Objective To assess the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE (1966 to November 2009), EMbase (from inception to September 2009), and The Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcome measures for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than those taking CNIs, but no differences were found in graft function (6-42-month follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the larger number of the blood Tregs in the patients treated with Rapa does not show any correlation with better graft function. Large-sample and high-quality clinical studies with longer follow-up are needed to thoroughly assess the efficacy of immunosuppressive drugs on Tregs and to reveal whether a relationship exists between Tregs and graft function.
Objective To explore the effects of several immunosuppressants on the cell numbers of cultured rat macrophages and Schwann’s cells. Methods The macrophages and Schwann’s cells were cultured from the newborn Wistar rats. Different concentrations of methylprednisolone(10-3, 10－4,10－6 and 10－8 mol/L), CsA(10－5, 10－6, 10－7 and 10－8 mol/L) and FK506(10-6, 10－7, 10－8 and 10－9 mol/L) were administrated to the cells, while control group was given no drugs. Twentyfour, 48 and 72 hours after administration, the cells from different concentrations were measured with MTT methods respectively. Theresults were compared and analyzed statistically. Results Only high concentration methylprednisolone (10-4 mol/L) and a certain range of concentrations of CsA (10-6，10-7 and 10-8 mol/L) and FK506 (10-7,10-8 and 10-9 mol/L) can provide protection to culturedrat macrophages. Under most concentrations, CsA and FK506 had no effects onthe cell number of cultured rat Schwann’s cell. Only with high concentration CsA (10-5 mol/L) and methylprednisolone (10-3 mol/L) could significantly decreased the cell number of Schwann’s cell. Long time (72 hours) and low dosage (10-8 mol/L) administration of methylprednisolone could significantlyprotect Schwann’s cell. Conclusion High concentration methylprednisolone and some certain concentration CsA and FK506 can protect cultured rat macrophages. But high concentration CsA and methylprednisolone prohibit the proliferation of Schwann’s cells. Only long time and low dosage methylprednisolonecan protect cultured rat Schwann’s cells.
OBJECTIVE: To sum up the clinical results of allogeneic humeral transplantation with vascular anastomosis, and evaluate the clinical significance. METHODS: From September to November 1979, 1 case with humeral shaft defect of 10 cm in length and 2 cases with tibia shaft defect of 12 cm in length were repaired by allogeneic humeral transplantation with vascular anastomosis. Azathiopurine and prednisone were applied for 3 months postoperatively. All cases were followed up for 20 years. RESULTS: Case 1 recovered well with good bone union and reconstruction after operation, and could work normally. In case 2, five chronic rejections were occurred during 3 years after operation, and recovered after treatment, the allograft bone was fractured after 2 years of operation, and unioned by autogeneous iliac bone transplantation. In case 3, the distal part of allograft bone was fractured after 46 months, and unioned by autogeneous iliac bone transplantation. The middle part of allograft bone was non-unioned after 20 years follow-up in case 3, but the patient could still work normally. CONCLUSION: The clinical results of allogeneic long bone transplantation can be improved by rational tissue matching test, application of effective immunosuppressive drugs in a certain period according to the principles of modern transplantation immunology.
【摘要】目的探讨肝肠联合移植的术式、免疫抑制治疗方案与效果。方法对一中年男性短肠综合征患者施行辅助性肝肠联合移植，术后患者免疫抑制治疗采用甲波尼龙（MP）、环孢素A（CsA）、环磷酰胺（CTX）与抗淋巴细胞球蛋白（ALG）处理。结果术后观察期内移植物存活良好。结论本例采用的免疫抑制治疗方案是成功的，且手术方法操作较为简便、易行。
Objective To evaluate the safety and efficacy of steroid withdrawal in modern triple immunosuppressant (Cycloproine/Tacrolimus, Mycophenolate Mofetil and Steroid) on renal transplantation recipients. Methods We searched MEDLINE (1966-Sep. 2005), OVID (1966-2004), EMBASE (1984-2004), The Cochrane Library (Issue 4, 2005), CBMdisc (1994-2005), and handsearched 7 Chinese Journals. Randomized controlled trials (RCTs) adopting modern triple immunosuppressant, and comparing steroid withdrawal (SW), group and steroid continuing group (SC) were selected. The quality of included studies was evaluated and graded according to Cochrane Reviewer’s Handbook 4.2.5, and meta-analysis was performed by using RevMan 4.2.7 software. Results Nine RCTs including 1 681 patients (845 in SW and 836 in SC) were identified. The average follow-up time was 6-12 months. No significant difference was found in using CsA or Tac in modern triple immunosuppressant. The results of our meta-analysis showed: ① the risk of acute rejection was two times higher in SW than SC (RR 2.05, 95% CI 1.54 to 2.72, P lt;0.000 01), mainly Banff grade I (mild) (RR 1.92, 95% CI 1.16 to 3.17, P =0.01); but no significant differences were found on Banff grade II and III between the two groups. ② the rate of graft and patient survival and chronic rejection were the same between two groups. ③ Steroid withdrawal decreased the incidence of opportunistic infection (mainly caused by simplex herpes virus and Candida) and urinary tract infection. While the incidence of CMV and sepsis infection has no significant difference between two groups. Conclusion Steroid withdrawal within 3 months in modern immunosuppressive regimen ① increases the risk of Banff Grade I rejection reaction, but the moderate and severe rejection are similar between the two groups; ② doesn’t affect the rate of graft, patient survival, and chronic rejection; ③ decreases the incidence of opportunistic and urinary tract infection, but doesn’t improve the CMV infection and sepsis. To prophylaxis serious infection, steroid withdrawal is worth considering under sufficient immunosuppressive regimen. The key point is to balance the benefit and harm for individual recipients.
自1989年巴西医生Raia开展人类首例活体肝移植（living donor liver transplantation, LDLT）以来，LDLT受体的优良预后及供体的安全性逐步得到了公认，加之“脑死亡”供肝的严重匮乏，LDLT技术迅速发展并被公认为是缓解供肝来源匮乏最有效的方法之一［1，2］。LDLT技术的发展大致经历了三个阶段： ①成人→儿童间活体肝移植（简称儿童活体肝移植，pediatric living donor liver transplantation, PLDLT）； ②成人→成人间活体肝移植(adulttoadult living donor liver transplantation, ALDLT)； ③急诊活体肝移植(emergency or highurgency living donor liver transplantation, ELDLT )。LDLT技术发展的每一阶段均是对前一阶段技术的总结和升华，技术难度和复杂性也逐步增加。
Neoadjuvant chemoradiotherapy or chemotherapy combined with surgery for locally advanced esophageal cancer has become the standard treatment, and despite the survival benefit, most patients still experience postoperative recurrence and distant metastasis. Immune checkpoint inhibitors play an anti-tumor role by activating T cells, and immunotherapy has become one of the important strategies for first-line and second-line treatment of advanced esophageal cancer with the continuous evolution of immunotherapy models. Regarding neoadjuvant immunotherapy for esophageal cancer, a large number of studies are being carried out and explored, which are expected to inject new vitality into neoadjuvant therapy for esophageal cancer. This article reviews the current clinical studies on neoadjuvant immunotherapy for esophageal cancer.