Differences in the expression of long noncoding RNAs in peripheral blood mononuclear cells indicate potential biomarkers for rheumatoid arthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. METHODS: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. RESULTS: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). CONCLUSION: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

[Correlation Analysis between Neutrophil-to-lymphocyte Ratio 
and the Risk of Malnutrition in Stage IV Primary Lung Cancer].

BACKGROUND: Malnutrition is commonly associated with poor prognosis in patients with malignant tumors. The neutrophil-to-lymphocyte ratio (NLR) is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases; however, its association with malnutrition in lung cancer patients is unclear. The aim of this study is to clarify the association between NLR and nutritional status in stage IV primary lung cancer and to further determine the optimal NLR cut-off that best predicts the risk of malnutrition. METHODS: A retrospective analysis of 209 patients admitted to the Department of Medical Oncology, Tianjin Medical University General Hospital with a primary diagnosis of stage IV lung cancer from May 2019 to February 2021 was performed, and the nutritional risk screening 2002 (NRS 2002) was used to examine their nutritional status. Patient demographic information, pathology, Karnofsky performance status (KPS) score, body mass index (BMI), comorbidities and clinical biochemical indicators were also included. The correlation between NLR and NRS 2002 was investigated. Receiver operating characteristic (ROC) curve was used to determine the best NLR cut-off predi cting malnutrition risk. Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS: The rate of patients with stage IV primary lung cancer at nutritional risk was 36.36% (76/209). A significant positive correlation was observed between NLR values and NRS 2002 risk score (r=0.765, P<0.001). The ROC curve analysis indicated that an NLR of 3.94 was the optimal cut-off for predicting malnutrition risk (area under the curve=0.747, 95%CI: 0.678-0.815, P<0.001), which showed a sensitivity of 55%, a specificity of 86%, a positive predictive value of 68%, and a negative predictive value of 77%. Patients in the NLR>3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group (69.49% vs 23.33%, P<0.001). Furthermore, NLR was identified as a risk factor for malnutrition in stage IV primary lung cancer patients. CONCLUSIONS: NLR is associated with the risk of malnutrition in stage IV primary lung cancer, and NLR can be used as one of the indicators for screening nutritional risk in patients with stage IV primary lung cancer.

Genetic Links Between Metabolic Syndrome and Osteoarthritis: Insights from Cross-Trait Analysis.

BACKGROUND: Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood. METHODS: Leveraging summary statistics from genome-wide association studies (GWASs) conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWASs to comprehensively assess the relationship of MetS and OA. RESULTS: We first detected an extensive genetic correlation between MetS and OA (rg=0.393, P=1.52×10-18), which was consistent in four MetS components, including waist circumference, triglycerides, hypertension and high-density lipoprotein cholesterol and OA with rg ranging from -0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through multi-trait Analysis of GWAS. Co-localization analysis founded 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, MR analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found. CONCLUSION: Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the two disorders.

CO-Tolerant Hydrogen Oxidation Electrocatalysts for Low-Temperature Hydrogen Fuel Cells.

The severe performance degradation of low-temperature hydrogen fuel cells upon exposure to trace amounts of carbon monoxide (CO) impurities in reformate hydrogen fuels is one of the challenges that hinders their commercialization. Despite significant efforts that have been made, the CO-tolerance performance of electrocatalysts for the hydrogen oxidation reaction (HOR) is still unsatisfactory. This Perspective discusses the path forward for the rational design of CO-tolerant HOR electrocatalysts. The fundamentals of the CO-tolerant mechanisms on commercialized platinum group metal (PGM) electrocatalysts via either promoting CO electrooxidation or weakening CO adsorption are provided, and comprehensive discussions based on these strategies are presented with typical examples. Given the recent progress, some emerging strategies, including blocking CO diffusion with a barrier layer and developing non-PGM HOR catalysts, are also discussed. We conclude with a discussion of the strengths and limitations of these strategies along with the perspectives of the major challenges and opportunities for future research on CO-tolerant HOR electrocatalysts.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.

A Secreted BBE-Like Enzyme Acting as a Drug-Binding Efflux Carrier Confers Microbial Self-Resistance to Mitomycin C.

The berberine bridge enzyme (BBE)-like flavoproteins have attracted continuous attention for their capability to catalyze various oxidative reactions. Here we demonstrate that MitR, a secreted BBE-like enzyme, functions as a special drug-binding efflux protein evolved from quinone reductase. Moreover, this protein provides self-resistance to its hosts toward the DNA-alkylating agent mitomycin C with a distinctive strategy, featured by independently performing drug binding and efflux.

Associations between air pollutants and acute exacerbation of drug-resistant tuberculosis: evidence from a prospective cohort study.

BACKGROUND: Short-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines. OBJECTIVE: To investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM10, PM2.5, SO2, NO2, CO and O3) based on a large prospective cohort in Anhui Province, China. METHOD: Patients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution. RESULTS: Short-term NO2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment. CONCLUSIONS: NO2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Hormonal and reproductive factors in relation to the risk of rheumatoid arthritis in women: a prospective cohort study with 223 526 participants.

OBJECTIVE: This study aimed to examine rheumatoid arthritis (RA) risk associated with hormonal and reproductive factors in women from the large cohort of the UK Biobank. METHODS: Data on hormonal and reproductive factors in women were collected from a prospective cohort of 223 526 UK Biobank participants. The potential relationship between reproductive factors and RA risk was assessed using restricted cubic spline. Hazard ratios (HR) were estimated using Cox proportional hazard regressions. RESULTS: During a median follow-up of 12.39 years, 3313 women with RA were identified. Age at menarche >14 years was associated with a greater RA risk (HR 1.13, 95% CI 1.02 to 1.26) compared with menarche at 13. The multiple adjusted HR for RA in women with menopause at <45 years was 1.46. Reproductive years <33 increased the risk of RA (HR 1.39, 95% CI 1.21 to 1.59). Compared with those with 2 children, women with ≥4 children were associated with a higher risk of RA (HR 1.18, 95% CI 1.04 to 1.34). Women who had a hysterectomy (HR 1.40, 95% CI 1.25 to 1.56) or oophorectomy (HR 1.21, 95% CI 1.08 to 1.35) had a higher risk of RA than those without a hysterectomy or oophorectomy. Both hormone replacement therapy (HRT) use (HR 1.46, 95% CI 1.35 to 1.57) and HRT duration (HR 1.02, 95% CI 1.01 to 1.03) were associated with a higher risk of RA. CONCLUSIONS: Some hormonal and reproductive factors were associated with a higher risk of RA. Hormonal and reproductive factors should be considered in risk assessment and formulating management plans in female patients with RA.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

Serum albumin mediates the associations between heavy metals and two novel systemic inflammation indexes among U.S. adults.

BACKGROUND: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce. OBJECTIVES: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin. METHODS: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI. RESULTS: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (PFDR<0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively. CONCLUSIONS: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association.

Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial. AIM: To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage. METHODS: The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg's test for publication bias was performed using Stata 13.0 software. RESULTS: Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg's test revealed no significant publication bias. CONCLUSION: The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage.

Verifying the Equivalence of Hawthorn Leaves Standard Decoction and Formula Granules by LC-MS and Oxidative Stress Test.

OBJECTIVE: To verify the equivalence of hawthorn leaves standard decoction and formula granules. METHODS: In this experiment, liquid chromatograph mass spectrometer (LC-MS) was used to examine the chemical composition of hawthorn leaves standard decoction and formula granules, separately. In addition, oxidative stress test was used to explore the antioxidant capacity of them. RESULTS: 71 chemical components were identified by LC-MS. Among them, 64 and 56 compounds were identified in the standard decoction and formula granules, respectively. There were a total of 49 common components, with no significant difference in content. Oxidative stress test showed that hawthorn leaves standard decoction and formula granules had no obvious toxicity to human umbilical vein endothelial cells. Compared with the model group, the same dose of hawthorn leaves formula granule and standard decoction could inhibit the secretion of lactate dehydrogenase and malondialdehyde (P < 0.05), and increase the content of superoxide dismutase (P < 0.01), with no statistically significant difference. CONCLUSIONS: There is no significant difference in the main active ingredients between the standard decoction and the formula granules, and the antioxidant activity in vitro is equivalent, providing an important theoretical basis for the further development of hawthorn leaves formula granules.

Global, Regional, and National Burden of CKD in Children and Adolescents from 1990 to 2019.

BACKGROUND AND AIMS: CKD is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs), and trends in the population are limited. We aimed to assess the global, regional, and national trends in CKD burden in children and adolescents. METHODS: In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence, and DALYs rates per 100,000 population for children and adolescents were reported at the global, regional, and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region, and socio-demographic index (SDI). RESULTS: Globally, the overall incidence of CKD (all stages including KRT) in children and adolescents showed an increasing trend (AAPC 0.44 [95% CI 0.36-0.52]) between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend (AAPC 0.46 [95% CI 0.42-0.51]). However, the DALYs of CKD showed a continuous decreasing trend (AAPC -1.18[-1.37- -0.99]). The population aged 15-19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries (AAPC 0.56 [0.45-0.67]). The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15-19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019. CONCLUSION: The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.

The role of m6A epigenetic modifications in tumor coding and non-coding RNA processing.

BACKGROUND: Epigenetic modifications of RNA significantly contribute to the regulatory processes in tumors and have, thus, received considerable attention. The m6A modification, known as N6-methyladenosine, is the predominant epigenetic alteration found in both eukaryotic mRNAs and ncRNAs. MAIN BODY: m6A methylation modifications are dynamically reversible and are catalyzed, removed, and recognized by the complex of m6A methyltransferase (MTases), m6A demethylase, and m6A methyl recognition proteins (MRPs). Published evidence suggests that dysregulated m6A modification results in abnormal biological behavior of mature mRNA, leading to a variety of abnormal physiological processes, with profound implications for tumor development in particular. CONCLUSION: Abnormal RNA processing due to dysregulation of m6A modification plays an important role in tumor pathogenesis and potential mechanisms of action. In this review, we comprehensively explored the mechanisms by which m6A modification regulates mRNA and ncRNA processing, focusing on their roles in tumors, and aiming to understand the important regulatory function of m6A modification, a key RNA epigenetic modification, in tumor cells, with a view to providing theoretical support for tumor diagnosis and treatment. Video Abstract.

CircUsp9x/miR-599/stim1 axis regulates proliferation and migration in vascular smooth muscle cells induced by oxidized-low density lipoprotein.

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS.

Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019.

As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its changes in the next 20 years, decomposed the trend according to demographic factors and epidemiological changes, and quantified the cross-country healthy inequalities, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. In 2019, there were more than 140 million cases of hearing loss worldwide, a 93.89% increase from 70 million cases in 1990. The age-standardized rate (ASR) also increased with an estimated annual percentage change of 0.08% per year. Population growth and aging are the major drivers contributing to the changes, accounting for 60.83% and 35.35%. Of note, the contribution of aging varies showing a gradual increasing trend with sociodemographic index (SDI) elevating. Also notable, there were significant health inequalities across 204 countries and territories, with slope index of inequality rising over time. Projection of the global burden of hearing loss from 2020 to 2040 indicated progressive increases in both case number and ASR. These reflect the heavy disease burden of hearing loss that needed more targeted and efficient strategies in its prevention and management.

Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.