Interleukin-18 (IL-18) is a potent proinflammatory cytokine, which can promote hepatitis B virus clearance. The latest studies find that genetic polymorphisms near the IL-28B gene are strongly associated with sustained viral response and spontaneous viral clearance in patients with chronically infected hepatitis C and hepatitis B. We investigated the effect of rs187238 and rs1946518 in IL-18 gene and rs8099917 in IL-28B gene on HBV recurrence in liver transplant patients. A total of 200 liver transplant recipients and relevant donors were enrolled in this study. The patients' mean follow-up was 39 month (range 10-65 month). All liver transplant recipients were in a stable stage. The total recipients (n = 200) were divided into end-stage liver disease secondary to hepatitis B (n = 140) and end-stage liver disease secondary to other diseases (n = 60) before transplantation. Recipients (n = 140) with hepatitis B before transplantation were defined to nonHBV recurrence group (n = 119) or HBV recurrence group (n = 21), which was positive for HBsAg or elevatory in HBV DNA (>2.0 × 10(2) IU mL(-1)) after transplantation. For the recipients (n = 140) had hepatitis B before transplantation, we studied the single-nucleotide polymorphisms (SNPs) of IL-18 gene (rs187238 and rs1946518) and IL-28B gene (rs8099917) by high-resolution melting (HRM) curve analysis. The serum levels of IL-18 and IFN-γ were tested by ELISA. The serums levels of IFN-γ were lower in HBV recurrence group than that in nonHBV recurrence group (P < 0.01). The genotype of IL-28B gene rs8099917 was associated with alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels in HBV-related liver transplant recipients (n = 140). The recipients with allele G (GG+GT) had higher ALT and AST levels (P < 0.05). No association was found between IL-18 gene and IL-28B gene polymorphisms with HBV recurrence in the liver transplant recipients or the donors. We identified that the IFN-γ was a protective factor of HBV recurrence after liver transplantation. The allele G of rs8099917 was associated with hepatitis B-related hepatocytes injury. The rs8099917 G allele subgroup should reinforce antiviral therapy.
Anisodamine and S. miltiorrhiza were both effective in reducing skin flap ischaemia and necrosis after mastectomy, although anisodamine was associated with a higher rate of adverse effects.
Background:The clinical value of perineural invasion (PNI) in patients with localized prostate cancer (PCa) is widely explored. However, its role in metastatic PCa (mPCa) remains unknown. Objectives: We aim to investigate the clinical significance of PNI in patients with mPCa. Materials and methods: Data of 515 mPCa patients between 2012 and 2018 were retrospectively studied. PNI and its intensity were identified by prostate biopsy. The prognostic value of PNI was evaluated by Kaplan-Meier curves and Cox proportional-hazards model. Results: Perineural invasion was detected in 170/515 (33.0%) cases. Among them 73/170 (42.9%) and 97/170 (57.1%) harbored unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. Compared to patients without PNI, those with PNI had statistically shorter castration-resistant PCa-free survival (CFS) and numerically shorter overall survival (OS) (mCFS: 15.4-vs. 18.5-Mo, p = 0.015; mOS: 63.8-vs. 71.4-Mo, p = 0.108). Patients harboring multi-PNI were associated with poorer clinical outcomes than those with uni-PNI (mCFS: 12.4-vs. 18.0-Mo, p = 0.040; mOS: 39.7-Mo vs. NR, p = 0.018) or those without PNI (mCFS: 12.4-vs. 18.5-Mo, p = 0.002; mOS: 39.7-vs. 71.4-Mo, p = 0.002). Totally, neither uni-PNI nor multi-PNI was an independent risk factor impacting survival outcomes in multivariate analyses. While remarkably, for patients with favorable/intermediate-risk mPCa, multi-PNI was an independent adverse prognosticator for both CFS and OS (CFS: HR: 1.705, 95% CI: 1.029-2.825, p = 0.038; OS: HR: 3.294, 95% CI: 1.464-7.413, p = 0.004). Discussion and Conclusion: This study filled the blank of the clinical significance of PNI in mPCa. We found that multi-PNI could distinguish men with relatively poor prognosis from patients initially regarded as with favorable survival outcomes by other prognosticators, and thus, avoid disease underestimation in this group of patients. Our finding would help physicians have a deeper understanding of the heterogeneity of mPCa and make better individualized therapeutic strategy.
BackgroundOur previous research has demonstrated decreased expression of CD4+CD25+Foxp3+ regulatory T cells (Tregs) enrolled in the pathogenesis of rheumatoid arthritis (RA). Anti-TNF-α mAb therapy could improve Tregs expansion in RA and associate with clinical amelioration of RA patients. STAT5 is reported to have effects on many aspects of immune function, particularly in regulatory T cell development.ObjectivesIn this study, we aim to monitor phosphoSTAT5 expression in Tregs and investigate its role in RA disease.MethodsFlowcytometry was employed to detect the phosphorylation level of STAT5 in CD3+CD4+ T cells, CD4+CD25high regulatory T cells and the expression of CD4+CD25+Foxp3+Tregs in peripheral blood of 20 patients with RA disease and 20 age and gender-matched normal controls. STAT5 mRNA expression in peripheral blood mononuclear cells (PBMC) were also monitored of these RA patients and normal controls.ResultsPhosphorylation level of STAT5 deceased in RA patients both in CD3+CD4+ T cells and in CD4+CD25high regulatory T cells, along with reduction of expression of CD4+CD25+Foxp3+ Tregs. Detection of mRNA also confirmed STAT5 down regulation in Tregs in RA patients.ConclusionsCompared with normal controls, the expression of CD4+CD25+Foxp3+Tregs decreased in RA patients. PhosphoSTAT5 reduction in CD3+CD4+ T cells, mainly in CD4+CD25high regulatory T cells contributed to impairment of CD4+CD25+Foxp3+ regulatory T cells in RA.ReferencesNiu Q, Cai B, Huang ZC, Shi YY, Wang LL. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2012 Sep;32(9):2731–6.Huang Z, Yang B, Shi Y, Cai B, Li Y, Feng W, Fu Y, Luo L, Wang L. Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis. Cell Immunol. 2012 Sep;279(1):25–9.Disclosure of InterestNone declared
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