【摘要】 目的 分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后出血性膀胱炎（hemorrhagic cystitis，HC）相关的危险因素，动态监测受者尿BK病毒（BK virus，BKV），分析其与HC发病的关系。 方法 回顾性分析2003年3月-2008年1月期间接受allo-HSCT的121例患者的资料，选择8个临床参数[年龄、性别、疾病类型、移植时疾病状态、供者类型、预处理方案、急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）、aGVHD的预防方案]作COX回归分析。采用SYBR Green染料实时荧光定量聚合酶链反应法对2006年9月-2008年1月42例allo-HSCT患者尿BKV载量进行动态监测，分析被检查者尿液BKV基因载量与HC发生以及严重程度的关系。 结果 121例患者中有24例发生HC，发病时间为术后0~63 d，中位时间40 d；持续时间7~150 d，中位时间22 d。Ⅱ~Ⅳ度aGVHD为HC的独立危险因素[RR=8.304，95%CI（1.223，56.396），P=0.030]。allo-HSCT受者尿液中BKV检出率为100%（42/42）。与正常人及未发生HC的allo-HSCT受者相比，HC患者尿中BKV基因载量具有更高平均峰值。 结论 Ⅱ~Ⅳ度aGVHD，尿中BKV DNA高载量与HC的发生有相关性。【Abstract】 Objective To identify the risk factors for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and define the quantitative relationship between BK virus (BKV) DNA load with HC. Methods The medical records of 121 patients undergoing allo-HSCT from March 2003 to January 2008 were retrospectively analyzed. Eight clinical parameters were selected for COX regression analysis, including age, sex, underlying disease, disease status at transplant, donor type, conditioning regimen, acute graft-versus-host disease (aGVHD), and GVHD prophylaxis. From September 2006 to January 2008, mid-stream urine samples were continuously collected from 42 patients with allo-HSCT. SYBR green real-time polymerase chain reaction, technique was utilized to define the quantitative relationship between BKV DNA load and HC. Results Twenty-four out of 121 patients developed HC. The median time of onset was 40 days after HSCT, ranged from 0 to 63 days. The disease lasted for 7 to 150 days, with a median duration of 22 days. Grade Ⅱ-Ⅳ aGVHD [RR=8.304, 95% CI (1.223,56.396); P=0.030] was identified as an independent risk factor for the occurrence of HC. BKV excretion was detected in 100% (42/42) of the recipients of allo-HSCT. When compared with asymptomatic patients and allo-HSCT recipients without HC, patients with HC had a significantly higher mean peak BKV DNA load. Conclusions Patients are at an increased risk of developing HC if they have grade Ⅱ-Ⅳ aGVHD. A correlation between the load of BKV and incidence of HC may exist.
Retinitis pigmentosa (RP) is an inherited retinal disease characterized by degeneration of retinal pigment epithelial cells. Precision medicine is a new medical model that applies modern genetic technology, combining living environment, clinical data of patients, molecular imaging technology and bio-information technology to achieve accurate diagnosis and treatment, and establish personalized disease prevention and treatment model. At present, precise diagnosis of RP is mainly based on next-generation sequencing technology and preimplantation genetic diagnosis, while precise therapy is mainly reflected in gene therapy, stem cell transplantation and gene-stem cell therapy. Although the current research on precision medicine for RP has achieved remarkable results, there are still many problems in the application process that is needed close attention. For instance, the current gene therapy cannot completely treat dominant or advanced genetic diseases, the safety of gene editing technology has not been solved, the cells after stem cell transplantation cannot be effectively integrated with the host, gene sequencing has not been fully popularized, and the big data information platform is imperfect. It is believed that with the in-depth research of gene sequencing technology, regenerative medicine and the successful development of clinical trials, the precision medicine for RP will be gradually improved and is expected to be applied to improve the vision of patients with RP in the future.
Objective To study the short and medium term effect of myocardial contractile force by implantation of endothelial progenitor cells （EPCs） in the myocardial infarction model. Methods Hundred and twenty SD rats were equally and randomly divided into experimental group and control group （60 rats in each group）. Acute myocardial infarction model was created by ligation of LAD. Autologous EPCs were purified from peripheral blood then implanted into the acute myocardial infarct site via topical injection. IMDM were used in control group. Specimens and muscle strip were harvested at 3, 6 weeks, 6, 8 and 12 months after EPCs implantation for contractile force study and to detect the expression of vascular endothelial growth factor（VEGF）, basic fibroblast growth factor （bFGF） and Ⅷ factor by immunohistology and video image digital analysis system. Results The expression of VEGF, bFGF and the microvessel counts in experimental group were much higher than those of control group（P〈 0.01） at 3, 6 weeks and 6 months after transplantation. The contractile force in experimental group was better than that in control group（P〈0.01） at the same time. But from 8 months after implantation, the contractile force and so on were not up in the experimental group. Conclusion EPCs, after being implanted into infarct myocardium, shows the ability of improvement of the contractile performance in infarcted myocardium by means of angiogenesis and vasculogenesis and the medium term results are persistent.
Replacement therapy of stem cells transplantation represents a potential treatment for neural retinal diseases. Despite the encouraging results in laboratory, the clinical application of cells replacement therapy is still difficult because the limitation of seed cells, immunologic rejection, oncogenicity and ethical problems, etc. Recent breakthrough in somatic reprogramming provides a promising solution overcoming these obstacles. Further researches on virus free reprogramming will make the clinical application of stem cell replacement therapy possible.
Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK-001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.