Effects of HDAC4 on IL-1β-induced matrix metalloproteinase expression regulated partially through the WNT3A/β-catenin pathway / 中华医学杂志(英文版)

BACKGROUND@#Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway.@*METHODS@#Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting.@*RESULTS@#IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells.@*CONCLUSION@#HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.

Chronic inflammation deteriorates structure and function of collagen fibril in rat temporomandibular joint disc / 国际口腔科学杂志·英文版

Collagen is the building component of temporomandibular joint (TMJ) discs and is often affected by inflammation in temporomandibular disorders. The macromechanical properties of collagen are deteriorated by chronic inflammation. However, the mechanism by which inflammation influences disc function remains unknown. The relationship between the ultrastructure and nanomechanical properties of collagen in inflamed discs should be clarified. Seven-week-old female Sprague-Dawley rats were randomly divided into two groups. Chronic TMJ inflammation was induced by intra-articular injection of complete Freund's adjuvant, and samples were harvested after 5 weeks. Picrosirius staining revealed multiple colours under polarized light, which represented alternative collagen bundles in inflamed discs. Using atomic force microscopy scanning, the magnitude of Young's modulus was reduced significantly accompanied with disordered collagen fibril arrangement with porous architecture of inflamed discs. Transmission electron microscopy scanning revealed a non-uniform distribution of collagen fibres, and oversized collagen fibrils were observed in inflamed discs. Fourier transform infrared microspectroscopy revealed a decrease in 1 338 cm/amide II area ratio of collagen in different regions. The peak positions of amide I and amide II bands were altered in inflamed discs, indicating collagen unfolding. Our results suggest that sustained inflammation deteriorates collagen structures, resulting in the deterioration of the ultrastructure and nanomechanical properties of rat TMJ discs.

Therapeutic effect and mechanism of three kinds of Dendrobium on constipation in rats with spleen Yin deficiency / 中国中药杂志

Books on Chinese herbal medicines have shown that Dendrobium has the effect of nourishing Yin and reinforcing Yin,usually used for constipation induced by spleen Yin deficiency in clinical application. D. huoshanense,as an independent species among many species of Dendrobium,has no experimental studies about its effects on spleen Yin deficiency-type constipation. The purpose of this experiment was to illustrate the therapeutic effect of D. huoshanense on the constipation of spleen Yin deficiency type in rats,investigate its preliminary mechanism,and compare it with the D. officinale and D. nobile contained in the Chinese Pharmacopoeia to clarify its characteristics. The spleen Yin deficiency model was replicated in 70 rats by the composite factor method,and then the model rats were randomly divided into 7 groups: model group,Liuwei Dihuang Pills group( LWDHP),D. huoshanense high( DHS-H),medium( DHS-M),low( DHS-L) dose groups,D. nobile group( DNS),and D. officinale group( DOS),and another 10 rats were used as normal group( Normal). After 7 continuous days of administration,the fecal water content and intestine propulsion rate of each group were detected. HE staining was used to observe the pathological damage of ileum and colon in each group. Immunohistochemistry and Western blot were used to detect aquaporin 3( AQP3) expressions,while the expression levels of the somatostatin( SS) and motilin( MTL) in the ileum of each group were detected by enzyme-linked immunosorbent assay. The results showed that as compared with the model group,the rats in each drug-administered group had increased number of fecal pellets,increased fecal water content,and the increased intestinal propulsion rate( P<0. 01),while the pathological damage of the ileum and colon was significantly reduced; the expression of AQP3 protein was significantly decreased( P<0. 01); the level of MTL was significantly increased and the level of SS was decreased( P<0. 01). All DHS groups showed a good dose-effect relationship,and the same dose treatment effect was equivalent to that of DOS,but it was superior to DNS. Therefore,DHS has a significant therapeutic effect on constipation of spleen Yin deficiency type,and its mechanism may be related to intestinal motility and water-liquid metabolism,with a good therapeutic effect.

Anti-inflammatory Effect of Dendrobii Huoshanense Herba / 中国实验方剂学杂志

Objective:To observe the anti-inflammatory effect of Dendrobii Huoshanense Herba. Method:Totally 60 Kunming mice were randomly divided into normal group, model group, high, middle and low-dose Dendrobii Huoshanense Herba groups (DHS-H, DHS-M, DHS-L, 4, 2, 1 g·kg-1) and dexamethasone acetate group (DXMS, 0.01 g·kg-1). The rats were intragastrically administered for 14 days. After the last administration for 1 h, a total of 20 μL of xylene was added to both sides of the right ear center of the mice to establish the ear swelling model. All of the mice were decapitated 1 h later, and the ear swelling inhibition rate of each group were calculated. Totally 36 healthy SD rats were divided into normal model, model group, DHS-H,DHS-M,DHS-L groups (2.8, 1.4, 0.7 g·kg-1) and DXMS acetate group. The rats were intragastrically administered for 7 days. One hour after the last intragastric administration, a foot swelling model was established through subcutaneous injection of 10%fresh egg white in the right hind limb toe of each group. The right hind paw circumference of each rat was measured at 0, 0.5, 1, 2, 3, 4, 5 h, and the paw swelling of the rats was calculated. Totally 60 SD rats were implanted subcutaneously with sterile dry cotton balls in the bilateral groin and grouped as above. All of the rats were intragastrically administered for 14 days since the next day. After the last administration, cotton balls were taken out, and the inhibition rate of granuloma was calculated. And the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ) in the serum of each group were detected. Result:Compared with the normal group, the ear swelling rate, the foot swelling degree were significantly increased in the model group(PPPPPα, IL-1β, IL-2, IL-6, and IFN-γ in the model group were higher than those in the normal group (Pα, IL-1β, IL-2, IL-6, and IFN-γ in Dendrobii Huoshanense Herba group and positive drug group were decreased significantly (PPConclusion:Dendrobii Huoshanense Herba could effectively inhibit acute and chronic inflammatory reactions.

Comparison of in-vitro anti-fibrotic effects of pirfenidone and nintedanib / 中国药理学通报

Aim To compare the mechanism of action of currently marketed pulmonary fibrosis drugs at the cellular level by evaluating the inhibitory effects of pirfenidone and nintedanib on the proliferation, migration and activation of human embryonic lung fibroblast HFL1. Methods The inhibitory effects of pirfenidone and nintedanib on TGF-β1/PDGF-induced HFL1 proliferation, migration and activation were evaluation of by MTT, scratch test,Q-PCR and Western blot. Results MTT, scratch test results showed that both pirfenidone and nintedanib could inhibit TGF-β1-induced fibroblast proliferation and migration, in which nintedanib had a higher titer than pirfenidone. In anti-activation experiments, both pirfenidone and nintedanib inhibited the expression of fibroblast activation markers mRNA and protein, and both inhibited the phosphorylation of Smad3 and inhibited the activation of TGF-β/ Smad3 signaling pathway. Nintedanib had a stronger inhibitory effect on TGF-β/Smad3 signaling pathway, which exerted 51 % inhibitory rate on Smad3 phosphorylation compared with 13% inhibitory rate of pirfenidone. Conclusions Both pirfenidone and nintedanib can inhibit the proliferation, migration and activation of myofibroblasts, where nintedanib has a higher inhibitory potency than pirfenidone does, and the inhibition of TGF-β/Smad3 signaling pathway is stronger.

Effect of body composition on dialysis quality(Kt/V): a single center study / 中华肾脏病杂志

Objective To investigate the relationship between body composition and adequacy of dialysis,and analyze the related risk factors for inadequate delivery of hemodialysis.Methods In a prospective clinical trial,two different methods determining dialysis dose were simultaneously applied:Kt/Vdau (conventional method with Daugirdas' formula) and Kt/Vbem [online clearance monitoring (OCM) measurement with Ⅴ measured by body composition monitor (BCM)].Using the value of 1.27 as the boundary,the patients were divided into two groups:Kt/Vbcm ＜ 1.27 group and Kt/Vbcm≥ 1.27 group.Clinical indices were compared between the two groups.Multiple linear regression was applied to analyze the potential impact factors of the difference between Kt/V values calculated by the two methods.Receiver operator characteristic (ROC) curve was applied to analyze meaningful factors.Results A total of 138 maintenance hemodialysis patients with age of (54.9±12.7) years old were enrolled,and 55.1％ of them were males.There was no significant difference between Kt/Vdau and Kt/Vbcm [1.432(1.235,1.718) vs 1.434 (1.244,1.642),P=0.823].Kt/Vdau was incidentally prone to falsely high values due to operative errors,whereas in these cases OCM-based measurement Kt/Vbcm delivered realistic values.An excellent correlation was observed between Kt/Vdau and Kt/Vbcm;the mean difference was 0.07,95％CI (-0.66-0.79);the correlation coefficient was 0.842(0.821-0.862).The patients in Kt/Vbcm≥ 1.27 group had older age,lower body mass index (BMI),lower height and weight,lower total body water (TBW),lower extracellular water,lower intracellular water,and lower lean tissue index (LTI) compared to those in Kt/Vbcm ＜ 1.27 group.Excellent correlations were observed between Kt/Vbcm and TBW or LTI (r=-0.834,P ＜ 0.001;r=-0.721,P ＜ 0.001).ROC curve analysis showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 87.1％ and 86.5％,with a threshold of 30 L for TBW.It also showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 60.4％ and 94.6％,with a threshold of 11.05 kg/m2 for LTI.Conclusions BCM can give more accurate parameters of urea distribution volume,thus modifying the result of Kt/V.TBW and LTI are important risk influencing factors for inadequately dialysis,and special attention should be paid to patients with TBW ＞ 30 L or LTI ＞ 11.05 kg/m2.

Effect of RBP4 on neurocognitive function in diabetic nephropathy with silent cerebral infarction / 重庆医学

Objective To observe the impairment effect of retinol binding protein 4(RBP4) on neurocognitive function in diabetic nephropathy(DN) patients with silent cerebral infarction(SCI) and to explore its mechanism.Methods Sixty patients with newly diagnosed DN and 30 healthy volunteers were selected as the study subjects and the DN cases were divided into the complicating SCI group(SCI,n=30) and non-complicating SCI group(NSCI,n=30) according to the imaging results.The degrees of neurological function deficit and Montreal cognitive assessment(MoCA) were evaluated.Serum RBP4 level was determined by ELISA and expressions of Lp-PLA2 and C-X-C chemokine receptor type 4(CXCR4) were determined by Western blot.Results Compared with the NSCI group,the neurocognitive function in the SCI group was subsided,the expression levels of RBP4,Lp-PLA2 and CXCR4 were increased(P＜0.05).The RBP4 level was positively correlated with the neurocognitive function impairment in SCI patients,moreover,there existed a regression correlation between them.Conclusion Serum RBP4 may serve as the predictive factor of DN complicating SCI and is positively correlated with neurocognitive dysfunction.Lp-PLA2/CXCR4 pathway activation may be one of its pathogenesis.

Association between ADAMTS14 gene polymorphism and the temporomandibular joint osteoarthritis in Chinese Han females / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association between single nucleotide polymorphisms (SNP) of ADAMTS14 gene rs4747096 and osteoarthritis of the temporomandibular joint in Chinese Han females.@*METHODS@#As a case-control study, a total of 213 Chinese Han females were involved in the present study, which contained 103 temporomandibular joint osteoarthritis patients and 110 healthy people who had no symptoms or signs of temporomandibular joint osteoarthritis as control. Peripheral blood samples were collected from each participant. Genomic DNAs of temporomandibular joint osteoarthritis patients and healthy control were extracted from peripheral venous blood, which were stored in -80 °C refrigerator by using DNA extraction kits. The designed primers were used for polymerase chain reaction (PCR) amplification of specific DNA fragments. Genotype was determined by sequencing the PCR products. The software Chromas 2.22 was used to analyze the genotype. The genotype distributions, allele frequencies and genetic models between the patients and controls were compared. The age distribution was checked by t-test. Genotype and allele frequency were detected by Chi-square test.@*RESULTS@#In the present study, there were no significant differences between the osteoarthritis patients and healthy controls in terms of age. The genotype distribution was in accordance with Hardy-Weinberg equilibrium in the two groups. The genotype frequency of the ADAMTS14 (rs4747096) in the experimental group was 38.8% (AA), 55.4% (AG), and 5.8% (GG), respectively. The genotype frequency in the control group was 40.9% (AA), 43.6% (AG), and 15.5% (GG), respectively. The difference of genotype frequency of the ADAMTS14 (rs4747096) was significant between the experimental group and the control group (P=0.047). There was no significant difference in allele frequency between the two groups (P=0.415). AA and AG genotypes significantly increased the risk of the disease compared with GG in dominant model (OR=1.114, 95% CI: 1.015-1.223, P=0.028).@*CONCLUSION@#A significant correlationship was found between the ADAMTS14 (rs4747096) SNP and the temporomandibular joint osteoarthritis in Chinese Han females. The distribution of rs4747096 may be different between temporomandibular joint osteoarthritis and healthy population.

A 15-year single centre retrospective study of antiphospholipid syndrome patients from Northern Malaysia

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively. Methodology: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed. Results: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis. Conclusion: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.

Effects of heterozygous blood purification on clearance of beta 2-microglobulin and microinflammatory state in patients on maintenance hemodialysis / 重庆医学

Objective To explore the effects of heterozygous blood purification on clearance of β2-microglohulin (β2-MG) and alleviation of microinflammatory state in patients on maintenance hemodialysis.Methods A total of 128 patients on maintenance hemodialysis for more than 6 months in the First Affiliated Hospital of Chongqing Medical University and the First Branch of the First Affiliated Hospital of Chongqing Medical University were enrolled and divided into the routine hemodialysis group and heterozygous blood purification group,64,cases in each group.The serum levels of β2-MG,high-sensitive C reactive protein (hs-CRP) and interleukin-6 (IL-6) of patients in the two groups were measured before and 6 months after the initiation of hemodialysis.Results After 6 months of treatment,the serum levels of β2-MG,hs-CRP and IL-6 were decreased in heterozygous blood purification group,compared with those before treatment,the differences were statistically significant (P＜0.05).In routine hemodialysis group,the serum level of β2-MG was decreased,and serum levels of hs-CRP and IL-6 were increased,,compared with those before treatment,no statistically significant difference was found (P＞0.05).Moreover,after 6 months of treatment,the serum levels of β2-MG,hsCRP and IL-6 in heterozygous blood purification group were significantly lower than those in the routine hemodialysis group (P＜ 0.05).Conclusion Heterozygous blood purification couldefficiently remove middle molecule toxins from blood,and alleviate microinflammatory status in patients on maintenance hemodialysis.

Clinical characteristics and etiologic analysis of scabies-associated glomerulonephritis / 重庆医学

Objective To understand the incidence and clinical characteristics of scabies-associated glomerulonephritis and to investigate its pathogenesis.Methods The patients with scabies from Qijiang District People's Hospital.were collected from the outpatient department and divided into the simple scabies group (A) and glomerulonephritis group (B) according to whether complicating glomerulonephritis.The general clinical indicators and serum C-reactive protein(CRP),complement components C3 and C4,immunoglobulin,TNF-α,IL-6,IL-1β and IL-18 in the early stage of the disease were determined and compared between the two groups.The differences of above indicators were collected and compared between before and after clinical cure in the patients with scabies-associated glomerulonephritis.Results Among 376 cases of scabies,16 cases developed glomerulonephritis.The clinical manifestations included glomerular hematuria and/or mild-moderate proteinuria.The kidney injury manifestations in 12 cases were completely disappeared at 2-6 months after scabies cure.The levels of serum CRP,IgG,TNF-α,IL-6,and IL-18 in the group B were significantly increased and the serum C3 level was significantly decreased compared with the group A,the differences were statistically significant(P＜0.05).The levels of serum IgG,hs-CRP,TNF-α,IL-6 and IL-18 after cure in 12 cases of clinically cured scabies-associated glomerulonephritis were significantly decreased and the serum C3 level was significantly increased,and the difference was statistically significant compared with the early onset stage(P＜0.05).Conclusion The majority of prognosis in scabies-associated glomerulonephritis is good.Its occurrence is closely correlated with immune and inflammatory reactions induced by sarcoptes mites irffection.

Clinical characteristic and correlative factors of maintenance hemodialysis patients with restless legs syndrome / 中华肾脏病杂志

Objective To explore the prevalence and the correlative factors of restless legs syndrome (RLS) in maintenance hemodialysis (MHD) patients.Methods The basic information and clinical laboratory results of 307 MHD patients were collected.The international RLS study group (IRLSSG) diagnostic criteria were applied to assess the presence and the severity of RLS.Binary logistic analysis was used for exploring correlative factors of RLS.Results The prevalence of RLS was 12.1％ in the MHD patients,with 73.0％ patients having mild-to-moderate symptoms and 83.8％ having chronic RLS.There was no significant difference between MHD patients with and without RLS in age,gender,dialysis age,daily urine,Kt/V,history of smoking,drinking,hemoglobin,serum creatinine,urea nitrogen,uric acid,calcium,phosphorus,magnesium,potassium,intact parathyroid hormone (iPTH),prealbumin,albumin and alkaline phosphatase.But the frequency of daily exercise in RLS group is significantly lower than that in non-RLS group (Z=-4.114,P ＜ 0.001).Logistic regression analysis showed that daily exercise was a correlative factor of RLS (B=-2.203,OR=0.111,95％CI 0.033-0.371,P ＜ 0.001).Conclusions RLS is a common complication in MHD patients,with chronic state and mild-to-moderate symptoms.RLS is correlated with daily exercise,which may be a scientific approach to treat or prevent this disease.

Effects of heterozygous blood purification on clearance of beta 2-microglobulin and microinflammatory state in patients on maintenance hemodialysis / 重庆医学

Objective To explore the effects of heterozygous blood purification on clearance of β2-microglohulin (β2-MG) and alleviation of microinflammatory state in patients on maintenance hemodialysis.Methods A total of 128 patients on maintenance hemodialysis for more than 6 months in the First Affiliated Hospital of Chongqing Medical University and the First Branch of the First Affiliated Hospital of Chongqing Medical University were enrolled and divided into the routine hemodialysis group and heterozygous blood purification group,64,cases in each group.The serum levels of β2-MG,high-sensitive C reactive protein (hs-CRP) and interleukin-6 (IL-6) of patients in the two groups were measured before and 6 months after the initiation of hemodialysis.Results After 6 months of treatment,the serum levels of β2-MG,hs-CRP and IL-6 were decreased in heterozygous blood purification group,compared with those before treatment,the differences were statistically significant (P＜0.05).In routine hemodialysis group,the serum level of β2-MG was decreased,and serum levels of hs-CRP and IL-6 were increased,,compared with those before treatment,no statistically significant difference was found (P＞0.05).Moreover,after 6 months of treatment,the serum levels of β2-MG,hsCRP and IL-6 in heterozygous blood purification group were significantly lower than those in the routine hemodialysis group (P＜ 0.05).Conclusion Heterozygous blood purification couldefficiently remove middle molecule toxins from blood,and alleviate microinflammatory status in patients on maintenance hemodialysis.

Endoscopic variceal ligation versus β-receptor blockers for prophylaxis of primary esophageal variceal bleeding: A meta-analysis of randomized controlled trials / 第二军医大学学报

Objective To compare the efficacy and safety of endoscopic variceal ligation (EVL) and β-receptor blockers (βB) administration for prophylaxis of primary esophageal variceal bleeding. Methods EMBASE, PubMed, CENTRAL, Wan-fang Database, CNKI database and Google Scholar were comprehensively searched in May 2015 for eligible full-text randomized controlled trials (RCTs). Endpoints of interest were first variceal bleeding, all-cause mortality, bleeding-related mortality and main adverse events. A fixed-effect model was firstly utilized to calculate the pooled odds risk (OR) with 95% confidence intervals (CIs). Results Fourteen studies involving 1 280 patients were identified fulfilled the inclusion criteria in this analysis. Compared with βB, EVL significantly reduced the incidence rate of first variceal bleeding (OR=0.67, 95%CI: 0.49-0.91,P=0.010, I2=21%). All-cause and bleeding-related mortality had no significant difference in the two groups (all-cause mortality [OR=1.14, 95%CI: 0.87-1.50, P=0.35, I2=0%] and bleeding-related mortality [OR=0.72, 95%CI: 0.44-1.17,P=0.19, I2=0%]). EVL had lower incidence rate of main adverse events than non-selective βB (OR=0.43, 95%CI: 0.29-0.64, P<0.000 1, I2=40%). However, compared with EVL, the incidence rate of main adverse events in Carvedilol was significantly lower (OR=10.59, 95%CI: 2.37-47.27, P=0.002). Conclusion EVL is more effective in preventing the primary esophageal variceal bleeding compared with βB, but the two methods have no differences in all-cause mortality or bleeding-related mortality.

Effect of autophagy on necroptosis of renal tubular epithelial cells in sub-total nephrectomy rats / 中国病理生理杂志

[ ABSTRACT] AIM: To explore whether autophagy is involved in the excessive death of renal tubular epithelial cells in subtotal nephrectomy ( SNx) rats and the relationship between autophagy and necroptosis in the kidney of SNx rats. METHODS:Male Sprague-Dawley rats were randomly assigned to control group ( n=6 ) and SNx group ( n=42 ) .The rats in SNx group were subjected to SNx.Sham surgery was performed in the rats in control group.The rats in SNx group were divided into subgroups at 0, 4, 8 and 12 weeks ( n=6) and the other rats in SNx group were divided into SNx+vehi-cle group, SNx+necrostatin-1 (Nec-1) group and SNx+3-methyladenine (3-MA) group.The expression of RIP1, RIP3, LC3 and beclin-1 at mRNA and protein levels was measured at 0, 4, 8 and 12 weeks by qPCR and immunohistochemistry. The effects of Nec-1 or 3-MA on the protein expression of LC3-I, LC3-II and beclin-1, and production of reactive oxygen species ( ROS) in the rat kidney were determined by Western blot and DCFH-DA staining.The death of renal tubular epi-thelial cells in the SNx rats was observed by TUNEL staining and electron microscopy.Finally, the effects of Nec-1 and 3-MA on blood urea nitrogen ( BUN) , serum creatinine ( SCr) and the pathological changes of the renal tissues were ana-lyzed.RESULTS:The highest mRNA and protein levels of RIP1, RIP3, LC3 and beclin-1 appeared at the 8th week after SNx (P cells were decreased in the SNx rats treated with Nec-1 and 3-MA (P<0.01), but 3-MA did not reduce the increased con-centration of ROS.In addition, treatment with Nec-1 and 3-MA obviously reduced BUN, SCr (P<0.05), glomeruloscle-rosis index and tubulointerstitial injury score (P<0.01).CONCLUSION:Autophagy participates in the excessive death of renal tubular epithelial cells in SNx rats.Inhibition of autograph prevents necroptotic cell death of renal tubular cells, and alleviates chronic renal injury in SNx rats.

Assessment of quality of life and its influence factors in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the quality of life (QOL) of maintenance hemodialysis (MHD) patients and its influencing factors.Methods A total of 257 MHD patients in our hospital were recruited in this study.Clinical data of the patients were collected,and the QOL was assessed by MOS 36 item short form health survey(SF-36).Nutritional status of patients was evaluated by modified quantitative subjective global assessment (MQSGA).Univariate analysis of variance,pearson correlation analysis and multiple linear stepwise regression analysis were performed to determine the effect of related factors on QOL scores.Results The scores of all scales of SF-36 evaluation in MHD patients were relatively lower than that of general population as reported before.Their physiological component summary (PCS) score decreased gradually as age grew,nevertheless,the mental component summary (MCS) score was highest in the group aged 41-60.The score was lower in patients with moderate to severe malnutrition or diabetic nephropathy when compared with other patients.Univariate analysis of variance also revealed that high SF-36 scores associated with higher education or income.Multivariate analysis indicated that PCS score and total SF-36 score of MHD patients were positively correlated with body mass index (BMI) and cholesterol,but negatively correlated with diabetic nephropathy,pulmonary artery systolic pressure and MQSGA score (all P ＜ 0.05).There was positive correlation between MCS score and income,yet negative correlation between MCS score and MQSGA score (all P ＜ 0.05).Conclusion MHD patients had relatively poor QOL.Primary diseases and nutritional status were probably the main influencing factors.Age,educated level,family income and pulmonary artery systolic pressure might also have effects on their QOL.

Study on HLA-DRB1 shared epitope in patients with IgA mesangial proliferative glomerulonephritis / 中国免疫学杂志

Objective:To explore the clinical correlation of HLA-DRB1 shared epitope with IgA mesangial proliferative glomer-ulonephritis( IgA MsPGN).Methods:The renal function were examined routinely,and HLA-DRB1 shared epitope were determined by PCR in a total of 164 patients with IgA MsPGN and 164 healthy subjects.The renal function and HLA-DRB1 shared epitope were compared in patients with IgA MsPGN and healthy subjects,and clinical correlation of HLA-DRB1 shared epitope and renal function were analyzed.Results:(1)24 h proteinuria,serum creatinine and serum urea nitrogen were significantly different in patients with IgA MsPGN and healthy subjects(P<0.01);(2)The high-frequency gene of HLA-DRB1 in patients with IgA MsPGN were DRB1*04, DRB1*07,DRB1*09,DRB1*11,DRB1*14 and DRB1*15;(3) The distribution frequency of DRB1*09 and DRB1*11 in patients with IgA MsPGN increased significantly(P<0.01 or P<0.05);(4)24 h proteinuria,serum creatinine and serum urea nitrogen in patients with IgA MsPGN with DRB1*09 and DRB1*11 were significantly different compared with those in patients with IgA MsPGN with other HLA-DRB1 shared epitope(P<0.01).Conclusion:HLA-DRB1 shared epitope is related to IgA MsPGN,DRB1*09 and DRB1*11 can increase the risk of IgA MsPGN,and related to the severity of glomerulonephritis.

The relationship between epithelial-mesenchymal transition and clinic pathology of IgA nephropathy / 重庆医学

Objective To analyze the correlation between the epithelial‐mesenchymal transition and the clinicopathologic features of IgA nephropathy .Methods A total of 168 patients diagnosed as IgA nephropathy by renal biopsy in Xinqiao hospital from Janu‐ary 2011 to December 2013 were divided into high expression of dual‐positive Snail and a‐SMA group (Group A ,117 cases) and low expression of dual‐positive Snail and a‐SMA group (Group B ,51 cases) according to results of immunohistochemical method .The clinical parameters (age ,gender ,course of disease ,BMI and chemical indicators) and renal pathology grade were compared by statis‐tical analysis .Results There were difference between group A and group B in the course of disease and BMI(P<0 .05) .There were differences between group A and group B in the incidences of creatinine ,blood urea nitrogen ,serum triglycerides and 24‐hour urine protein amount (P<0 .05) .The percentage of Lee′s grade Ⅰ ,Ⅱ ,Ⅲ in group B was significant ,while percentage of Lee′s gradeⅣ + Ⅴin group A was significant .The expression of Snail and a‐SMA in grade Ⅳ + Ⅴ was more than that in grade Ⅰ + Ⅱ (40 .2%vs .9 .4% ) ,and the difference between two groups was statistically significant (P< 0 .05) .Conclusion The expression of Snail and‐SMA were related with 24‐hour urine protein amount and kidney function in IgA nephropathy ;and Lee′s grade was severe in patients with high expression of Snail and‐SMA .

Effects of serum from the obesity patients with diabetic mellitus on TLR4/NF-κB pathway in human THP-1 monocytes / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of serum from the obesity patients and obesity patients with Diabetic mellitus on toll-like receptor 4/Nuclear factor -κB p65 (TLR/NF-κB) pathway in human THP-1 monocytes and to explore the inflammatory immune response in obesity.@*METHODS@#Peripheral serum was isolated from healthy volunteers (the control group), the obesity patients (Ob group) and the obesity patients with diabetic mellitus (the Ob with DM group), respectively, 20 in each group. THP-1 monocytes were incubated with the serum for 48 h. The monocytes and culture supernatant were collected. The phosphorylation level of NF-κB p65 protein in THP-1 monocytes was evaluated by Western blot as well as immunofluorescence assay. The TLR4 mRNA expression was evaluated by RT-PCR. ELISA was used to measure the monocyte chemotactic protein-1 (MCP-1) levels in the culture supernatant.@*RESULTS@#In the presence of serum, the obesity group and the obesity with diabetic mellitus group showed the up-regulated phosphorylation level of NF-κB p65 protein and TLR4 mRNA expression in THP-1 monocytes compared with the healthy control group (both P<0.05), and the MCP-1 levels in the obesity patients were up-regulated significantly compared with the healthy control group [healthy control group (26.4 ± 3.9) pg/mL, Ob group (45.8 ± 10.0) pg/mL, Ob with DM group (58.0 ± 15.3) pg/mL; P<0.05]. These parameters were further up-regulated in the obesity patients with diabetic mellitus patients.@*CONCLUSION@#The serum from the obesity patients or the obesity patients with diabetes can induce monocyte dysfunction, which might be related to the activation of TLR4/NF-κB signaling pathway.

Mice mode of high intraocular pressure established by laser photocoagulation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish an experimental model of high intraocular pressure in mice by laser photocoagulation and to prepare for future research. METHODS: Experimental model of high intraocular pressure was induced unilaterally in 44 C57BL/6 mice. The fellow eye served as a control. TONO-PEN AVIA Tonomter was used to measure intraocular pressure (IOP) to guarantee IOP value at 1, 2, 4, 8wk. Slit-lamp biomicroscopy was performed throughout the period and the structural changes were assessed histologically. And then, their eyes were enucleated, postfixed, cryoprotected, and embedded in optimal cutting temperature medium. After hematoxylin and eosin stain ( HE stain ) , cryosections of the retina were observed under light microscope. TdT-mediated biotin-dUTP nick end labeling ( TUNEL ) was performed on the retinal sections to determine apoptosis rate. RESULTS: IOP of laser-treated eyes was significantly higher than that of control eyes from 1-8wk (P CONCLUSION: The laser photocoagulation of limbus causes chronic elevation of IOP and this method may be a promising experimental model for the investigation of biological mechanisms of glaucomatous retinal ganglion cell damage.