间充质干细胞治疗支气管肺发育不良的研究进展

支气管肺发育不良( bronchopulmonary dysplasia,BPD)常见于早产儿。20世纪80年代以来随着医疗技术的提高,早产儿成活率逐渐升高,同时BPD发病率也逐渐增加。目前,BPD的常规治疗并不理想,故亟需寻求一种新创性疗法减轻BPD造成的呼吸系统损伤,提高生活质量。近年来,间充质干细胞( mesenchymal stem cell,MSC)的研究为BPD的治疗提供了新切入点。该文就MSC治疗BPD的可能作用机制及目前研究现状进行了初步探讨。     

Rehabilitative intervention during and after pediatric hematopoietic stem cell transplantation: An analysis of the existing literature

Hematopoietic stem cell transplantation is a therapeutic strategy for several oncohematological diseases. It increases survival rates but leads to a high incidence of related effects. The objective of this paper was to examine the existing literature on physical exercise interventions among pediatric HSCT recipients to explore the most often utilized rehabilitative assessment and treatment tools. Studies published from 2002 to April 1, 2015 were selected: 10 studies were included. A previous literary review has shown that rehabilitation programs have a positive impact on quality of life. Our analysis identified some significant outcome variables and shared intervention areas.     

Safety of peritoneal and pleural drain placement in pediatric stem cell transplant recipients with severe veno‐occlusive disease

Hepatic VOD (veno‐occlusive disease) is a serious complication of HSCT (hematopoietic stem cell transplantation) and has historically been associated with high mortality. This obstruction to hepatic flow often results in fluid collections in the peritoneal and pleural cavities. Catheter placement to drain ascites or pleural fluid may reduce intra‐abdominal hypertension and/or improve respiratory parameters. The safety of these interventions among critically ill, immunocompromised children is unknown. Among 32 HSCT recipients (2000–2012) with severe VOD, we assessed the primary outcome of procedural complication from peritoneal drain placement. Twenty‐four (75%) patients underwent peritoneal drain placement. No patient sustained visceral perforation or hemorrhage with drain placement. Overall mortality was 47% (n = 15). The procedure was not associated with increased overall mortality (p > 0.99). Eight (25%) peritoneal drains required replacement for malfunction. Of 24 patients with peritoneal drains, one (4%) patient had a positive culture from ascitic fluid. Eight (25%) patients underwent pleural drain placement. No pleural drain‐related procedural complication or infection occurred. Four (50%) of the eight patients with pleural drains had de‐escalation in oxygen requirement at drain removal, compared to time of placement. In this study, peritoneal and pleural drains were safe interventions for children with severe VOD.     

Haploidentical hematopoietic stem cell transplantation for paediatric high‐risk T‐cell acute lymphoblastic leukaemia

Paediatric HR T‐cell ALL demonstrates dismal prognosis with chemotherapy, and poor outcomes could be improved with allo‐SCT. HID‐SCT is an almost immediately available choice; however, few studies have focused on the outcomes of HID‐SCT for paediatric HR T‐ALL. Forty‐eight consecutive HR T‐ALL children who underwent HID‐SCT were included. Survival outcomes and factors predictive of outcomes were retrospectively analysed. Of the 48 patients, 35 were in CR1, 10 in CR2, and three in relapse. The cumulative incidence of grade 3/4 aGVHD was 10.4% and that of extensive cGVHD was 28.4%. The CIR at three yr was 30.8% and that of NRM at three yr was 14.7%. At a median follow‐up of 20.0 (range 2.5–124.2) months, the three‐yr LFS was 54.4%. Children who received transplants during CR1 had a better LFS (65.7% vs. 26.0%, p = 0.008) and a lower relapse rate (19.8% vs. 56.7%, p = 0.014) compared to those during non‐CR1. HID‐SCT is feasible for HR T‐ALL children, and survival outcomes are better when performed in CR1 compared to non‐CR1. Prospective clinical trials would be needed to confirm that.     

非血缘脐血干细胞移植治疗X连锁慢性肉芽肿7例

目的探讨非血缘脐血干细胞移植(UR-UCBT)治疗X连锁慢性肉芽肿(X-CGD)的疗效。方法回顾性分析2007年5月至2015年5月海军总医院收治7例X-CGD患儿进行UR-UCBT的临床资料并复习相关文献。给7例X-CGD患儿进行UR-UCBT,6例为单份脐血,1例为双份脐血。HLA配型4例全相合,2例5个位点相合,1例4个位点相合。预处理选用白消安/环磷酰胺/兔抗人T-淋巴细胞免疫球蛋白(ATG),其中6例在其基础上加氟达拉滨(Flu)。于0 d回输脐血,有核细胞中位数为8.51×10~7/kg,CD34~+细胞中位数为3.81×10~5/kg。预防移植物抗宿主病(GVHD)采用环孢霉素A/吗替麦考酚酯,其中1例在其基础上加甲基泼尼松龙。结果 ANC≥0.5×10~9/L和PLT≥20×10~9/L的中位天数分别是+14 d和+30 d。4例出现Ⅰ~Ⅲ度急性GVHD,给予激素后均控制。在+30 d所有患儿通过PCR-SSO/FISH检测均为供者型完全嵌合。ECGD酶活力均于+1个月恢复正常。CYBB基因异常者+2个月未检测出突变基因。随访中位时间10(5~101)个月,未发生慢性GVHD,1例+3个月死于心功能衰竭,现存活6例酶活力均恢复正常,为无病存活。结论非血缘脐血能快速有效的提供造血干细胞,能耐受HLA多个位点不相合,UR-UCBT可对X-CGD起到根治性治疗作用。     

全膝关节翻修术中采用金属垫片结合髓内延长杆重建骨缺损和关节稳定性的早期临床疗效

目的探讨全膝关节翻修术中采用金属垫片结合髓内延长杆重建非包容性骨缺损和关节稳定性的早期临床疗效。方法笔者自2013-12—2015-06对17例(17膝)AORIⅡ型非包容性骨缺损患者进行全膝关节翻修术,采用金属垫片重建骨缺损,恢复关节线水平,联合使用髓内延长杆加强翻修假体的稳定性。结果所有患者获得平均30.5(6~45)个月随访,无髌骨脱位、伸膝迟滞及膝关节前方疼痛等。术前膝关节KSS临床评分(24.5±7.9)分,功能评分(33.8±8.9)分,术后膝关节KSS临床评分(82.2±6.8)分,功能评分(85.5±8.1)分,术后KSS评分较术前明显提高,差异有统计学意义(t=41.328,P0.001;t=31.116,P0.001);膝关节活动度术前(63.9±9.9)°,术后(100.0±9.5)°,术后较术前明显提高,差异有统计学意义(t=8.512,P0.001);术后复查X线示假体位置及力线良好,假体周围未发现透亮带。结论全膝关节翻修术中采用金属垫块结合髓内延长柄能重建非包容性骨缺损及增加膝关节稳定性,恢复关节线水平,重建软组织平衡,简化手术操作,膝关节稳定性好,翻修成功率高,早期临床疗效满意。     

Concepts in regenerative medicine: Past,present, and future in articular cartilage treatment

Regenerative medicine is emerging with great interest and hope from patients, industry, academia, and medical professionals. Cartilage regeneration, restoration, or repair is one of the prime targets that remains largely unsolved, and many believe that regenerative medicine can possibly deliver solutions that can be widely used to address the current gap(s) in treatment. In the United States, Europe, Australia, and India the regulation of regenerative based treatments has become a big debate. Although the rules and regulations remain unclear, clinicians that are interested should carry-on with the best available guidelines to ensure safety and compliance during delivery in clinical practice to avoid regulatory infraction. Many have made significant investment of time, resources, and facilities in recent years to provide new regenerative treatment options and advance medical care for patients. Instead of reinventing the wheel, it would be more efficient to adopt currently accepted standards and nomenclature borrowed from transplantation science, and cord blood storage industries. The purposes of this article are to provide some historical background to the field of regenerative medicine as it applies to cartilage, and how this field has developed. This will be followed by a separate discussion on regulatory oversight and input and how it has influenced access to care. Furthermore, we discuss current clinical techniques and progress, and ways to deliver these treatments to patients safely, effectively, and in a cost sensitive manner, concluding with an overview of some of the promising regenerative techniques specific to cartilage.     

Humanized Mouse Models for Transplant Immunology

Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models and translated into clinical practice; however, many of the newly available drugs are human‐specific reagents. Furthermore, many species‐specific differences exist between mouse and human immune systems. Recent advances in the development of humanized mice, namely, immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important preclinical model system for evaluation of new drugs and identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as preclinical models for the study of human allograft responses.