AAV-based gene transfer

Gene therapy remains an attractive form of treatment for a variety of diseases, both inherited and acquired. Recent experience in clinical gene therapy has highlighted important safety issues pertaining to gene delivery in humans. As such, the choice of gene delivery system for individual applications is fundamentally important and must afford efficiency and safety. Adeno-associated viral (AAV) vectors have unique potential among the repertoire of vector systems currently available. Here, we highlight recent developments to suggest that AAV vectors will play a key role in the future deployment of genetic medicine in humans.     

Hematopoietic cell transplantation for Crohn’s disease;is it time?

INTRODUCTION Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract which commonly affects young adults. It follows a relapsing and remitting course and there is no known cure. However, approximately 10% to 15% have chronic …     

高迁移率族蛋白B1诱导巨噬细胞Janus激酶/信号转导及转录激活子通路活化的研究

目的 初步探讨高迁移率族蛋白B1(HMGB1)致炎效应的信号转导机制。方法 清洁级雄性Wistar大鼠，取其腹腔巨噬细胞，培养3d后以10mg／L HMGB1刺激。刺激完毕后直接在培养瓶中裂解细胞，分别采用免疫沉淀、免疫印迹法和凝胶阻滞分析等技术观察不同时间点Janus激酶2(JAK2)、信号转导及转录激活子—1(STAT1)以及STAT3的活化情况。结果 HMGB1可诱导大鼠腹腔巨噬细胞STAT1、STAT3在短时间内(2h)活化，其中STAT3活化最为迅速，10min即可达到活化高峰。但HMGB1不能在短时间内(2h)诱导JAK2活化。结论 JAK／STAT途径可能参与了HMGB1致炎效应的信号转导机制。     

国人全膝关节假体置换胫骨近端截骨面至腘血管距离的测量及意义

目的:测量国人全膝关节假体置换术胫骨近端截骨面后缘至腘窝血管之间的距离,以期为临床全膝关节置换术中避免损伤腘窝血管提供参考数据。方法:选择2006-06/12于解放军第二军医大学长征医院体检的50名正常成人(53膝),男29名(31膝),女21名(22膝)。所有观察对象均知情同意,且得到医院伦理道德委员会批准。对所有膝关节进行MRI扫描,在胫骨外侧平台以下10mm水平横断面上辨认腘动静脉,并测量胫骨近端截骨面后缘至腘窝动静脉的距离。结果:53膝全部进入结果分析,无脱落。①男性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.7±2.5,7.3±2.3)mm,95%可信区间分别为5.8～7.6mm,6.5～8.1mm。②女性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.6±1.9,7.1±2.7)mm,95%可信区间分别为:5.8～7.4mm,5.9～8.3mm。③不同性别观察对象胫骨近端截骨面后缘至腘血管的距离差异无显著性意义(P>0.05)。结论:腘窝血管紧邻全膝关节假体置换术胫骨近端截骨面后缘,不同性别间无明显差异。全膝关节假体置换术中进行胫骨近端截骨,特别是后方操作时需特别谨慎,以避免损伤腘窝血管。     

Novel SOX2 partner-factor domain mutation in a four-generation family

Anophthalmia (no eye), microphthalmia (small eye) and associated ocular developmental anomalies cause significant visual handicap. In most cases the underlying genetic cause is unknown, but mutations in some genes, such as SOX2, cause ocular developmental defects, particularly anophthalmia, in a subset of patients. Here, we describe a four-generation family with a p.Asp123Gly mutation in the highly conserved partner-factor interaction region of the SOX2 protein, which is important for cell-specific actions of SOX2. The proband in this family has bilateral anophthalmia and several other family members have milder ocular phenotypes, including typical optic fissure coloboma. Expression studies indicate that Sox2 is expressed in the eye at the site of closure of the optic fissure during development. The SOX2 mutation in this family implicates the partner-factor interaction region of SOX2 in contributing to the specificity of SOX2 action in optic fissure closure. Our findings indicate that investigation of SOX2 in a broad range of eye anomaly patients aids in the determination of particular functions of SOX2 in development.     

Identification of malaria hot spots for focused intervention in tribal state of India: a GIS based approach

Background  

In India, presently malaria shows a declining trend whereas Plasmodium falciparum (Pf) cases show an up trend. In central India, specifically, Madhya Pradesh (M.P.) a forested and tribal area, control of malaria is logistically difficult and outbreaks are frequently recorded, reasons for this being inadequate surveillance, poor reporting, a time lag in reporting to decision makers and a lack of geo referenced information to pin point the trouble spots for a timely preventive action.     

Randomized trial of skin closure after laparotomy for gynaecological surgery

BACKGROUND: New suture materials may provide patients with a better cosmetic outcome at similar pain and wound complication rate. METHODS: To assess pain and cosmetic outcome among patients randomized to receive wound closure after laparotomy for gynaecological surgery using staples, polyglecaprone 25 or polyglecaprone 6211 subcuticular sutures. RESULTS: Overall, 90 patients (87.4% consent rate) were randomized. There was no difference in wound complications and pain between the three groups. Patients randomized to polyglecaprone 6211 subcuticular sutures rated the cosmetic result at 1 and 6 weeks after surgery somewhat lower than patients randomized to the two alternative groups; however, at 3 months after surgery, all three groups rated the cosmetic result as similar. CONCLUSIONS: This study suggests that the three wound closure methods have similar short-term pain and cosmetic outcomes, as well as a similar rate of wound complications, leaving the decision of the most appropriate closure method to individual surgeons.     

Evidence of mitochondrial dysfunction in obese adolescents

Aim: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect and elucidate whether a lower metabolic rate is present. Methods: In a group of 34 obese adolescents (age <16 years and body mass index above the age‐related 95th percentile), and an age‐ and gender‐matched group of 32 lean adolescent, thyroid stimulating hormone (TSH) and basal oxygen consumption were measured and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. Results: Significant increase in TSH (3.06 ± 1.56 mU/L vs. 2.33 ± 0.91 mU/L, p < 0.05) and a decrease in VO₂ (129 ± 16 mL O₂/m²*min vs. 146 ± 15 mL O₂/m²*min, p < 0.05) were observed in obese adolescents compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 ± 1962 a.u. vs. 7608 ± 2328 a.u., p < 0.05) and mitochondrial membrane potential (11426 ± 3861 a.u. vs. 14017 ± 5536 a.u., p < 0.05) in obese adolescents compared with lean adolescents. These results are even more pronounced in adolescents with obese mothers. Conclusion: In obese adolescents, the increased TSH and lowered VO₂ propose a lowered basal metabolic rate and the impaired mitochondrial function suggests a decreased thyroid hormone stimulation of mitochondrial energy production. The maternal in‐heritage is suggestive of a basal metabolic defect or mitochondrial resistance for TH.