Bta-miR-149-3p suppresses inflammatory response in bovine Sertoli cells exposed to microcystin-leucine arginine (MC-LR) through TLR4/NF-kB signaling pathway.

This study explored the regulatory role of bta-miR-149-3p in the inflammatory response induced by microcystin-leucine arginine (MC-LR) exposure in bovine Sertoli cells. The research endeavored to enhance the comprehension of the epigenetic mechanisms underlying MC-LR-induced cytotoxicity in Sertoli cells and establish a foundation for mitigating these effects in vitro. In this study, we elucidated the regulatory mechanism of bta-miR-149-3p in the MC-LR-induced inflammatory response by verifying the target gene of bta-miR-149-3p through luciferase assays and treating the cells with a bta-miR-149-3p inhibitor for 24 h. The results demonstrate that nuclear factor κB (NF-κB) acts as a downstream target gene of bta-miR-149-3p, which inhibits the MC-LR-induced inflammatory response in bovine Sertoli cells. This inhibition occurs by regulating the downregulation of tight junction constitutive proteins of the blood-testis barrier (BTB) through the suppression of the TLR-4/NF-κB signaling pathway (p < 0.05) and the up-regulation of the adhesion junction protein ß-catenin (p < 0.05). Notably, MC-LR exposure resulted in the up-regulation (p < 0.05) of inflammatory cytokines (IL-6, IL-1ß, and NLRP3) and the down-regulation (p < 0.05) of BTB tight junction constitutive proteins (ZO-1, Occludin) in Sertoli cells. Furthermore, the BTB constitutive protein ZO-1 exhibited significant down-regulation in Sertoli cells pretreated with the bta-miR-149-3p inhibitor compared to controls (p < 0.05), while Occludin showed no significant difference from CTNNB1 (p > 0.05). In summary, our findings suggest that bta-miR-149-3p suppresses the MC-LR-induced inflammatory response and alterations in the expression of BTB proteins in bovine Sertoli cells by inhibiting the TLR-4/NF-κB signaling pathway.

Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles.

Direct oxidative coupling of inert C(sp3 )-H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α-methyl substituted N-heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry.

The effect of nursing intervention on self-care self-efficacy and genes related to anxiety in patients with bone marrow transplantation.

Leukemia patients, after bone marrow transplantation, face many problems that hurt their self-efficacy in self-care. The present study aimed to determine the effect of health promotion strategies on the self-efficacy of patients undergoing bone marrow transplantation in self-care. The expression level of two genes affecting anxiety (i.e., 5-hydroxytryptamine receptor 1A (5-HT1A) and Corticotropin Releasing Hormone Receptor 1 (CRHR1)) was also investigated. For this purpose, this semi-experimental study was conducted before and after in bone marrow transplant candidate patients. Sixty patients were randomly divided into test and control groups. The test group received training on health promotion strategies, and the control group was treated according to the department's routine. Then the self-efficacy of the two groups was compared before and thirty days after the intervention. Also, the expression level of two genes was done by real-time PCR. Data analysis was done using descriptive statistics and paired t-tests, independent t-tests, analysis of covariance, and chi-square in SPSS 11.5 software. The results showed that there was no significant difference between the demographic variables of the two groups. The self-efficacy of the test group in the general scale and dimensions of adaptability, decision-making, and stress reduction increased compared to the control group and themselves before the training (p>0.001). The difference in self-efficacy scores in all dimensions before the intervention was statistically significant (p<0.05). The genetic evaluations also confirmed the obtained results. According to the expression of 5-HT1A and CRHR1 genes, the level of these genes which directly relate to anxiety were significantly decreased after intervention in the test group. In general, teaching health promotion strategies to bone marrow transplant patients can increase the confidence of these patients in taking care of themselves in the treatment process, which will ultimately lead to more survival and a higher quality of life in these patients.

The C(sp3)-H bond functionalization of thioethers with styrenes with insight into the mechanism.

A metal-free inactive C(sp3)-H bond functionalization of thioethers with styrenes using TBHP as an initiator and DBU as a base has been developed. This transformation has broken through the low activity of thioethers and realized moderate yields. Herein extended experiments were conducted to confirm the radical relay process, reaction energy and intermediate transformations.

TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer.

BACKGROUND: Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. RESULTS: Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. CONCLUSION: TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.

Epidemiology and lifestyle survey of non-alcoholic fatty liver disease in school-age children and adolescents in Shenyang, Liaoning.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is diagnosed increasingly in children and adolescents. We aimed to investigate the prevalence and related influencing factors of NAFLD in school-aged children and adolescents in Shenyang, Liaoning Province. Furthermore, we analyzed the relationship between lifestyle and fatty liver. METHODS: We conducted aprospective cohort study of 1309 school-aged children and adolescents between the ages of 7 and 18 years who underwent physical examination from November to December 2019. In addition, they were collected age, gender, learning stage, height, weight, BMI, waist circumference, hip circumference, and waist-hip ratio. Finally, a portion of the population was selected to complete a questionnaire survey to explore the impact of lifestyle habits on fatty liver disease. RESULTS: NAFLD was present in 23.83% of subjects. The prevalence of children and adolescents was 22.73% and 24.43%, respectively. Fatty liver prevalence differs significantly by gender and learning stages. The highest rate of fatty liver was seen in obese children (71.68%). Moreover, exercise, diet, and parental factors can affect children with fatty liver. CONCLUSIONS: NAFLD is very prevalent in children and adolescents in Shenyang city. Due to the close relationship between NAFLD and obesity, lifestyle plays a major role in the occurrence of NAFLD. TRIAL REGISTRATION: The First Affiliated Hospital of China Medical University, [2020] 2020-258-2. Registered 6 June 2020-Retrospectively registered.

[Protective effect of ginsenoside Rg_1 aganist diabetic retinopathy by inhibiting NLRP3 inflammasome in type 2 diabetic mice].

Ginsenoside Rg_1, one of the main active components of precious traditional Chinese medicine Ginseng Radix et Rhizoma, has the anti-oxidative stress, anti-inflammation, anti-aging, neuroprotection, and other pharmacological effects. Diabetic retinopathy(DR), the most common complication of diabetes, is also the main cause of impaired vision and blindness in the middle-aged and the elderly. The latest research shows that ginsenoside Rg_1 can protect patients against DR, but the protection and the mechanism are rarely studied. This study mainly explored the protective effect of ginsenoside Rg_1 against DR in type 2 diabetic mice and the mechanism. High fat diet(HFD) and streptozotocin(STZ) were used to induce type 2 diabetes in mice, and hematoxylin-eosin(HE) staining was employed to observe pathological changes in the retina of mice. The immunohistochemistry was applied to study the localization and expression of nucleotide-binding oligomerization domain-like receptors 3(NLRP3) and vascular endothelial growth factor(VEGF) in retina, and Western blot was used to detect the expression of nuclear factor-kappa B(NF-κB), p-NF-κB, NLRP3, caspase-1, interleukin-1ß(IL-1ß), transient receptor potential channel protein 6(TRPC6), nuclear factor of activated T-cell 2(NFAT2), and VEGF in retina. The results showed that ginsenoside Rg_1 significantly alleviated the pathological injury of retina in type 2 diabetic mice. Immunohistochemistry results demonstrated that ginsenoside Rg_1 significantly decreased the expression of NLRP3 and VEGF in retinal ganglion cells, middle plexiform layer, and outer plexiform layer in type 2 diabetic mice. According to the Western blot results, ginsenoside Rg_1 significantly lowered the expression of p-NF-κB, NLRP3, caspase-1, IL-1ß, TRPC6, NFAT2, and VEGF in retina of type 2 diabetic mice. These findings suggest that ginsenoside Rg_1 can significantly alleviate DR in type 2 diabetic mice, which may be related to inhibition of NLRP3 inflammasome and VEGF. This study provides experimental evidence for the clinical application of ginsenoside Rg_1 in the treatment of DR.

Light-Promoted and Tertiary-Amine-Assisted Hydroxysulfenylation of Alkenes: Selective and Direct One-Pot Synthesis of ß-Hydroxysulfides.

A light-promoted and tertiary-amine-assisted strategy for efficient hydroxysulfenylation of both electron-rich and electron-deficient alkenes with thiophenols to selectively and directly access ß-hydroxysulfides in one pot is described herein. In contrast to the previously reported thiol-oxygen co-oxidation reactions, this simple and sustainable approach features mild reaction conditions, high efficiency, and excellent functional group tolerance.

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection.

BACKGROUND: Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. METHODS: This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. RESULTS: Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. CONCLUSIONS: The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

Peptide-Assisted 2-D Assembly toward Free-Floating Ultrathin Platinum Nanoplates as Effective Electrocatalysts.

We demonstrate the 2-D anisotropic formation of ultrathin free-floating Pt nanoplates from the assembly of small nanocrystals using T7 peptide (Ac-TLTTLTN-CONH2). As-formed nanoplates are rich in grain boundaries that can promote their catalytic activities. Furthermore, we demonstrate that a minor number of Pd atoms can selectively deposit on and stabilize the grain boundaries, which leads to enhanced structure stability. The Pd-enhanced Pt polycrystal nanoplates show great oxygen reduction reaction activities with 15.5 times higher specific activity and 13.7 times higher mass activity than current state-of-the-art commercial Pt/C electrocatalysts as well as 2.5 times higher mass activity for hydrogen evolution reaction compared with Pt/C.

[Research progress on anti-alcoholic gastric injury active components and mechanisms of Chinese herbal medicine].

Alcohol is considered to be one of the main causes for gastric injury, and alcoholic gastric injury has been becoming one of the global health problems, which seriously affects the quality of human life. Many studies suggest that the active components extracted from Chinese herbal medicine can effectively reduce the degree of alcohol-induced gastric injury. The active components and its mechanism of anti-alcoholic gastric injury of Chinese herbal medicine reported in recent five years were preliminarily summarized according to the classification of terpenoids, flavonoids, polyphenols, polysaccharides, volatile oils, phenylpropanoids and alkaloids in this paper. The terpenoids could improve oxidative stress and inflammatory response by regulating relevant signaling pathways. The flavonoids are mainly related to antioxidant and anti-inflammatory properties. The polyphenols mainly regulate the level of relevant factors involved in inflammatory pathway, oxidative stress and apoptosis pathway. The polysaccharides could enhance the ability of gastric mucosal defense factor by inhibiting oxidative stress injury and inflammatory response. Phenylpropanoids could enhance the gastric mucosal defense factor. The volatile oils mainly inhibit H~+/K~+-ATPase activity or inflammatory reaction. Alkaloids are closely related to the inhibition of inflammatory response and the improvement of antioxidant system. This paper aims to provide reference for further research and development of Chinese herbal medicine against alcoholic gastric injury.

Surface-Engineered PtNi-O Nanostructure with Record-High Performance for Electrocatalytic Hydrogen Evolution Reaction.

Hydrogen holds the potential of replacing nonrenewable fossil fuel. Improving the efficiency of hydrogen evolution reaction (HER) is critical for environmental friendly hydrogen generation through electrochemical or photoelectrochemical water splitting. Here we report the surface-engineered PtNi-O nanoparticles with enriched NiO/PtNi interface on surface. Notably, PtNi-O/C showed a mass activity of 7.23 mA/µg at an overpotential of 70 mV, which is 7.9 times higher compared to that of the commercial Pt/C, representing the highest reported mass activity for HER in alkaline conditions. The HER overpotential can be lowered to 39.8 mV at 10 mA/cm2 when platinum loading was only 5.1 µgpt/cm2, showing exceptional HER efficiency. Meanwhile, the prepared PtNi-O/C nanostructures demonstrated significantly improved stability as well as high current performance which are well over those of the commercial Pt/C and demonstrated capability of scaled hydrogen generation.

Analysis of predictive factors for immunosuppressive response in anti-phospholipase A2 receptor antibody positive membranous nephropathy.

BACKGROUND: Serum anti-phospholipase A2 receptor (PLA2R) antibody was correlated with disease activity of membranous nephropathy(MN). The predictive value of antibody titer changes on immunosuppressive response remains unknown. We investigated predictive value of dynamic change of anti-PLA2R antibody and 24-h urine protein (24hUP) for clinical response of MN. METHODS: This was a retrospective cohort study including 47 Chinese MN patients with positive anti-PLA2R antibody in a tertiary referral hospital between January 2012 and March 2014. Patients received cyclophosphamide (CTX, n = 23), or cyclosporine (CYA, n = 24) regimen, respectively. We monitored serum anti-PLA2R titer and 24hUP at one, three and six-month follow-up. RESULTS: At baseline, total patients were 42 ± 14 years old with 29/18 male/female ratio. The median 24hUP was 5.80(3.56,9.41) g/d. The median baseline anti-PLA2R antibody titer was 66.4(31.9, 188.0) RU/mL. Baseline 24hUP and eGFR between subgroups were not significantly different. The differences of relative reduction between antibody titer and 24hUP at one month were statistically significant (CTX group 94.2% vs. 46.8%, P < 0.001; CYA group 54.6% vs. 4.6%, P = 0.04). Only in CTX group, the relative reduction of 24hUP at one month was correlated with composite remission at six-month(P = 0.03). Area under the curve of 24hUP relative reduction in CTX group at one-month for predicting composite remission at six months was 0.85(95%CI 0.65~1.05, P = 0.04). The cutoff value of one-month's 24hUP relative reduction for predicting six-month's composite remission in CTX group was 15.3%, with high sensitivity (83.3%) and specificity (100%). CONCLUSIONS: Compared with relative reduction of antibody titer, relative reduction of 24hUP at one-month follow-up in CTX group had a better predictive value for six-month's composite remission.

Sodium Selenite inhibits mitophagy, downregulation and mislocalization of blood-testis barrier proteins of bovine Sertoli cell exposed to microcystin-leucine arginine (MC-LR) via TLR4/NF-kB and mitochondrial signaling pathways blockage.

This study was conducted to investigate the ameliorative effect of selenium on microcystin-LR induced toxicity in bovine Sertoli cells. Bovine Sertoli cells were pretreated with selenium (Na2SeO3) for 24 h after which selenium pretreated and non-pretreated Sertoli cells were cultured in medium containing 10% heat activated fetal bovine serum FBS+ 80 µg/L MC-LR to assess its ameliorative effect on MC-LR toxicity. The results show that selenium pretreatment inhibited the MC-LR induced mitophagy, downregulation and mislocalization of blood-testis barrier constituent proteins in bovine Sertoli cells via NF-kB and cytochrome c release blockage. The observed downregulation of electron transport chain (ETC) related genes (mt-ND2, COX-1, COX-2) and upregulation of inflammatory cytokines (IL-6, TNF-α, IL-1ß, IFN-γ, IL-4, IL-10, 1 L-13, TGFß1) in non-pretreated cells exposed to MC-LR were ameliorated in selenium pretreated cells. There was no significant difference (P > 0.05) in the protein levels of blood-testis barrier constituent proteins (ZO-1, occludin, connexin-43, CTNNB1, N-cadherin) and mitochondria related genes (mt-ND2, COX-1, COX-2, ACAT1, mtTFA) of selenium pretreated Sertoli cell compared to the control. Taken together, we conclude that selenium inhibits MC-LR caused Mitophagy, downregulation and mislocalization of blood-testis barrier proteins of bovine Sertoli cell via mitochondrial and TLR4/NF-kB signaling pathways blockage.

Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis.

Objective To investigate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) with nephrotic syndrome with a systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library and Clinical Trials (December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission (CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated. Result Seven studies involved 120 patients (73% were men) were included in our systematic review and meta-analysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric (four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44 (36.7%) had immunosuppressive treatment]. In 12- and 24-month, 56% (95%CI, 0.47-0.65) and 68% (95%CI, 0.41-0.87) patients could reach remission, while 15% (95%CI, 0.09-0.23) and 20% (95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions. Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Fibronectin Glomerulopathy Caused by the Y973C Mutation in Fibronectin: A Case Report and Literature Review.

Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin. We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome. Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation. However, this mutation was not found in her parents. She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.

A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy.

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ 2=18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

[Pathogenic Mechanisms of the Focal Segmental Glomerulosclerosis and Its Role in the Progression of IgA Nephropathy].

Focal segmental glomerulosclerosis (FSGS),a common pathological change in kidney diseases,may be caused by primary factors or multiple secondary factors. Its pathogenic mechanism remains a hot topic in kidney disease research. FSGS-like pathologic changes are highly in IgA nephropathy. It has been speculated that FSGS in IgA nephropathy might be caused by hemodynamics changes,and podocyte injury,which,however,have not been well documented. Our current review focuses on the pathogenesis of secondary FSGS and its role in the progression of IgA nephropathy,with an attempt to provide more insights in the treatment of IgA nephropathy.

Efficacy and Safety of Tacrolimus versus Cyclosporine A for Idiopathic Membranous Nephropathy:A Network Meta-analysis.

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy△.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm2) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m2 vs. -8.1±21.4 ml/min per 1.73 m2, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.