS: From August 2020 to February 2022, women who underwent 42-day postpartum examination in Changfeng Women's Center and Shuangfeng Hospital of Hefei were recruited. Their depression and anxiety symptoms were assessed using EPDS Scale and GAD Scale, respectively, and smoking and passive smoking status during pregnancy were collected. Multivariate Logistic regression was used to analyze the independent and combined effects of smoking and passive smoking during pregnancy on postpartum depression, anxiety and depression and anxiety comorbidities. RESULTS: A total of 2 447 parturients were included, whose mean age was(29.23±4.20) years old.58.6% of parturients lived in urban areas.97.2% parturients had unassisted reproduction and 73.5% pregnancy intention was spontaneous. Among them, 362(14.8%) had depression, 523(21.4%) had anxiety, and 270(11.0%) had depression and anxiety comorbidities. In an independent analysis of effects, maternal smoking during pregnancy was statistically associated with postpartum depression(OR=3.86, 95%CI 2.37-6.28), anxiety(OR =2.58, 95%CI 1.60-4.17) and depressive anxiety comorbidity(OR = 3.34, 95%CI 2.00-5.71). Maternal passive smoking during pregnancy was also positively associated with the risk of postpartum depression(OR = 1.56, 95%CI 2.00-5.71), anxiety(OR=1.71, 95%CI 1.24-2.37) and depression and anxiety comorbidities(OR = 1.52, 95%CI 1.02-2.28), and the higher the frequency of exposure to passive smoking, the higher risk of depression, anxiety, and depressive and anxiety comorbidities. No interaction between smoking during pregnancy and passive smoking exposure on postpartum depression(RERI = 0.69, 95%CI-4.62-6.00; AP = 10.84, 95%CI-73.37-95.04; S= 0.58, 95%CI 0.02-15.18), anxiety(RERI=0.27, 95%CI 0.05-0.49; AP=4.02, 95%CI-0.52-8.57; S=0.78, 95%CI 0.64-0.94) and depression and anxiety comorbidities(RERI = 0.07, 95%CI-0.25-0.39; AP=1.74, 95%CI-6.03-9.52; S=0.93, 95%CI 0.68-1.27)was observed. CONCLUSION: Both smoking and passive smoking during pregnancy were positively associated with the risk of postpartum depression, anxiety and depressive anxiety comorbidity.

Biodegradation of nitrate and p-bromophenol using hydrogen-based membrane biofilm reactors in parallel.

ABSTRACTP-bromophenol (4-BP) is a toxic halogenated phenolic organic compound. The conventional treatment processes for 4-BP elimination are costly and inefficient, with complete mineralization remaining a challenge for water treatment. To overcome these limitations, we investigated the treatment of 4-BP in a membrane biofilm reactor (MBfR) using hydrogen as an electron donor. The pathway of 4-BP degradation within the H2-MBfR was investigated through long-term operational experiments by considering the effect of nitrate and 4-BP concentrations, hydrogen partial pressure, static experiments, and microbial community diversity, which was studied using 16S rRNA. The results showed that H2-MBfR could quickly remove approximately 100% of 4-BP (up to 20 mg/L), with minimal intermediate product accumulation and 10 mg/L of nitrate continuously reduced. The microbial community structure showed that the presence of H2 created an anaerobic environment, and Thauera was the dominant functional genus involved in the degradation of 4-BP. The genes encoding related enzymes were further enhanced. This study provides an economically viable and environmentally friendly bioremediation technique for water bodies that contain 4-BP and nitrates.

Preparation of a Molecularly Imprinted Silica Nanoparticles Embedded Microfiltration Membrane for Selective Separation of Tetrabromobisphenol A from Water.

The ubiquitous presence of tetrabromobisphenol A (TBBPA) in aquatic environments has caused severe environmental and public health concerns; it is therefore of great significance to develop effective techniques to remove this compound from contaminated waters. Herein, a TBBPA imprinted membrane was successfully fabricated via incorporating imprinted silica nanoparticles (SiO2 NPs). The TBBPA imprinted layer was synthesized on the 3-(methacryloyloxy) propyltrimethoxysilane (KH-570) modified SiO2 NPs via surface imprinting. Eluted TBBPA molecularly imprinted nanoparticles (E-TBBPA-MINs) were incorporated onto a polyvinylidene difluoride (PVDF) microfiltration membrane via vacuum-assisted filtration. The obtained E-TBBPA-MINs embedded membrane (E-TBBPA-MIM) showed appreciable permeation selectivity toward the structurally analogous to TBBPA (i.e., 6.74, 5.24 and 6.31 of the permselectivity factors for p-tert-butylphenol (BP), bisphenol A (BPA) and 4,4'-dihydroxybiphenyl (DDBP), respectively), far superior to the non-imprinted membrane (i.e., 1.47, 1.17 and 1.56 for BP, BPA and DDBP, respectively). The permselectivity mechanism of E-TBBPA-MIM could be attributed to the specific chemical adsorption and spatial complementation of TBBPA molecules by the imprinted cavities. The resulting E-TBBPA-MIM exhibited good stability after five adsorption/desorption cycles. The findings of this study validated the feasibility of developing nanoparticles embedded molecularly imprinted membrane for efficient separation and removal of TBBPA from water.

Advanced glycation end products promote the progression of chronic kidney diseases by targeting calpain 6.

Advanced glycation end products (AGEs) are produced by glycosylation or oxidation of proteins and lipids and are tightly involved in the chronic kidney disease (CKD) process. Calpain 6 (CAPN6) is a non-classical calpain that has been reported to be overexpressed in CKD. This study aimed to explore the effects of AGEs in CKD progress and their correlation with CAPN6. AGEs production was measured using ELISA. The CCK-8 assay was used to test cell proliferation. mRNA and protein levels were tested using qRT-PCR and western blot. The progress of glycolysis was tested by calculating the ATP and ECAR content in HK-2 cells. The expression of AGEs and CAPN6 was significantly increased in patients with CKD3, CKD4, and CKD5. AGEs treatment inhibited cell proliferation and glycolysis and accelerated apoptosis. Additionally, CAPN6 knockdown effectively reversed the effects of AGEs in HK-2 cells. In addition, overexpressed CAPN6 played similar role to AGEs, which suppressed cell proliferation and glycolysis and facilitated apoptosis. Moreover, the administration of 2-DG, a glycolysis inhibitor, counteracted the effects of CAPN6 silencing in HK-2 cells. Mechanistically, CAPN6 interacts with NF-κB and PDTC reduced CAPN6 expression in HK-2 cells. This investigation revealed that AGEs facilitate CKD development in vitro by modulating the expression of CAPN6.

Mom's Good Mood: screening and management of perinatal depression within primary healthcare system in China-protocol for an effectiveness-implementation design study.

INTRODUCTION: The management of perinatal depression (PND) is challenging in China. The Thinking Healthy Programme (THP), developed under the core theory of cognitive-behavioural therapy, is an evidence-based approach that is recommended as a psychosocial intervention for managing PND in low/middle-income countries. Sparse evidence has been generated, however, to assess the effectiveness of THP and guide its implementation in China. METHODS AND ANALYSIS: A hybrid type II effectiveness-implementation study is ongoing in four cities in Anhui Province, China. A comprehensive online platform, Mom's Good Mood (MGM), has been developed. Perinatal women are screened using the WeChat screening tool (ie, Edinburgh Postnatal Depression Scale embedded as metrics) in clinics. Different intensities of the intervention are delivered through the mobile application for different degrees of depression, according to the stratified care model. The THP WHO treatment manual has been tailored to be the core component of intervention. Guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, process evaluations will be conducted to identify the facilitators and barriers to implementation and to modify the implementation strategy; summative evaluations will be carried out to examine the effectiveness of MGM in the management of PND within the primary healthcare system in China. ETHICS AND DISSEMINATION: Ethics approval and consent for this programme were obtained from Institutional Review Boards in China: Anhui Medical University, Hefei, People's Republic of China (20170358). Results will be submitted to relevant conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800016844.

Utilization and performance of long-term care system for older people with disabilities and dementia in Zhejiang Province, China.

Introduction: To explore changes in performance, weaknesses, and utilization of the long-term care (LTC) system for older people with disabilities and dementia (OPWDD) in Zhejiang Province, China, thereby providing a reference for decision-making amid a progressively aging population. Methods: A performance evaluation model of the LTC system for OPWDD was constructed using three dimensions: input, process, and outcome. Performance indicators and trends were calculated based on data collected from statistical yearbooks, documents, and work reports of the Bureau of Statistics and other government departments in Zhejiang Province, China, published in 2015-2021. Results: Significant improvements were observed in most LTC performance indicators for OPWDD, such as input, process, and outcome, with notable enhancements in fairness, accessibility, and affordability of LTC services. By 2021, there were 6.20 nursing and rehabilitation beds in medical institutions and 3.77 general practitioners per 1,000 people aged 65 and above, up 144.14% and 13.73%, respectively, from 2015. The rate of health management for older people was 70.91%, representing a 10.33% increase from 2015. The actual reimbursement ratio of hospitalization expenses covered by basic medical insurance for older people rose 7.05%, from 72.76% in 2015 to 77.89% in 2021. Social security satisfaction rose 12.4%, from 71.3% in 2015 to 83.7% in 2021. Certain indicators, however, showed no significant improvement and tended to decline, such as the number of beds at older care institutions and caregivers per 1,000 people aged 65 and over. Discussion: It is imperative to further balance the allocation of care resources, using a people-centered and integrated LTC system. The proportion of rehabilitation and nursing beds for older people should be consistently increased to effectively alleviate the shortage of care beds. Furthermore, a talent incentive policy should be improved to train caregivers and provide whole-person and whole-life course care based on OPWDD needs.

Novel compound heterozygous mutations in the AFG3L2 gene in a Chinese child with microcephaly, early-onset seizures, and cerebral atrophy.

Background: The most common disease caused by biallelic AFG3L2 mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic AFG3L2 mutations has been increasing in recent years. Methods: A retrospective analysis was performed on a child with microcephaly and recurrent seizures. The child underwent physical and neurological examinations, laboratory tests, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Trio-whole-exome sequencing (trio-WES) was performed to identify possible causative mutations. Results: We described a child who exhibited early-onset and intractable epilepsy, developmental regression, microcephaly, and premature death. Neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum, corpus callosum, brainstem, cerebellar vermis, and basal ganglia. On trio-WES, two novel compound heterozygous mutations, c.1834G > T (p.E612*) and c.2176-6T > A in the AFG3L2 gene, were identified in this patient. Conclusions: Our findings have expanded the mutation spectrum of the AFG3L2 gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.

Association of polycyclic aromatic hydrocarbons exposure with child neurodevelopment and adult emotional disorders: A meta-analysis study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been demonstrated to be neurotoxic. OBJECTIVES: To summarize the existing epidemiological studies to quantify the effects of PAHs exposure on child neurodevelopment and adult emotional disorders. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We conducted a systematic literature search for studies of child neurodevelopment and adult emotional disorders published in English up to April 2022 in the databases of PubMed, Web of Science and Embase using combinations of MeSH terms and Entry terms, and the articles were filtered out according to data availability. A variety of common PAHs were included in the meta-analysis: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene and benzoapyrene (BaP). STUDY EVALUATION AND SYNTHESIS METHODS: We extracted the content of each article, summarized its design characteristics and performed quality evaluation. We combined the odds ratio (OR) available in various studies to obtain the risk of PAHs exposure and adaptive, language, social, attention, motor skills and child depression/anxiety in children ≤ 15 years old. In addition, we also conducted a meta-analysis on the relationship between PAHs exposure and the risk of depression in adults. RESULTS: We included a total of 16 epidemiological studies (4 cross-sectional studies and 12 cohort studies). The sample size of all included studies ranged from 110 to 9625. Prenatal exposure to PAHs was found to be associated with increased risk of social behavior (OR = 1.60, 95% CI: 1.00-2.54), attention (OR = 2.99, 95% CI: 1.48-6.02), motor skill problems (OR = 1.91, 95% CI: 1.27-2.86) and any adverse neurodevelopmental outcome in children (OR = 2.10, 95% CI: 1.69-2.62). In addition, we found that PAHs exposure could increase the risk of adult depression, with 2-hydroxyfluorene exposure showing the highest combined OR (OR = 1.48, 95% CI: 1.10-2.00). CONCLUSIONS: The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. Steps should be taken to enhance the biomonitoring of PAHs and to reduce the exposure in general population.

Evaluation of selenite reduction under salinity and sulfate stress in anaerobic membrane bioreactor.

Current microbial reduction technologies have been proven to be suitable for decontaminating industrial wastewaters containing high concentrations of selenium (Se) oxyanions, however, their application is strictly limited by the elemental Se (Se0) accumulation in the system effluents. In this work, a continuous-flow anaerobic membrane bioreactor (AnMBR) was employed for the first time to treat synthetic wastewater containing 0.2 mM soluble selenite (SeO3 2-). The SeO3 2- removal efficiency by the AnMBR was approachable to 100% in most of the time, regardless of the fluctuation in influent salinity and sulfate (SO4 2-) stress. Se0 particles were always undetectable in the system effluents, owing to their interception by the surface micropores and adhering cake layer of membranes. High salt stress led to the aggravated membrane fouling and diminished content ratio of protein to polysaccharide in the cake layer-contained microbial products. The results of physicochemical characterization suggested that the sludge-attached Se0 particles presented either sphere- or rod-like morphology, hexagonal crystalline structure and were entrapped by the organic capping layer. According to the microbial community analysis, increasing influent salinity led to the diminished population of non-halotolerant Se-reducer (Acinetobacter) and increased abundance of halotolerant sulfate reducing bacteria (Desulfomicrobium). In the absence of Acinetobacter, the efficient SeO3 2- abatement performance of the system could still be maintained, as a result of the abiotic reaction between SeO3 2- and S2- generated by Desulfomicrobium, which then gave rise to the production of Se0 and S0.

Causal effects of physical activity on the risk of overall ovarian cancer: A Mendelian randomization study.

Objective: Inconsistent results were reported on the association of physical activity with ovarian cancer. However, given the limitations of confounders and inverse causation, the validity of the association remained unclear. Therefore, we conducted a two-sample Mendelian randomization analysis, which can effectively avoid the aforementioned interference, to evaluate whether physical activity had a protective effect on ovarian cancer. Methods: The exposure of interest was physical activity (both self-reported moderate-to-vigorous physical activity and accelerometer-measured physical activity). Summary statistics for physical activity traits were recruited from the UK Biobank (n = 91,084-377,234), whereas ovarian cancer summary genetic data were obtained from a genome-wide association study involving 25,509 cases and 40,941 healthy individuals. The inverse variance weighted approach was used as the primary Mendelian randomization method. Sensitivity analyses using Mendelian randomization-Egger regression, weighted median, and Mendelian randomization pleiotropy residual sum and outlier were also performed. Results: The Mendelian randomization analyses indicated that there was no effect of moderate-to-vigorous physical activity (odds ratio, 1.11; 95% confidence interval: 0.66-1.85; P = 0.702), accelerometer-measured "average acceleration" (0.99 [0.91-1.08]; P = 0.848), and "overall activity" physical activity (0.97 [ 0.48-1.95]; P = 0.927) on the risk of overall ovarian cancer. However, "overall accelerations" physical activity (0.18 [0.05-0.64]; P = 0.008) were suggestively related to a lower risk of endometrioid ovarian cancer. Conclusions: The Mendelian randomization analyses suggested that physical activity may not help to decrease the risk of overall ovarian cancer.

Smoking, alcohol consumption, and frailty: A Mendelian randomization study.

Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design. Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation. Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: ß = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: ß = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: ß = -0.090; 95% CI = -0.151 to -0.029; p = 0.003; multivariable MR ß = -0.153; 95% CI = -0.212 to -0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation. Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty.

Joint effects of recent stressful life events and adverse childhood experiences on perinatal comorbid anxiety and depression.

BACKGROUND: Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. METHODS: Based on a longitudinal study, 1082 participants receiving prenatal care in Ma'anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. RESULTS: Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p < 0.05). As the number of SLEs increased, the risk of CAD increased (p for trend < 0.05). Specific types of SLEs were associated with CAD in different periods, while only interpersonal events were consistently associated with risks of CAD throughout the whole perinatal period. The joint effects of SLEs with ACEs on CAD were identified throughout the perinatal period, with the highest observed in the first trimester (aOR = 7.47, 95% CI: 3.73-14.95; p for trend < 0.001). CONCLUSION: Our study demonstrated independent associations of recent SLEs and their joint effects with ACEs with risks of perinatal CAD. SLEs combined with ACEs should be recognized as a major risk factor for perinatal CAD and managed at the earliest time to prevent and control CAD.

Looking Beyond Th17 Cells: A Role for Th17.1 Cells in Thyroid-associated Ophthalmopathy?

Thyroid-associated ophthalmopathy (TAO), an ordinary extrathyroid syndrome of Graves' disease (GD), is closely associated with immunity. T helper (Th) 17, Th1, and Th2 cells in Th lineages are thought to be related to the disease pathogenesis. Recently, there has been growing evidence that Th17.1 cells are involved in the development and progression of TAO. The characteristics of this pathology are similar to those of Th1 and Th17 lymphocytes, which secrete interferon (IFN)-γ and interleukin (IL)-17A. This paper reviews the potential role of the Th17.1 subgroup pathogenesis of TAO. The therapeutic effects of drugs that can modulate Th17.1 cell populations are also highlighted. Rich Th17.1 cells exist in peripheral blood and ocular tissues of patients suffering from thyroid eye disease (TED), especially those with severe or steroid-resistant TAO. The bias of Th17.1 cells to secrete cytokines partly determines the pathological outcome of TAO patients. Th17.1 cells are important in regulating fibrosis, adipocyte differentiation, and hyaluronic acid production. In summary, the Th17.1 subpopulation is essential in the onset and progression of TED, and targeting Th17.1 cell therapy may be a promising therapeutic approach.

Sleep behaviors and Parkinson's disease: A bidirectional Mendelian randomization analysis.

OBJECTIVE: Whether the quantity and quality of sleep are the risk factors for the development of Parkinson's disease remains unclear though it has now been confirmed that the quality of sleep among patients with Parkinson's disease is affected at the prodromal and clinical stages. Accordingly, this study aimed to examine the bidirectional causal relationships of multiple sleep-related phenotypes with Parkinson's disease using a two-sample Mendelian randomization (MR) method. METHODS: The summary-level data collected from the published genome-wide association studies was used for analysis. Besides, the genetic relationships between different sleep-related phenotypes, including self-reported and accelerometer measured traits, were estimated for the risk and age at the onset of Parkinson's disease. To conduct MR analysis, inverse variance weighted, weight median, MR-Egger, and MR-PRESSO method were mainly used. Moreover, sensitivity analyses were carried out to examine the pleiotropic effect. RESULTS: In general, there was insufficient evidence to support the causal effect of sleep-related phenotypes on risk (N cases/controls = 33,674/449,056) and age at the onset (N cases = 28,568) of Parkinson's disease. However, the results of this study indicated that the later onset age of Parkinson's disease was related to the frequent occurrence of insomnia (OR [95% CI] 1.007 [1.003, 1.011], P < 0.001) after the adjustment for multiple testing. CONCLUSIONS: The results of this study suggest that insomnia-associated single nucleotide polymorphisms are more frequent in later onset Parkinson's disease patients compared to earlier onset patients. However, given the limitations of statistical power and potential bias, further validation should be still conducted through larger population research.

Establishment of noncycloplegic methods for screening myopia and pre-myopia in preschool children.

Purpose: Pre-myopia, a non-myopic refractive state, is a key concern for myopia prevention because of its association with a significantly higher risk of myopia in children under 3 years of age. Amid the myopia pandemic, its onset at younger ages is increasing, yet research on screening methods for myopia and pre-myopia in preschool children remains limited. This study aimed to establish effective noncycloplegic screening methods for myopia and pre-myopia in preschool children. Methods: This cross-sectional study included 16 kindergartens in Shanghai, China. Uncorrected distance visual acuity (UDVA) was recorded using a logMAR visual acuity chart. Pre- and post-cycloplegic refractions were obtained using an auto-refractor (TopconKR-800). Noncycloplegic axial length (AL) and corneal curvature radius (CR) were measured using the IOL Master-700. Logistic regression models were developed to establish accurate noncycloplegic screening methods for myopia and pre-myopia. Results: A total of 1,308 children with a mean age of 4.3 ± 0.9 years were included; among them 640 (48.9%) were girls. The myopia prevalence rate was 2.8% (n = 36), and the prevalence of pre-myopia was 21.9% (n = 286). Pre-myopia screening (cycloplegic spherical equivalent [SE] ≤ -0.5 < SE ≤0.75 diopters [D]) using UDVA exhibited an area under the receiver operating curve (AUC) of 0.52, noncycloplegic SE had an AUC of 0.70 and AL had an AUC of 0.63. The accuracy of combining the SE and AL/CR ratio was among the best with the least number of checks used, and the AUC was 0.74 for pre-myopia screening and 0.94 for myopia screening (cycloplegic SE ≤ -0.5 D). The addition of UDVA did not further improve the accuracy. Conclusion: Using UDVA alone did not achieve good accuracy in pre-myopia or myopia screening of young children. Under non-cycloplegic conditions, the combination of AL/CR and SE demonstrated favorable results for pre-myopia and myopia screening of preschool children.

Gut microbiota and thyroid-associated ophthalmopathy. / è‚ é“èŒç¾¤ä¸Žç”²çŠ¶è ºç›¸å ³çœ¼ç— .

Thyroid-associated ophthalmopathy (TAO) is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults. Due to the complex clinical manifestations and prolonged course,TAO seriously affect the physical and mental health of patients.The pathogenesis of TAO has not been fully elucidated and the treatment lacks specificity. Therefore, in-depth research on the pathogenesis of TAO is to find effective treatments. In recent years, studies have suggested that there is gut microbiota disorder in TAO, and the risk factors of TAO can promote gut microbiota disorder. Disordered gut microbiota can participate in the occurrence and development of TAO via influencing T cell differentiation, mimicking autoantigens, and influencing host non-coding RNA expression. Modulating the gut microbiota also has therapeutic effects on TAO and is a promising therapeutic approach.