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.

Global, regional and national burden of CKD in children and adolescents from 1990 to 2019.

BACKGROUND: Chronic kidney disease(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 kidney replacement therapy) in children and adolescents showed an increasing trend [AAPC 0.44 (95% confidence interval 0.36-0.52)] between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend [AAPC 0.46 (0.42-0.51)]. However, the DALYs of CKD showed a continuous decreasing trend [AAPC -1.18 (-1.37 to -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.

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.

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.

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.

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.

Emerging roles of air pollution and meteorological factors in autoimmune eye diseases.

Autoimmune eye diseases (AEDs), a collection of autoimmune inflammatory ocular conditions resulting from the dysregulation of immune system at the ocular level, can target both intraocular and periorbital structures leading to severe visual deficit and blindness globally. The roles of air pollution and meteorological factors in the initiation and progression of AEDs have been increasingly attractive, among which the systemic and local mechanisms are both involved in. Exposure to excessive air pollution and extreme meteorological conditions including PM2.5/PM0.1, environmental tobacco smoke, insufficient sunshine, and high temperature, etc., can disturb Th17/Treg balance, regulate macrophage polarization, activate neutrophils, induce systemic inflammation and oxidative stress, decrease retinal blood flow, promote tissue fibrosis, activate sympathetic nervous system, adversely affect nutrients synthetization, as well as induce heat stress, therefore may together deteriorate AEDs. The crosstalk among inflammation, oxidative stress and dysregulated immune system appeared to be prominent. In the present review, we will concern and summarize the potential mechanisms underlying linkages of air pollution and meteorological factors to ocular autoimmune and inflammatory responses. Moreover, we concentrate on the specific roles of air pollutants and meteorological factors in several major AEDs including uveitis, Graves' ophthalmopathy (GO), ocular allergic disease (OAD), glaucoma, diabetic retinopathy (DR), etc.

Global Chronic obstructive pulmonary disease burden attributable to air pollution from 1990 to 2019.

BACKGROUND: The disease burden attributable to chronic obstructive pulmonary disease (COPD) is significant worldwide. Some studies have linked exposure to air pollution to COPD, but there has been little research on this. METHODS: We aimed to assess the COPD-related disease burden attributable to air pollution from multiple epidemiological perspectives. This study conducted a three-stage analysis. Firstly, we reported on the burden of disease worldwide in 2019 by different subgroups including sex, age, region, and country. Secondly, we studied the trends in disease burden from 1990 to 2019. Finally, we explored the association of some national indicators with disease burden to look for risk factors. RESULTS: In 2019, the death number of COPD associated with air pollution accounted for 2.32% of the total global death, and the number of DALY accounted for 1.12% of the global DALY. From 1990 to 2019, the death number of COPD associated with air pollution increased peaked at 1.41 million in 1993, fluctuated, and then declined. We found the same temporal pattern of DALY. The corresponding age-standardized rates had been falling. At the same time, the burden of COPD associated with air pollution was also affected by some national indicators. CONCLUSIONS: This study indicated that air pollution-related COPD contributed to a significant global disease burden. We called for health policymakers to take action and interventions targeting vulnerable countries and susceptible populations.

The effect of air pollution exposure on the risk of outpatient visits for periodontitis: a time-series study.

This study aimed to determine if air pollution affected the risk of periodontitis outpatient visits. We collected the records of 56,456 periodontitis outpatient visits in Hefei, China, from January 1，2014 to December 31，2021. The relationship between air pollution and periodontitis outpatient visits was evaluated using distributed lag nonlinear and generalized linear models. Additional analyses were performed, stratifying the data by age, season, and sex. Subgroup analyses showed a significantly higher risk of periodontitis outpatient visits due to NO2 exposure during the warm season compared with the cold season. Moreover, O3 exposure was associated with a lower risk of periodontitis outpatient visits in the cold season. The findings suggest that NO2 exposure is associated with an increased risk of periodontitis outpatient visits, whereas O3 exposure is associated with a decreased risk of periodontitis outpatient visits. Season is found to be an effect modifier in these associations.

Increased circulating sclerostin levels in rheumatoid arthritis patients: an updated meta-analysis.

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.

Air pollution exposure and auto-inflammatory and autoimmune diseases of the musculoskeletal system: a review of epidemiologic and mechanistic evidence.

Auto-inflammatory and autoimmune diseases of the musculoskeletal system can be perceived as a spectrum of rheumatic diseases, with the joints and connective tissues are eroded severely that progressively develop chronic inflammation and lesion. A wide range of risk factors represented by genetic and environmental factors have been uncovered by population-based surveys and experimental studies. Lately, the exposure to air pollution has been found to be potentially involved in the mechanisms of occurrence or development of such diseases, principally manifest in oxidative stress, local and systemic inflammation, and epigenetic modifications, as well as the mitochondrial dysfunction, which has been reported to participate in the intermediate links. The lungs might serve as a starting area of air pollutants, which would cause oxidative stress-induced bronchial-associated lymphoid tissue (iBALT) to further to influence T, B cells, and the secretion of pro-inflammatory cytokines. The binding of aromatic hydrocarbon receptor (AhR) to the corresponding contaminant ligands tends to regulate the reaction of Th17 and Tregs. Furthermore, air pollution components might spur on immune and inflammatory responses by damaging mitochondria that could interact with and exacerbate oxidative stress and pro-inflammatory cytokines. In this review, we focused on the association between air pollution and typical auto-inflammatory and autoimmune diseases of the musculoskeletal system, mainly including osteoarthritis (OA), rheumatoid arthritis (RA), spondyloarthritis (SpA) and juvenile idiopathic arthritis (JIA), and aim to collate the mechanisms involved and the potential channels. A complete summary and in-depth understanding of the autoimmune and inflammatory effects of air pollution exposure should hopefully contribute new perspectives on how to formulate better public health policies to alleviate the adverse health effects of air pollutants.

Associations between particulate matter air pollutants and hospitalization risk for systemic lupus erythematosus: a time-series study from Xi'an, China.

Air pollution exposure is an important environmental risk factor involved in the development of systemic lupus erythematosus (SLE). This study was conducted to investigate the relationships between particulate matter (PM) air pollutants exposure and the risk of SLE admission in Xi'an, China. The records of SLE admission, air pollutants and meteorological data were retrieved from the First Affiliated Hospital of Xi'an Jiaotong University, the Xi'an Environmental Monitoring Station and China Meteorological Data Network, respectively. A distributed lagged nonlinear model combined with Poisson generalized linear regression was used to evaluate the effect of air pollution on SLE admission. Exposure-response curves showed positive associations of PM ≤ 2.5 (PM2.5) and 10 microns (PM10) in aerodynamic diameter exposures with the risk of SLE admission. Subgroup analyses showed that PM2.5 exposure was associated with the increased risk of SLE admission in women, age over 65 years old, and during the cold season, and PM10 exposure showed an increased risk of SLE in women and during the cold season, but additional tests did not observe the significant associations of PM2.5 and PM10 exposure with SLE admission between subgroups. In addition, null associations of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2) with the risk of SLE admission were found. Our study indicates that PM2.5 and PM10 exposures have significant effects on the risk of SLE admission, and early measures should be taken for high PM2.5 and PM10 exposure to protect vulnerable populations, rational use of limited health care resources.

Association between air pollution exposure and outpatient visits for dermatomyositis in a humid subtropical region of China: a time-series study.

In recent years, a growing number of studies have found that air pollution plays critical roles in the onset and development of autoimmune diseases, but few studies have shown an association between air pollutants and dermatomyositis (DM). We sought to investigate the relationship between short-term exposure to air pollution and outpatient visits for DM and to quantify the burden of DM due to exposure to air pollutants in Hefei, China. Daily records of hospital outpatient visits for DM, air pollutants and meteorological factors data in Hefei from January 1, 2018 to December 31, 2021 were obtained. We used a distributed lag non-linear model (DLNM) in conjunction with a generalized linear model (GLM) to explore the association between air pollution and outpatient visits for DM, and conducted stratified analyses by gender, age and season. Moreover, we used attributable fraction (AF) and attributable number (AN) to reflect the burden of disease. A total of 4028 DM clinic visits were recorded during this period. High concentration nitrogen dioxide (NO2) exposure was associated with increased risk of DM outpatient visits (relative risk (RR) 1.063, 95% confidence interval (CI) 1.015-1.114, lag 0-5). Intriguingly, exposure to high concentration ozone (O3) was associated with reduced risk of outpatient visits for DM (RR 0.974, 95% CI 0. 0.954-0.993, lag 0-6). The results of stratified analyses showed that the cold season (vs. warm season) were more susceptible to outpatient visits for DM associated with NO2 and O3 exposure. In addition, we observed that an increased risk of DM outpatient visits was attributable to high concentration NO2 exposure, while high concentration O3 exposure was associated with a decreased risk of DM outpatient visits. This study provided a scientific basis for the etiology research and health protection of DM.

New-onset autoimmune phenomena post-COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented setback for global economy and health. Vaccination is one of the most effective interventions to substantially reduce severe disease and death due to SARS-CoV-2 infection. Vaccination programmes are being rolled out globally, but most of these vaccines have been approved without extensive studies on their side-effects and efficacy. Recently, new-onset autoimmune phenomena after COVID-19 vaccination have been reported increasingly (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). Molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants seem to be substantial contributors to autoimmune phenomena. However, whether the association between COVID-19 vaccine and autoimmune manifestations is coincidental or causal remains to be elucidated. Here, we summarize the emerging evidence about autoimmune manifestations occurring in response to certain COVID-19 vaccines. Although information pertaining to the risk of autoimmune disease as a consequence of vaccination is controversial, we merely propose our current understanding of autoimmune manifestations associated with COVID-19 vaccine. In fact, we do not aim to disavow the overwhelming benefits of mass COVID-19 vaccination in preventing COVID-19 morbidity and mortality. These reports could help guide clinical assessment and management of autoimmune manifestations after COVID-19 vaccination.

Dickkopf-1 as a promising therapeutic target for autoimmune diseases.

Dickkopf-1 (DKK-1) is mostly known as a mature inhibitor of classic Wnt signaling pathways, which plays a critically role in regulating bone formation and bone metastasis. In recent years, the roles of DKK-1 played in bone resorption, bone formation, immune homeostasis and inflammation have been investigated. The role of DKK-1 in the pathogenesis and treatment of autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), etc, has attracted widespread attention. Various studies have found that DKK-1 may be used as a biomarker for the occurrence and development of ADs, and as a potential target for the treatment of ADs. In this review, we have briefly summed up the intricate immunological functions and regulatory mechanisms of DKK-1 in ADs, aiming to further learning more about the role of DKK-1 involved in the pathogenesis of ADs and provide an outlook for the potential future researches.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis.

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis. METHODS: Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH < 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH < 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10-4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH < 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.

Association of leptin and leptin receptor genes variants and pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population.

BACKGROUND: The aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population. METHODS: This study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). RESULTS: We found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P > 0.05), as well as the results of the dominant model and recessive model (all P > 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012). CONCLUSIONS: LEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

Novel coronavirus mutations: Vaccine development and challenges.

The ongoing global pandemic of novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 has a significant impact on global health and economy system. In this context, there have been some landmark advances in vaccine development. Over 100 new coronavirus vaccine candidates have been approved for clinical trials, with ten WHO-approved vaccines including four inactivated virus vaccines, two mRNA vaccines, three recombinant viral vectored vaccines and one protein subunit vaccine on the "Emergency Use Listing". Although the SARS-CoV-2 has an internal proofreading mechanism, there have been a number of mutations emerged in the pandemic affecting its transmissibility, pathogenicity and immunogenicity. Of these, mutations in the spike (S) protein and the resultant mutant variants have posed new challenges for vaccine development and application. In this review article, we present an overview of vaccine development, the prevalence of new coronavirus variants and their impact on protective efficacy of existing vaccines and possible immunization strategies coping with the viral mutation and diversity.

Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients.

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients. METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G). RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety. CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.