基因治疗中载体的研究

基因治疗是当今研究领域中的热点课题之一，其中的难点之一是如何将目标基因导入靶点——即载体的选择。近年来，随着研究的深入，已从最初的理化转染技术发展到利用各种微生物的特性达到转染目的。笔者通过对近年来国外基因治疗研究中有关载体的选择、各自的优缺点及其在不同临床治疗中的应用作一分析、比较，阐述了基因治疗这一新兴领域中关于载体的国外动态及其应用前景。     

超声微泡造影剂用于基因转染方面的辐照参数优化

随着微泡作为一种新型基因载体可行性[1]研究的逐步深入和超声介导微泡破坏增强基因转染机制认识的不断加深,超声与微泡在基因治疗领域中的应用日益广泛。目前,国内外学者在这方面开展了大量的研究,在其过程中超声辐照参数的选择尤为重要,如何选择最佳的超声辐照条件是许多学者     

纳米基因载体的研究进展

近年来，基因治疗迅速发展。基因治疗的主要过程是目的基因的获取和高效的基因转染。基因治疗成败的关键是基因治疗的载体系统。高效、安全是载体应具备的最基本条件。目前基因转染常用的载体有病毒型载体和非病毒型载体。病毒型载体在当前批准进入临床试验的基因治疗中占75％，转染效率通常在90％以上，但病毒蛋白有诱发机体产生免疫反应、体内潜在的病毒复制、生产成本高、不能反复应用、无靶向性等缺点。特别是在1999年的基因治疗临床试验中出现腺病毒载体致人死亡事件后，人们把注意力与希望逐步转向非病毒载体。非病毒型载体虽然制备简单、无免疫原性和比较安全，但是转染效率低是其致命缺点，尤其是在血清蛋白存在的情况下。所以寻找一种既高效又安全的基因载体是基因治疗领域面临的最紧要课题。     

基因治疗中非病毒载体研究进展

肿瘤基因治疗的最大挑战之一是研制安全有效的基因转染载体。在基因转染载体中,非病毒载体以其低毒性、低免疫原性、低致瘤性及易于制备等优点具有良好的应用前景。本文以裸DNA、阳离子脂质体、阳离子多聚物聚乙烯亚胺及壳聚糖、分子偶联体等为代表,从其性质、介导转染的机制、影响转染效率的因素等方面阐述非病毒载体在肿瘤基因治疗方面的研究进展。     

基因治疗中非病毒载体研究进展

肿瘤基因治疗的最大挑战之一是研制安全有效的基因转染载体。在基因转染载体中,非病毒载体以其低毒性、低免疫原性、低致瘤性及易于制备等优点具有良好的应用前景。本文以裸DNA、阳离子脂质体、阳离子多聚物聚乙烯亚胺及壳聚糖、分子偶联体等为代表,从其性质、介导转染的机制、影响转染效率的因素等方面阐述非病毒载体在肿瘤基因治疗方面的研究进展。     

改性壳聚糖作为基因递送载体的研究进展

基因治疗在替代功能障碍基因和肿瘤治疗方面具有良好的应用前景。基因治疗有3个基本要素:目的基因、表达载体和递送载体,其中递送载体的构建和改进,一直是基因治疗研究的重点。递送载体有病毒载体和非病毒载体两类。病毒载体的转染效率较高,但也存在一些明显缺点,如免疫原性高、毒性大、目的基因容量小、靶向特异性差、制备较复杂及费用较高等[1],因此人们愈来愈重视非病毒载体的研究。其中壳聚糖及其衍生物是研究的热点之一。1壳聚糖壳聚糖是甲壳类动物的甲壳质脱乙酰化后得到的阳离子多糖类物质。壳聚糖安全无毒,在体内可降解成水和二氧化…     

基因转染技术及其在白血病研究中的应用

随着人类基因组计划的完成,分子生物学研究进入后基因组时代,基因转染技术也成为重要的实验手段,被广泛应用于基因功能研究及基因治疗。基因转染的方法包括化学法、物理法、生物法,它们各有优缺点。现主要概述基因转染的基本方法及其在白血病基因功能研究及基因治疗中的应用。     

重组腺病毒相关病毒载体基因治疗研究进展

在基因治疗的研究过程中，已经报道过的载体包括病毒性载体和非病毒性载体，但都因其目的基因表达的一过性和较为严重的宿主免疫排斥反应而使其应用受限。相比之下，重组腺病毒相关病毒载体（rAAV载体）有明显的优势：（1）对宿主没有致病性；（2）能稳定转染宿主细胞，具有较长时期的基因表达能力；（3）极低的免疫原性；（4）有广泛的宿主群，可转染分化及未分化细胞。本文就rAAV载体在基因治疗中的研究进展做一综述。     

基因治疗病毒载体的研究及应用

基因治疗是指将人的正常基因或有治疗作用的基因导入人体靶细胞以纠正基因的缺陷或发挥治疗作用,因此它可用来治疗一些后天性和遗传性疾病,其成功与否的关键是载体。目前应用的载体主要有包括病毒和非病毒载体,但在基因治疗中应用最为广泛的载体是病毒载体。本文就近年来病毒载体系统在基因治疗中的应用及其改进等方面的研究进行综述。     

非病毒载体在基因治疗中的研究进展

基因治疗作为当今最有前景的治疗方法之一,目前还存在许多问题需要研究解决,其主要问题是如何将治疗基因送入目的细胞或组织并有效发挥作用。由于基因治疗中的病毒载体安全性备受诟病,因此,安全性较高的非病毒载体已成为研究的热门领域。本文主要回顾了基因治疗中的非病毒载体,尤其是脂质体及多聚物载体近年来的研究进展,以期了解其研究发展方向。     

Effect of labour induction on rates of stillbirth and cesarean section in post-term pregnancies

BACKGROUND: Meta-analyses of randomized controlled trials suggest that elective induction of labour at 41 weeks' gestation, compared with expectant management with selective labour induction, is associated with fewer perinatal deaths and no increase in the cesarean section rate. The authors studied the changes over time in the rates of labour induction in post-term pregnancies in Canada and examined the effects on the rates of stillbirth and cesarean section. METHODS: Changes in the proportion of total births at 41 weeks' and at 42 or more weeks' gestation, and in the rate of stillbirths at 41 or more weeks' (versus 40 weeks') gestation in Canada between 1980 and 1995 were determined using data from Statistics Canada. Changes in the rates of labour induction and cesarean section were determined using data from hospital and provincial sources. RESULTS: There was a marked increase in the proportion of births at 41 weeks' gestation (from 11.9% in 1980 to 16.3% in 1995) and a marked decrease in the proportion at 42 or more weeks (from 7.1% in 1980 to 2.9% in 1995). The rate of stillbirths among deliveries at 41 or more weeks' gestation decreased significantly, from 2.8 per 1000 total births in 1980 to 0.9 per 1000 total births in 1995 (p < 0.001). The stillbirth rate also decreased significantly among births at 40 weeks' gestation, from 1.8 per 1000 total births in 1980 to 1.1 per 1000 total births in 1995 (p < 0.001). The magnitude of the decrease in the stillbirth rate at 41 or more weeks' gestation was greater than that at 40 weeks' gestation (p < 0.001). All hospital and provincial sources of data indicated that the rate of labour induction increased significantly between 1980 and 1995 among women delivering at 41 or more weeks' gestation. The associated changes in rates of cesarean section were variable. INTERPRETATION: Between 1980 and 1995 clinical practice for the management of post-term pregnancy changed in Canada. The increased rate of labour induction at 41 or more weeks' gestation may have contributed to the decreased stillbirth rate but it had no convincing influence either way on the cesarean section rate.     

CT导向下^125I粒子组织间种植治疗头颈部肿瘤的临床研究

目的探讨CT引导下放射性^125I组织间种植治疗头颈部恶性肿瘤的可行性。方法搜集整理我院2006年6月-2008年12月,对26例头颈部癌术后或放化疗后复发或转移患者行植放射性^125I组织间种植治疗患者的临床资料。结果26例均顺利完成手术,每例种植粒子12～54颗,中位数23颗。术后未发生出血、感染、粒子移位等严重并发症。28例随访3～24个月,平均16个月,局部控制率术后3个月为54％（14／26）,6个月72％（18／25）,12个月47％（11／23）,2年37％（6／16）。结论放射性^125I粒子种植治疗头颈部肿瘤是一种安全、有效、可行的治疗方法,其近期疗效值得肯定。     

甲状腺疾病再次手术中喉返神经的显露与保护

目的探讨甲状腺疾病再次手术中喉返神经的显露与保护。方法回顾性分析214例甲状腺疾病再次手术的临床资料,问隔较近再次手术或甲状腺癌外侵的患者从带状肌外侧、胸锁乳突肌前缘入路,在上纵膈气管食管沟外侧区或入喉处显露喉返神经,伴淋巴结转移的患者从肿大淋巴结旁显露喉返神经;再次手术间隔时间较长、良性或肿瘤未外侵的甲状腺癌从颈前中线显露甲状腺,从甲状腺中静脉平面的侧后方或甲状腺下动脉区显露喉返神经。结果全组共解剖显露喉返神经344条（右侧188条,左侧156条）,单侧显露84例,双侧显露130例。喉返神经入喉处显露44条,甲状腺中静脉平面的侧后方显露104条,甲状腺下动脉区显露40条,上纵膈气管食管沟外侧区124条,肿大淋巴结旁32条。其中首次手术于外院,术后当天即声音嘶哑的2例,入院再次手术时发现喉返神经在入喉处被缝线结扎。全组喉返神经分支损伤0．87％（3／344）。结论甲状腺再次手术时,熟悉并识别喉返神经正常、变异或病理状况下的解剖,避开粘连、疤痕组织,选择适当的解剖途径显露喉返神经,可降低术中喉返神经的损伤发生。     

Adenosquamous cell carcinoma of the cervix--a clinical analysis of 23 cases

From January 1976 through December 1985, 895 patients with cervical carcinoma were treated with radical hysterectomy and pelvic lymphadenectomy. The surgical specimens of 23 cases were proved to be adenosquamous cell carcinoma, the incidence being 2.6%. Among them, 15 were at stage IB, 7 were at stage IIA and one was at stage IIB. The overall 5-year survival rate was 55.0% and there was no difference between patients at stage IB and IIA. During the same period the 5-year survival rate of squamous cell carcinoma was 87.5% for patients at stage IB and 75.0% for patients at stage IIA. Pelvic lymph node metastasis and parametrial involvement are considered to be poor prognostic factors. When metastasis or invasion happens, the metastatic or invasive lesions can be found in the form of pure squamous carcinoma or adenocarcinoma. Postoperative adjuvant radiotherapy (external irradiation plus brachytherapy) seems to be effective in preventing recurrence. Chemotherapy (PVB regimen) needs more clinical evaluation. In this study, when metastasis or recurrence developed, the response to radiotherapy and/or chemotherapy were poor and 75% of patients died within one year.     

Risk factors for extended disruption of family function after severe injury to a child.

OBJECTIVE: To identify risk factors for long-lasting disruption of family function following pediatric trauma that can be measured at the time of trauma. DESIGN: Prospective, exploratory study. Personal interviews were conducted at the time of admission and 6 months and 1 year after discharge. SETTING: Level I regional pediatric trauma centre. PARTICIPANTS: One hundred and five families (86% of those eligible) with a child admitted to hospital for severe trauma with an Abbreviated Injury Scale (AIS) score of 4 or higher or with two or more injuries in different body parts and AIS scores of 2 or higher were recruited; 13 families were lost to follow-up at 6 months or 1 year, so their data were not included in the analyses. MAIN OUTCOME MEASURES: Family function status (normal or abnormal compared with function before the injury), demographic characteristics of the parents and child, injury severity, presence of maternal psychologic disorder, presence of child behaviour abnormality and functional status of the child. MAIN RESULTS: At 6 months and at 1 year 41 families (45%) and 21 families (23%) respectively reported that their family lives had not returned to normal. The relative odds for disruption of family life were about five times higher (95% confidence limits [CL] 1.4 and 19.7) and four times higher (95% CL 1.1 and 14.0) for single-parent families than for families with married parents living together at 6 months and 1 year respectively. The presence of maternal psychologic disorders at admission and increased age of the injured child were also significantly associated with extended disruption of family function. Injury severity and functional status at discharge were not good predictors of family function. CONCLUSIONS: Severe injury to a child places a heavy strain on normal family function. In particular, single parents and parents experiencing mental or emotional problems at the acute stage of the injury need help in coping with their reactions to the trauma and may benefit from individual or group counseling.     

Factors associated with a malignant or benign course of multiple sclerosis

Eight hundred thirty-four patients with multiple sclerosis (MS) in King and Pierce Counties, Washington, and in Los Angeles County, California, with symptomatic onset between 1960 and 1969 were followed up for disability status in 1980. A higher proportion of the 375 patients who were not walking or deceased in 1980 had a late age of onset, resided in Los Angeles County, had motor or coordination symptoms at onset, and reported adverse responses to heat exposure and favorable responses to cold exposure, whereas a higher proportion of the 299 patients still walking without aids had early onset age and vision, speech, or sensory symptoms, or all three, at onset. The results suggest (1) that both host factors (age at first manifestation of symptoms and types of symptoms at onset) and environmental factors (place of residence and exposure to heat and cold) are determinants of disease course and (2) that most patients with MS should avoid exposure to heat.     

烟雾病的临床分析

目的分析moyamoya病的临床及影像学特征以提高对该病的诊断水平。方法选择2005年9月-2011年10月中国医科大学附属盛京医院收治的17例moyamoya病患者的资料进行回顾性分析,总结其临床及影像学特点,结合文献进行归纳。结果 17例moyamoya病患者,男8例,女9例;儿童组21个月至15岁,8例;成人组34-53岁,9例。数字减影血管造影(digital subtraction angiography,DSA)检查4例,磁共振成像(magnetic resonance imaging,MRI)+磁共振血管造影(magnetic resonance angiography,MRA)检查10例,CT血管成像(computerized tomography angiography,CTA)检查2例,DSA+MRA检查1例。3例单侧血管典型改变,8例双侧颈内动脉虹吸段狭窄或闭塞,10例双侧大脑前动脉起始部狭窄或闭塞,12例双侧大脑中动脉起始部狭窄或闭塞,2例双侧大脑后动脉起始部狭窄或闭塞,17例颅底大量纤细紊乱血管形成。结论Moyamoya病发病率低。发病年龄分布呈两组高峰。儿童患者大多表现为脑缺血。成人患者一部分表现为颅内出血,一部分则表现为脑缺血。典型的MRA提示双侧颈内动脉虹吸段和/或大脑前动脉及大脑中动脉起始段狭窄或闭塞,侧支血管形成脑底异常血管网时可确诊。对于缺乏常见危险因素的中青年患者或多发性脑梗塞的儿童患者,应及时行头MRI+MRA或DSA检查,除外moyamoya病。     

Plastic bread-bag clips in the gastrointestinal tract: report of 5 cases and review of the literature

Plastic bread-bag clips have been identified as a cause of local perforation or obstruction at many sites in the gastrointestinal tract. This study is the largest case series yet reported, consisting of 3 cases presenting as small-bowel perforation, 1 case in which the clip was found incidentally in the small bowel at laparotomy during vascular surgery and 1 case in which the clip was found incidentally in the small bowel at autopsy. In all cases there was no radiographic evidence to suggest a foreign body in the gastrointestinal tract. People older than 60 years of age who have either partial or full dentures seem to be particularly at risk for the accidental ingestion of these devices. If accidentally ingested, plastic bread-bag clips represent a significant health hazard. As the population ages, small-bowel perforation secondary to ingestion of such clips may occur with increasing frequency. The authors recommend elimination or redesign of the clips, to prevent their being swallowed and becoming impacted in the small bowel or to allow them to be identified in the gastrointestinal tract by conventional radiography.     

The Cardiff Cervical Cytology Study: prevalence of cytological grades and initial histological findings

Among 45 266 women in the Cardiff Cervical Cytology Survey the peak prevalence of suspicious or positive smears was 11.2/1000 at age 45-50 years and of dyskaryosis 10.2/1000 at age 25-29. A suspicious or positive cytological picture at prevalence testing was associated with occult or clinical invasion in 24% of cases, and only 4% of patients with suspicious or positive smears were normal histologically. When dyskaryosis was detected in the prevalence test 20% had carcinoma in situ or microinvasion and 3% had occult or clinically invasive carcinoma. One hundred and twenty-nine (51%) women with dyskaryotic smears did not have a biopsy initially (that is, within two years of the prevalence test), but they were followed up at regular intervals. Subsequently 15 of the 129 gave smears consistently dyskaryotic or worse cytologically and were subjected to biopsy. Of these, two showed dysplasia, 12 carcinoma in situ, and one clinically invasive carcinoma. These findings emphasise the need for repeat cytological or histological examination in any woman with evidence of dyskaryosis in a cervical smear.     

The role of temperature and light on inhibition of development of Cooperia oncophora

Infective Cooperia oncophora larvae were temperature and light conditioned by holding them at various temperatures and daily light intensities for up to 56 days prior to administration to parasite-free calves via stomach tube. The calves were killed either on day 20 or day 21 postinfection. A marked (up to 80.5%) inhibition of development occurred in larvae held at 4 degrees C while little or no inhibition occurred in larvae held at room temperature or in fresh larvae. Marked inhibition also occurred in larvae held at 15 degrees C for 56 days while a low rate of inhibition occurred in larvae held at 17 degrees C for 42 days. Low incidence of inhibition was recorded in two of four calves given larvae held at ambient temperatures of mid-summer while appreciable inhibition of development of larvae occurred in two calves permitted to graze during the second and third week of September in 1975. Temperature conditioning of C. oncophora eggs for 27 days did not result in inhibition of development of infective larvae subsequently cultured from the eggs. Photoperiod or the presence of light did not have any appreciable effect on the development of inhibition of C. oncophora under the conditions of these investigations.