椎间盘退变的机制及修复

背景：目前为止,椎间盘退变源性腰痛的发病机制研究并不十分清楚明了,对于其治疗的手段也多种多样,但效果不一。目的：综述近年国内外椎间盘退变机制及修复的研究进展。方法：由第一作者检索至2014年11月为止 PubMed数据(http://www.ncbi.nlm.nih.gov/PubMed)及CNKI中国期刊全文数据库(http://www.cnki.net/),以“椎间盘退变因素,椎间盘源性腰痛,椎间盘退变治疗”等为检索词,共检索到78篇相关文献,排除重复研究,共30篇文献符合纳入标准。结果与结论：综合大量国内外科研人员对椎间盘退变的研究,目前比较推崇的退变因素包括形态学上的改变、炎性递质和细胞外基质的变化、生长因子的作用等,治疗上仍处于对其形态学的修复方面,其中经皮穿刺椎间盘减压、椎体融合、人工椎间盘置换、动态稳定系统等手术治疗方法对椎间盘退变引起的症状有确切的疗效。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

天然牡蛎壳纳米体复合型骨材料修复骨缺损

背景：研究发现,牡蛎壳等很多海洋生物外壳等形成矿物质盐的过程与人体实际情况较为接近。 目的：观察天然牡蛎壳纳米体复合型骨材料修复骨缺损的效果。 方法：取30只成年大耳白兔,制作双侧桡骨骨缺损模型,随机均分为两组,实验组于骨缺损处植入天然牡蛎壳纳米体复合型骨材料,对照组于骨缺损处植入医用硫酸钙可注射型植骨材料,植入后2,8,12周进行X射线检查,了解植入骨材料周围组织生长结合情况;于第12周末获得双侧桡骨,利用生物力学测试系统检测桡骨抗弯曲强度,并利用彩色图像分析仪定量分析成骨情况。 结果与结论：植入后2周,两组骨材料密度较周边正常骨组织呈偏低,缺损与材料间边界清晰,未发现明显骨修复现象;植入后8周,两组骨材料均被较厚软组织全部包裹,实验组血管成分显著减少;植入后12周,两组骨材料紧密结合相邻组织,包裹骨材料的组织质地较韧,二者之间无界线,实验组桡骨表面形态已恢复至正常水平,在形态和质地结构方面与正常组织无明显区别,对照组仍存在明显投射分界影像。实验组桡骨抗弯曲强度和成骨量均显著大于对照组(P < 0.05)。表明天然牡蛎壳纳米体复合型骨材料修复骨缺损可以获得更好的桡骨抗弯曲强度,并促进新骨形成。     

涤纶布修补胸壁肿瘤切除后巨大胸壁缺损46例

背景：涤纶布作为一种临床常用耗材,取材简单,价格低廉,具有较高的坚韧度及延展性,可作为一种良好的修复材料使用。 目的：观察涤纶布用于巨大胸壁修补的实际疗效。 方法：选择46例胸壁肿瘤患者,其中男29例,女17例,年龄39-73岁。将46例患者随机均分为观察组与对照组,观察组患者切除胸壁肿瘤后采用涤纶布修补巨大胸壁缺损,对照组采用自体带蒂侧胸壁筋膜皮瓣修补巨大胸壁缺损,记录两组患者临床疗效及患者满意度。 结果与结论：术后全组病例均能胜任日常工作,无死亡及严重并发症发生,其中2例术后发生局部积液,经切口引流后好转,所有患者胸廓外观良好,呼吸运动时重建处无不适感。随访6-24个月,复查X射线片复查显示重建胸廓良好,未见移植松动、异物排斥反应、胸壁畸形等,无复发及严重并发症。观察组临床疗效及患者满意度优于对照组(P < 0.05)。结果表明涤纶布用于巨大胸壁修补的治疗,具有疗效显著、安全可靠的特点。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程      

锁定钢板与普通钢板置入内固定修复肱骨近端骨折的预后对比

背景：肱骨近端骨折采用切开复位内固定的方法,对组织的损伤较大,对局部血运有明显损害,但是随着材料学的发展和修复技术的进步,并发症已明显下降。 目的：对比锁定钢板和普通钢板在肱骨近端骨折修复方面的差异。 方法：上海交通大学医学院附属同仁医院骨科自2012年2月至2014年10月收治移位较大及粉碎性肱骨近端骨折患者68例,根据内固定方案分为两组,锁定钢板组32例采用锁定钢板内固定,常规钢板组36例采用T型钢板、三叶草钢板内固定。治疗后第2,4,6,12,24周时在门诊进行随访,采用Neer评分系统评估肩关节功能治疗满意率。在内固定取出之前进行复查,观察患者并发症发生情况。 结果与结论：常规钢板组的治疗满意率明显低于锁定钢板组,差异有显著性意义(75%,81%,P < 0.05)。在并发症方面,锁定钢板组未发现断钉断板、肩缝撞击、肱骨头坏死及感染病例,发现疼痛者6例;常规钢板组发现断钉断板5例、肩缝撞击5例、疼痛者8例、肱骨头坏死2例、感染2例,常规钢板组治疗后并发症发生率显著高于锁定钢板组,差异有显著性意义(P < 0.05)。提示肱骨近端骨折的内固定材料应以锁定钢板作为首选,无论是修复满意度还是在修复后并发症方面,均优于常规内固定方法。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

新生大鼠脊髓运动神经元的纯化培养与鉴定

背景：神经元是有丝分裂后的细胞,体外培养很难存活。脊髓运动神经元的分离、纯化和培养同时也是细胞培养的技术难点。 目的：建立新生大鼠脊髓运动神经元培养体系,并予以分类鉴定和测定其纯度。 方法：取新生大鼠脊髓腹侧组织分离成细胞悬液,经密度梯度离心及差速贴壁后纯化培养,采用免疫细胞化学双标染色法对培养盖片上的细胞予以鉴定、分类,结合Hoechst荧光染核,计数各细胞成分的含量。 结果与结论：细胞贴壁生长良好,神经元占85.8%,其中运动神经元达71.6%,星形胶质细胞占7.8%,NF200和胶质纤维酸性蛋白染色皆为阴性的细胞占6.4%。结果说明,取新生大鼠腹侧脊髓组织结合密度梯度离心及差速贴壁接种法可以培养出高纯度的脊髓运动神经元。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

正畸牙移动过程中尼古丁摄入对牙周组织影响

背景：吸烟是严重影响牙周组织和牙根健康的危险因素之一,烟草中的尼古丁会加速牙周病患者牙周组织的破坏。 目的：分析正畸牙移动过程中不同剂量尼古丁作用下牙周组织内环氧化酶2及mRNA表达的变化规律。 方法：将110只SD大鼠随机分为5组,空白对照组10只,生理盐水组和尼古丁0.5,0.75,1 mg/kg组各25只。除空白组外所有大鼠使用50 g力牵拉一侧上颌第1磨牙向近中移动。生理盐水组每日腹腔注射0.1 mL生理盐水;尼古丁组每日腹腔注射0.5,0.75,1 mg/kg尼古丁酒石酸溶液。各组大鼠分别在加力1,3,5,7,14 d时处死取上颌组织,苏木精-伊红染色观察牙周组织变化,免疫组织化学染色计数破牙骨质细胞阳性细胞,原位杂交染色法检测环氧化酶2在牙周组织中表达的平均吸光度值。 结果与结论：尼古丁各剂量组在各加力时间点破牙骨质细胞数目均高于未注射尼古丁组,且环氧化酶2阳性细胞表达强度也均高于未注射尼古丁组。随尼古丁注射剂量增大,破牙骨质细胞数目也逐渐增加(P < 0.05),加力7 d时各组破牙骨质细胞数目均达到峰值;环氧化酶2阳性细胞表达强度也随尼古丁注射剂量增大而增强(P < 0.05),加力5 d时表达强度达到峰值。结果表明,在相同加力时间点,破牙骨质细胞数目随剂量增大而增多,且环氧化酶2阳性细胞表达强度也随剂量增加而增强。正畸牙移动过程中的尼古丁摄入会造成牙周组织的破环,且尼古丁摄入剂量的高低直接影响牙周组织的破坏程度。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

p120-Catenin Down-Regulation and Epidermal Growth Factor Receptor Overexpression Results in a Transformed Epithelium That Mimics Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model.Esophageal cancer is the eighth most common cancer type¹ in the United States, ranking as the seventh leading cause of cancer-related mortality in the United States² and fifth worldwide.³ Esophageal cancers are classified into two distinct histological subtypes with unique clinical behaviors: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. ESCC is a highly aggressive malignancy that is typically diagnosed at an advanced tumor stage.^3–5 The disease develops as the result of a multistep process, arising as squamous dysplasia in the stratified squamous epithelium of the esophageal mucosa and subsequently invading through the submucosa and muscle layers of the esophagus.⁶ ESCC is aggressive, with a high rate of direct local invasion to adjacent organs, such as the aorta, respiratory tract, and lungs.⁷ The underlying molecular pathogenesis and biological features of this invasive mechanism in ESCC are not known and are understudied because of the lack of existing models available.p120-Catenin (p120ctn; alias CTNND1) is a tumor suppressor gene whose down-regulation is correlated with poorly differentiated tumors and a metastatic phenotype in several cancers, including prostate, lung, and adenocarcinoma of the gastroesophageal junction.^8–10 It has been shown previously that p120ctn is either down-regulated or lost in 35% to 60% of ESCC tumors.^11,12 Epidermal growth factor receptor (EGFR) is the most commonly overexpressed oncogene in many cancer types, including ESCC,¹³ with the ability to modulate signal transduction pathways involved in tumor cell migration, proliferation, angiogenesis, and inhibition of apoptosis.^14,15 EGFR is overexpressed in 43% to 97% of ESCC patients,^15–18 and its overexpression is significantly correlated with the depth of tumor invasion.¹⁵Because p120ctn is so often down-regulated or lost and EGFR is so often overexpressed in ESCC, we focused on investigating the cooperation between these pathways in ESCC. In addition, we used a novel and relevant three-dimensional (3D) tissue culture model using immortalized human esophageal keratinocytes (EPC1-hTERT) grown to form an epithelium on an extracellular matrix embedded with human esophageal fibroblasts¹⁹ with which to study the disease.This model constitutes a complete stratified squamous epithelium, histologically resembles in vivo esophageal epithelium, and recreates the normal differentiation program of the esophagus.^19–21 We assessed the intersection of two genetic events (namely, down-regulation of the tumor suppressor p120ctn and overexpression of the oncogene EGFR), and its ability to lead to an invasive ESCC phenotype. Our data suggest that p120ctn down-regulation and EGFR overexpression in our 3D model are able to mimic human ESCC.     

Paeoniflorin protects HUVECs from AGE-BSA-induced injury via an autophagic pathway by acting on the RAGE

The aim of our study was to investigate the protective effects of Paeoniflorin (PF) against injury induced by AGE-modified bovine serum albumin (AGE-BSA) in human umbilical vein endothelial cells (HUVECs), and to examine the underlying mechanisms of these effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine cell viability. Protein expression levels were determined by western blotting. For function-blocking experiments, we used small interfering RNA molecules (siRNA) for function-blocking experiments. At 6 h, we found that 100 μg/mL AGE-BSA reduced the viability of HUVECs. However, pretreatment with PF restored cell viability in a dose-dependent manner. AGE-BSA increased the levels of microtubule-associated protein light chain 3-II (LC3-II) and the receptor for advanced glycation end products (RAGE). Expression of p62 protein was also increased, but not at a statistically significant level. Pretreatment with PF further increased levels of LC3-II and RAGE, but reduced the expression of p62. In cells transfected with Atg5 and RAGE siRNA, cell viability and expression of LC3-II decreased in both the AGE-BSA and PF + AGE-BSA treatments. PF can protect HUVECs from AGE-BSA-induced injury by upregulating autophagy and promoting the completion of autophagy flux. RAGE plays an important role in this autophagic protection effect.     

Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor recurrence

Chordoma is a rare and low-malignant neoplasm which is considered to arise from notochord remnants. Due to its large resistance to chemotherapy and radiotherapy, surgical resection so far is the prior treatment for chordoma. However, the recurrence rate is high even after complete surgical resection. Recently, targeted cancer therapy has been demonstrated to be effective in several other tumors, while the related research on chordoma is rare. Mitogen-activated protein kinase signaling pathway is acknowledged to participate in tumor development, in which Raf-1 and extracellular regulated protein kinase 1/2 (ERK1/2) play vital roles. In this study, we evaluated the expression of Raf-1 and ERK1/2 by immunohistochemical staining in 42 chordoma tissue and 16 distant normal tissue. Moreover, we also investigated the correlations of Raf-1 and ERK1/2 expression with clinical features in sacral chordoma. Expression of Raf-1 and ERK1/2 was both significantly higher in sacral chordoma tissue than distant normal tissue (P = 0.008, P = 0.019). Raf-1 positive expression was related to surrounding muscle invasion (P = 0.032) and chordoma recurrence (P = 0.002), but the results did not indicate any association with patients’ age, gender, tumor size and location. ERK1/2 was associated with tumor size (P = 0.044) instead of other clinical factors (P > 0.05). Spearman correlation test showed close relation between ERK1/2 and Raf-1 (P = 0.001, r = 0.518). Kaplan–Meier survival Curve and log-rank test showed that Raf-1 positive expression was associated with shorter continuous disease-free survival time (CDFS) (P = 0.001), while ERK1/2 had no relation to CDFS (P = 0.961). Conclusively, Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients.     

Cellular Profiles of Bronchoalveolar Lavage Fluid and Their Prognostic Significance for Non-HIV-Infected Patients with Pneumocystis jirovecii Pneumonia

The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PCP) has not been adequately evaluated. The objective of this study was to analyze the cellular profiles of BAL fluid and to evaluate their prognostic significance in non-HIV-infected patients with PCP. A 7-year retrospective cohort study of 166 non-HIV-infected adult patients with PCP who underwent BAL was performed in a tertiary care hospital. The median total BAL fluid white blood cell count was 180/μl (interquartile range, 80 to 330) and was unaffected by the severity of PCP. The median percentages of BAL fluid neutrophils, lymphocytes, and alveolar macrophages were 13.1%, 31.7%, and 30.2%, respectively. The median percentage of BAL fluid neutrophils was significantly higher in severe than in mild-to-moderate PCP (20.4% versus 6.0%, P < 0.001), as was the absolute neutrophil count (24/μl versus 13/μl, P = 0.001). The percentage of BAL fluid neutrophils was an independent predictor of 30-day (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI], 1.01 to 1.03) and 60-day (aOR, 1.02; 95% CI, 1.01 to 1.04) mortalities. The 30-day and 60-day mortalities increased at rates of 15% (P = 0.006) and 21% (P < 0.001) per 10% increment of BAL fluid neutrophil levels, respectively. The degree of BAL fluid pleocytosis was relatively low without regard to the severity of PCP. The percentage of BAL fluid neutrophils can be used as a prognostic marker in non-HIV-infected patients with PCP.