加味甘草干姜汤联合维生素B12治疗复发性口腔溃疡的临床效果

目的：探讨加味甘草干姜汤联合维生素B12治疗复发性口腔溃疡（ROU）的临床效果。方法：选取2016年8月至2018年8月重庆市人民医院收治的ROU患者124例作为研究对象，随机分成观察组和对照组，每组62例。对照组口服维生素B12治疗，观察组在此基础上内服加味甘草干姜汤治疗，疗程均为14 d。比较2组疗效及安全性。结果：观察组总有效率达96.8%（60/62），显著高于对照组85.5%（53/62），差异有统计学意义（P<0.05）。与治疗前比较，2组治疗后疼痛指数、溃疡面积和平均溃疡期均显著改善，差异有统计学意义（P<0.05），外周血CD3+、CD4+水平和CD4+/CD8+比值及唾液中链球菌、韦荣菌数量均显著上升，差异有统计学意义（P<0.05），外周血CD8+水平均显著下降，差异有统计学意义（P<0.05）；且观察组比对照组对以上指标的改善更显著，差异有统计学意义（P<0.05）。2组均未见明显不良反应。随访6个月，观察组复发率为11.3%（7/62），较对照组的25.8%（16/62）显著降低，差异有统计学意义（P<0.05）。结论：加味甘草干姜汤联合维生素B12治疗ROU的整体疗效确切，可能与其显著纠正外周血T淋巴细胞亚群免疫失衡、维持口腔微环境稳态有关。     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

龙胆泻肝胶囊治疗肝胆湿热型分泌性中耳炎临床研究

目的:研究龙胆泻肝胶囊治疗肝胆湿热型分泌性中耳炎(SOM)的效果。方法:选取78例肝胆湿热型分泌性中耳炎患者,按随机数字表法分为试验组和对照组各39例。2组均采用鼓膜穿刺术治疗,对照组术后给予头孢克洛和氯雷他定抗感染治疗,试验组给予龙胆泻肝胶囊。评价2组治疗效果,检测治疗前后血清干扰素γ(IFN-γ)和白细胞介素-4(IL-4)水平,计算IFN-γ/IL-4,进行中医证候评分,观察患耳含积液情况。结果:试验组总有效率为92.31%,高于对照组71.79%(P<0.05)。治疗前,2组IFN-γ、IL-4和IFN-γ/IL-4比较,差异无统计学意义(P>0.05)。治疗后,2组IFN-γ、IL-4和IFN-γ/IL-4较治疗前降低,且试验组IFN-γ、IL-4和IFN-γ/IL-4均低于对照组,差异均有统计学意义(P<0.05)。治疗前,2组各项中医症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组各项中医症状评分及总分较治疗前降低,试验组各项中医症状评分及总分均低于对照组,差异有统计学意义(P<0.05)。试验组耳内含积液率为71.79%,低于对照组89.74%(P<0.05)。结论:采用龙胆泻肝胶囊治疗肝胆湿热型分泌性中耳炎,疗效令人满意,能够显著改善患者症状,可下调IFN-γ、IL-4表达,调节Th1/Th2平衡,值得临床推广应用。     

复发性口腔溃疡免疫细胞的效应

复发性口腔溃疡是口腔科常见多发性疾病,与多种因素导致的自体免疫失衡有关。表现为免疫细胞活性和数量上的改变,特别是高表达或不正常表达CD4+、 CD8+细胞以及 CD4+/ CD8+的改变,并伴有多种细胞因子的变化,包括 IL-2 、IL-6、IL-8﹑IL-10、INF-γ 和TNF-α等多种细胞因子的异常表达以及相关细胞因子的基因突变导致的基因多态性。T淋巴细胞介导的细胞免疫在复发性口腔溃疡疾病的发生、发展过程中起重要作用。     

New immunosuppressive agents in transplantation

Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.     

Treponemal antibody in CSF and cellular immunity in peripheral blood of syphilitic patients with persisting positive rapid plasma regain

The ratio of patients with RPR constant positive more than 2 years despite receiving standard syphilis treatment has been reported to be 11.54%~31.3%. The current interpretations on this phenomenon are cellular immune function restrained and the existence of neurosyphilis or asymptomatic neurosyphilis. We conducted this study to detect the treponemal antibody in cerebrospinal fluid (CSF) and lymphocyte subsets in peripheral blood of syphilis patients with persisting RPR positive more than 2 years without neurologic signs, and then explore their relationship. In this study, Treponemal antibody in CSF of 46 syphilitic with HIV negative were measured by syphilis serum test and compared with that of 5 neurosyphilis. Lymphocyte subsets were measured by flow cytometry (FCM) and compared with that of 30 healthy controls. We observed that treponemal antibody in CSF was detected not only in 12 cases (25.21%) of 46 treated patients, but also in 5 neurosyphilis. The ratio of lymphocyte subsets revealed that CD3⁺, CD4⁺ T cells and natural killer (NK) cells showed no significant differences between the patient and healthy controls (P > 0.05), while CD8⁺ T cells in patients were significant higher than that in healthy controls (P < 0.001). Lymphocyte subsets showed no significant differences between the patients with treponemal antibody positive and negative in CSF (P > 0.05). In conclusion, the treponemal antibody in CSF of treated patients suggests that part of them were asymptomatic neurosyphilis and with cellular immunodifeciency. And there is no significant relationship between asymptomatic neurosyphilis and cellular immunodeficiency in peripheral blood.     

辅助性T淋巴细胞17在肝细胞癌发生发展中的作用

肝细胞癌是世界上最常见的恶性肿瘤之一,对于如何提高肝细胞癌治愈率和降低其复发及转移一直是人们研究的重点。辅助性T淋巴细胞(Th)17是一种重要的CD4+Th亚型,在感染、自身免疫反应及肿瘤微环境中具有重要作用。介绍了Th17及其相关细胞因子的发现,归纳了其在肝细胞癌发生及进展过程中的作用机制及相关临床意义,为Th17在肝细胞癌治疗新靶点及判断预后方面提供一些见解。     

Short-term prognostic effects of circulating regulatory T-Cell suppressive function and vascular endothelial growth factor level in patients with non-small cell lung cancer and obstructive sleep apnea

ObjectiveTo determine if suppressive function of regulatory T-cells (Tregs) and vascular endothelial cell growth factor (VEGF) levels are closely associated with prognosis of patients with non-small cell lung cancer (NSCLC) and obstructive sleep apnea (OSA).MethodsPeripheral blood from 20 OSA patients, 44 newly diagnosed NSCLC patients with (n = 22) and without (n = 22) OSA was collected. Forkhead box protien 3 plus (Foxp3⁺) and CTLA-4⁺ Tregs ratio were analyzed with flow cytometry. Levels of VEGF, IL-10 and TGF-β₁ were analyzed with enzyme-linked immuno sorbent assay. NSCLC patients with and without OSA were followed up for two years. Optimal cutoff values were determined by receiver operating characteristic curves. Survival analysis were performed using the Kaplan–Meier test.ResultsNSCLC patients with OSA showed higher Foxp3⁺Tregs ratio, higher plasma VEGF and TGF-β₁ levels when compared with NSCLC patients without OSA (P < 0.05). In NSCLC patients with OSA or not, subjects with higher Foxp3⁺Treg ratio, higher TGF-β₁ and VEGF levels tended to have poor mean survival time and two-year overall survival (OS, Foxp3⁺Treg: 636.7 vs. 704.8 days, 59.0% vs. 82.6%, P = 0.125; TGF-β₁: 637.8 vs. 698.4 days, 57.0% vs. 84.4%, P = 0.054; VEGF: 642.9 vs. 677.5 days, 48.6% vs. 81.3%, P = 0.074). Multivariate Cox regression adjusted for disease stage and receipt of systemic treatments, confirmed the links between high VEGF level and worse OS (HR: 1.003; 95% CI: 1.001–1.005; P = 0.021).ConclusionsOSA may up-regulate the expression of circulating TGF-β₁, VEGF and Foxp3⁺Tregs expression in NSCLC patients. Elevated VEGF level is closely associated with worse short-term survival in NSCLC patients with OSA or not.