Axonal autophagy during regeneration of the rat sciatic nerve**★

BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma surrounding the axon body was derived from the neuronal cell membrane; the condensed axoplasm contained many autophagic vacuoles at all levels. A large number of neurofilaments, microtubules, and microfilaments were arranged in a criss-cross pattern. The autophagic vacuoles exhibited acidic phosphatase activity. Axonal bodies were absorbed after degradation from day 7 onwards, and macrophages were observed rarely in the formative cavity. CONCLUSION: The degenerating axons were cleared mainly by axonal autophagy and Schwann cell phagocytosis during regeneration of the rat sciatic nerve, and macrophages exhibited only an assisting function.     

Axonal autophagy during regeneration of the rat sciatic nerve**★

BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model. DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma surrounding the axon body was derived from the neuronal cell membrane; the condensed axoplasm contained many autophagic vacuoles at all levels. A large number of neurofilaments, microtubules, and microfilaments were arranged in a criss-cross pattern. The autophagic vacuoles exhibited acidic phosphatase activity. Axonal bodies were absorbed after degradation from day 7 onwards, and macrophages were observed rarely in the formative cavity. CONCLUSION: The degenerating axons were cleared mainly by axonal autophagy and Schwann cell phagocytosis during regeneration of the rat sciatic nerve, and macrophages exhibited only an assisting function. Key Words: axon; autophagy; nerve regeneration     

连梅汤干预2型糖尿病大鼠脂肪组织微炎症的实验研究

目的：观察连梅汤对自发2型糖尿病大鼠（OLETF大鼠）脂肪组织MCP-1、SREBP-1c、FAS蛋白及mRNA表达的影响,探讨连梅汤干预T2DM的脂肪组织微炎症机制。方法：将成模OLETF大鼠随机分为模型组、二甲双胍组、连梅汤组,以LETO大鼠为空白对照组。采用免疫组化、RT-PCR法检测腹腔脂肪组织MCP-1、SREBP-1c、FAS蛋白及mRNA的表达。结果：连梅汤组的脂肪组织MCP-1、SREBP-1c、FAS蛋白及mRNA表达水平较模型组明显减低（P〈0.01,P〈0.05）。结论：连梅汤防治T2DM的作用机制可能与改善脂肪组织微炎症及脂代谢紊乱有关。     

三叉神经鞘瘤的诊断和治疗

目的探讨三叉神经鞘瘤的诊断和治疗方法。方法对我科1991年～1998年手术治疗并经病理证实的17例三叉神经鞘瘤进行回顾性分析。根据Jefferson的肿瘤分类方法：Ⅰ型（中颅窝型）3例，采用颞下入路和颞眶颧入路切除；Ⅱ型（后颅窝型）6例，采用额颞眶颧入路和枕下乳突后入路切除；Ⅲ型（哑铃型）8例，分别采用颞下入路、枕下乳突后入路和幕上、下联合入路切除。结果三叉神经鞘瘤临床上主要表现为三叉神经损害的症状和体征，早期进行CT、MR检查均可明确诊断，三叉神经鞘瘤应尽早手术治疗，并争取全切，以期根治。本组全切16例，次全切1例。10例门诊随访2年～5年无复发者。结论三叉神经鞘瘤早期进行CT、MR检查均可明确诊断，显微手术治疗是最佳方法，正确选择手术入路是肿瘤全切的前提条件。近年提倡颅底手术入路切除肿瘤。     

Cerebellopontine angle neurenteric cyst with focal malignant features

Neurenteric cysts are uncommon cystic lesions lined by endodermal‐derived epithelium, which are rarely found in the CNS, especially in the intracranial region. Although recurrences and disseminations of these cysts have been reported, only one case of intracranial malignant transformation has previously been described. Here we report a cerebellopontine angle neurenteric cyst in a 26‐year‐old woman. The cyst wall was lined by columnar epithelium with atypical nuclei and high MIB‐1 index. In addition, stromal invasion was found in the subepithelial areas, which shows malignant features. Dissemination was speculated on MRI 6 months after total excision of the original cyst.     

外源重组基因表达产物亚细胞定位的研究现状

目的：将外源基因通过重组然后在宿主细胞中表达,以研究其功能.资料来源：应用计算机检索Medlinel997-01/2004-12与外源基因重组表达产物亚细胞定位的相关文献,检索词“foreign recombined gene,subcellure location”等分别进行检索提炼,限定文献语种为English.资料选择：就检索到的500余篇资料进行初审,纳入标准：①有关外源基因重组策略.②与表达产物定位检测方法相关.排除标准：文献中重复研究、综述、Meta分析类文章.未排除文章中资料是否应用了随机、对照和盲法.资料提炼：共收集到80余篇关于外源基因重组表达后定位相关的文章.其中研究内容相似的,以近5年内发表在较权威杂志者优先.对符合标准的38篇文献进行分析.资料综合：外源重组基因在宿主细胞中表达后,可以通过多种方法进行亚细胞定位,如报告基因,免疫电镜,免疫荧光技术等,且大规模的外源重组基因亚细胞定位具有重要的意义.结论：因为外源重组基因表达产物的功能与其在宿主细胞中的定位有重要的关系,所以研究其在宿主细胞中的亚细胞定位,对研究外源重组基因表达产物的功能或未知新基因的功能来说有很重要的意义.     

Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.     

启膈散的研究

启膈散出自《医学心悟》一书,该方组方严谨,配伍得当,多用于治疗食管类疾病且疗效确切。近年来,围绕此方的研究不断深化,临床和药理研究都取得了新进展。根据搜集的文献可以看出,启膈散的临床研究多与治疗食管相关疾病为主,尤其是对于食管癌的治疗应用相对成熟。对其他疗效确切疾病的治疗也多是与“噎膈”症状或病机相近的疾病,这对启膈散在临床应用提供了新思路。启膈散的药理学研究多以食管癌为着手点,不断发现对疾病产生作用的多条信号通路,并以此阐明作用机制。启膈散的治疗作用不单局限于食管癌,但对于治疗有效其他疾病的药理学研究却少之又少,值得进一步探索。笔者将从临床研究、药理学研究两方面对启膈散的研究进展作简要概述。