Analysis of clinical, pathological features and prognosis of microscopic polyangiitis / 中国医师进修杂志

Objectives:To analyze the clinical features of microscopic polyangiitis (MPA), and observe the clinical outcomes of different pathological types.Methods:The clinical data of 61 patients with MPA in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2019 were analyzed retrospectively. According to age, the patients were divided into ≥ 60 years old group (46 cases) and<60 years old group (15 cases). According to the initial serum creatinine, the patients were divided into ≥ 500 μmol/L group (18 cases) and<500 μmol/L group (43 cases). The basic data and laboratory examination results of the patients were recorded, and the disease activity was evaluated by Birmingham systemic vasculitis activity score (BVAS). Twenty-three patients with complete pathological data were pathologically classified and followed up to assess their clinical outcomes. The progression to end-stage renal disease (ESRD) or death was defined as the endpoint.Results:Ferritin in ≥60 years old group was significantly higher than that in<60 years old group: 452 (289, 792) μg/L vs. 210 (119, 451) μg/L, and there was statistical difference ( P<0.05). The fever rate, hemoglobin and platelets in creatinine ≥ 500 μmol/L group were significantly lower than those in creatinine<500 μmol/L group: 3/18 vs. 48.8% (21/43), 77.5 (62.8, 86.0) g/L vs. 85.0 (77.0, 104.0) g/L and 192 (147, 234) × 10 9/L vs. 257 (208, 365) × 10 9/L, the gastrointestinal involvement and BVAS in creatinine ≥ 500 μmol/L group were significantly higher than those in creatinine<500 μmol/L group: 16/18 vs. 25.6% (11/43) and 20.0 (16.0, 23.3) scores vs. 15.0 (12.0, 19.0) scores, and there were statistical differences ( P<0.05 or<0.01). Pearson correlation analysis result showed that BVAS was positively correlated with creatinine ( r = 0.42, P<0.01), negatively correlated with hemoglobin ( r = -0.42, P<0.01), but it had no correlation with erythrocyte sedimentation rate and platelets ( r = 0.05 and 0.04, P>0.05). Among the 23 patients with completed the clinical outcome statistics, endpoint events occurred in 5 of 6 patients with crescent renal pathology, and in 7 of 12 patients with severe renal interstitial injury. Kaplan-Meier survival curve analysis result showed that the average survival time in ESRD MPA patients was significantly shorter than that in non ESRD MPA patients (41.2 months vs. 63.5 months), and there was statistical difference ( χ2 = 0.48, P = 0.028). Conclusions:The clinical manifestations of elderly MPA patients are similar to those of young MPA patients. Creatinine≥500 μmol/L or anemia at initial onset indicate higher vasculitis activity in MPA. The prognosis of MPA patients with pathological manifestations of crescent or severe interstitial injury is poor, and the survival rate of ESRD is lower than that of non ESRD patients.

Risk factors and early diagnosis of sepsis caused by liver abscess / 中华急诊医学杂志

Objective@#To analyze the clinical features and microbial characteristics of patients with pyogenic liver abscess (PLA), and to determine the risk factors and biomarkers for early diagnosis of sepsis caused by PLA.@*Methods@#The demographic and clinical data of 198 patients with liver abscess admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2013 to June 2017 were analyzed retrospectively. Patients with non-bacterial liver abscess, death on admission and tumor metastasis were excluded. The 198 patients with liver abscess were divided into the sepsis group and non-sepsis group according to the disease progression. The general data of the two groups were analyzed to explore the risk factors of sepsis caused by liver abscess, biomarkers for early diagnosis, and the prognosis. Patients with positive culture were further divided into the Klebsiella pneumoniae group and non-Klebsiella pneumoniae group, and the general clinical data of the two groups were analyzed. Among the PLA patients with positive culture, 80.0% were Klebsiella pneumoniae, followed by E. coli. SPSS 19.0 software was used for statistical analysis, and univariate and logistic multivariate regression analysis was used to determined the risk factors of sepsis induced by PLA. The diagnostic value of white blood cell, neutrophil percentage and procalcitonin (PCT) at admission on the progression of liver abscess to sepsis was evaluated by the receiver operating characteristic (ROC) curve, area under the curve (AUC), sensitivity and specificity.@*Results@#The mortality of patients with sepsis caused by liver abscess was 20.8%. The white blood cell count, neutrophil percentage, and PCT at admission predicted the progression of sepsis in PLA patients, and the AUC were 0.76 (95%CI: 0.623-0.898), 0.818 (95%CI: 0.691-0.945), and 0.869 (95%CI: 0.765-0.974), respectively. Patients with diabetes were prone to develop sepsis after the occurrence of liver abscess. There was no significant difference in microbial characteristics between the sepsis group and non-sepsis group. Length of stay (LOS) in patients with sepsis was significantly prolonged [(19.6±12.5) d vs (16.0±9.3) d, P=0.033].@*Conclusions@#Diabetes is an independent risk factor for the progression of liver abscess to sepsis. Klebsiella pneumoniae is the first pathogen of liver abscess. Patients with elevated glycated hemoglobin (≥9.9%) are prone to develop sepsis. White blood cell count (≥12.55×109/L), percentage of neutrophils (≥84.8%), and PCT (≥6.96 ng/mL) in patients with liver abscess indicated the progresses to sepsis, and thus the LOS of patients with sepsis is significantly prolonged and the mortality is significantly increased.

Risk factors and early diagnosis of sepsis caused by liver abscess / 中华急诊医学杂志

Objective To analyze the clinical features and microbial characteristics of patients with pyogenic liver abscess (PLA),and to determine the risk factors and biomarkers for early diagnosis of sepsis caused by PLA.Methods The demographic and clinical data of 198 patients with liver abscess admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2013 to June 2017 were analyzed retrospectively.Patients with non-bacterial liver abscess,death on admission and tumor metastasis were excluded.The 198 patients with liver abscess were divided into the sepsis group and non-sepsis group according to the disease progression.The general data of the two groups were analyzed to explore the risk factors of sepsis caused by liver abscess,biomarkers for early diagnosis,and the prognosis.Patients with positive culture were further divided into the Klebsiella pneumoniae group and non-Klebsiella pneumoniae group,and the general clinical data of the two groups were analyzed.Among the PLA patients with positive culture,80.0％ were Klebsiella pneumoniae,followed by E.coli.SPSS 19.0 software was used for statistical analysis,and univariate and logistic multivariate regression analysis was used to determined the risk factors of sepsis induced by PLA.The diagnostic value of white blood cell,neutrophil percentage and procalcitonin (PCT) at admission on the progression of liver abscess to sepsis was evaluated by the receiver operating characteristic (ROC) curve,area under the curve (AUC),sensitivity and specificity.Results The mortality of patients with sepsis caused by liver abscess was 20.8％.The white blood cell count,neutrophil percentage,and PCT at admission predicted the progression of sepsis in PLA patients,and the AUC were 0.76 (95％CI:0.623-0.898),0.818 (95％CI:0.691-0.945),and 0.869 (95％CI:0.765-0.974),respectively.Patients with diabetes were prone to develop sepsis after the occurrence of liver abscess.There was no significant difference in microbial characteristics between the sepsis group and non-sepsis group.Length of stay (LOS) in patients with sepsis was significantly prolonged [(19.6±12.5) d vs (16.0±9.3) d,P=0.033].Conclusions Diabetes is an independent risk factor for the progression of liver abscess to sepsis.Klebsiella pneumoniae is the first pathogen of liver abscess.Patients with elevated glycated hemoglobin (≥ 9.9％) are prone to develop sepsis.White blood cell count (≥ 12.55×109/L),percentage ofneutrophils (≥ 84.8％),and PCT (≥ 6.96 ng/mL) in patients with liver abscess indicated the progresses to sepsis,and thus the LOS of patients with sepsis is significantly prolonged and the mortality is significantly increased.

Oxidative stress impairs myocyte autophagy, resulting in myocyte hypertrophy.

NEW FINDINGS: What is the central question of this study? Does oxidative stress induce impairment of autophagy that results in myocyte hypertrophy early after pressure overload? What is the main finding and its importance? In cultured myocytes, hydrogen peroxide decreased autophagy and increased hypertrophy, and inhibition of autophagy enhanced myocyte hypertrophy. In rats with early myocardial hypertrophy after pressure overload, myocyte autophagy was progressively decreased. The antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol prevented the decrease of myocyte autophagy and attenuated myocyte hypertrophy early after pressure overload. These findings suggest that oxidative stress impairs myocyte autophagy that results in myocyte hypertrophy. ABSTRACT: Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces an impairment of autophagy that results in myocyte hypertrophy. H9C2 cardiomyocytes pretreated with the autophagy inhibitor 3-methyladenine were exposed to 10 and 50 µm hydrogen peroxide (H2 O2 ) for 48 h. Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation. The animals were killed 24, 48 or 72 h after surgery. In a separate group, the AAC and sham-operated rats randomly received the antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol for 72 h. In H9C2 cardiomyocytes, H2 O2 decreased the ratio of microtubule-associated protein light chain 3 (LC3) II to LC3 I and increased P62 and phosphorylated ERK (p-ERK) proteins and myocyte surface area. 3-Methyladenine further increased H2 O2 -induced p-ERK expression. In rats after AAC, the heart to body weight ratio was progressively increased, the LC3 II/I ratio was progressively decreased, p62 and p-ERK expression was increased, and expression of Beclin1, Atg5 and Atg12 was decreased. N-Acetyl-cysteine or tempol prevented the decreases in the LC3 II/I ratio and Beclin1 and Atg5 expression and attenuated the increases in LV wall thickness, myocyte diameter and brain natriuretic peptide expression in AAC rats. In conclusion, oxidative stress decreases Beclin1 and Atg5 expression that results in impairment of autophagy, leading to myocyte hypertrophy. These findings suggest that antioxidants or restoration of autophagy might be of value in the prevention of early myocardial hypertrophy after pressure overload.

Role of silent mating type information regulation 2 homolog 1 on lipopolysacchride-induced mitochondrial injury in insulinoma cell lines-1 / 中华急诊医学杂志

Objective To investigate the role of silent mating type information regulation 2 homolog 1(SIRT-1) in lipopolysaccharide (LPS)-induced mitochondrial injury on INS-1(insulinoma cell lines-1)cells. Methods INS-1 cells were divided into 5 groups: control group, 1 mg/L LPS group, LPS group with 10 μmol/L RSV (resveratrol) pretreatment for 1 h, LPS group with 20 μmol/L EX527 pretreatment for 1 h, LPS group together with EX527 pretreatment for 1 h, then incubated these INS-1 cells with RSV and LPS for 24 h. The cell viability and ATP generation were detected, then total, cytoplasmic and mitochondrial protein were isolated from INS-1 cells. The protein expression of SIRT1, TLR4, acetylated FoxO1, and cytochrome C (CytC), Mfn1 (mitofusion1), Mfn2 (mitofusion2), and Fis1 (fission1) were tested by Western-blot. Mfn1, Mfn2, and Fis1 genes expression were detected by real-time PCR. The comparison of multiple groups was performed by one-way ANOVA. LSD-t method was used to compare between every two groups. Results After 1 mg/L LPS stimulation for 24 h, there was decreased cell viability (n=4, F=13.98, P<0.01) and ATP generation (n=4, F=27.92, P<0.05) in INS-1 cells. RSV pretreatment could maintain ATP production, but it could not reverse the EX527-induced ATP decrease (P>0.05). Furthermore, RSV upregulated gene and protein expression of SIRT1, Mfn1 and Mfn2, whereas decreased TLR4 and Fis1 expression. LPS-induced CytC released to cytoplasm was alleviated by RSV (P<0.01), but there was no significant change about FoxO1 protein expression (P>0.05). Conclusions RSV may regulate FoxO1 acetylation followed by its effects on SIRT1 activity, which may be partly the mechanism of mitochondrial damage induced by LPS on INS-1 cells.

Progressive Reduction in Myocyte Autophagy After Myocardial Infarction in Rabbits: Association with Oxidative Stress and Left Ventricular Remodeling.

BACKGROUND/AIMS: The alterations in myocyte autophagy after myocardial infarction (MI) and the underlying mechanisms have not been fully understood. In this study, we investigated the temporal changes of myocyte autophagy in the remote non-infarcted myocardium in rabbits after MI and the relationships between alterations of myocyte autophagy and left ventricular (LV) remodeling and myocardial oxidative stress. METHODS: Rabbits were assigned to MI or sham operation. Rabbits with MI or sham were randomly assigned to receive chloroquine, an autophagy inhibitor, antioxidant vitamins C and E or placebo for 4 weeks. H9C2 cardiomyocytes were subjected to hypoxia or hydrogen peroxide (H2O2) treatment. RESULTS: MI rabbits exhibited progressive increases of LV end-diastolic dimension (EDD), and decreases of LV fractional shortening (FS) and dP/dt over 8 weeks. Myocyte autophagy assessed by the scores of LC3 and Beclin1 expression was progressively decreased at 1, 4 and 8 weeks after MI. The ratio of LC3 II/I and Beclin1 and Atg5 proteins were also decreased at 4 weeks after MI. There was a negative correlation between autophagy and LV EDD and a positive correlation between autophagy and LV FS and dP/dt. The autophagy inhibitor chloroquine worsened LV remodeling after MI. Decreased myocyte autophagy was associated with increased myocardial 4-hydroxynonenal. Antioxidant vitamins C and E prevented the decrease in myocyte autophagy after MI. In cultured H9C2 cardiomyocytes, the LC3 II/I ratio was decreased at 4 and 8 h after exposure to hypoxia, and the change was associated with increased 8-hydroxy-2-deoxyguanosine. A low concentration of H2O2 decreased the LC3 II/I ratio. CONCLUSION: Progressive reduction in myocyte autophagy in the remote non-infarcted myocardium was associated with myocardial oxidative stress and LV remodeling after MI. Antioxidants prevented the reduction in myocyte autophagy after MI, suggesting that oxidative stress mediates reduction in myocyte autophagy that contributes to post-MI remodeling.

TLR4 expression on pancreatic islet beta cell of septic rat and its significance / 中华急诊医学杂志

Objective To investigate the Toll like receptor-4 (TLR4) expression on pancreatic islet beta-cell of septic rat and its effects on glucose regulation.Methods SD male septic rats were made with LPS intra-abdominal injection in a dose of 5 mg/kg body weight and it repeated once 3 h later.Rats were randomly (random number) divided into four groups randomly (n =5 in each):normal control group,LPS group,LPS antibody group and PLS with LPS antibody group.The expression and protein level of TLR4 were measured by RT-PCR,Western-blot and immunochemistry analysis respectively.IVGTT (intra-venous glucose tolerant test) was used to measure the glucose and insulin levels 6 hours after LPS administration and as well as in control group,and then their AUC were calculated.Results The TLR4 protein and mRNA expressed on pancreatic islet beta-cell of normal rat were significantly up-regulated 6 hours after LPS administration,while its up-regulation could be inhibited when LPS antibody was used in advance (P ＜ 0.01).Rat blood glucose levels were higher at 10,30,60 and 120 min in LPS group and insulin levels were lower at 30,60,120 min compared with normal control (P ＜ 0.01).LPS antibody improved the insulin secretion and then blood glucose level distinctly decreased during 30-120 min period after LPS challenge proved by IVGTT test.Conclusions TLR4 expression up-regulated on pancreatic islet beta-cell of septic rat and LPS-TLR4 system might be a mechanism of stress hyperglycemia genesis.

Effects of oxidative stress induced by high glucose in endothelial cells / 上海第二医科大学学报

Objective To explore the effects of oxidative stress in porcine iliac endothelial cells(PIECs) induced by high glucose. Methods After being intervened by high glucose for some time, dihydroethidium (DHE) or dihydrorhodamine 123 (DHR123) was used as a reactive oxygen species(ROS) capture. The mean fluorescent intensity(MFI) of above probes which were the products of intracellular oxidation was detected by fluorescent microscopy and flow cytometry, and the level of ROS was thus measured. With lucigenin as chemiluminescence agent, luminescence changes were detected by chemiluminescence analyzer after addition of NADPH to observe the effect of high glucose on activity of NADPH oxidase(NOX). Results Intracellular MFI was markedly elevated with the concentration of high glucose and time of exposure to high glucose. It was revealed by flow cytometry that the NOX activity was significantly activated compared with normal medium treated PIECs(P

Effects of high glucose on oxidative stress of human peritoneal mesothelial cells / 上海第二医科大学学报

Objective To explore the effects of high glucose on oxidative stress of human peritoneal mesothelial cells(HPMCs).Methods HPMCs were cultured in vitro and identified by immunohistochemistry, and cells of second generation were selected. After HPMCs were treated by glucose with different concentrations for some time, MTT method was employed to detect the cell viability. 2’,7’-dichlorofluorescein diacetate (DCFH-DA) was used as a reactive oxygen species (ROS) capture. The cell viability of HPMCs and ROS level were analysed after being intervened by glucose with different concentrations and for different time. Results Viability of HPMCs was significantly inhibited in a dose-and time-dependent manner by high glucose(P

Effects of advanced glycation end products on oxidative stress in endothelial cells / 上海第二医科大学学报

Objective To explore the effect of advanced glycation end products(AGEs) on the oxidative stress in porcine vascular endothelial cells(PIECs). Methods After being intervened by AGEs for some time,cell viability was detected by MTT.2′,7′-dichlorofluorescein diacetate(DCFH-DA) was used as a reactive oxygen species(ROS) capture agent.The fluorescent intensity of 2′,7′-dichlorofluorescein(DCF),which was the product of cellular oxidation of DCFH-DA,was detected by flow cytometry,and the level of ROS was thus measured. Results Viability of PIECs was inhibited by AGEs in a dose-and time-dependent fashion(P