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.

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).

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.

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.

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study.

OBJECTIVES: Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. METHODS: We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P < 5 × 10-8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. RESULTS: The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. CONCLUSION: Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

Predictors of coronary artery calcification and its association with cardiovascular events in patients with chronic kidney disease.

OBJECTIVE: To investigate the predictors of coronary artery calcification (CAC) and its association with cardiovascular events (CVE) in patients with stage 3-5 chronic kidney disease (CKD). METHOD: Two hundred ninety CKD patients in our nephrology department were enrolled from 2018 to May 2019. The levels of matrix Gla protein (MGP) and interleukin 6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA) method in 131 CKD patients of all. CAC was evaluated via computed tomography (CT). The covariate factors were analyzed by binary logistic regression analysis. We conducted the visits to explore the prevalence of CVE in 276 CKD patients, and covariate factors were analyzed by Cox proportional hazard model. RESULTS: The prevalence of CAC was up to 57.93%. We found that age, diabetes mellitus, hyperphosphatemia, dialysis duration, and the neutrophil-lymphocyte ratio (NLR) were positively associated with CAC in all patients. In 131 patients, we demonstrated that higher IL-6 and lower MGP levels were associated with CAC. A Cox proportional hazard model demonstrated that moderate to severe CAC was correlated with an increased risk for CVE [Hazard Ratio (HR): 7.250; 95% confidence interval (CI): 3.192-16.470], and a higher MGP level was associated with a reduced risk for CVE (HR: 0.340; 95% CI: 0.124-0.933). CONCLUSIONS: The prevalence of CAC in patients with CKD is a significant issue. Older age, hyperphosphatemia, dialysis duration, diabetes mellitus, IL-6, and the NLR are associated with CAC. In addition, higher MGP levels represent protective factor for CAC. Moderate to severe CAC, and lower MGP levels are associated with an increased risk for CVE. Abbreviations: AGEs: Advanced glycosylation end products; CAC: Coronary artery calcification; CACS: Coronary artery calcification score; Ca: Calcium; CI: confidence interval; CKD: Chronic kidney disease; CVE: Cardiovascular events; CT: Computed tomography; ELISA: Enzyme-linked immunosorbent assay; Hb: hemoglobin; HR: Hazard ratio; hs-CRP: high-sensitivity C-reactive protein; IL-6: Interleukin 6; iPTH: Intact parathyroid hormone; Mg: Magnesium; MGP: Matrix Gla protein; NF-κB: nuclear factor-kappa gene binding; NRL: Neutrophil-lymphocyte ratio; Runx2: Runt-related transcription factor 2; RRT: Renal replacement therapy; P: Phosphorus; Scr: Serum creatinine; TNF--alpha: Tumor necrosis factor--alpha; TC: Total cholesterol; TG: Triglyceride; VSMC: vascular smooth muscle cel.

Elevated circulating asymmetric dimethylarginine levels in rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I2. Publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.

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.

Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population.

To explore the association of LEP and leptin receptor (LEPR) gene single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

Serum sclerostin values are associated with abdominal aortic calcification and predict cardiovascular events in patients with chronic kidney disease stages 3-5D.

AIM: The purpose of this study was to investigate the possible association of circulating concentrations of sclerostin with abdominal aortic calcification (AAC) and cardiovascular outcomes in patients with chronic kidney disease stage 3-5. METHODS: One hundred and sixty-one patients with CKD3-5D were enrolled. The patients were divided into two groups according to the presence of AAC: an AAC group (n = 99) and a non-AAC group (n = 62). The concentration of serum sclerostin was measured using an enzyme-linked immunosorbent assay (ELISA). AAC was evaluated using abdominal lateral X-ray examination. The follow-up intervals ranged from 7 to 29 months (median 16 months), and cardiovascular events (CVEs) were recorded. RESULTS: The prevalence of vascular calcification (VC) was 61.5% (99/161). Serum sclerostin was significantly higher in an AAC group than in a non-AAC group (P < 0.001), but the concentration in the moderate-to-severe AAC group was lower than in the mild AAC group (P < 0.001). Binary logistic regression analysis revealed that high serum sclerostin, high serum calcium, diabetes, and old age were independently correlated with AAC. Patients with higher sclerostin values had a reduced risk of major cardiovascular events (log-rank test, P = 0.001). CONCLUSION: Serum sclerostin values are associated with the presence of AAC, but are lower when AAC is moderate to severe. Higher values are predictive of reduced short-term cardiovascular events. Taken together, these results suggest that sclerostin may have a role in the development of or the response to vascular calcification.

Evidence of epistatic interaction between DPP4 and CCR6 in patients with rheumatoid arthritis.

OBJECTIVE: A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS: Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design. RESULTS: A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. CONCLUSION: The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.

The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity.

Recently, many studies have shown that Single immunoglobulin interleukin-1 receptor related protein (SIGIRR), a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects autoimmune responses in animal model of systemic lupus erythematosus (SLE). However, the role of SIGIRR in the pathogenesis of human SLE has not been widely explored. In this study, we analyzed the frequency of SIGIRR-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of SLE patients and its correlation with disease activity as well as the clinical data. Circulating SIGIRR-positive CD4+ T cells were quantified in 51 SLE patients and 38 healthy controls by using flow cytometer. Results showed that the percentages of SIGIRR-positive CD4+ T cells were decreased in the PBMCs of SLE patients compared with healthy controls (Z = -5.49, P < 0.001). The frequency of SIGIRR-positive CD4 + T cells were also significantly decreased in SLE patients with nephritis than those without nephritis (Z = -3.71, P < 0.001). In addition, there was significant correlation between the percentages of SIGIRR-positive CD4+ T cells and SLEDAI score (r s = -0.74, P < 0.001), 24-hour urine protein (r s = -0.62, P < 0.001), Scr (r s = -0.65, P < 0.001), ESR (r s = -0.60, P < 0.001), C3 (r s = 0.53, P < 0.001) as well as C4 (r s = 0.52, P < 0.001). However, there was no correlation between the proportion of SIGIRR-positive CD4+ T cells and glucocorticoid dose (P = 0.59). In summary, decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR may be involved in the pathogenesis of SLE.

[Prokaryotic Expression and Immunoreactivity Analysis on Profilin of Toxoplasma gondii].

OBJECTIVE: To clone and express the profilin (PRF) gene of Toxoplasma gondii, and analyze the immunoreactivity. METHODS: Total RNA was extracted from tachyzoites of T. gondii RH strain. The coding region of TgPRF was amplified with a pair of specific primers. PCR product was digested with double restriction enzyme and ligated into pET30a(+) vector. The recombinant pET30a(+)-TgPRF plasmid was transformed into E. coli DH5α with positive clones confirmed by the double restriction enzyme digestion, PCR and sequencing. The correct plasmid was transformed into E. coli BL21 and induced by IPTG. The expressed proteins were purified with Ni-NTA affinity chromatography and analyzed by SDS-PAGE. Western blotting with rabbit anti-T. gondii serum was used to analyze its antigenicity. RESULTS: The product of RT-PCR was with 492 bp. pET30a-TgPRF was confirmed by the double restriction enzyme digestion, PCR and sequencing. SDS-PAGE analysis showed that the expressed product was a soluble protein with a relative molecular weight of 35,000. Western blotting assay revealed that rTgPRF was recognized by rabbit anti-T. gondii serum. CONCLUSION: TgPRF gene has been expressed in prokaryotic expression system and shows immunoreactivity.

Study of the radiotherapy sensitizea-tion of retroperitoneal lymph node metastasis in patients by sodium glycididazole.

To observe the radiotherapy sensitization effect of retroperitoneal lymph node metastasis in patients by sodium glycididazole in recent clinical efficacy and toxicity. A total of 42 patients admitted with metastasis and recurrence of retroperitoneal lymph node from September 2006 to December 2009 were classified with the method of case-control. After three dimensional conformal radiation therapy with or without sodium glycididazole (800 mg/m²) for sensitization, the results of recent clinical efficacy, relief of pain, and Karnofsky score were obtained. Tumor remission rate of patients in sensitization group (with sodium glycididazole) at post-radiotherapy 3 months was significant higher than that in control group (without sodium glycididazole) (52% vs. 24%; P<0.05). Oral dose of morphine daily, and Karnofsky score in anterior-posterior radiotherapy of patients in the sensitization group were significant different with those in the control group (93 ± 12 and 42 ± 6 mg vs. 94 ± 12 and 20 ± 5 mg and (65 ± 4) and (90 ± 9) vs. (64 ± 5) and (80 ± 10), respectively; P<0.01). Sodium glycididazole has positive radiotherapy sensitization to the metastasis or recurrence of retroperitoneal lymph node for digestive tract cancer, which could obviously improve the life quality or release the pain for patients.

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.

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.

Therapeutic potential of SIGIRR in systemic lupus erythematosus.

Single immunoglobulin IL-1-related receptor (SIGIRR), which is also known as Toll/interleukin-1 receptor 8, is a member of the interleukin-1 receptor (IL-1R) family. Different from other typical IL-1R superfamily members, SIGIRR seems to exert negatively modulates in immune responses. Several previous studies demonstrated that SIGIRR influences chronic inflammatory or autoimmune diseases, such as intestinal inflammation, rheumatoid arthritis and psoriatic arthritis. Recent work has explored the role of SIGIRR in systemic lupus erythematosus (SLE), for example, the role of SIGIRR protects the mice from hydrocarbon oil-induced lupus has been reported. These results indicate that SIGIRR may represent a novel target for the treatment of SLE. In this review, we will discuss the SIGIRR and the therapeutic potential of modulating the pathway in SLE.

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.

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.