Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

AIM:To investigate immunosuppressive agents used to treat inflammatory bowel disease(IBD)in East China. METHODS:A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital,College of Medicine,Zhejiang University from June 2000 to December 2007.Data regarding demographic,clinical characteristics and immunosuppressants usage were analyzed. RESULTS:A total of 227 eligible patients were evaluated in this study,including 104 patients with Crohn’s disease and 123 with ulcerative colitis.Among the patients,61 had indications for immunosuppressive agents use.However,only 21 (34.4%)received immunosuppressive agents.Among the 21 patients,6(37.5%)received a subtherapeutic dose of azathioprine with no attempt to increase the dosage.Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo,15 patients went into remission,four patients were not affected and one relapsed.Among these 20 patients,four patients suffered from myelotoxicity and one suffered from hepatotoxicity.CONCLUSION:Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries.Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.

Novel immunosuppressive agents in kidney transplantation

Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.

Systematic Review and Meta-analysis:Immunosuppressive Agents for the Treatment of Primary Biliary Cholangitis

Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selected by searching PubMed,Web of Science and Cochrane Library databases.The primary outcome was defined as the need for mortality or liver transplantation.Adverse effects and liver biochemical variables were a secondary outcome.Results:Nine randomized controlled trials,involving six different treatment regimens with a total of 996 patients,were included in the analysis.On meta-analysis,IAs was not associated with a reduction in risk of mortality or liver transplantation(risk ratio[RR]:0.92,95% confidence interval[CI]:0.69-1.22,P=0.57,P=0%),and have resulted in more adverse effects(RR:1.44,95%CI:1.08-1.92,P=0.01,P=19%).Subgroup analysis showed that IAs monotherapy caused adverse effects such as diarrthea,abdominal pain,and renal insufficiency(RR:1.36,95% CI:1.01-1.82,P=0.04,P=48%).IAs therapy did not prominently improve markers of liver function except for alkaline phosphatases(weighted mean difference[WMD]:-0.38,95% CI:-0.62 to-0.14,P=0.002).Conclusions:IAs cannot reduce the risk of mortality or liver transplantation,whether in IAs monotherapy or combination therapy,and even be associated with more adverse effects.

Current state of renal transplant immunosuppression:Present and future

For kidney transplant recipients, immunosuppression commonly consists of combination treatment with a calcineurin inhibitor, an antiproliferative agent and a corticosteroid. Many medical centers use a sequential immunosuppression regimen where an induction agent, either an anti-thymocyte globulin or interleukin-2 receptor antibody, is given at the time of transplantation to prevent early acute rejection which is then followed by a triple immunosuppressive maintenance regimen. Very low rejection rates have been achieved at many transplant centers using combinations of these agents in a variety of protocols. Yet, a large number of recipients suffer chronic allograft injury and adverse events associated with drug therapy. Regimens designed to limit or eliminate calcineurin inhibitors and/or corticosteroid use are actively being pursued. An ideal immunosuppressive regimen limits toxicity and prolongs the functional life of the graft. This article contains a critical analysis of clinical data on currently available immuno-suppressive strategies and an overview of therapeutic moieties in development.

Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents?

Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT recipients.Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly tolerated.To improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been developed.The aim of this review is to summarize the use of DAAs in LT HCV patients.PubMed,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this purpose.To date,only three clinical studies on the topic have been published and most of the available data are in abstract form.Although a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness.Moreover,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable.In conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.

Protective effect of glucocorticoid-free immunosuppressive regimen in allogenic islet transplantation

BACKGROUND: The most common complication after allogenic islet transplantation is rejection. This study was to evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation. METHODS: Tacrolimus(FK506)+mycophenolate mofetil (MMF) and FK506+MMF+prednisone (Pred) were administered respectively for 2 weeks to inhibit rejection after allogenic islet transplantation in rats, which were compared with the control group. The concentrations of blood glucose, insulin and C-peptide were determined dynamically in recipients and the sites of transplantation were observed morphologically. RESULTS: As compared with the control group without immunosuppressive agents, FK506+MMF and FK506+MMF+Pred could prolong the survival time of grafts significantly. There were many morphologically intact islets in the liver of recipients 2 months after transplantation. Group FK506+MMF kept normal levels of blood glucose, insulin and C-peptide beyond 60 days after transplantation. In contrast, group FK506+MMF+Pred secreted less C-peptide(P<0.05) and maintained a higher level of blood glucose concentration (P<0.01) after the operation. There was no significant difference in insulin concentrations between the two groups. The level of blood glucose beyond the first 2 weeks after drug withdrawal in group FK506+MMF+Pred decreased obviously (P<0.05), and the secretion of insulin and C-peptide increased. These results were compared with those the first 2 weeks after transplantation and the first 2 weeks after drug withdrawal. CONCLUSIONS: Both regimens of FK506+MMF and FK506+MMF+Pred could provide effective immunosup-pression. Moreover the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side-effects.

血清IL-2、sST2表达与特发性膜性肾病免疫抑制剂治疗反应性的相关性

目的探讨特发性膜性肾病患者血清白介素-2(IL-2)、可溶性生长刺激表达基因2蛋白(sST2)表达水平与免疫抑制剂治疗反应性的相关性。方法选取2020年1月至2022年10月于医院接受免疫抑制剂治疗的135例特发性膜性肾病患者,于入院时检测患者血清IL-2、sST2,并于治疗完成后测定24 h尿蛋白定量,依据患者治疗反应性分为缓解组与未缓解组。对比两组患者一般资料及入院时血清IL-2、sST2水平,采用点二列相关性分析血清IL-2、sST2水平与特发性膜性肾病免疫抑制剂治疗反应性的关系,并绘制受试者工作特征(ROC)曲线评估血清IL-2、sST2水平预测特发性膜性肾病免疫抑制剂治疗反应性的价值。结果135例特发性膜性肾病患者中共有132例完成规律治疗,经免疫抑制剂治疗6个月后,101例患者疾病缓解,纳入缓解组,其余31例患者纳入未缓解组。未缓解组年龄、入院时肾功能分级、疾病分期、血清IL-2、sST2水平均高于缓解组,差异有统计学意义(P<0.05);点二列相关性分析显示,血清IL-2、sST2水平与特发性膜性肾病免疫抑制剂治疗反应性不良风险呈正相关(r 1=0.428,P 1<0.001;r 2=0.344,P 2<0.001);绘制ROC曲线,结果显示,血清IL-2、sST2预测特发性膜性肾病免疫抑制剂治疗反应性不良的曲线下面积均>0.7,具有一定预测价值,且联合预测价值更高。结论血清IL-2、sST2表达水平与特发性膜性肾病患者免疫抑制剂治疗反应性密切相关,二者表达水平越高,治疗反应性越差,且联合检测可作为预测特发性膜性肾病患者免疫抑制剂治疗反应性的敏感指标。

1例糖尿病合并疑似肝移植术后免疫抑制剂致高脂血症患者的药学监护

目的为糖尿病合并肝移植术后免疫抑制剂致高脂血症患者的临床合理用药和药学监护提供参考。方法临床药师参与1例糖尿病合并疑似肝移植术后免疫抑制剂致高脂血症患者的治疗过程。由于患者血糖控制不佳,临床药师与医生共同调整降糖方案为三餐前分别皮下注射赖脯胰岛素注射液18、12、16单位,睡前皮下注射甘精胰岛素注射液16单位;由于患者发生高脂血症,临床药师结合相关指南并通过梳理其免疫抑制剂剂量调整时间轴及血脂水平变化趋势,明确血脂异常升高的可能诱因为免疫抑制剂,建议给予瑞舒伐他汀钙片5 mg,qd降脂治疗,分别将吗替麦考酚酯胶囊和他克莫司胶囊降至500 mg,bid和2 mg,bid,并开展用药宣教及药学监护。结果医生采纳临床药师的建议。患者经治疗后,血糖、血脂水平明显改善,准予带药出院。结论临床药师通过建议加用他汀类药物、调整免疫抑制剂剂量、开展药学监护等药学服务手段,优化患者个体化用药方案,保障了患者用药的安全性和有效性。

长期使用传统免疫抑制剂治疗皮肤病的不良反应比较

目的:比较患者长期(>12周)使用各传统免疫抑制剂后出现的不良反应。方法:收集2019年1月至2023年10月期间长时间(>12周)使用甲氨喋呤、环磷酰胺、环孢素、吗替麦考酚酯和沙利度胺药物的患者检查资料,对血常规、肝功能、肾功能实验室检查进行回顾性分析。结果:共1507例使用传统免疫抑制剂患者纳入分析,其中甲氨喋呤1142例,环磷酰胺135例,环孢素67例,吗替麦考酚酯66例,沙利度胺97例,不良反应发生率分别为:38.18%,56.30%,44.30%,27.27%,22.39%。最常见的不良反应依次为肝功能损伤(24.22%),肾功能损伤(12.61%)和骨髓抑制(9.69%)。患者使用免疫抑制剂引起的不良反应发生率与用药时长存在相关性。结论:长期服用传统免疫抑制剂可导致不良反应的发生,最常引起不良反应的药物为环磷酰胺。因此,对于长期服用此类药物的患者应进行定期监测。

劈离式肝移植术后成功妊娠分娩1例并文献复习

目的探讨劈离式肝移植(SLT)术后患者妊娠分娩的临床管理经验。方法收集1例我院器官移植中心收治的SLT术后妊娠并成功分娩患者的临床资料,并复习相关文献。结果患者因“自身免疫性肝炎后肝硬化(失代偿期)”接受同种异体原位SLT,术后出现轻度急性排斥反应,经调整免疫抑制药物治疗后好转。患者术后2年自然妊娠,因既往服用麦考酚钠肠溶片,选择终止妊娠并停用该药。术后3年再次妊娠并出现移植物波动,予调整抗排异药物剂量、保肝对症治疗、先兆早产保胎治疗等处理,最终在肝移植科、产科和新生儿科等相关学科共同指导下,于孕35周剖宫产诞下1名健康女婴。结论SLT受者虽然孕期可能出现移植物功能波动、早产等情况,但在多学科共同合作、科学指导用药及密切随访监测下,亦可以获得满意预后。

风湿性多肌痛误诊为类风湿关节炎六例临床分析

目的 探讨风湿性多肌痛(PMR)的临床特点及误诊原因和防范措施。方法 回顾性分析2020年3月—2023年3月收治的被误诊为类风湿关节炎(RA)PMR 6例的临床资料。结果 本组4例无诱因出现多处外周关节轻微疼痛持续1个月~1.5年,疼痛加剧3 d;2例肩颈部肌肉僵痛,全身关节痛,并伴发热症状。6例均误诊为RA,误诊时间9 d~6个月。给予相应治疗后效果不佳,进一步完善相关检查,磁共振发现患者疼痛处无侵袭或破坏性病变,查抗环瓜氨酸肽抗体阴性,使用小剂量糖皮质激素治疗有效。详细询问家族史,并结合疼痛部位的特点及检查、试验治疗结果,最终确诊为PMR。给予小剂量糖皮质激素联合非甾体抗炎药或不同的免疫抑制剂治疗,症状消失后减量维持治疗,效果较好。结论 PMR临床表现多样化,缺少特异性实验检查指标,极其容易误诊为RA。临床医师需加强对该病的鉴别诊断能力,及时完善相关检查,减少PMR误诊或漏诊。

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

双歧杆菌四联活菌片联合抗生素对重症肺炎患儿的肺部超声评分、肠道菌群及炎症因子水平的影响

【目的】探讨双歧杆菌四联活菌片联合抗生素对重症肺炎(SP)患儿的肺部超声评分(LUS)、肠道菌群及炎症因子水平的影响。【方法】选取2021年1月至2023年8月本院收治的102例SP患儿,依据随机数字表法分为对照组(常规对症治疗及抗生素治疗)和观察组(在对照组的基础上联合双歧杆菌四联活菌片),每组51例。比较两组临床疗效及治疗前后肺功能指标[第1秒用力呼气容积(FEV_(1))、肺活量(VC)、LUS]、肠道菌群(大肠杆菌、双歧杆菌、肠球菌、乳酸杆菌)、炎症因子[白细胞介素(IL-10)、C反应蛋白(CRP)、可溶性细胞间黏附分子1(sICAM-1)、肿瘤坏死因子(TNF-α)]水平。【结果】观察组总有效率高于对照组,差异有统计学意义(P<0.05)。治疗后,两组FEV_(1)及VC高于治疗前,两组LUS低于治疗前,且观察组与对照组比较,差异有统计学意义(P<0.05);两组双歧杆菌、乳酸杆菌水平高于治疗前,肠球菌及大肠杆菌低于治疗前,且观察组与对照组比较,差异有统计学意义(P<0.05);两组血清IL-10水平高于治疗前,CRP、sICAM-1、TNF-α水平低于治疗前,且观察组与对照组比较,差异有统计学意义(P<0.05)。【结论】双歧杆菌四联活菌片联合抗生素治疗SP患儿临床疗效较好,可抑制炎症反应,改善患儿肺功能。

结缔组织病相关间质性肺病合并肺癌16例临床分析

目的对16例结缔组织病相关间质性肺病(CTD-ILD)合并肺癌患者的临床特点进行分析,以提高对该类疾病的认知。方法回顾性分析住院治疗的CTD-ILD合并肺癌的16例患者的临床资料,包括一般资料、临床表现、辅助检查、肺癌病理分型、TNM分期、治疗及预后。结果16例CTD-ILD合并肺癌患者中男12例,女4例;CTD-ILD确诊时平均年龄(64.7±9.2)岁,肺癌确诊时平均年龄(66.6±8.7)岁。合并肺癌患者以影像学发现肺占位(62.5%)为最常见的首发症状,其次为咳嗽咳痰、胸痛(各占12.5%)。肺癌病理类型以腺癌(8例,50.0%)最常见,其次为小细胞肺癌(4例,25.0%)。CTD-ILD确诊时间早于肺癌者(8例,50.0%)最常见,中位时间36.0(11.3,57.0)个月,其次为同时确诊者7例(43.8%),CTD-ILD确诊时间晚于肺癌者1例(6.3%)。肺癌TNM分期以Ⅳ期(9例,56.25%)最常见。16例患者随访1~64个月,中位时间8.5(1.5,14.3)个月;11例(68.8%)死亡,8例(72.7%)死于感染,3例(27.3%)死于终末期肺癌。结论对于CTD-ILD患者需密切随访,定期进行影像学的监测,有助于早期发现肺癌,改善预后。

文拉法辛联合美多芭治疗对帕金森病伴抑郁患者心理状态及运动功能的影响

【目的】探讨文拉法辛联合美多芭治疗对帕金森病伴抑郁患者心理状态及运动功能的影响。【方法】98例帕金森病伴抑郁患者随机分为观察组和对照组,每组49例。对照组口服美多芭治疗,观察组另给予盐酸文拉法辛缓释胶囊治疗。治疗前和治疗8周后,比较两组患者的心理状态[汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD-24)]、运动功能[帕金森病评定量表第三部分(UPDRSⅢ)、起立行走测试(TUGT)、Berg平衡量表(BBS)]、炎症因子[白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)]、生活质量[帕金森病症生活品质问卷(PDQ-39)和WHO生活质量评价量表(QOL)]及不良反应发生率。【结果】两组患者治疗后HAMA、HAMD-24评分较治疗前显著降低(P<0.05),且观察组上述评分均低于对照组(P<0.05)。两组治疗后UPDRSⅢ、TUGT较治疗前降低,BBS评分较治疗前升高(P<0.05),且观察组各项指标优于对照组(P<0.05)。两组治疗后IL-2、TNF-α、CRP较治疗前降低(P<0.05),且观察组低于对照组(P<0.05)。两组治疗后PDQ-39评分较治疗前降低,QOL评分较治疗前升高(P<0.05),且观察组各项评分优于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。【结论】文拉法辛联合美多芭能有效改善帕金森病伴抑郁患者的抑郁状态,增强其运动功能,提高生活质量,值得临床推广应用。

22例获得性血友病A患者的临床特点及预后

目的探讨获得性血友病A(AHA)患者的临床特点及治疗结局。方法AHA患者22例为研究对象,收集一般临床资料(人口统计学数据、基础疾病、出血部位及发病至确诊时间等);抽取AHA患者空腹静脉全血,采用凝血分析仪检测凝血功能指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)及国际标准化比值(INR)],采用Bethesda法检测血浆凝血因子抗体并确定高低抗体滴度、凝血分析仪检测凝血因子Ⅷ活性(FⅧ:C)及判断减低程度;所有患者行人重组活化凝血因子Ⅶ(rFⅦa)、凝血酶原复合物(PCC)及1-去氨基-8-d-精氨酸血管加压素(DDAVP)等一般止血治疗及相关的清除抗体治疗[糖皮质激素(GC)单用或联合环磷酰胺(CTX),利妥昔单抗(RTX)单用或联合GC或其他免疫抑制剂如环孢素(CsA)、他克莫司(FK506)等]治疗并随访收集患者治疗、生存情况、出血情况、血常规、FⅧ抗体滴度变化、抗体清除时间、治疗相关不良事件及死因等。结果22例AHA患者男女比例为1∶2.14,起病中位年龄59.95岁;有出血表现19例,严重出血13例;诊断时FⅧ∶C中位数1.37%、FⅧ抗体平均滴度6.9×10^(-3) BU/L,高滴度FⅧ抗体组和低滴度FⅧ抗体组AHA患者出血严重程度比较、差异有统计学意义(P<0.05);rFⅦa治疗11例,低滴度抗体者加大剂量FⅧ治疗4例;使用免疫抑制清除抗体治疗15例,抗体清除患者10例,平均抗体转阴时间(47.3±14.4)d,死亡4例;GC组、GC+CTX组及GC+其他药物组AHA患者的抗体清除时间比较,差异有统计学意义(P<0.05);AHA患者出现3级以上骨髓抑制8例,感染5例,库欣综合征1例。结论AHA以育龄期女性为主,出血是其主要临床表现;高滴度抗体患者及FⅧ活性重度减低患者更容易出现严重出血;止血首选rFⅦa或PCC旁路替代治疗,清除抗体可使用GC或者GC+免疫抑制剂治疗。

特发性膜性肾病患者脂代谢对免疫抑制剂联合糖皮质激素治疗效果的影响

目的探讨特发性膜性肾病患者脂代谢对免疫抑制剂联合糖皮质激素治疗效果的影响。方法86例行免疫抑制剂联合糖皮质激素治疗的特发性膜性肾病患者根据治疗效果分为未好转组和好转组,比较两组的基线资料和脂代谢指标,分析治疗效果的相关影响因素。结果治疗6个月后,86例特发性膜性肾病患者中16例未好转,占比18.60%。未好转组的TC、TG水平高于好转组(P<0.05)。Logistic回归分析显示,TC、TG水平是特发性膜性肾病患者免疫抑制剂联合糖皮质激素治疗效果的影响因素(OR>1,P<0.05)。结论特发性膜性肾病患者的脂代谢水平会对免疫抑制剂联合糖皮质激素的治疗效果产生影响。

抗体偶联药物联合免疫抑制剂治疗局部晚期或转移性尿路上皮癌的研究进展

尿路上皮癌(UC)作为一种泌尿系统常见的恶性肿瘤,其患病人数不断增加,部分患者初治时已发展为无法外科手术的局部晚期或远处转移UC(la/mUC),目前的标准治疗方案是以铂类为基础的化疗,但不良反应和治疗效果并不理想。近年来,抗体偶联药物联合免疫检查点抑制剂治疗策略正逐渐成为癌症精准医疗研究的新焦点,为该类患者带来了新的治疗选择。当前这一领域的相关临床试验取得诸多成果,该文旨在对最近的研究进展进行全面回顾。

枯草芽孢杆菌中一个受二硫键还原剂诱导并与伸长因子Tu同源的蛋白质

分析了β-巯基乙醇（β-ME）和二硫苏糖醇（DTT）对枯草芽孢杆菌（Bacillussubtilis细胞蛋白质组分的影响。在LB培养基中，β-ME和DTT处理能诱导一个50kD蛋白质（P50）的合成。在正常生长条件下P50是一个组成性（constitutive）成的细胞质蛋白质。热激也能诱寻P50，但是孢子形成（sporulation）不能诱导P50。在Schaeffer孢子形成培养基中，β-ME和DTT都不能诱导P5O，表明二硫键还原剂诱导P50的能力依赖于特定的生理条件。用VS蛋白酶有限降解P50，得到4个主要的多肽片段，测定了其中两个片段的N-端氨基酸序列。同源性检索发现P50高度同源于蛋白质合成的伸长因子Tu。

PD-1/PD-L1抑制剂在治疗恶性黑色素瘤中引起白癜风样脱色的机制及研究进展

近年来,越来越多的肿瘤患者从免疫检查点抑制剂(ICPIs)中获得了显著疗效。其中,程序性细胞死亡受体-1/配体-1(PD-1/PD-L1)抑制剂是第二代ICPIs,已被批准用于多种晚期恶性肿瘤的治疗。随着其广泛使用,免疫相关不良反应(irAEs)也逐渐引起人们的关注,白癜风就是其中一种,尤其在恶性黑色素瘤患者治疗中较多出现。本文对恶性黑色素瘤患者使用PD-1/PD-L1免疫抑制剂引起白癜风样脱色的发生机制进行综述,旨在为阐明PD-1/PD-L1与免疫相关不良反应的关系提供可能的理论依据。