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.
ObjectiveTo observe the clinical efficacy of combined immunosuppressant therapy for patients with chronic refractory immune thrombocytopenia purpura (ITP) and its effects on platelete-associated antibody (PAIG) level. MethodsBetween February 2009 and February 2013, 22 patients with refractory ITP were randomly divided into immunosuppressive drugs combination treatment group and single drug treatment group. The combination treatment group was treated with methylprednisolone and intravenous immunoglobulin (IVIG), and after the fast increasing of platelet count, combined chemotherapy consisting of two or three kinds of immunosuppressive agents was adopted. The single treatment group was also treated with methylprednisolone and IVIG, but took only one immunosuppressive agent after the fast increasing of platelet count. The treatment maintained for 3 to 6 months. The duration of follow-up was 6-36 months. We used flow cytometry to detect PAIG of the patients. ResultsThe total effective rate of combination treatment group was 81.8%, significantly higher than that of the single treatment group (36.4%) (P<0.05). PAIG decreased obviously in both the two groups, and the PAIG level of the combination treatment group was much lower than that of the single treatment group (P<0.05). ConclusionImmunosuppresant combination chemotherapy is a powerful approach for patients with refractory ITP, and it can decrease patient's PAIG level simultaneously.
The corticosteroids are the firstline therapeutical agents for noninfectious uveitis patients, but systemic corticosteroids are ineffective for some chronic or recurrent patients, and have many long term usagerelated side effects; these patients may need treatment of immunosuppressive agents and/or biologic agents. However, the mechanism, indication, efficacy and sideeffects of each type of the immunosuppressive agents or biologic agents are not identical. In clinical practice, we should use different and sensitive immunosuppressive agents or biologic agents for different types of uveitis, and watch their efficacy and toxic effects closely. In order to improve the effectiveness of the treatment, the classification, efficacy and existing concerns of commonly used uveitis drugs need to be further clarified.
ObjectiveTo investigate the diagnosis, clinical features, treatment and outcome of pure red cell aplasia (PRCA) caused by human parvovirus B19 (HPV-B19) infection in kidney recipients. Method The clinical courses of six patients with PRCA caused by HPV-B19 infection after renal transplantation in West China Hospital between May 2018 and April 2019 were retrospectively investigated. Results The six patients showed obvious anemia symptoms, lacking rash, joint pain and other clinical symptoms of viral infection. The hemoglobin level of five patients got totally remission from a course of intravenous immunoglobulin (IVIG) treatment, and anemia symptoms like fatigue, weakness got notable improvement. One patient had no improvement after two courses of IVIG treatment, and his anemia was significantly improved after the third IVIG course combined with immunosuppressant conversion(from tacrolimus to cyclosporine), and one patient with recurrence accepted a repeated course of IVIG treatment and obtained remission of severe anemia again. The median time of reticulocyte firstly rose to above 0.084×1012/L from the day of IVIG treatment ended was 3.50 (1.25, 5.00) days, and the median time required for a 30 g/L increase in hemoglobin to the end of IVIG treatment was 16.00 (9.25, 31.25) days. No serious adverse reactions occurred and all patients had stable graft function. Conclusions The main clinical manifestations of PRCA caused by HPV-B19 infection after kidney transplantation are anemia symptoms, lacking other clinical symptoms of viral infection. HPV-B19 DNA detection combined with blood routine examination, reticulocyte count and bone marrow cytology (or none) can diagnose HPV-B19 infection. High dose of IVIG is effective and safe, and a repeated course is still effective when the infection recurs. For refractory PRCA that IVIG monotherapy fail, a combination with conversion from tacrolimus to cyclosporine can effectively improve the anemia without graft dysfunction.
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。
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.
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.