Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians

Summary

Osteoporotic fracture (OF) is a serious outcome of osteoporosis. Important risk factors for OF include reduced bone mineral density and unstable bone structure. This genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

Introduction

Bone mineral density (BMD) and femoral neck cross-sectional geometric parameters (FNCSGPs) are under strong genetic control. DNA copy number variation (CNV) is an important source of genetic diversity for human diseases. This study aims to identify CNVs associated with BMD and FNCSGPs.

Methods

Genome-wide CNV association analyses were conducted in 1,000 unrelated Caucasian subjects for BMD at the spine, hip, femoral neck, and for three FNCSGPs —cortical thickness (CT), cross-section area (CSA), and buckling ratio (BR). BMD was measured by dual energy X-ray absorptiometry (DEXA). CT, CSA, and BR were estimated using DEXA measurements. Affymetrix 500K arrays and copy number analysis tool was used to identify CNVs.

Results

A CNV in VPS13B gene was significantly associated with spine, hip and FN BMDs, and CT, CSA, and BR (p?<?0.05). Compared to subjects with two copies of the CNV, carriers of one copy had an average of 14.6%, 12.4%, and 13.6% higher spine, hip, and FN BMD, 20.0% thicker CT, 10.6% larger CSA, and 12.4% lower BR. Thus, a decrease of the CNV consistently produced stronger bone, thereby reducing osteoporotic fracture risk.

Conclusions

VPS13B gene, via affecting BMD and FNCSGPs, is a novel osteoporosis risk gene.     

单鼻孔蝶窦入路治疗老年人垂体腺瘤

目的探讨经单鼻孔蝶窦入路显微手术切除老年人垂体腺瘤的手术方法和疗效以及并发症的围手术期处理。方法回顾性分析我科在1995年1月～2005年12月采用本法治疗老年人垂体腺瘤54例,其中大腺瘤23例,巨大腺瘤31例。31例伴有垂体功能低下,经病理和内分泌学检查证实垂体PRL腺瘤18例,GH腺瘤5例,ACTH腺瘤7例,多分泌功能细胞腺瘤3例,无功能腺瘤21例。结果本组肿瘤全切除23例,次全切除20例,大部分切除11例。随访0．5～7．5年,治愈27例,缓解21例,复发3例,死亡1例,失访2例。结论本手术方法能最大限度地保护脑功能、创伤小、手术并发症少、术后恢复快、住院时间短,特别适宜治疗老年人垂体腺瘤。     

High levels of β‐catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self‐renewal makes them an excellent cell source for bone regeneration and repair. However, their bone‐regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of β‐catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P‐PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of β‐catenin in P‐PDLSCs than in H‐PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of β‐catenin suppresses the noncanonical Wnt/Ca²⁺ pathway, leading to increased proliferation but reduced osteogenic differentiation of P‐PDLSCs. Downregulation of the levels of β‐catenin by treatment with dickkopf‐1 (DKK‐1) leads to activation of the noncanonical Wnt/Ca²⁺ pathway, which, in turn, results in the promotion of osteogenic differentiation in P‐PDLSCs. Interestingly, β‐catenin can affect both the canonical Wnt/β‐catenin pathway and the noncanonical Wnt/Ca²⁺ pathway. Our data indicate that β‐catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. © 2011 American Society for Bone and Mineral Research     

关节镜下自体腘绳肌肌腱移植重建膝前交叉韧带的临床观察

目的探讨关节镜下自体腘绳肌肌腱移植重建膝前交叉韧带的临床疗效。方法自2006年12月-2010年1月,对215例膝关节前交叉韧带损伤患者采用关节镜下自体腘绳肌肌腱移植重建（包括单束和双束）。比较患者术前、术后Lysholm膝关节评分和膝关节稳定性改变。结果本组215例中210例获得随访,1例患者在术后6周出现膝关节内感染,予行关节镜下清理、抗感染等处理后治愈。术前和术后1个月、术后6个月、术后1年Lysholm膝关节评分分别比较差异均有统计学意义（P〈0.05）。术前215例患者物理检查均表现为膝关节不稳,术后所有患膝不稳定表现消失。结论关节镜下自体腘绳肌肌腱移植重建膝前交叉韧带疗效可靠,依据病人实际情况个性化合理选择单双束重建。     

Nuss手术矫治漏斗胸412例

目的 探讨非胸腔镜辅助下Nuss手术治疗漏斗胸的手术方法并总结治疗经验.方法 2005年10月到2011年6月非胸腔镜辅助下Nuss手术治疗漏斗胸412例,其中男329例,女83例.年龄2岁8个月～28岁5个月,平均7岁8个月.其中102例行内固定取出手术.结果 患儿均顺利完成手术,无术中严重并发症发生.手术平均40 min,出血(10±2) ml.结论 非胸腔镜辅助Nuss手术安全可行,并且不用进入胸腔操作,手术创伤更小,耗时更短,微创效果更好.     

白介素18对结肠癌sw480细胞移植瘤HIF-1α表达的影响

目的 观察人白介素18(hIL-18)对结肠癌sw480细胞的抑制效应及hIL-18对sw480细胞移植瘤缺氧诱导因子-1α(HIF-1α)表达的影响.方法 噻唑蓝(MTT)法及流式细胞术(FCM)检测结肠癌sw480细胞、转染携带绿色荧光蛋白表达质粒的pEGFP-sw480细胞、转染携带hIL-18基因表达质粒(pE...     

微创经皮肾镜取石术治疗先天性异常肾合并结石患者并发症的护理

总结21例先天性异常肾合并结石患者行微创经皮肾镜取石术后并发症的观察及护理经验.21例术后发生出血2例,结石残留5例,严重感染1例,尿外渗3例,经及时发现并予以积极有效的治疗和护理,无一例因术后并发症而发生严重后果.提出术后大出血、结石残留、术后感染是微创经皮肾镜取石术较常见的并发症,加强对并发症的观察及护理对提高手术...     

Spontaneous rupture of the left common iliac vein

A 63-year-old woman was admitted because she presented with acute lower abdominal pain and left leg pain without any history of trauma. Lower extremity venous duplex ultrasound demonstrated deep vein thrombosis in the left lower extremity. Computed tomography scan revealed high-density, irregular clumps in the pelvic region and a soft-tissue mass shadow in the right lower abdomen. Emergency laparotomy revealed a 1.5-cm longitudinal tear in the left common iliac vein. The vein was repaired primarily and the postoperative course was uneventful.     

血红素加氧酶-1对心跳骤停复苏大鼠神经功能的影响

目的 探讨血红素加氧酶-1(HO-1)对心跳骤停复苏大鼠神经功能的影响.方法 雄性SD大鼠65只,随机分为四组:心跳骤停复苏组(Ⅰ组,20只)、氯化高铁血红素组(Ⅱ组,20只)、锡原卟啉组(Ⅲ组,20只)和假手术组(Ⅳ组,5只).Ⅰ组在心跳骤停后进行标准的心肺复苏直至恢复自主循环( ROSC);Ⅱ和Ⅲ组分别在心跳骤停前12h或1h经腹腔注射15 mg/kg的氯化高铁血红素或30 μmol/kg锡原卟啉Ⅸ,并进行心肺复苏;Ⅳ组不进行窒息心跳骤停.记录心跳骤停复苏各组的复苏参数,于ROSC后4d对各组进行神经功能缺陷评分(NDS),随后断头取脑,计数海马CA1区存活神经元数、TUNEL阳性细胞数及caspase 3阳性细胞数.结果 心跳骤停复苏各组的复苏参数差异无统计学意义.与Ⅳ组比较,Ⅰ、Ⅱ和Ⅲ组NDS评分明显升高(P＜0.05);与Ⅰ组比较,Ⅱ组NDS评分显著降低(P＜0.05).海马CA1区染色显示:与Ⅳ组比较,Ⅰ、Ⅱ和Ⅲ组存活神经元数显著减少,TUNEL阳性细胞数和caspase 3阳性细胞数明显增加(P＜0.05);与Ⅰ组比较,Ⅱ组TUNEL阳性细胞数和caspase 3阳性细胞数减少(P＜0.05).结论 诱导HO-1的表达可改善心跳骤停复苏后大鼠的神经功能,其机制可能与改善海马CA1区神经元的存活,抑制神经元凋亡有关.