Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

从天价医药费事件折射出当前我国医疗机构存在的问题

目前，我国许多医院的医疗卫生工作人员在为患者进行医疗卫生服务的过程中，为了医院和个人的经济利益，存在着过度医疗消费现象。最典型的是哈尔滨医科大学第二附属医院发生的天价医药费事件。导致这种现象出现的原因是由于法律的不健全、制度的不完善等而导致的监督力度不够，加之有些医务工作者在经济利益的驱使下使自己的职业道德滑坡，从而导致了老百姓看病贵现象的出现。     

Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective.

BACKGROUND: Despite major improvement in surgical techniques and intensive care management, stroke remains one of the most devastating complications of coronary artery bypass grafting (CABG). We aimed to determine factors predicting the occurrence of stroke during CABG. A special interest was focused on preoperative therapies. METHODS: We prospectively enrolled 810 consecutive candidates for CABG alone in a specific database, including all pre- and perioperative data (history, clinical, therapeutic, cardiac catheterization, surgical and intensive care data). Univariate tests and then multiple logistic regression analysis were used to determine independent predictive factors. RESULTS: During the first postoperative month, stroke occurred in 11 cases and transient ischemic attack (TIA) in 4 additive cases (cumulative rate: 1.85%). After the multivariate analysis, the following factors remained significant (p<0.05) in the predictive model, with corresponding odds ratios between brackets: redo cardiac surgery (7.45), unstable cardiac status (4.74), past history of cerebrovascular disease (4.14), past history of peripheral arterial disease (3.55), whereas the presence of preoperative statins was protective (0.24, 95% IC: 0.07-0.78). The addition of perioperative data (aortic calcification, postoperative arrhythmia, on/off-pump surgery) did not change the final predictive model. CONCLUSION: To our knowledge, this is the first real-world observational report highlighting the interest of statins for the prevention of stroke in the very special situation of CABG. Even though according to randomized trials coronary patients have a benefit from these drugs, a special level of interest should be directed towards those presenting the above-mentioned risk factors.     

比较4种影像技术对早期股骨头缺血性坏死的诊断敏感性

目的评价CR,CT,ECT和MRI在早期股骨头缺血性坏死(ANFH)中的诊断价值。方法回顾性分析16例23髋经手术、病理证实为早期(符合国际骨循环研究会(ARCO)分期标准Ⅰ期-Ⅱ期)股骨头缺血性坏死患者的CR,CT,ECT和MRI的影像学特征及其检查结果。结果CR诊断早期ANFH11髋,阳性率为47.8%,CT诊断早期ANFH14髋,阳性率为60.9%,ECT诊断诊断早期ANFH21髋,阳性率为91.3%,MRI诊断早期ANFH22髋,阳性率为95.7%。经统计学处理,X2=19.38,P<0.01,CR,CT,ECT和MRI四者敏感性的差异具有显著性意义。结论对早期股骨头缺血性坏死影像学诊断而言,CR诊断敏感性较低,CT可提供较多的诊断信息,ECT和MRI的敏感性高于CT及CR,MRI可准确地诊断早期股骨头缺血性坏死。     

大学生生命教育研究

大学生自杀和校园暴力不断发生在被誉为天子之骄子的象牙塔内。对大学生的这种生命意识淡漠现象仅作心理化的理解和处理并不能从根本上解决问题。心理问题只是问题的表象，对生命缺乏应有的尊重，生命意义缺失和生命关怀的缺位是其深层的原因，生命教育势在必行。     

醋酸精氨酸对创烧伤患者预后的影响及安全性分析——86例多中心、随机、双盲、安慰剂对照试验

目的观察服用醋酸精氨酸对创烧伤患者预后的影响及可能出现的不良反应。方法采用多中心、随机、双盲、安慰剂平行对照的研究方法,将96例创烧伤患者(实际完成86例)随机分为治疗组和对照组,治疗组41例,服用醋酸精氨酸0．4 g·kg-1·d-1;对照组45例,服用安慰剂酪氨酸,剂量同前,均连用7 d。两组患者采用等氮、等热量的营养支持疗法。比较患者创面(切口)愈合时间、住院时间及不良反应发生情况。结果创伤患者治疗组(29例)创面(切口)愈合时间和住院时间分别为(11．1±2．8)、(19±6)d,明显短于对照组(13．2±5．5)、(22±6)d(33例,P< 0．05);烧伤患者治疗组(12例)创面愈合时间和住院时间各为(20±5)、(28±6)d,与对照组(22±8)、(29±8)d(12例)比较,差异无统计学意义(P>0．05)。在整个试验过程中,患者出现的不良反应为恶心、腹泻,其中治疗组1例占2．44％,对照组1例占2．22％,两组比较差异无统计学意义(P= 1．000)。以上不良反应停药后消失。结论服用醋酸精氨酸能显著促进创伤患者创面(切口)愈合,缩短住院时间,且无明显不良反应,但对烧伤患者的预后无明显改善,这可能与病例数较少有关,其确切疗效有待于通过大样本的临床试验予以确定。     

Survivin在食管癌中的表达及其与bcl-2表达关系的相关研究

目的探讨Survivin在食管癌组织中的表达及其与bcl-2蛋白表达的相关性。方法应用免疫组织化学SP法,检测Survivin、bcl-2蛋白在68例食管癌组织和20例正常食管组织中的表达。结果Survivin蛋白在正常食管组织中低表达或不表达,68例食管癌组织中,49例表达阳性,占72.1%。Survivin蛋白表达与分化程度、淋巴结转移密切相关(P<0.05)。食管癌组织bcl-2蛋白表达阳性、阴性组中,Survivin蛋白阳性表达率分别为94.7%(36/38)和43.3%(13/30),两者比较,差异有统计学意义(P<0.05)。Survivin蛋白表达与bcl-2蛋白表达密切相关。结论Survivin在食管癌组织中表达上调,通过抑制细胞凋亡,在食管癌的发生中起到重要作用;凋亡相关基因bcl-2的上调与Survivin的表达可能在食管癌变中起协同作用。     

原发性肾上腺皮质癌的诊治分析

目的总结和提高原发性肾上腺皮质癌的诊治水平。方法回顾分析16例肾上腺皮质癌患者的临床资料。根据其临床症状、内分泌功能测定、影像学特点做出诊断，手术治疗并随访。结果16例患者中，内分泌功能紊乱者8例，以库欣征、性征异常、醛固酮增多症为主。超声、CT、MRI测定肿瘤直径为4．8～19．5cm，平均7．8cm。3例有远处转移。行根治性切除术13例，侵及同侧肾脏者做肾和肾上腙切除术2例，肾上腺肿瘤并腔静脉癌栓切除2例，腔静脉部分切除1例。病理结果：Ⅰ其耳2例，Ⅱ期8例，Ⅲ期3例，Ⅳ期3例。随访3-62个月，手术2年以上的11例患者中有6例仍存活，但1例肺转移，1例骨转移；死亡5例，平均存活26个月。结论肾上腺皮质癌患者预后差。影像学检查结合临床症状是早期诊断的关键，根治性手术是惟一有效的治疗方法。     

Orem自理模式在人工髋关节置换术患者护理中的运用

目的探讨Orem自理模式在人工髋关节置换术患者中的运用效果.方法对10例人工髋关节置换术患者进行Orem自理模式干预,观察患者的治疗护理效果、康复时间、并发症.结果手术均获成功,无1例发生并发症,平均住院16.5 d.随访3个月至2年,均能步行和日常生活自理.结论Orem自理模式干预能有效改善患者的治疗护理效果,提高患者自我护理能力.     

前列腺癌的诊断和治疗进展前列腺癌的早期诊断

一、概况 在欧美国家,前列腺癌(Pca)是50岁以上男子最常见的恶性肿瘤,也是男性癌肿死亡的第二位原因(仅次于肺癌).因此,应重视Pca的筛查和早期诊断.尽管我国目前Pca发生率远低于欧美国家,但由于对本病的重视程度和防治力度不够,大多数患者出现症状而就诊时已为较晚期,失去了根治手术的机会,5年和10年生存率低,而医疗费用却上升较快.