Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a multi-dimensional autoimmune disease involving numerous tissues throughout the body. The chromatin accessibility landscapes in immune cells play a pivotal role in governing their activation, function, and differentiation. Aberrant modulation of chromatin accessibility in immune cells is intimately associated with the onset and progression of SLE. AREAS COVERED: In this review, we described the chromatin accessibility landscapes in immune cells, summarized the recent evidence of chromatin accessibility related to the pathogenesis of SLE, and discussed the potential of chromatin accessibility as a valuable option to identify novel therapeutic targets for this disease. EXPERT OPINION: Dynamic changes in chromatin accessibility are intimately related to the pathogenesis of SLE and have emerged as a new direction for exploring its epigenetic mechanisms. The differently accessible chromatin regions in immune cells often contain binding sites for transcription factors (TFs) and cis-regulatory elements such as enhancers and promoters, which may be potential therapeutic targets for SLE. Larger scale cohort studies and integrating epigenomic, transcriptomic, and metabolomic data can provide deeper insights into SLE chromatin biology in the future.

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Association of sudden sensorineural hearing loss with meteorological factors: a time series study in Hefei, China, and a literature review.

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.

Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: a population-based study.

OBJECTIVE: To evaluate the trends and cross-country inequalities of global osteoarthritis (OA) burden over the last 30 years, and further predicted its changes to 2035. METHODS: The estimates and 95% uncertainty intervals (UIs) for incidence, prevalence, and disability-adjusted life-years (DALYs) of OA were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We described OA epidemiology at global, regional, and national levels, analyzed 1990-2019 trends in OA burden from overall, local, and multi-dimension scopes, decomposed OA burden according to population size, age structure, and epidemiologic changes, quantified cross-country inequalities in OA burden using standard health equity methods recommended by World Health Organization, and predicted changes of OA burden to 2035. RESULTS: GBD 2019 estimated 527,811,871 (95% UIs: 478,667,549 to 584,793,491) prevalent cases, 41,467,542 (95% UIs: 36,875,471 to 46,438,409) incident cases and 18,948,965 (95% UsI:9,571,298 to 37,659,660) DALYs cases of OA worldwide in 2019, with the highest cases in East Asia and highest age-standardized rate (ASR) in high-income North America. The global burden of OA increased overall from 1990 to 2019 with the fastest growth observed in the first decade of the 21st century. Decomposition analysis revealed that OA knee (62.78%), women (60.47%), and middle sociodemographic index (SDI) quintile (32.35%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. A significant increase in SDI-related inequalities was detected, and the gap in DALYs between the highest SDI country and the lowest SDI country increased from 179.5 (95% CI: 149.3 to 209.8) per 100,000 in 1990 to 341.9 (95% CI: 309.5 to 374.4) per 100,000 in 2019. Notably, although the ASR of incidence, prevalence, and DALYs of OA was predicted to decrease annually from 2020 to 2035, the case number of these metrics was predicted to keeping increasing, with predicted values of 52,870,737 (95% UI: 39,330,063 to 66,411,411), 727,532,373 (95% UI: 542,765,783 to 912,298,962), and 25,986,983 (95% UI: 19,216,928 to 32,757,038) in 2035, respectively. CONCLUSIONS: As a major public health issue, the global burden of OA showed an overall increasing trend from 1990 to 2019, which was primarily driven by population growth and aging. Countries with high SDI shouldered disproportionately high OA burden, and the SDI-related inequalities across countries exacerbated over time. This study highlighted great challenges in the control and management of OA, including both growing case number and distributive inequalities worldwide, which may be instructive for better making public health policy and reasonably allocating medical source.

Identification of lipid-modifying drug targets for autoimmune diseases: insights from drug target mendelian randomization.

BACKGROUNDS: A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. OBJECTIVES: This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. METHODS: Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. RESULTS: There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10- 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10- 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10- 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10- 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). CONCLUSIONS: Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

Two Decades of Publications in Journals Dedicated to Autoimmunity: A Bibliometric Analysis of the Autoimmunity Field from 2004 to 2023.

To carry out an in-depth analysis of the scientific research on autoimmunity, we performed the first bibliometric analysis focusing on publications in journals dedicated to autoimmunity (JDTA) indexed by science citation index during the period 2004-2023. Using bibliometric analysis, we quantitatively and qualitatively analyzed the country, institution, author, reference and keywords information of publications in JDTA, so as to understand the quantity, publication pattern and publication characteristics of these publications. The co-occurrence networks, clustering map and timeline map were created by CiteSpace and VOSviewer software to visualize the results. The CiteSpace was also used to analyze the strongest citation burst of keywords, which could describe the frequency, intensity and time period of high-frequency keywords, and indicate the research hotspots in the field. A total of 5 710 publications were analyzed, and their annual distribution number was basically stable from 2004 to 2023, fluctuating around 300. The United States and Italy led the way in terms of the number of publications, followed by France and China. For international cooperation, the developed countries represented by the United States cooperate more closely, but the cooperation was localized, reflecting that there was no unified model of autoimmunity among countries. UDICE-French Research Universities had the greatest number of publications. Subsequently, the number of publications decreased slowly with the ranking, and the gradient was not large. Eric Gershwin and Yehuda Shoenfeld stood out among the authors. They had an excellent academic reputation and great influence in the field of autoimmunity. The results of keyword analysis showed that JDTA publications mainly studied a variety of autoimmune diseases, especially SLE and RA. At the same time, JDTA publications also paid special attention to the research of cell function, autoantibody expression, animal experiments, disease activity, pathogenesis and treatment. This study is the first to analyze the publications in JDTA from multiple indicators by bibliometrics, thus providing new insights into the research hotspots and development trends in the field of autoimmunity.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

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.

MicroRNAs as Key Regulators in RA and SLE: Insights into Biological Functions.

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.

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.

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.

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.

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.

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.