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.

Diosmin ameliorates renal fibrosis through inhibition of inflammation by regulating SIRT3-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. METHODS: The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1ß, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-ß1 and then treated with diosmin (75 µM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. RESULTS: Diosmin attenuated UUO-induced renal fibrosis and TGF-ß1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1ß, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-ß1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-ß1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. CONCLUSIONS: Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

The prevalence and influencing factors of frailty in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: To investigate the prevalence and influencing factors of frailty and pre-frailty in chronic kidney disease (CKD) patients and thereby provide a scientific basis for effective avoidance of frailty in patients with CKD. METHODS: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library, CNKI, VIP, CBMdisc, and Wanfang databases were searched for relevant studies published till December 31, 2021. The summary results were described as odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). A meta-analysis was performed using StataSE12.0. RESULTS: Fifteen published studies, which enrolled a total of 3294 CKD patients, met the inclusion criteria. The combined prevalence of frailty in CKD patients was 38.1% (95% CI 29.7-46.5%) and pre-frailty was 37.9% (95% CI 32.7-43.1%). The main factors influencing frailty in CKD patients were age (SMD 0.524, 95% CI 0.326-0.723), diastolic blood pressure (SMD - 0.294, 95% CI - 0.518 to - 0.071), body mass index (BMI) (SMD - 0.267, 95% CI - 0.471 to - 0.064), grip strength (SMD - 0.929, 95% CI - 1.233 to - 0.626), hemoglobin level (SMD - 0.346, 95% CI - 0.448 to - 0.243), serum albumin level (SMD - 0.533, 95% CI - 0.655 to - 0.411), Charlson Comorbidity Index (SMD 0.421, 95% CI 0.150-0.692), multiple medications (SMD 0.625, 95% CI 0.354-0.895), Mini-Mental State Examination (MMSE) score (SMD - 0.563, 95% CI - 0.846 to - 0.280), and female (OR 2.391, 95% CI 1.236-4.627). CONCLUSION: Frailty is common in CKD patients. The prevalence of frailty among CKD patients was related to age, diastolic blood pressure, BMI, grip strength, hemoglobin and serum albumin levels, Charlson Comorbidity Index, multiple medications, MMSE score, and female.

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.

Identification of basement membrane markers in diabetic kidney disease and immune infiltration by using bioinformatics analysis and experimental verification.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide. Basement membranes (BMs) are ubiquitous extracellular matrices which are affected in many diseases including DKD. Here, the authors aimed to identify BM-related markers in DKD and explored the immune cell infiltration in this process. The expression profiles of three datasets were downloaded from the Gene Expression Omnibus database. BM-related differentially expression genes (DEGs) were identified and Kyoto encyclopaedia of genes and genomes pathway enrichment analysis were applied to biological functions. Immune cell infiltration and immune function in the kidneys of patients with DKD and healthy controls were evaluated and compared using the ssGSEA algorithm. The association of hub genes and immune cells and immune function were explored. A total of 30 BM-related DEGs were identified. The functional analysis showed that BM-related DEGs were notably associated with basement membrane alterations. Crucially, BM-related hub genes in DKD were finally identified, which were able to distinguish patients with DKD from controls. Moreover, the authors observed that laminin subunit gamma 1(LAMC1) expression was significantly high in HK2 cells treated with high glucose. Immunohistochemistry results showed that, compared with those in db/m mouse kidneys, the levels of LAMC1 in db/db mouse kidneys were significantly increased. The biomarkers genes may prove crucial for DKD treatment as they could be targeted in future DKD treatment protocols.

Dialysis vintage is associated with a high prevalence and severity of unpleasant symptoms in patients on hemodialysis.

Background: The burden of physical and emotional symptoms caused by somatic illness is present in most dialysis patients. However, it's unclear how symptom burden varies among patients with different dialysis vintages. We sought to examine differences in the prevalence and severity of unpleasant symptoms in hemodialysis patients with diverse dialysis vintage cohorts.Methods: This cross-sectional study included patients on maintenance hemodialysis at the Second Hospital of Anhui Medical University. We used the Dialysis Symptom Index (DSI) to determine the associated unpleasant symptoms, which is a validated survey to assess symptom burden/severity (higher scores indicate more severe symptoms), over June 2022 - September 2022.Results: We studied 146 patients: 35 (24%) had a dialysis vintage of ≤12 months (group 1) and 111 (76%) had a dialysis vintage of >12 months (group 2). Concerning Group 1 patients, the prevalence and severity of unpleasant symptoms were significantly higher in Group 2, the most common individual symptoms included feeling tired or lack of energy and trouble falling asleep (i.e., 75-85% of patients in each group), with dialysis vintage being an independent influencing factor (adjusted OR, 0.19; 95% CI, 0.16 to 0.23). Lower hemoglobin levels, iron stores, and dialysis adequacy levels are correlated with longer dialysis vintage.Conclusion: We observed a high prevalence of unpleasant symptoms and symptom clusters in a diverse dialysis vintages hemodialysis cohort. Further studies are needed to accurately and routinely define the symptom burden of chronic patients with chronic kidney disease (CKD).

Analysis of the potential biological mechanisms of diosmin against renal fibrosis based on network pharmacology and molecular docking approach.

BACKGROUND: Interstitial fibrosis is involved in the progression of various chronic kidney diseases and renal failure. Diosmin is a naturally occurring flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether diosmin protects kidneys by inhibiting renal fibrosis is unknown. METHODS: The molecular formula of diosmin was obtained, targets related to diosmin and renal fibrosis were screened, and interactions among overlapping genes were analyzed. Overlapping genes were used for gene function and KEGG pathway enrichment analysis. TGF-ß1 was used to induce fibrosis in HK-2 cells, and diosmin treatment was administered. The expression levels of relevant mRNA were then detected. RESULTS: Network analysis identified 295 potential target genes for diosmin, 6828 for renal fibrosis, and 150 hub genes. Protein-protein interaction network results showed that CASP3, SRC, ANXA5, MMP9, HSP90AA1, IGF1, RHOA, ESR1, EGFR, and CDC42 were identified as key therapeutic targets. GO analysis revealed that these key targets may be involved in the negative regulation of apoptosis and protein phosphorylation. KEGG indicated that pathways in cancer, MAPK signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway were key pathways for renal fibrosis treatment. Molecular docking results showed that CASP3, ANXA5, MMP9, and HSP90AA1 stably bind to diosmin. Diosmin treatment inhibited the protein and mRNA levels of CASP3, MMP9, ANXA5, and HSP90AA1. Network pharmacology analysis and experimental results suggest that diosmin ameliorates renal fibrosis by decreasing the expression of CASP3, ANXA5, MMP9, and HSP90AA1. CONCLUSIONS: Diosmin has a potential multi-component, multi-target, and multi-pathway molecular mechanism of action in the treatment of renal fibrosis. CASP3, MMP9, ANXA5, and HSP90AA1 might be the most important direct targets of diosmin.

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.

Pathogenetic and Therapeutic Role of Gut Microbiome in Immunoglobin A Nephropathy.

Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephritis, which is mainly characterized by excessive IgA deposition in the glomerular mesangial area. Although exploring the pathogenesis of IgAN and improving the treatment strategies continuously, the exact pathogenesis of IgAN remains unclear and the disease still leads to high mortality. Recently, emerging evidence has demonstrated that dysregulated intestinal mucosal immunity and gut microbiome imbalance may play a combined role in the development and progression of IgAN. It has been suggested that reconstructing the intestinal microenvironment and maintaining the stability and metabolic balance of gut microbiome are expected to become new treatment strategies. Meanwhile, inhibiting mucosa-associated lymphoid tissue (MALT) controlled by the gut microbiome may become an alternative treatment, especially used to reduce the excessive production of IgA in IgAN. In this review, we summarized the correlation between gut microbiome and the pathogenesis of IgAN, as well as the therapeutic potential of gut microbiome in this disease.

Causal effect of polyunsaturated fatty acids on bone mineral density and fracture.

Background: Polyunsaturated fatty acids (PUFAs) are closely related to osteoporosis. To test their causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods: We analyzed the causal relationship between four PUFAs measures, n-3 PUFAs (n-3), n-6 PUFAs (n-6), the ratio of n-3 PUFAs to total fatty acids (n-3 pct), and the ratio of n-6 PUFAs to n-3 PUFAs (n-6 to n-3), and five measures of osteoporosis, including estimated bone mineral density (eBMD), forearm (FA) BMD, femoral neck (FN) BMD, lumbar spine (LS) BMD, and fracture, using two-sample MR analysis. In order to verify the direct effect between PUFAs and BMD, we chose interleukin-6 (IL-6), tumor necrosis factor-ß (TNF-ß), and bone morphogenetic proteins 7 (BMP-7), three markers or cytokines strongly related to BMD, as possible confounding factors, and analyzed the possible causal relationships between them and PUFAs or BMD by MR. Inverse variance weighting (IVW), MR-Egger, weighted and weighted median were conducted. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to evaluate the potential pleiotropy of instrumental variables (IVs) and outliers were identified by MR-PRESSO. Cochran's Q statistic was used to detect the heterogeneity among IVs. Leave-one-out sensitivity analysis was used to find SNPs that have a significant impact on the results. All results were corrected by the Bonferroni correction. Results: The IVW results showed that n-3 PUFAs (OR = 1.030, 95% CI: 1.013, 1.047, P = 0.001) and n-6 PUFAs (OR = 1.053, 95% CI: 1.034, 1.072, P < 0.001) were positively correlated with eBMD, while n-6 to n-3 (OR = 0.947, 95% CI: 0.924, 0.970, P < 0.001) were negatively correlated with eBMD. These casual relationships still existed after Bonferroni correction. There were positive effects of n-3 PUFAs on FA BMD (OR = 1.090, 95% CI: 1.011, 1.176, P = 0.025) and LS BMD (OR = 1.056, 95% CI: 1.011, 1.104, P = 0.014), n-3 pct on eBMD (OR = 1.028, 95% CI: 1.002, 1.055, P = 0.035) and FA BMD (OR = 1.090, 95% CI: 1.011, 1.174, P = 0.025), n-6 to n-3 on LS BMD (OR = 1.071, 95% CI: 1.021, 1.124, P = 0.005); negative effects of n-3 pct on fracture (OR = 0.953, 95% CI: 0.918, 0.988, P = 0.009) and n-6 to n-3 on FA BMD (OR = 0.910, 95% CI: 0.837, 0.988, P = 0.025). However, these causal effects all disappeared after Bonferroni correction (all P > 0.0025). None of IL-6, TNF-ß, and BMP-7 had a causal effect on PUFA and BMD simultaneously (all P > 0.05). Conclusion: Evidence from this MR study supports the genetically predicted causal effects of n-3, n-6, n-3 pct, and n-6 to n-3 on eBMD. In addition, n-3 not only associate with FA BMD and LS BMD through its own level and n-6 to n-3, but also link to fracture through n-3 pct.

Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases.

Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.

Environmental factors influencing the risk of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.

Axial and frontal X-ray fluoroscopy technique of the sustentaculum tali can improve the accuracy of sustentacular screw placement.

INTRODUCTION: Calcaneal fractures, especially those involving the articular surface, should be anatomically reduced as much as possible. Fixing the fracture by placing a screw into the sustentaculum tali from the lateral side of the calcaneus is generally considered to be the key to successful surgery. However, due to the limited visibility during surgery, it is not easy to place screws into the sustentaculum tali accurately. The purpose of this study was to explore a new fluoroscopy method for the sustentaculum tali and verify the value of this method in improving screw placement accuracy. METHODS: In this study, a total of 42 human foot and ankle specimens were dissected and measured. The shape and position of the sustentaculum tali were observed, and the influence of adjacent bones on imaging findings was analysed. The axial and frontal X-ray fluoroscopy method to view the sustentaculum tali was formulated, and the appropriate projection angle through anatomical and image measurements was explored. Thirty specimens were randomly selected for screw placement, and the direction of the screw was dynamically adjusted under the new imaging method. The success rate of sustentacular screw placement was evaluated. RESULTS: The anteversion angles of the sustentaculum tali were 30.81 ± 2.21° and 30.68 ± 2.86° by anatomical and imaging measurements, respectively. There was no statistically significant difference in the anteversion angle between the two measurement methods. Harris heel views should be obtained at 30° to identify the sustentaculum tali on axial X-ray images. Frontal X-ray imaging was performed perpendicular to this projection angle. Through frontal and axial X-ray imaging, the position and shape of the sustentaculum tali can be clearly observed, and these factors are seldom affected by adjacent bones. Under the new fluoroscopy method, the screws were placed from the anterior region of the lateral wall of the calcaneus to the sustentaculum tali. A total of 60 screws were placed in the 30 specimens; of these, 54 screws were in good position, 2 screws penetrated the cortical bone, and 4 screws did not enter the sustentaculum tali. The success rate of sustentacular screw placement was 90% (54/60). CONCLUSIONS: Axial and frontal X-ray images of the sustentaculum tali can clearly show the shape of the structure, which improves sustentacular screw placement accuracy.

Early Humoral Responses of Hemodialysis Patients After Inactivated SARS-CoV-2 Vaccination.

Purpose: To detect antibody responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis and to investigate vaccine-related adverse events. Patients and Methods: A total of 120 hemodialysis (HD) patients and 24 healthy controls (HCs) who had not been previously infected with SARS-CoV-2 and had received their first dose of the inactivated vaccine (CoronaVac; Sinovac Biotech Ltd) were recruited for this study. All participants were scheduled to receive a second dose of inactivated SARS-CoV-2 vaccine. Serum-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the SARS-CoV-2 were detected at least 14 days after the second dose of vaccine using a commercial kit. Positive and negative results were defined as a sample/cutoff (S/CO) ratio≥1.00 and <1.00, respectively. Vaccination-related adverse events were assessed using a standardized questionnaire. Results: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and the self-reported vaccination-related adverse events between HD patients and HCs. The analysis results for HD patients suggest that 82 (68.3%) and 27 (22.5%) tested positive for IgG and IgM, respectively. The levels of IgG were higher than IgM levels (P<0.0001). In addition, the IgG-positive group had significantly higher serum albumin levels than the IgG-negative group (P<0.05). Only mild vaccine-related adverse events were observed in two patients (1.66%) and in one healthy individual (4.2%). Conclusion: The seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar between HD and HCs. The inactivated SARS-CoV-2 vaccine is effective and safe in inducing near-term immunity in hemodialysis patients.

Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: This study aimed to investigate the seroreactivity of Coronavirus disease 2019 (COVID-19) vaccination and its adverse events among systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, and healthy controls (HCs). METHODS: A total of 60 SLE patients, 70 RA patients and 35 HCs, who received a complete inactivated COVID-19 vaccine (Vero cells) regimen, were recruited in the current study. Serum IgG and IgM antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2, and the self-reported vaccination-related adverse events among SLE patients, RA patients and HCs. The inactivated COVID-19 vaccines appeared to be well-tolerated and moderately immunogenic. In addition, case-only analysis indicated that in SLE patients, the disease manifestation of rash and anti-SSA autoantibody were associated with seroprevalence of IgG antibody against SARS-CoV-2, whereas the uses of ciclosporin and leflunomide had influence on the seroprevalence of IgM antibody against SARS-CoV-2. In RA patients, rheumatoid factor (RF) appeared to be associated with the seroprevalence of IgG antibody against SARS-CoV-2. CONCLUSION: Our study reveals that the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar among SLE, RA and HCs, suggesting that COVID-19 vaccine is safe and effective for SLE and RA patients to prevent from the pandemic of COVID-19.

Levels of the macrophage migration inhibitory factor and polymorphisms in systemic lupus erythematosus: a meta-analysis.

INTRODUCTION: Several published results have established variations in respect to plasma/serum macrophage migration inhibitory factor (MIF) levels and gene polymorphisms with systemic lupus erythematosus (SLE). This study gave a more concise estimation on the MIF levels for SLE patients and established the association between MIF polymorphisms and SLE. MATERIAL AND METHODS: All articles were searched from PubMed, Embase, Web of Science, Wan-Fang, Chinese Biological Medical Literature, and China National Knowledge Infrastructure up to 6th October 2017, with no language restriction. Pooled standard mean difference with 95% confidence interval was evaluated using random effect model. Thirteen articles were used for this meta-analysis, with 620 SLE patients and 779 healthy controls assessed for MIF levels, and 2,159 SLE patients and 2,574 healthy controls considered for MIF-173 C/G and MIF-794 CATT polymorphisms. RESULTS: There was a significant higher MIF levels in SLE patients than in healthy controls (p = 0.004). The subgroup analysis showed Asians and ages < 30 had higher MIF levels in SLE patients than in healthy controls. It was evident that patients with systemic lupus erythematosus diseases activity index scores < 8 and ≥ 8, and disease duration for both year < 5 and ≥ 5 of SLE had higher MIF levels when compared to healthy controls. We found a significant association between SLE and MIF-173 C/G, but not MIF-794 CATT. CONCLUSIONS: This study provided evidence of significant higher MIF levels in SLE patients and supported the association of MIF-173 C/G and SLE. However, we were not able to establish an association between MIF-794 CATT and SLE.

Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.

Emerging role of air pollution in chronic kidney disease.

Chronic kidney disease (CKD), a global disease burden related to high rates of incidence and mortality, manifests as progressive and irretrievable nephron loss and decreased kidney regeneration capacity. Emerging studies have suggested that exposure to air pollution is closely relevant to increased risk of CKD, CKD progression and end-stage kidney disease (ESKD). Inhaled airborne particles may cause vascular injury, intraglomerular hypertension, or glomerulosclerosis through non-hemodynamic and hemodynamic factors with multiple complex interactions. The mechanisms linking air pollutants exposure to CKD include elevated blood pressure, worsening oxidative stress and inflammatory response, DNA damage and abnormal metabolic changes to aggravate kidney damage. In the present review, we will discuss the epidemiologic observations linking air pollutants exposure to the incidence and progression of CKD. Then, we elaborate the potential roles of several air pollutants including particulate matter and gaseous co-pollutants, environmental tobacco smoke, and gaseous heavy metals in its pathogenesis. Finally, this review outlines the latent effect of air pollution in ESKD patients undergoing dialysis or renal transplant, kidney cancer and other kidney diseases. The information obtained may be beneficial for further elucidating the pathogenesis of CKD and making proper preventive strategies for this disease.

Elevated levels of serum IL-36α in patients with systemic lupus erythematosus.

The present study aimed to investigate the levels of IL-36α and its association with disease activity in patients with systemic lupus erythematosus (SLE). A total of 60 patients with SLE and 29 healthy controls were enrolled in the present study. Disease activity was evaluated using the SLE disease activity index (SLEDAI). The serum levels of IL-36α, IL-36 receptor antagonist (IL-36Ra) and IL-17 were assessed using ELISA. The levels of IL-36α in patients with SLE were significantly higher compared with those of healthy controls. There was a significant increase in IL-36α in the active SLE group (SLEDAI score ≥5) compared with that of the healthy controls (P<0.001). The serum IL-36α levels were higher in patients with active SLE than in patients with quiescent disease (P=0.012). IL-36Ra was downregulated in patients with SLE (P=0.007). The serum IL-17 levels were elevated in patients with SLE (P=0.036), and a positive correlation was observed between the IL-36α and IL-17 levels (r=0.453, P=0.003). The serum IL-36α levels were associated with SLEDAI (r=0.374, P=0.003), proteinuria (r=0.329, P=0.010) and complement 3 (r=-0.336, P=0.009). Patients who were receiving glucocorticoid treatment had lower IL-36α levels than those who were not receiving glucocorticoid treatment (P=0.003). Patients with lupus nephritis had higher serum IL-36α levels compared with those found in patients without lupus nephritis (P=0.037). The serum IL-36α concentration was elevated in patients with SLE, and was correlated with disease activity and IL-17 levels. The aberrant serum IL-36α levels observed in the present study and its clinical association with SLE suggest the important role of IL-36α in onset and progression of SLE. In addition, the association of IL-36α with IL-17 level indicates its involvement in the regulation of T helper 17 cytokines.