胚胎嗅鞘细胞再移植治疗晚期脊髓损伤1例

目的:对晚期脊髓损伤患者开展嗅鞘细胞再移植治疗,探讨其对神经功能的继续改善效果。方法:①患者男性,27岁,哈萨克斯坦籍,2001年9月20日遭霰弹枪击急诊手术后,双下肢不能运动及感觉消失,尿便失禁,右下肢阵发性钝痛。诊断为陈旧性完全性脊髓损伤(T12),美国脊髓损伤协会标准脊髓功能分级为A级。2002年9月30日第1次行脊髓胚胎嗅鞘细胞移植术,2007年2月5日行第2次脊髓胚胎嗅鞘细胞移植术。治疗方案患者知情同意。②取4个月流产胚胎(孕妇及其家属均知情同意)的嗅球,消化成单个嗅鞘细胞后培养2周,细胞浓度约2×1010L-1。于患者相应脊髓损伤上端(平T11椎体)做1个锁孔,直径约3cm,在脊髓损伤部位与正常脊髓交界处沿中线于无血管区,分两点用4.5号细针共注入100μL(第1次手术)、50μL(第2次手术)嗅鞘细胞悬液,细胞数均为1×106个。第2次移植术前进行供、受体细胞HLA配型,术后口服FK506胶囊2mg,2次/d,共42d。结果:①第1次术后3个月,排尿能控制6h,双足运动功能改善,性功能改善,阴茎勃起功能改善,疼痛减轻。②第2次术后10d,双下肢双足皮肤泌汗功能改善,右下肢疼痛减轻,腹部皮肤感觉稍有好转,针刺觉左侧由术前T10皮节消失好转至T10减退。较第2次移植前椎旁躯体感觉诱发电位有所改善,双侧椎旁电位从T10下降到T12。结论:胚胎嗅鞘细胞二次移植能继续改善晚期脊髓损伤患者的神经功能。但移植的细胞数量、容积、注射点位置等需深入探讨。     

升高空气压力减轻烫伤大鼠组织水肿及加速愈合

目的:应用升高空气压力来减轻大鼠深Ⅱ度烫伤后创面组织水肿,观察其效果及对愈合的影响。方法:实验于2004-12/2006-06在扬州大学医学院外科实验室完成。①实验分组:Wistar雄性大鼠36只,随机分为两组:实验组18只,对照组18只。②实验方法:大鼠以硫化钠脱毛剂脱去背部体毛,24h后采用苯巴比妥腹腔注射麻醉,水浴法(80℃,时间6s)造成背部4cm×4cm深Ⅱ度烫伤(病理切片证实),腹腔立即注射林格氏液5mL复苏。实验组动物伤后在高于大气压2.45kPa的压力箱内饲养,对照组箱内压力与大气压同。③实验评估:喂养48h后麻醉下处死大鼠,取伤部组织皮肤测定组织含水量;在伤后1,3,6,12h检测创面组织液渗出量;观察创面愈合率及愈合时间。结果:36只大鼠均进入结果分析。伤后48h实验组组织含水量低于对照组(P<0.05)。实验组在伤后1,3,6,12h创面组织液渗出量低于对照组(P<0.05)。实验组创面愈合时间短于对照组(P<0.05)。结论:升高空气压力可以降低创面的液体渗出,减轻组织水肿,缩短创面愈合时间。     

小干扰RNA抑制neuro-2a细胞内源β位淀粉样前体蛋白裂解酶1基因的表达

目的:分析小干扰RNA(small interference RNA,siRNA)抑制neuro-2a细胞内源β位淀粉样前体蛋白裂解酶1基因(Beta-site APP cleaving enzyme protein,BACE1)的表达情况。方法:实验于2004-12/2006-06在中山大学中山医学院和上海交通大学农业与生物学院完成。①用脂质体将EGFP基因表达载体pEGFP-C1 Vector和体外转录合成的针对EGFP基因的小干扰RNA(siEGFP)分别或同时转染neuro-2a细胞,在倒置荧光显微镜下计算EGFP在neuro-2a细胞中的表达率。②将体外转录合成的siBACE1-1,siBACE1-2,siBACE1-3转染neuro-2a细胞,干扰24,48,72h后分别用Real time RT-PCR定量分析siBACE1对内源BACE1基因表达的抑制率和干扰的时效性。结果:①外源EGFP基因转染neuro-2a细胞后,43%neuro-2a细胞高表达EGFP蛋白。通过转染siEGFP则可有效抑制EGFP基因表达。②3个干扰位点的siBACE1对BACE1基因表达有不同的抑制效率,siBACE1-3使BACE1m RNA表达水平下降60%,siBACE1-1为13%,siBACE1-2对BACE1 mRNA无明显的抑制作用。③siBACE1抑制内源BACE1基因的表达与干扰时间相关,siBACE1干扰24h、48h后BACE1 mRNA的表达与正常组无明显差异(P>0.05),但干扰72h后,siBACE1-3和siBACE1-1均使BACE1 mRNA表达量下降。结论:体外转录合成的siBACE1能有效抑制neuro-2a细胞内源BACE1基因表达,其抑制率与BACE1基因的干扰位点和干扰时间相关。     

Current management and future perspectives of metastatic renal cell carcinoma

Over the last number of years, the treatment of metastatic renal cell cancer has evolved tremendously with the advent of targeted therapy. Previously, immunotherapies, such as interferon alpha and interleukin‐2, were the only treatment options available for this chemoresistant malignancy. Currently, seven additional agents, including sunitinib, sorafenib, axitinib, pazopanib, bevacizumab, everolimus and temsirolimus, have been approved for use in metastatic renal cell cancer, with several more in development. The efficacy of these agents depends primarily on inhibition of the vascular endothelial growth factor and mammalian target of rapamycin pathways, and have drastically improved the outcomes of patients diagnosed with metastatic renal cell cancer. This article reviews the major treatment advances that have occurred for metastatic renal cell cancer with the advent of targeted treatments, summarizes the evidence to support their use and addresses clinical issues that have arisen with them. To help guide clinicians in their decision‐making with these emerging therapeutic choices, the evidence for sequencing and combining these agents, and the need for biomarkers will be addressed. The role of surgical management options, such as cytoreductive nephrectomy and metastectomy, in the era of targeted treatment is also reviewed. Several novel treatments are also on the horizon, which might serve as future avenues for treatment advancement in metastatic renal cell cancer.     

Single‐port laparoscopic cholecystectomy: A comparative study in 106 initial cases

Introduction: Laparoscopic cholecystectomy has been the standard of care for gallbladder diseases since the late 1980s. Many surgeons have rapidly adopted single‐port laparoscopic cholecystectomy for gallbladder pathologies. The aim of the present study was to analyze the clinical outcome in initial single‐port laparoscopic cholecystectomy. Methods: Data from 106 consecutive single‐port laparoscopic cholecystectomies between May 2008 and April 2009 were analyzed retrospectively. We divided the patients into two groups – an early group (group I, n=56) and a late group (group II, n=50) – to compare clinical outcomes. During each procedure, only one longitudinal transumbilical incision, 1.5 to 2.0 cm in length, was made to access the abdominal cavity. A multichannel port system was assembled with existing devices. Standard laparoscopic instruments were used to perform each cholecystectomy. Results: Patient demographics did not differ between the two groups. Of the eight cases that were converted to conventional laparoscopic surgery, seven were part of group I (P=0.063). Mean operation time for single‐port laparoscopic cholecystectomy was significantly shorter in group II (58.2 versus 71.6 min, P=0.004). There were two operative complications in group I, which were successfully managed with laparoscopic surgery. There was no statistical difference in occurrence of operative complication and hospital stay between the two groups. Conclusion: Single‐port laparoscopic cholecystectomy can be safely performed for various gallbladder lesions in selected cases, and the operation time improved with accumulation of cases.     

Trimethoprim‐sulfamethoxazole compared with benzathine penicillin for treatment of impetigo in Aboriginal children: A pilot randomised controlled trial

We conducted a pilot randomized controlled trial comparing trimethoprim‐sulfamethoxazole to benzathine penicillin for treatment of impetigo in Aboriginal children. Treatment was successful in 7 of 7 children treated with trimethoprim‐sulfamethoxazole and 5 of 6 treated with benzathine penicillin. Trimethoprim‐sulfamethoxazole achieved microbiological clearance and healing of sores from which β‐hemolytic streptococci and community‐associated methicillin‐resistant Staphylococcus aureus were initially cultured.     

脑内注射白细胞介素-1β对淋巴结细胞应激免疫抑制因子生成的影响

our previous work showed that a suppressive factor( a protein with largemolecular weight in serum was induced by restraint stress in mice and rats,which suppressed Con Ainduced lymphocyte proliferation.It was also found that the generation of serum suppressive factorwas under control of the central nervous system.Our further study showed thatintracerebroventricular(icv )injection of interleukin 1 receptor antagonist(IL-1Ra)antagonised thegeneration of serum suppressive factor induced by restraint stress and icv injection of interleukin-1β(IL-1β)increased the generation of the suppressive factor.Our experiment also showed that the serumsuppressive factor induced by restraint stress was first made in lymph tissue and then released intoblood.The present work was designed to investigate the role of IL-1 in the brain in generation of thesuppressive factor in lymph node in mice.Icv injection of IL-1β( 1 pg/mouse) was shown tosignificantly increase the generation of the suppressive factor in lymph node.Icv injection of IL-1Ra,however ,antagonised generation of the suppressive factor.In mice without restraint stress,both thesuppressive factor in serum and in lymph node were found to be induced in dose-dependent manner byicv injection of IL-1β.Taken together,these results suggest that IL-1β in brain played a veryimportant role in generation of the suppressive factor in lymph node.The positive correlation betweenthe suppressive action of lymph node and of serum added to the evidence that lymph tissue is probablythe source of the serum suppressive factor.     

血小板激活因子对大鼠脑血管通透性的影响及药物的保护作用

颈内动脉注射血小板激活因子(PAF),再给伊文思蓝,可见脑实质染色程度加深,而颈内动脉只注射伊文思蓝,脑实质未见染色。而我们合成的新药SZ-1可剂量依赖性地抑制PAF诱导的脑实质伊文思蓝染色程度的加深。在体外培养的脑微血管平滑肌细胞上,PAF能显著刺激~(14)-花生四烯酸的释放,而SZ-1能剂量依赖性地抑制这种释放,提示PAF在脑内产生的损害除与其他因素相关外,还与其刺激花生四烯酸释放有密切关系,SZ-1对PAF引起的脑部损害有保护作用。