Ankylosing Spondylitis Patients Display Aberrant ERAP1 Gene DNA Methylation and Expression.

BACKGROUND: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is known to participate in the pathogenesis of ankylosing spondylitis (AS). This study aimed to evaluate the relationship between promoter methylation and mRNA levels of ERAP1 and AS susceptibility. METHODS: DNA methylation levels of 100 AS patients and 100 healthy controls (HCs) were tested using a targeted bisulfite sequencing assay. To verify the results of DNA methylation, mRNA levels of ERAP1 were measured in 20 AS patients and HCs used quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: The DNA methylation levels of two CpG islands containing 31 loci in ERAP1 promoter were measured. ERAP1_1 (P< .001) and ERAP1_2 (P< .001) islands were significantly hypermethylated in AS patients compared with HCs. In the verification study, the mRNA levels of ERAP1 were significantly decreased in AS patients. The ROC curve analysis showed that the sensitivity, specificity and area under curve were 0.717, 0.737, and 0.779 of differential methylated CpG loci of ERAP1 for AS diagnosis. In AS patients, the methylation levels of EARP1 were associated with family history, non-steroidal anti-inflammatory drugs use, X-ray classification, and clinical manifestations. CONCLUSIONS: Our study demonstrated that the ERAP1 gene is significantly hypermethylated, and mRNA levels of EARP1 decreased, in AS patients. Our findings suggested that the aberrant methylation of ERAP1 promoter may be involved in the pathogenesis of AS and could be considered as a diagnostic tool and therapeutic target of AS.Abbreviations AS: Ankylosing Spondylitis; AUC: Area Under Curve; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; CI: Confidence Interval; CpG: Cytosine-guanine Dinucleotide; CRP: C-reactive Protein; ERAP1: Endoplasmic Reticulum Aminopeptidase 1; ESR: Erythrocyte Sedimentation Rate; EWAS: Epigenome-Wide Association Study; HLA: Human Leukocyte Antigen; OR: Odds Ratio; PCR: Polymerase Chain Reaction; ROC: Receiver Operating Characteristic; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs.

Association between IL-17A and IL-17F gene polymorphism and susceptibility in inflammatory arthritis: A meta-analysis.

OBJECTIVES: The association between Interleukin (IL)-17A and IL-17F gene polymorphism with inflammatory arthritis were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17F gene polymorphism with ankylosing spondylitis (AS), osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We searched Medline up to August 2019. The summary Odds Ratio (OR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the relationship between IL-17A and IL-17F gene polymorphism with genetic susceptibility of AS, OA and RA. RESULTS: A total of 19 studies with 5298 cases and 5675 healthy controls were included. There were significant associations between rs2275913 G allele with OA, RA susceptibility (P < .05) but not AS. Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to AS and OA in Caucasian populations (P < .001) but not Mongolians. A significant association between rs763780 and RA susceptibility was detected in Caucasian populations (P < .05). CONCLUSION: IL-17F gene rs763780 C allele confers increased risk of inflammatory arthritis in Caucasians; IL-17A gene rs2275913 G allele are protective for OA susceptibility in Mongolians. More well-designed studies with larger sample size are needed to elucidate the role of IL-17A gene rs2275913 G allele in inflammatory arthritis, especially AS.

B7-H3: A promising therapeutic target for autoimmune diseases.

B7-H3 as a newly identified costimulatory molecule that belongs to B7 ligand family, is broadly expressed in both lymphoid and non-lymphoid tissues. The overexpression of B7-H3 has been verified to be correlated with the poor prognosis and poor clinical outcome of several human cancers. In recent years, researchers reveal that B7-H3 is involved in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), Sjögren's syndrome (SS), ankylosing spondylitis (AS), etc. In this review, we will discuss the biological function of B7-H3 and summarize the progress made over past years regarding its role in the occurrence and development of autoimmune diseases. The insights gained from these findings could serve as the foundation for future therapies of these diseases.

The prevalence and risk factors of prostatic calculi in Han Chinese: a cross-sectional study based on health examinations.

PURPOSE: Prostatic calculi (PCal) are commonly present with prostate disease; we aim to map the incidence and associated clinical risk factors of PCal in Han Chinese. MATERIAL AND METHODS: We retrospectively selected men who sought a medical check-up in 2018. Basic clinical items, including age, weight, height, prostate specific antigen (PSA), uric acid (UA), fasting blood glucose (FBG), urinalysis results, and transabdominal prostate ultrasound, were recorded. Univariate and logistic regression analyses were performed to evaluate whether these factors were associated with the presence of PCal. RESULT: We recorded the parameters of laboratory tests and clinical information from 14,427 men; men with PCal comprised 51.65% of the total group and 76.61% of the subgroup of benign prostate hyperplasia (BPH) patients. All the enrolled parameters showed meaningful differences, but the logistic regression analysis only indicated significant effects related to age (OR = 1.044, 95% CI = 1.040-1.047, and p < .001), body mass index (BMI) (OR = 1.035, 95% CI = 1.022-1.048, and p < .001), UA (OR = 0.999, 95% CI = 0.999-1.000, and p = .029), BPH (OR = 2.923, 95% CI = 2.678-3.191, and p < .001), and prostate cysts (OR = 0.609, 95% CI = 0.471-0.788, and p < .001). The odds ratio of the predicted combined model is 1.068. CONCLUSIONS: PCal was detected in 51.65% of men among healthy Han Chinese and in 76.61% of BPH patients. Age, BMI, UA, BPH, and prostate cysts were independent risk factors for the presence of PCal.

Neutrophil lymphocyte ratio in patients with ankylosing spondylitis: A systematic review and meta-analysis.

Objective: The aim of this meta-analysis was to investigate the association of neutrophil lymphocyte ratio (NLR) with AS (ankylosing spondylitis) patients.Methods: PubMed, Web of Science, Cochrane Library, Elsevier Science Direct and Google Scholar databases (up to 30 September 2018) were searched to collect all pertinent articles. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random effects model.Results: Totally 10 studies contained 765 AS patients and 701 healthy controls were included in our meta-analysis. The results indicated that there were significant statistical differences between AS patients and healthy controls in NLR (SMD = 0.418, 95%CI = 0.239-0.598, p < .001). Meanwhile, the results of subgroup analysis showed, in the subgroup of C-reactive protein (CRP) ≥10 and the two subgroups of BASDAI (the Bath AS Disease Activity Index), NLR levels in AS were significantly higher than in control (all p < .001). The results of subgroup analysis and meta-regression suggested that BASDAI and CRP were likely associated with NLR in AS patients.Conclusion: The current meta-analysis provides evidence that NLR is a reasonable measure to detect systemic inflammation in AS patients. Besides, NLR may be able to indicate disease activity in patients with AS.

Serum Sclerostin and Bone Morphogenetic Protein-2 Levels in Patients with Ankylosing Spondylitis: A Meta-Analysis.

Various studies have investigated the serum sclerostin and bone morphogenetic protein-2 (BMP-2) levels in patients with ankylosing spondylitis (AS), but the results were inconsistent. The aim of this meta-analysis was to synthetically assess the associations of serum levels of sclerostin and BMP-2 with AS. Multiple electronic databases were searched to locate relevant articles published before November 2018. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Totally, 21 studies were included. Meta-analysis results showed no significant difference between AS group and control group in serum sclerostin levels (SMD = 0.098, 95% CI - 0.395 to 0.591, p = 0.697). Nevertheless, serum BMP-2 levels in AS patients were higher than that in controls (SMD = 1.184, 95% CI 0.209 to 2.159, p = 0.017). Subgroup analysis demonstrated that European and South American AS patients had lower serum levels of sclerostin than controls. AS patients with age ≥ 40 years, erythrocyte sedimentation rate (ESR) ≤ 20 mm/h and Bath Ankylosing Spondylitis Functional Index (BASFI) < 4 had statistically significant lower serum sclerostin concentrations compared to controls. Chinese and Korean AS patients as well as patients with lower CRP had higher serum BMP-2 levels than controls, and country may be a source of heterogeneity across the studies. No publication bias existed and sensitivity analysis confirmed the stability of results. Serum BMP-2, but not sclerostin levels may be closely related to the development of AS.

Age, height, BMI and FBG predict prostate volume in ageing benign prostatic hyperplasia: Evidence from 5285 patients.

AIMS: Several studies have reported a potential association between prostate volume (PV) and prostate disease. Here, we classified the risk factors for PV among benign prostatic hyperplasia (BPH) patients. METHODS: In all, 4293 BPH patients with available clinical information were enrolled. Body mass index (BMI) was obtained as weight divided by height squared. PV was calculated as length × width × height (cm) × π/6. Mann-Whitney U tests were used to determine the differences between PV subgroups. Univariate and multiple linear regression tests were performed to uncover the connection between clinical features and PV. The differences in the age, BMI, height and fasting blood glucose (FBG) of the subgroups were evaluated by Kruskal-Wallis tests and adjusted with Bonferroni post hoc correction. A nomogram was created to directly illustrate the mutual interaction of amalgamator parameters. RESULTS: PV did not influence the incidence of kidney stones (P = .815), whereas prostate calculi were positively associated with an enlarged prostate (>30 mL) (P < .001). Age (adjusted R = 0.363, P < .001), height (adjusted R = 0.088, P < .001), BMI (adjusted R = 0.039, P = .013) and FBG (adjusted R = -0.034, P = .027) were the independent risk/protective factors related to enlarged PV among BPH patients. The nomogram illustrated the predictive risk of an enlarged prostate (>30 mL) in men. The area under the ROC curve value was 0.659 in the training cohort and 0.677 in an internal validation cohort. CONCLUSIONS: Age, height and BMI were positive independent risk factors of enlarged PV in BPH patients, and FBG had a protective role.

Lack of association between mean platelet volume and disease activity in systemic lupus erythematosus patients: a systematic review and meta-analysis.

Currently, many studies have focused on the possibility of using mean platelet volume (MPV) as a biomarker for disease activity in patients with systemic lupus erythematosus (SLE). To derive a more accurate estimation, a meta-analysis was conducted. Embase, PubMed, The Cochrane Library database and several Chinese databases (up to Nov 1 2017) were used to acquire published literatures on association of MPV levels with disease activity in SLE patients. Fixed-effects or random-effect model analysis was performed to calculate pooled standard mean difference (SMD) with 95% confidence interval (CI). Heterogeneity test was tested by the Q statistic and quantified using I2. A funnel plot and Egger's linear regression test were used to evaluate the potential publication bias. A total of 618 articles were identified, nine studies with 376 active SLE patients and 270 inactive SLE patients were finally included. No significant difference in MPV level was found between active SLE patients and inactive SLE patients (SMD = - 0.05, 95% CI: - 0.83, 0.73). Subgroup analyses stratified by age or region also demonstrated consistent results. No significant publication bias was observed (P > 0.05). The sensitivity analysis showed no significant change when any one study was excluded. In summary, our meta-analysis does not support the use of MPV as an indicator for monitoring disease activity in SLE patients. Further longitudinal studies with larger sample size are warranted to unveil the possibility of using MPV as a biomarker of disease activity.

Effect of Short Message Service on Management of Pulmonary Tuberculosis Patients in Anhui Province, China: A Prospective, Randomized, Controlled Study.

BACKGROUND To explore the significance of short message service (SMS) on the management of pulmonary tuberculosis (TB) patients in reinforcing the treatment adherence and health awareness, and provide scientific evidences for popularizing this model and formulating related polices and measures. MATERIAL AND METHODS Six counties (districts) were selected by stratified cluster sampling method, and randomly divided into control group and intervention group. Pulmonary TB patients eligible to the study criteria were included in the study. SMS management and regular education of core knowledge about pulmonary TB were carried out in SMS group patients. The conventional directly observed therapy (DOT) was carried out in control group. Data was collected by questionnaire method. RESULTS A total of 350 patients were included in the study, including 160 cases in the SMS group and 190 cases in the control group. There were 270 males (77.1%) and 80 females (22.9%). The treatment completion rate in SMS group (96.25%) was significantly higher than that in the control group (86.84%) (χ²=9.52, P=0.002). Both the interrupted treatment rate and the missed dose rate in the SMS group were significantly lower than those in the control group (χ²=10.41, P=0.001; χ²=28.54, P<0.001). After a period of treatment, the reexamination rate of SMS group patients was significantly higher than that in control group (except the reexamination rate after 5 months treatment). CONCLUSIONS The management of pulmonary TB patients by SMS can effectively reinforce the completed treatment rate of pulmonary TB patients and reduce their missed dose rate and interrupted treatment rate, and further enhance their reexamination awareness. Therefore, SMS on the management of patients may be a new promising therapeutic strategy for pulmonary TB.

Comparison of plasma/serum levels of procalcitonin between infection and febrile disease flare in patients with systemic lupus erythematosus: a meta-analysis.

Currently published data regarding the potential role of procalcitonin (PCT) for the discrimination between systemic lupus erythematosus (SLE) flare and infection are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Published literatures from PubMed, Embase, and the Cochrane Library were obtained. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2. Eight studies including 205 SLE flare patients and 198 SLE patients with infection were finally incorporated in the meta-analysis after examining title, type, abstracts, and full text. No significant differences in plasma/serum PCT levels were found between SLE patients with flare and SLE patients with infection when all studies were pooled into the meta-analysis (pooled SMD = - 0.45, 95% CI = - 0.96 to 0.06). However, subgroup analysis showed that Asian SLE patients with infection had higher plasma/serum PCT levels when compared with SLE patients with flare (p < 0.001). Overall, there is no significant difference in plasma/serum PCT levels between SLE patients with flare and SLE patients with infection. However, plasma/serum PCT levels are significantly higher in Asian SLE patients with infection.

Decreased flow-mediated dilatation in patients with rheumatoid arthritis: a meta-analysis.

OBJECTIVES: To derive a more precise comparison of flow-mediated dilatation (FMD%) of the brachial artery between patients with rheumatoid arthritis (RA) and normal controls by performing a meta-analysis of appropriate studies. METHODS: PubMed and EMBASE databases were searched for all relevant articles. STATA (V.12.0) software was used to perform the meta-analysis. Quality estimation of all appropriate studies was evaluated according to the Newcastle-Ottawa Scale (NOS). Standardised mean difference (SMD) with 95% CIs were calculated with a random-effects model. The Cochrane Q test and I2 statistic were used to evaluate the heterogeneity. Funnel plot and Egger's test were conducted to assess the publication bias. RESULTS: In total, 464 articles were obtained after searching the two databases. Ten studies were included in the meta-analysis on the basis of the inclusion and exclusion criteria. Significant heterogeneity was observed among these 10 studies (Q=102.89, p<0.001, I2=91.3%) with random-effects modelling. The results showed that the RA group had significantly lower FMD% (SMD: -1.405; 95% CI -1.992 to -0.817; p<0.001) than the control group. Egger's test (p=0.004) indicated that the funnel plot showed a skewed or asymmetrical shape and publication bias existed. Sensitivity analyses suggested the robustness and credibility of our results. CONCLUSIONS: FMD% in patients with RA is significantly decreased compared with healthy controls. FMD% is an important early marker of atherosclerosis. It may be used as a parameter to forecast cardiovascular disease in patients with RA.

The burden of depression, anxiety and schizophrenia among the older population in ageing and aged countries: an analysis of the Global Burden of Disease Study 2019.

Background: Depression, anxiety and schizophrenia among older persons have become global public health challenges. However, the burden of these disorders in ageing and aged countries has not been analysed. Aims: To investigate the burden of depression, anxiety and schizophrenia among older adults in ageing and aged countries. Methods: Using data from the Global Burden of Disease Study 2019, we calculated the estimated annual percentage change (EAPC) in the age-standardised incidence rates (ASIR) and age-standardised disability-adjusted life years (DALYs) rates (ASDR) for depression, anxiety and schizophrenia of older people in ageing countries (China, India, Indonesia) and aged countries (Japan, Italy, Portugal) between 1990 and 2019. Trends in incidence and DALYs were analysed by gender and age. Results: In 2019, the highest incidence of depression, anxiety and schizophrenia in the older population in aged countries was in Japan (927 271.3 (752 552.3-1 125 796.5), 51 498.2 (37 625.7-70 487.3) and 126.0 (61.0-223.2), respectively), while the highest incidence in ageing countries was in China (5 797 556.9 (4 599 403.4-7 133 006.5), 330 256.1 (246 448.9-445 987.4) and 1067.7 (556.2-1775.9), respectively). DALYs for these disorders were similar, with the highest in Japan and China. From 1990 to 2019, the ASIR for depressive disorders decreased in aged countries but increased in ageing countries; the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries. The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia. The ASIR for depressive disorders was higher in older women, while the opposite was observed in anxiety disorders and schizophrenia. Notably, the conditions of burden of depressive disorders, anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome. Conclusions: The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries. Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.

Interpretable machine learning for predicting chronic kidney disease progression risk.

Objective: Chronic kidney disease (CKD) poses a major global health burden. Early CKD risk prediction enables timely interventions, but conventional models have limited accuracy. Machine learning (ML) enhances prediction, but interpretability is needed to support clinical usage with both in diagnostic and decision-making. Methods: A cohort of 491 patients with clinical data was collected for this study. The dataset was randomly split into an 80% training set and a 20% testing set. To achieve the first objective, we developed four ML algorithms (logistic regression, random forests, neural networks, and eXtreme Gradient Boosting (XGBoost)) to classify patients into two classes-those who progressed to CKD stages 3-5 during follow-up (positive class) and those who did not (negative class). For the classification task, the area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate model performance in discriminating between the two classes. For survival analysis, Cox proportional hazards regression (COX) and random survival forests (RSFs) were employed to predict CKD progression, and the concordance index (C-index) and integrated Brier score were used for model evaluation. Furthermore, variable importance, partial dependence plots, and restrict cubic splines were used to interpret the models' results. Results: XGBOOST demonstrated the best predictive performance for CKD progression in the classification task, with an AUC-ROC of 0.867 (95% confidence interval (CI): 0.728-0.100), outperforming the other ML algorithms. In survival analysis, RSF showed slightly better discrimination and calibration on the test set compared to COX, indicating better generalization to new data. Variable importance analysis identified estimated glomerular filtration rate, age, and creatinine as the most important predictors for CKD survival analysis. Further analysis revealed non-linear associations between age and CKD progression, suggesting higher risks in patients aged 52-55 and 65-66 years. The association between cholesterol levels and CKD progression was also non-linear, with lower risks observed when cholesterol levels were in the range of 5.8-6.4 mmol/L. Conclusions: Our study demonstrated the effectiveness of interpretable ML models for predicting CKD progression. The comparison between COX and RSF highlighted the advantages of ML in survival analysis, particularly in handling non-linearity and high-dimensional data. By leveraging interpretable ML for unraveling risk factor relationships, contrasting predictive techniques, and exposing non-linear associations, this study significantly advances CKD risk prediction to enable enhanced clinical decision-making.

Global burden of myocarditis and cardiomyopathy in children and prediction for 2035 based on the global burden of disease study 2019.

Background: Myocarditis and cardiomyopathy are commonly occurring cardiovascular diseases that seriously threaten children's health. It was urgent to update the global incidence and mortality of childhood myocarditis and cardiomyopathy, and to predict the incidence rate of 2035 by the Global Burden of Disease database. Methods: The Global Burden of Disease study data from 1990 to 2019 in 204 countries and territories were used to determine: global incidence and mortality rates of childhood myocarditis and cardiomyopathy from 0 to 19 by five age groups; relationship between sociodemographic index (SDI) and incidence and mortality rates by age group; and, based on an age-period-cohort model, the projected incidence of childhood myocarditis and cardiomyopathy for 2035. Results: From 1990 to 2019, global age-standardized incidence rate decreased by 0.1% (95% UI 0.0-0.1) to 7.7% (95% UI 5.1-11.1). Boys had higher age-standardized incidence of childhood myocarditis and cardiomyopathy than girls [9.12, (95% UI 6.05-13.07) vs. 6.18, (95% UI 4.06-8.92)]. Childhood myocarditis and cardiomyopathy affected 121,259 (95% UI 80,467-173,790) boys and 77,216 (95% UI 50,684-111,535) girls in 2019. At the regional level, SDI changes in most areas showed no meaningful difference. In East Asia and high-income Asia Pacific, increased SDI was associated with decreased and increased incidence rate, respectively. In 2019, 11,755 (95% UI 9,611-14,509) children died from myocarditis and cardiomyopathy worldwide. Age-standardized mortality rate decreased significantly by 0.4% (95% UI 0.2-0.6)-0.5% (95% UI 0.4-0.6). Number of deaths from childhood myocarditis and cardiomyopathy in 2019 was highest in the <5-year-old group [7,442 (95% UI 5,834-9,699)]. Myocarditis and cardiomyopathy incidence in 10-14- and 15-19-year-olds is projected to increase by 2035. Conclusion: Global data on childhood myocarditis and cardiomyopathy from 1990 to 2019 showed a decreasing trend in incidence and mortality, and an increasing trend in older children, especially in high SDI regions.

Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study.

Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis. Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) -18, IL-1ß, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines. Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.

Global burden and risk factors of musculoskeletal disorders among adolescents and young adults in 204 countries and territories, 1990-2019.

BACKGROUND: Current studies on musculoskeletal (MSK) disorders mainly focus on the elderly, while adolescents and young adults (AYAs) are often neglected despite their unique epidemiology, healthcare needs and societal implications. To bridge this gap, we evaluated the global burden and temporal trends of MSK disorders among AYAs from 1990 to 2019, as well as their common categories and main risk factors. METHODS: Data on the global burden and risk factors of MSK disorders were obtained from the Global Burden of Diseases study 2019. Age standardized rates for incidence, prevalence and disability-adjusted life-years (DALYs) were calculated using the world population age standard, and their temporal trends were evaluated by estimated annual percentage changes (EAPC). Locally estimated scatterplot smoothing (LOESS) regression was used to explore the association between two variables. RESULTS: Over the past 30 years, MSK disorders have become the third leading cause of global DALYs among AYAs, with 36.2%, 39.3%, and 21.2% of increases in incident cases, prevalent cases and DALYs, respectively. In 2019, age standardized incidence, prevalence and DALY rates for MSK disorders were positivity associated with socio-demographic index (SDI) among AYAs in 204 countries and territories. The global age-standardized prevalence and DALY rates of MSK disorders began to increases among AYAs since 2000. In the last decade, countries with high SDI not only presented the only increase in age-standardized incidence rate across all SDI quintiles (EAPC = 0.40, 0.15 to 0.65), but also displayed the most rapid increases in age-standardized prevalence and DALY rates (EAPC = 0.41, 0.24 to 0.57; 0.39, 0.19 to 0.58, respectively). Low back pain (LBP) and neck pain (NP) were the most common MSK disorders among AYAs, accounting for 47.2% and 15.4% of global DALYs of MSK disorders in this population, respectively. Rheumatoid arthritis (RA), osteoarthritis (OA), and gout exhibited increasing trends in global age-standardized incidence, prevalence, and DALY rates among AYAs over the past 30 years (all EAPC >0), whereas LBP and NP showed declining trends (all EAPC <0). Occupational ergonomic factors, smoking and high BMI accounted for 13.9%, 4.3%, and 2.7% of global DALYs for MSK disorders among AYAs, respectively. The proportion of DALYs attributable to occupational ergonomic factors was negatively associated with SDI, whereas the proportions attributable to smoking and high BMI increased with SDI. Over the last 30 years, both the proportions of DALYs attributable to occupational ergonomic factors and smoking have consistently decreased globally and across all SDI quintiles, while the proportion attributable to high BMI has increased. CONCLUSIONS: MSK disorders have emerged as the third leading cause of global DALYs among AYAs over the past three decades. Countries with high SDI should make more efforts to tackle the dual challenges posed by the high levels and rapid increases in age standardized incidence, prevalence, and DALY rates in the last decade.

Assessing the association between the circulating levels of inflammatory cytokines and the risk of tuberculosis: A bidirectional two-sample mendelian randomization study.

BACKGROUND: Numerous observational studies have previously reported an association between inflammatory cytokines and tuberculosis (TB). However, the causal relationship between these factors remains unclear. Consequently, we conducted two-sample Mendelian randomization (MR) analyses to ascertain the causal link between levels of inflammatory cytokines and the risk of TB. METHODS: Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene. SNP was obtained from genome-wide association studies (GWAS) of 8293 individuals of Finnish. TB data was obtained from the UK Biobank, which included 46,293 individuals of European ancestry (comprising 2277 TB cases and 46,056 controls). Two-sample, bi-directional MR analyses using inverse-variance weighted (IVW) method as the primary analysis. Followed by comprehensive sensitivity analyses to validate the robustness of results. RESULT: The study showed that the causal relationship between circulating levels of interleukin (IL)-7 and risk of TB (odds ratio [OR] = 1.001, 95% confidence intervals [CIs]: 1.000, 1.003. p = 0.047). No causal associations were observed between other influencing factors and the occurrence of TB. Furthermore, the analysis revealed that TB infection exhibited negative causal associations with macrophage inflammatory protein 1 alpha ([MIP-1α], OR = 0.007, 95% CI: 0.000, 0.192. p = 0.004), IL-2 (OR = 0.014, 95% CI: 0.010, 0.427. p = 0.014), interleukin-2 receptor alpha chain([IL-2rα], OR = 0.019, 95% CI: 0.001, 0.525. p = 0.019) and basic fibroblast growth factor ([bFGF], OR = 0.066, 95% CI: 0.006, 0.700. p = 0.024). CONCLUSION: The study has illuminated the causal link between inflammatory cytokines and TB, thereby enhancing our comprehension of the potential mechanisms underlying TB pathogenesis. This discovery offers promising avenues for the identification of novel therapeutic targets in TB treatment. These insights may ultimately pave the way for more effective treatment approaches, thereby improving patient outcomes.

Increased Circulating Pentraxin 3 Levels in Patients with Rheumatoid Arthritis: A Meta-analysis.

BACKGROUND: Pentraxin 3 (PTX3), a soluble pattern recognition molecule, not only acts as a promising indicator reflecting the disease activity of rheumatoid arthritis (RA) patients but exerts essential pathogenic roles in the progression of RA and serves as a potential therapeutic target for RA patients. Our study intends to systematically evaluate the circulating PTX3 levels and their potential influencing factors in RA patients. METHODS: Articles regarding the circulating PTX3 levels of RA patients were identified in Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases. Standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were calculated and further illustrated by the forest plot. Egger's regression test and sensitivity analysis were conducted to assess the publication bias and stability of the results, respectively. RESULTS: Twenty articles with 21 individual studies were recruited in our meta-analysis. The overall results revealed that compared to healthy controls, RA patients had significantly higher circulating PTX3 levels (pooled SMD = 0.97, 95% CI: 0.48 to 1.45). Subgroup analyses further demonstrated that compared to healthy controls, RA patients of age ≤ 50 years, 2.6 < disease activity score in 28 joints (DAS28) ≤ 3.2, 3.2 < DAS28 ≤ 5.1, DAS28 > 5.1, C-reactive protein (CRP) levels > 10 mg/L, erythrocyte sedimentation rate (ESR) > 20 mm/h, and disease duration > 5 years had significantly higher circulating PTX3 levels, respectively; whereas RA patients of age > 50 years, DAS28 ≤ 2.6, CRP levels ≤ 10 mg/L, ESR ≤ 20 mm/h and disease duration ≤ 5 years had no significantly altered circulating PTX3 levels, respectively. Additionally, no matter whether the patients were of Caucasian ethnicity or not, circulating PTX3 levels were significantly increased in RA patients. CONCLUSION: Compared to healthy controls, circulating PTX3 levels are significantly increased in RA patients, which are influenced by age, disease activity, CRP levels, ESR, and disease duration.

Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analysis with trial sequential analysis.

OBJECTIVES: The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics. METHODS: Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results. RESULTS: A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85-11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions. CONCLUSIONS: IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA.

The rapid and efficient strategy for SARS-CoV-2 Omicron transmission control: analysis of outbreaks at the city level.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. Hence, control measures are continuously being optimized to guard against large-scale coronavirus disease 2019 (COVID-19) outbreaks. This study aimed to explore the relationship between the intensity of control measures in response to different SARS-CoV-2 variants and the degree of outbreak control at city level. METHODS: A retrospective study was conducted in 49 cities with COVID-19 outbreaks between January 2020 and June 2022. Epidemiological data on COVID-19 were extracted from the National Health Commission, People's Republic of China, and the population flow data were sourced from the Baidu migration data provided by the Baidu platform. Outbreak control was quantified by calculating the degree of infection growth and the time-varying reproduction number ([Formula: see text]). The intensity of the outbreak response was quantified by calculating the reduction in population mobility during the outbreak period. Correlation and regression analyses of the intensity of the control measures and the degree of outbreak control for the Omicron variant and non-Omicron mutants were conducted, respectively. RESULTS: Overall, 65 outbreaks occurred in 49 cities in China from January 2020 to June 2022. Of them, 66.2% were Omicron outbreaks and 33.8% were non-Omicron outbreaks. The intensity of the control measures was positively correlated with the degree of outbreak control (r = 0.351, P = 0.03). The degree of reduction in population mobility was negatively correlated with the Rt value (r = - 0.612, P < 0.01). Therefore, under the same control measure intensity, the number of new daily Omicron infections was 6.04 times higher than those attributed to non-Omicron variants, and the Rt value of Omicron outbreaks was 2.6 times higher than that of non-Omicron variants. In addition, the duration of non-Omicron variant outbreaks was shorter than that of the outbreaks caused by the Omicron variant (23.0 ± 10.7, 32.9 ± 16.3, t = 2.243, P = 0.031). CONCLUSIONS: Greater intensity of control measures was associated with more effective outbreak control. Thus, in response to the Omicron variant, the management to restrict population movement should be used to control its spread quickly, especially in the case of community transmission occurs widely. Faster than is needed for non-Omicron variants, and decisive control measures should be imposed and dynamically adjusted in accordance with the evolving epidemic situation.