重组人生长激素对局灶性脑缺血再灌注小鼠运动功能的改善作用及其机制

观察重组人生长激素对局灶性脑缺血再灌注小鼠运动功能的影响,探讨其可能的作用机制。     

Clinicopathological features of antineutrophil cytoplasmic antibodies associated vasculitis with glomerular IgA deposits

Objective To investigate the clinical manifestations, renal pathology and prognosis of antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) accompanied with renal glomerular IgA deposition. Methods A retrospective analysis was performed at the First Affiliated Hospital of Zhejiang University College of Medicine. Patients diagnosed with AAV associated renal injury by renal biopsy from February 2004 to February 2017 were enrolled. Patients with antiglomerular basement membrane antibody-mediated nephritis, systemic lupus erythematosus nephritis, Henoch Schonlein purpura nephritis, hepatitis B virus associated nephritis and other known etiology were excluded. According to immunofluorescence examination, the patients were divided into IgA deposition group and pauci-immune complex deposition group. The differences in clinical manifestation, pathological features and prognosis were compared between groups. Results A total of 150 AAV cases were included, among which 25 cases were with IgA deposition and 125 cases with pauci-immune complex deposition. The level of serum albumin in IgA deposition group was higher than that in pauci-immune complex deposition group [(35.0±6.2) g/L vs (32.6±5.3) g/L, P=0.049], but the titer of MPO-ANCA was lower [24.8(10.4, 71.8) U/ml vs 63.0(21.9, 100.0) U/ml, P=0.044] in IgA deposition group. There was no significant difference between two groups in other laboratory indexes and renal pathological findings. The median follow-up time was 15.2 months in IgA deposition group and 8.9 months in pauci immune complex deposition group. During the follow-up there were 8 patients (32.0%) in IgA deposition group and 29 patients (23.2%) in pauci immune complex deposition group on maintaining dialysis; 2 patients (8.0%) in IgA deposition group and 7 patients (5.6%) in pauci immune complex deposition group died. There was no significant difference between two groups in patients' outcomes. Conclusions AAV patients with glomerular IgA deposition and AAV patients with typical glomerular immunoglobulin complex deposition are similar as regards clinical appearance and prognosis.     

Kugel手术与腹腔镜完全腹膜外疝修补术的比较研究

目的比较Kugel疝修补术与腹腔镜完全腹膜外疝修补术(TEP)治疗腹股沟疝的临床效果。方法回顾性分析2009年8月至2013年7月,南方医科大学附属小榄医院收治的385例腹股沟疝患者的临床资料,根据腹膜外疝修补术方式分为Kugel组(163例)与TEP组(222例)。比较二组患者手术时间、住院时间、恢复正常活动时间、住院费用、术后腹股沟区疼痛情况、术后并发症等。结果二组患者手术时间、住院时间、切口感染、疝复发率比较,差异无统计学意义(t=0.018、5.563、χ2=0.647、0.048,P=0.057、0.206、0.421、0.826);术后腹股沟区疼痛发生率、恢复正常活动时间、血清肿发生率,TEP组明显少于Kugel组(χ2=5.958、t=24.545、χ2=4.438,P=0.015、0.000、0.035);住院费用Kugel组低于TEP组(t=8.072,P=0.000)。结论 TEP与Kugel 2种术式治疗腹股沟疝均可取得良好疗效,TEP具有术后疼痛轻、恢复快等优点,但住院费用较高,临床医师需根据患者的经济水平、意愿以及术者水平等综合选择最佳的手术方式。     

The genetic polymorphism and expression profiles of NLRP3 inflammasome in patients with chronic myeloid leukemia

NLRP3 inflammasome has been recently reported as an important risk factor in the development of cancer. But the relationship between polymorphisms of NLRP3 inflammasome related genes and chronic myeloid leukemia (CML) is rarely reported. Therefore, the aim of the present study was to investigate the association of five genetic polymorphisms (NLRP3, IL-1β, IL-18, CARD8 and NF-κB) in 267 CML patients and 344 healthy controls. We found that the AT genotype of CARD8 (rs2043211) was significantly higher compared to TT genotype in high and intermediate risk CML patients. IL-1β (rs16944) polymorphism in early molecular response at 6?months was marginally different, with more GG and less AA genotype in BCR-ABL^IS >1% group. IL-18 (rs1946518) polymorphism was significantly different with more GG genotype in BCR-ABL^IS >1% group at 6?months. We also demonstrated that WBC count of newly diagnosed patients carrying AG genotype was significantly higher than that of GG or AA genotype of IL-1β (rs16944). The onset age of patients carrying ins/ins genotype of NF-κB (rs28362491) was significantly older than that of ins/del and del/del genotype. Moreover, IL-1β or NLRP3 mRNA expression was decreased and IL-18 mRNA expression was increased significantly in CML patients compared with controls. In conclusion, the genetic polymorphisms of NLRP3 inflammasome may be served as potential predictors for CML.     

Function of T regulatory type 1 cells is down-regulated and is associated with the clinical presentation of coronary artery disease

T regulatory type 1 (Tr1) cells can promote tolerance and suppress inflammation. Atherosclerosis may be induced by the proinflammatory activation of cells in the vasculature and the immune system. Hence, we wondered whether defects in Tr1 function were a contributing factor to coronary artery disease (CAD). Data showed that the frequency of IL-10⁺ Tr1 cells was significantly lower in CAD patients than in controls. Compared to healthy controls, Tr1 cells from CAD patients presented lower CTLA-4 but higher PD-1 expression, in addition to lower IL-10 secretion. When co-incubated with Tconv cells, the CD4⁺CD49b⁺LAG-3⁺CD45RO⁺ Tr1 cells presented IL-10-dependent inhibitory effects, and those from CAD patients presented significantly lower suppression capacity than those from healthy controls. Interestingly, the characteristics of Tr1 cells were associated with clinical features of CAD patients. The frequency of Tr1 cells and the IL-10 and LAG-3 expression by Tr1 cells were negatively correlated with the BMI of the CAD patients. In addition, the Tr1 frequency and the LAG-3 and CTLA-4 expression on Tr1 cells were lower in CAD patients with higher numbers of narrowed vessels. Together, these results suggest that in CAD, Tr1 cells present multiple defects, which are associated with the clinical presentation of the disease.     

Screening HCV genotype-specific epitope peptides based on conserved sequence analysis and B cell epitope prediction in HCV E2 region

The high mutation rate of the hepatitis C virus (HCV) genome increases the genotype diversity and renders the detection of the virus more difficult. Therefore, prediction and assessment of highly conserved and strongly antigenic epitope polypeptide sequences have become a focus of current research. The E2 region is the target binding region of neutralizing antibodies. HCV genomics, especially the high mutation rate of E2 region sequence, makes its genotyping more and more diverse, and the detection of HCV and genotype is becoming more and more strict. In this study, four HCV B cell epitope polypeptides were constructed based on assessment of conserved sequences in the HCV E2 region and prediction of B cell epitopes, including sequences specific to genotype 1A (DC-13: 434-DTGWLAGLFYYHK-446), genotype 1B (HC-13: 434-HTGFLAALFYAKS-446), genotype 4D (NC-13: 434-NTGFLASLFYTHK-446), and a consensus sequence (FC-9: 447-FNSSGCPER-455). Epitope polypeptides combined with serum from 29 HCV-infected or 25 non-HCV-infected individuals were assayed by enzyme-linked immunosorbent assay (ELISA), and differences were analyzed by T/T’ test methods in SPSS v20.0 software. Binding levels of genotype 1A, 4D, and consensus epitope polypeptides with sera of HCV-infected patients were higher than those of non-infected individuals. Moreover, binding of genotype 1B epitope polypeptides with serum of HCV 1B-infected patients was higher than that of HCV 2A-infected patients. While the screening results of HCV genotype-specific epitope polypeptides were preliminary, these findings indicated that we successfully established an HCV and genotype serological ELISA detection method. Such an approach would facilitate the discovery of epitope polypeptides which may become new antigen candidates in peptide vaccine development for the prevention of HCV infection.