APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age‐dependent manner

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid β peptide (Aβ) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter, 1 exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aβ oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL‐induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2011 American Society for Bone and Mineral Research.     

Inorganic Phosphate Induces Mammalian Growth Plate Chondrocyte Apoptosis in a Mitochondrial Pathway Involving Nitric Oxide and JNK MAP Kinase

Chondrocytes in the hypertrophic zone of the growth plate undergo apoptosis during endochondral bone development via mechanisms that involve inorganic phosphate (Pi) and nitric oxide (NO). Recent evidence suggests that Pi-dependent NO production plays a role in apoptosis of cells in the resting zone as well. This study examined the mechanism by which Pi induces NO production and the signaling pathways by which NO mediates its effects on apoptosis in these cells. Pi decreased the number of viable cells based on MTT activity; the number of TUNEL-positive cells and the level of DNA fragmentation were increased, indicating an increase in apoptosis. Blocking NO production using the NO synthase (NOS) inhibitor l-NAME or cells from eNOS^−/− mice blocked Pi-induced chondrocyte apoptosis, indicating that NO production is necessary. NO donors NOC-18 and SNOG both induced chondrocyte apoptosis. SNOG also upregulated p53 expression, the Bax/Bcl-2 expression ratio, and cytochrome c release from mitochondria, as well as caspase-3 activity, indicating that NO induces apoptosis via a mitochondrial pathway. Inhibition of JNK, but not of p38 or ERK1/2, MAP kinase was able to block NO-induced apoptosis, indicating that JNK is necessary in this pathway. Pi elevates NO production via eNOS in resting zone chondrocytes, which leads to a mitochondrial apoptosis pathway dependent on JNK.     

3.0T术中磁共振成像导航在神经外科手术应用的初步经验

目的 探讨3.0 T术中磁共振成像(iMRI)导航在神经外科手术应用的临床价值.方法 回顾性分析2010年9月至2011年3月,在具备诊断和手术功能的"3.0 T iMRI数字一体化神经外科手术中心"施行的各类颅脑手术122例,包括临床资料、iMRI实时影像导航对手术进程和手术结果的影响等.结果 122例患者手术室内扫描2～4次,平均2.6次.各种扫描图像质量皆优良.iMRI技术使脑胶质瘤(60例)手术全切除率从71.7%提高到90.0%,患者的近期致残率为6.7%,远期致残率3.3%.iMRI技术使垂体大腺瘤(29例)手术全切除率从75.9%提高到93.1%.未发生与应用iMRI数字一体化神经外科手术有关的并发症(如感染等).同期完成2500余人次MRI诊断性检查.结论 3.0 T iMRI神经导航的应用,为脑胶质瘤与垂体大腺瘤手术进程的实时引导、切除范围的精确判断以及脑功能与代谢信息的定量分析提供了客观依据,真正实现了脑肿瘤的最大程度安全切除.

Abstract：

Objective To report the preliminary experience in clinical application of 3.0 T intraoperative magnetic resonance imaging (iMRI) neuronavigation system in China. Methods From September 2010 to March 2011, a consecutive series of 122 patients with intracranial lesions underwent operations in guidance with 3.0 T iMRI. A retrospective analysis was conducted regarding clinical efficiency.Results Among 122 procedures, the numbers of intraoperative scanning were 2-4 times with an average of 2.6.The qualities of images were excellent. Due to the discovery and further possibility of resection of residual tumors, the ratio of gross total resection was increased from 71.7% to 90.0% in cerebral gliomas(n =60), while from 75.9% to 93.1% in macroadenomas (n =29).There were 6.7% of all patients occurred postoperative paralysis, but only 3.3% of patients had persistent paralysis at 1-2months follow-up.There was no iMRI-related adverse event occurred. During the same period, more than 2500 patients underwent diagnostic MRI scanning. Conclusions 3.0 T iMRI neuronavigation system provides high-quality intraoperative structural, functional and metabolic images for real time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.The system is cost-effective.     

Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation

The distinction of malignant mesothelioma from reactive mesothelial proliferation remains to be a major challenge for surgical pathologists. In this study, we investigated whether insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), an oncofetal protein, can be used as a biomarker to distinguish between malignant and reactive mesothelial cells. A total of 109 cases (mesothelioma, n=45; reactive mesothelial proliferation, n=64) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic staining in 33 of 45 (73%) mesothelioma cases. In contrast, the expression of IMP3 was undetectable in all (64 cases) benign reactive mesothelial proliferations. Among the IMP3-positive mesotheliomas, 27 (82%) exhibited diffuse IMP3 expression. The vast majority of IMP3-positive subtypes of mesotheliomas showed IMP3 expression in >50% of malignant cells, as this diffuse staining pattern occurred in 17 (81%) cases of epithelial, 4 (100%) cases of sarcomatoid, and 6 (75%) cases of mixed types of mesothelioma. In addition, 2 cases, which were initially diagnosed as atypical mesothelial proliferations and later confirmed to be mesotheliomas, showed diffuse IMP3 expression. Our findings suggest that IMP3 is a new positive biomarker for malignant mesothelioma. IMP3 immunohistochemical staining can be used as an adjunct tool in the distinction of malignant mesothelioma from reactive mesothelial proliferations.     

侧卧位微创经皮肾镜碎石术治疗肾结石的临床应用价值

目的:探讨侧卧位在微创经皮肾镜手术中的临床应用价值.方法:回顾性分析2007年1～12月采用侧卧位微创经皮肾镜手术治疗肾结石患者56例的临床资料:单侧结石48例,双侧结石8例.肾单发结石38例,肾鹿角形结石18例.结石最大经2.4～6.7 cm.结果:平均手术时间85 min,平均住院12天.45例次单发肾结石手术中,38例次行单通道一期手术;7例次因术中发现肾积脓,留置造瘘管后改二期手术;19例次肾鹿角形结石均采用双通道取石,其中一期手术取石8例次,二期手术取石11例次.术前血红蛋白112±28 g/L,一期手术后1～3天检查血红蛋白为102.5±31.5 g/L.术后需用ESWL辅助治疗17例.总结石排净率为92.3%.结论:侧卧位是泌尿外科医生最熟悉的手术体位,也是进行微创经皮肾镜手术的理想手术体位,特别是B超定位穿刺技术的广泛应用,更应该推广使用侧卧位进行微创经皮肾镜手术.     

经后路手术切除内固定矫正治疗先天性半椎体畸形

目的回顾性分析4例由先天性半椎体造成的脊柱侧弯和后凸畸形经后路一次半椎体切除植骨固定矫正术的手术治疗效果。方法4例患者,半椎体的位置均在胸腰段,手术采用后路切口,切除半椎体后,内固定矫正畸形,植骨融合,术后平均随访时间为12月,术前、术后拍摄站立位的脊柱正侧位片。结果所有患者均有不同程度的侧弯和后凸畸形,侧弯角由术前的34^o矫正至11^o,后凸角由术前18^o矫正至6^o,躯干位移从15mm恢复至5mm,无任何手术并发症,无内固定断裂脱落,均融合。结论此手术方法对患有半椎体导致先天性脊柱畸形的患儿是有效、安全的方法。     

肾嫌色细胞癌的诊断和治疗（附五例报告）

目的 提高肾嫌色细胞癌的诊治水平。方法 回顾性分析5例肾嫌色细胞癌资料,结合文献复习进行讨论。结果 3例肾部分切除术,2例行根治性肾切除术,随访个月至4年,4例无瘤存活,1例于术后1年死于中风。结论 肾嫌色细胞癌是一种低度恶性的肾细胞癌,确诊有赖于影像学检查及典型病理表现,治疗以手术为主。     

Clinical and experimental study on facial paralysis in temporal bone fracture

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Effects of nicotine and cotinine on porcine arterial endothelial cell function

BACKGROUND. There has been a significant amount of research on the effects of nicotine on vascular biology; however, little is known about the effects of cotinine, the metabolic product of nicotine. This study used a novel vascular perfusion system to study the effects of nicotine and cotinine on the vascular endothelial cell function. METHODS: Porcine common carotid arteries were cultured in a novel vascular perfusion system with nicotine or cotinine or as controls. After 24 h, vessels were precontracted with norepinephrine and subsequently relaxed with acetylcholine. Vessel diameters were recorded and analyzed. After culture, samples were taken for en face, immunohistochemistry, and RT-PCR for eNOS. Porcine coronary arteries were incubated as controls or with nicotine or cotinine and tested on a myograph system to measure contraction and relaxation. RESULTS: Porcine carotid arteries treated with nicotine and cotinine showed a 27.2% and a 41.2% reduction in endothelial-dependent relaxation, respectively, as compared to control vessels (P<0.05). Rings of coronary arteries treated with nicotine relaxed similarly to control rings while cotinine-treated rings failed to relax to endothelial-dependent stimulation. RT-PCR for eNOS mRNA showed a 23. 2 and a 24.1% reduction in eNOS expression for nicotine- and cotinine-treated vessels, respectively (P<0.01). Additionally, immunohistochemical staining for eNOS showed less dense staining on nicotine- and cotinine-treated vessels as compared to controls. En face preparations showed normal endothelial cell morphology in all groups, but cell density decreased slightly in vessels treated with nicotine and cotinine. CONCLUSION: These results indicate that cotinine may have even more effect on the impairment of endothelial-dependent vasorelaxation than nicotine for the regulation of vessel tone in porcine carotid and coronary arteries.