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.

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.

Prevalence of coronary artery calcification and its association with mortality, cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis.

PURPOSE: To date, the prevalence and prognostic role of coronary artery calcification (CAC) in patients with chronic kidney disease (CKD) have been investigated in several studies, but have yielded conflicting results. The aim of this meta-analysis is to derive a more precise estimation of CAC prevalence in CKD patients and its association with cardiovascular events and mortality. METHODS: The relevant literature was identified and evaluated from inception until July 2018 through multiple search strategies on PubMed, Embase, and Web of Science. Cross-sectional or cohort (baseline data) studies reporting CAC prevalence were included. Data extracted from eligible studies were used to calculate effect estimates (ESs) and 95% confidence intervals (95%CI). We searched databases for observational studies that explored baseline CAC and subsequent cardiovascular or all-cause mortality risk in CKD patients. RESULTS: The meta-analysis included 47 studies; 38 of these were included in the final analysis of CAC prevalence. The pooled prevalence of CAC in random effect model was 60% (95%CI 53-68%). CAC was positively associated with an increased risk of all-cause mortality (hazard ratio [HR] 3.44; 95%CI 2.40-4.94), cardiovascular mortality (HR 3.87; 95%CI 2.06-7.26), and cardiovascular events (HR 2.09; 95%CI 1.19-3.67), when comparing individuals in the top CAC score group to those in the bottom CAC score group. CONCLUSIONS: The pooled prevalence of CAC is highly prevalent. CAC is independently associated with all-cause and cardiovascular mortality risk as well as cardiovascular events among CKD patients. In view of the high heterogeneity, larger clinical trials are still needed.

Glycyrrhizin inhibits LPS-induced inflammatory mediator production in endometrial epithelial cells.

Endometriosis is a continuous inflammation of uterine endometrium that usually affects women of reproductive age. Glycyrrhizin, a triterpene isolated from the roots and rhizomes of licorice (Glycyrrhiza glabra), has been known to have anti-inflammatory effect. The purpose of this study was to investigate the anti-inflammatory effect of glycyrrhizin on LPS-stimulated mouse endometrial epithelial cells (MEEC). The levels of TNF-α, IL-1ß, and PGE2 were measured by ELISA. The expression of COX-2, iNOS, TLR4, and NF-ĸB were detected by western blot analysis. The results showed that glycyrrhizin significantly suppressed LPS-induced TNF-α, IL-1ß, NO, and PGE2 production. Also, LPS-induced iNOS and COX-2 expression were attenuated by glycyrrhizin. Furthermore, glycyrrhizin significantly attenuated TLR4 expression and NF-κB activation induced by LPS in MEEC. In conclusion, the present study demonstrated that glycyrrhizin inhibited LPS-induced inflammatory response by inhibiting TLR4 signaling pathway in MEEC. Glycyrrhizin may be used as a potential agent for the treatment of endometriosis.

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.

Exploring the variations in molecular characteristics of dissolved organic matter driven by aquaculture types.

In recent decades, global aquaculture has expanded rapidly, raising concerns about coastal environmental degradation due to unregulated or poorly regulated discharge of aquaculture tailwater. Despite the crucial role of dissolved organic matter (DOM) in biogeochemical processes and aquatic biodiversity, the influence of aquaculture type on the molecular characteristics of DOM remains largely unexplored. Herein, this study investigated the variations in chemical and spectroscopic properties as well as molecular characteristics and composition of DOM across different aquaculture types including crustacean, fish and shellfish. Our findings revealed notable differences in DOM quantities among different aquaculture types, with crustacean and fish aquaculture water containing higher DOM amount compared to shellfish aquaculture water. This disparity can be attributed to the more frequent formulated feeds of crustacean and fish in contrast to shellfish aquaculture. Furthermore, distinct differences were also observed in the characteristics and composition of DOM among the different aquaculture waters. Specifically, DOM in shellfish aquaculture water exhibited a higher abundance of unsaturated and reduced molecules as well as increased aromaticity compared to the other two aquaculture waters. Conversely, DOM from fish aquaculture water showed a greater contribution from terrestrial origin characterized by elevated levels of plant-based components such as lignin-like and tannin-like compounds. Interestingly, DOM from shellfish aquaculture water contained lower levels of microbial-derived components such as lipid-like and protein-like compounds, likely due to reduced microorganism populations resulting from lower nutrients availability and higher salinity. Overall, these significant variations in characteristics and composition of DOM underscore the potential impacts of aquaculture type on the DOM biogeochemical cycle and the environmental quality in aquatic ecosystems.

NOTCH1 mutation associates with impaired immune response and decreased relapse-free survival in patients with resected T1-2N0 laryngeal cancer.

Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.

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.

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.

Circadian clock genes as promising therapeutic targets for autoimmune diseases.

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.

Increased Serum Levels of Soluble B7-H4 in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Members of B7 family are reported to regulate lymphocytes activation, transmit both costimulatory and co-inhibitory signals, control T cell-mediated immune responses and tolerance. Among which B7-H4 is reported to regulate the immune response negatively. OBJECTIVE: To investigate the plasma concentration of soluble B7-H4 (sB7-H4) and its clinical significance in systemic lupus erythematosus (SLE). METHODS: Fifty-six SLE patients with or without active SLE (ASLE) and 29 age- and gender-matched healthy volunteers were recruited. Plasma concentration of sB7-H4 was measured using sandwich ELISA kits. RESULTS: Compared with healthy subjects, the concentration of sB7-H4 was significantly higher in patients with SLE (p=0.006). Plasma sB7-H4 concentration in patients with lupus nephritis (LN) were also significantly higher than healthy subjects (p=0.008), but no difference was found between LN and SLE patients without LN (non-LN). Additionally, the sB7-H4 concentration in patients was negatively correlated with the SLE disease activity index score (SLEDAI) (r=-0.3055, p=0.022). Compared with inactive disease, the concentration of sB7-H4 in ASLE patients was significantly lower (p=0.002). There were statistical significances between the positive and negative groups with decreased leukocytes or thrombocytes (p=0.012; p=0.033; respectively), but no statistically significant difference was found in other positive and negative serum laboratory indicators. CONCLUSIONS: The increased level of sB7-H4 in patients suggests that this pathway might be involved in the pathogenesis of SLE. However, the exact mechanism or physiological role of sB7-H4 in SLE pathogenesis remains to be investigated.

[Experimental study in renal protective effect of tranilast on rats with adriamycin nephropathy].

OBJECTIVE: To investigate the effect and mechanism of tranilast on the adriamycin-induced nephrotic syndrome of rats. METHODS: Twenty four rats were randomly divided into 4 groups: normal control group, model group, irbesartan treatment group and tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein. The rats in the other groups were uninephrectomized and injected with adriamycin 5 mg/kg via the tail vein one week later. Rats in model group underwent gavage to receive the sodium carboxymethylcellulose, rats in irbesartan treatment group to receive the irbesartan with 10 mg/kg x d, and rats in tranilast treatment group to receive the tranilast with 400 mg/kg. Rats were then sacrificed at the end of week 8. The body weight, 24 hours urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) of each group rats were measured for the study. Renal pathological changes were evaluated. And immunohistochemistry was used to examine the expression of transforming growth factor beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). In situ hybridization was used to measure the expression of a-smooth muscle actin (alpha-SMA) mRNA in the kidney. RESULTS: Compared with the untreated nephrotic syndrome rats, the proteinuria and Scr of rats treated with tranilast were significantly reduced (P < 0.05); Compared with model group, the renal pathological changes of rats in tranilast treatment group were decreased, with glomerular sclerosis to be markedly lower; Tranilast could decrease the expression of TGF-beta1, TIMP-1 and alpha-SMA mRNA in the kidney of rats with adriamycin nephropathy. CONCLUSIONS: Tranilast has a renoprotective effect on adriamycin-induced nephrotic syndrome in rats, of which the mechanism may be related to that tranilast can depress the expression of TGF-beta1, and TIMP-1 in the kidney, with result in decreasing the synthesis and secretion of extracellular matrix. And tranilast inhibits the transdifferentation of renal primary cells, regulates the synthesis and degradation system of extracellular matrix.

Decreased Serum/Plasma Vitamin D levels in SLE Patients: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: The evidence regarding the association between serum/plasma vitamin D (VitD) concentrations and systemic lupus erythematosus (SLE) is inconsistent. The study was based on relevant results from literatures that were identified and evaluated. The aim of this meta-analysis is to determine circulating VitD in SLE patients and explore influencing factors. METHODS: Studies examining VitD levels in SLE patients were identified through targeted searches in the PubMed and EMBASE databases (up to December 2017). Data extracted from eligible studies was synthesized to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI). A fixed or a random effects model was applied to calculate the pooled SMDs and ORs depending on heterogeneity across studies. RESULTS: A total of 24 studies, including 6017 patients and 18,417 controls were included. The pooled analysis suggested that VitD levels were significantly lower in SLE patients compared with those in controls [SMD= -0.09, 95%CI= -0.12 to -0.06, P < 0.001]. When the studies were stratified by ethnicity, VitD concentrations were also significantly lower in Asian, Caucasian and African patients. When the studies were stratified by age, gender, VitD level was lower in patients than that in controls. Subgroup analyses stratified by measurement type (expect for radioimmunoassay) also demonstrated consistent results. Moreover, VitD insufficiency was more prevalent in SLE patients than healthy controls [OR=6.57, 95%CI=4.64-9.29]. CONCLUSION: Compared with healthy controls, SLE patients had lower concentration of VitD. Additionally, the prevalence of VitD insufficiency is more common in SLE patients.

Increased ratio of Th17 cells to SIGIRR+CD4+ T cells in peripheral blood of patients with SLE is associated with disease activity.

To investigate the clinical significance of the ratio of T helper cell 17 (Th17) cells to single immunoglobulin IL-1-related receptor (SIGIRR)+ cluster of differentiation (CD4)+ T cells in patients with systemic lupus erythematosus (SLE), novel data and data from previous studies were analyzed. The frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) and their correlation with clinical data were evaluated in 48 patients with SLE and 38 healthy controls through flow cytometry. Compared with healthy controls, the percentage of Th17 cells was significantly increased in the PBMCs of patients with SLE (Z=-5.82, P<0.001). Compared with inactive SLE (ISLE), the percentage of Th17 cells in active SLE (ASLE) were significantly increased (Z=-4.26, P<0.0001). Compared with patients without lupus nephritis, the frequency of Th17 cells was significant increased (Z=-2.20, P=0.028). The frequency of Th17 cells was inversely correlated with the frequency of SIGIRR+CD4+ T cells (r=-0.61, P<0.001). The ratio of Th17 cells to SIGIRR+CD4+ T cells in ASLE was significantly increased compared with healthy controls or patients with ISLE (P<0.001) and was inversely correlated with complement component 3 and complement component 4, and positively correlated with SLE disease activity index and 24-h proteinuria (P<0.05). In summary, increased numbers of Th17 cells and decreased numbers of SIGIRR+CD4+ T cells in patients with SLE suggested that SIGIRR+CD4+ T and Th17 cells may be involved in the pathogenesis of SLE.

Deficiency in ClC-3 chloride channels prevents rat aortic smooth muscle cell proliferation.

Recent growing evidence suggests that chloride (Cl-) channels are critical to the cell cycle. In cultured rat aortic vascular smooth muscle cells (VSMCs), we have previously found that Cl- channel blockers inhibit endothelin-1 (ET-1)-induced cell proliferation. The present study was designed to further identify the specific Cl- channels responsible for VSMC proliferation. Due to the lack of a specific blocker or opener of any known Cl- channels, we used the antisense strategy to investigate the potential role of ClC-3, a member of the voltage-gated Cl- channel gene family, in cell proliferation of cultured rat aortic VSMCs. With [3H]-thymidine incorporation and immunoblots, we found that ET-1-induced cell proliferation was parallel to a significant increase in the endogenous expression of ClC-3 protein. Transient transfection of rat aortic VSMCs with antisense oligonucleotide specific to ClC-3 caused an inhibition in ET-1-induced expression of ClC-3 protein and cell proliferation of VSMCs in the same concentration- and time-dependent pattern, whereas sense and missense oligonucleotides resulted in no effects on ClC-3 protein expression and cell proliferation. These results strongly suggest that ClC-3 may be the Cl- channel involved in VSMC proliferation and thus provide compelling molecular evidence linking a specific Cl- channel to cell proliferation. The full text of this article is available at http://www.circresaha.org.

[Study of matrine's use on the reversion of obtained multi-drug resistance of mice S80 tumour cell].

OBJECTIVE: To Observe the effect caused by matrine's used on the reversion of obtained multi-drug resistance of mice S180's tumour cell induced by chemotherapy of Cisplatin + 5-FU + Cytoxan (PFC) and discuss its molecular mechanism. METHODS: Patterned the methods of PFC chemotherapy in clinic, the mice were given Cisplatim 3 mg/kg x ip once a week and Cytoxan, CTX and 5-FU 3 mg/kg x ip once everyday for 4 weeks to set up the mice models of multi-drug resistance of S180 tumor cell. At the same time, gave the mice models matrine 4 weeks, and observed the P170, LRP, TOPO II by flow cytometry. RESULTS: matrine could obviously reduce the express of P170, LRP and the activiation of TOPO II, correlated with mulit-drug resistance tumour cells which were induced by chemotherapy. CONCLUSION: Matrine, with its adjustment of correlated biotic active matter, can intervene the ocurrence of the multidrug resistance of tumor cells induced by chemotherapy.

Association between rs6887695 and 3'-untranslated region polymorphisms within the interleukin-12B gene and susceptibility to autoimmune diseases in Asian and European population: A meta-analysis.

BACKGROUND: The associations between rs6887695 and 3'-untranslated region (3'-UTR) single-nucleotide polymorphisms (SNPs) within interleukin-12B (IL-12B) and autoimmune diseases (ADs) remain controversial and inconclusive. The aim of this study was to evaluate the association between IL-12B (3'-UTR A/C and rs6887695 C/G SNPs) and ADs by meta-analysis. METHODS: PubMed and EMBASE were exhaustively searched for studies on the association between IL-12B SNPs and ADs. Publication bias was examined by a funnel plot and Egger's test. The robustness of the pooled results was assessed by sensitivity analysis. A fixed- or a random-effects model was applied to calculate the pooled odds ratios (ORs). RESULTS: A total of 34 studies were included in this meta-analysis. The pooled results demonstrated that IL-12B rs6887695 SNPs were significantly associated with the risk of ADs. However, there was no significant association between IL-12B 3'-UTR SNPs and ADs. When the studies were stratified by ethnicity, significant association between IL-12B 3'-UTR SNPs and ADs was observed in both Asian and European population. In addition, allele A within 3'-UTR of IL-12B gene was found to be a protective factor for T1DM, but a risk factor for psoriasis. CONCLUSION: The IL-12B 3'-UTR and rs6887695 SNPs are associated with susceptibility to ADs.

[The interference in correlated molecular mechanism obtained multi-drug resistance of mouse S180's tumour cell for different alkaloid].

OBJECTIVE: To observe the base of the interference in correlated biotic active matter obtained multi-drug resistance induced by chemotherapy for different alkaloid, and to supervise the use in clinic to restrain the multi-drug resistant of chemotherapy, and thereby to improve the curative effect. METHOD: After bestowing subter-dosage unite chemotherapeutant to ascites S180 mouse to set up the mouse models of multi-drug resistance of S180 tumour cell, and giving the mouse matrine, terandrine, oxymatrine and berberine hydrooh loride for 4 weeks, the P170, LRP, TOPOII, Fas and apoposis were determined by flow cytometry. RESULT: Matrine and terandrine could obviously reduce the express of P170, LRP and the activation of TOPOII, and increase the ratio of the express of Fas and the apoposis of drug resistant tumour cell. And at the same time it could obviously reduce the express of intercellular adhesion molecule(CD54). CONCLUSION: Matrine and terandrine can interfere in MDR which results from chemotherapeutics by the adjustment of correlated biotic active matter, besides, the different degree of alkaloid effect with different configuration.