INPP5E 基因影响小鼠胚胎神经管闭合的 分子机制研究

目的 探讨肌醇多聚磷酸5- 磷酸酶（INPP5E）基因影响小鼠胚胎神经管闭合的分子机制。 方法 采用前期复制的神经管缺陷（NTD）小鼠模型,在体视显微镜下观察胚胎表型、苏木精- 伊红染色情况, 测量胚胎顶臀长、体重等指标;重亚硫酸盐测序法检测NTD 组及对照组胚胎发育第11.5 天小鼠胚胎神经组 织中INPP5E 基因启动子区DNA 甲基化情况;实时荧光定量聚合酶链反应和Western blotting 检测胚胎神经组 织中INPP5E 蛋白和mRNA 相对表达量;超高效液相色谱串联质谱法检测胚胎神经组织中叶酸（FA）、5- 甲 基四氢叶酸（5-MeTHF）、5- 甲酰四氢叶酸（5-FoTHF）及同型半胱氨酸（Hcy）水平。结果 NTD 组小 鼠胚胎神经组织INPP5E 基因启动子区甲基化水平、INPP5E 蛋白和mRNA 相对表达量在胚胎发育第11.5 天 时较对照组低（P <0.05）。NTD 组胚胎神经组织的FA 和Hcy 水平较对照组升高（P <0.05）,而5-MeTHF 和5-FoTHF 水平较对照组低（P <0.05）。结论 INPP5E 基因在调节小鼠胚胎神经管闭合中起重要作用。FA 代谢紊乱引起的INPP5E 基因启动子区甲基化水平降低,可能通过影响其表达水平参与NTD 的发生。     

单羧酸转运蛋白4(MCT4)在前列腺癌中的表达及调控研究

目的 探讨单羧酸转运蛋白4（monocarboxylate transporters 4,MCT4）在前列腺癌组织及细胞系中的表达情况,明确其在前列腺癌细胞中的调控作用。方法 应用免疫组织化学方法检测MCT4蛋白在前列腺癌（prostate cancer,PCa）、良性前列腺增生（benign prostatic hyperplasia,BPH）及癌旁组织（para-carcinoma tissues,PCT）中的表达,分析其与前列腺癌Gleason评分及淋巴结转移的关系。免疫印迹（Western blotting）法检测不同前列腺癌细胞系中MCT4蛋白表达差异,分析抑制MCT4蛋白表达对N-cadherin、E-cadherin及pERK1/2的调控作用。结果 免疫组化检测显示,MCT4蛋白在前列腺癌、前列腺增生及癌旁组织中均有表达;但PCa中MCT4表达水平明显高于BPH及PCT（P=0.003）。另外,MCT4蛋白表达与前列腺癌是否有淋巴结转移密切相关,转移组显著高于非转移组（P=0.022）。Western blotting检测结果显示,在前列腺正常上皮细胞及激素依赖性前列腺癌细胞LNCap中MCT4表达较弱,而在恶性程度较高的去势抵抗性前列腺癌细胞PC3及DU145中表达明显增强。抑制PC3细胞中MCT4表达可以使N-cadherin及pERK1/2的蛋白表达下降,而使E-cadherin蛋白表达水平升高。结论 单羧酸转运蛋白4可能参与上皮间质转化（epithelial-mesenchymal transition,EMT）进程及ERK1/2通路的调控,促进前列腺癌的进展和转移,对前列腺癌的临床诊断和治疗有重要意义。     

加速康复外科在腹腔镜泌尿外科上尿路手术中的应用效果分析

目的 对比加速康复外科（enhanced recovery after surgery,ERAS）方案和常规康复外科（conventional recovery after surgery,CRAS）方案在腹腔镜泌尿外科上尿路手术中的安全性和有效性。方法 收集本中心2016年6月至2017年9月行腹腔镜泌尿外科上尿路手术治疗的患者共62例,其中2016年6月至2017年5月,33例采用CRAS方案,2017年5月至2017年9月29例采用ERAS方案。两组患者年龄、体质量指数、中位查尔森合并症指数、中位麻醉评分及术前实验室检查等差异均无统计学意义。对两组患者的围术期资料和术后30 d内的合并症进行比较。结果 所有手术均顺利完成。两组患者在术中入晶体液量[1 000（525~1 100）mL vs 1 100（1 000~1 350）mL]、术中入胶体液量[500（500~500）mL vs 500（500~1 000）mL]、胃管拔出时间[0 d vs 1（1~1）d]、恢复普食时间[1（1~2）d vs 2（1~3）d]差异有统计学意义（P<0.05）。在手术时间、术中出血量、引流管拔出时间、术后住院时间、腹腔镜术式构成比例等方面均差异无统计学意义（P>0.05）。ERAS方案组和CRAS方案组分别有3例（10.3%）和5例（15.2%）Clavien-Dindo 1级合并症,差异不具有统计学意义（P=0.573）。两组均无患者术后再入院。结论 ERAS方案对比CRAS方案可以在不增加合并症的基础上缩短患者恢复普通饮食时间,推进患者术后康复,在腹腔镜泌尿外科上尿路手术中的应用是安全和可行的,但还需要大样本量随机对照研究进行全面评估。     

CT-Guided Core Needle Biopsy of Pleural Lesions: Evaluating Diagnostic Yield and Associated Complications

ObjectiveThe purpose of this study was to retrospectively evaluate the diagnostic accuracy and complications of CT-guided core needle biopsy (CT-guided CNB) of pleural lesion and the possible effects of influencing factors.ResultsDiagnostic accuracy, sensitivity, specificity, PPV, and NPV were 89.2%, 86.1%, 100%, 100%, and 67.8%, respectively. The influencing factors had no significant effect in altering diagnostic accuracy. As far as complications were concerned, occurrence of pneumothorax was observed in 14 (16%) out of 88 patients. Multivariate analysis revealed lesion size/pleural thickening as a significant risk factor (odds ratio [OR]: 8.744, p = 0.005) for occurrence of pneumothorax. Moreover, presence of pleural effusion was noted as a significant protective factor (OR: 0.171, p = 0.037) for pneumothorax.ConclusionCT-guided CNB of pleural lesion is a safe procedure with high diagnostic yield and low risk of significant complications.     

急性创面无干扰伤口愈合的护理研究进展

介绍无干扰伤口愈合的概念及其在急性创面处理中的应用现状,分析无干扰伤口愈合在急性创面愈合中的促进因素及效果评价,以期为医护人员在临床实践中重视将急性创面处于无干扰愈合环境,结合患者情况,制定最佳的创面处理方案提供参考。     

Detection of coronary artery stenosis with sub-milliSievert radiation dose by prospectively ECG-triggered high-pitch spiral CT angiography and iterative reconstruction

Objectives

To evaluate the diagnostic accuracy of sub-milliSievert (mSv) coronary CT angiography (cCTA) using prospectively ECG-triggered high-pitch spiral CT acquisition combined with iterative image reconstruction.

Methods

Forty consecutive patients (52.9?±?8.7 years; 30 men) underwent dual-source cCTA using prospectively ECG-triggered high-pitch spiral acquisition. The tube current-time product was set to 50 % of standard-of-care CT examinations. Images were reconstructed with sinogram-affirmed iterative reconstruction. Image quality was scored and diagnostic performance for detection of ≥50 % stenosis was determined with catheter coronary angiography (CCA) as the reference standard.

Results

CT was successfully performed in all 40 patients. Of the 601 assessable coronary segments, 543 (90.3 %) had diagnostic image quality. Per-patient sensitivity for detection of ≥50 % stenosis was 95.7 % [95 % confidence interval (CI), 76.0-99.8 %] and specificity was 94.1 % (95 % CI, 69.2-99.7 %). Per-vessel sensitivity was 89.5 % (95 % CI, 77.8-95.6 %) with 93.2 % specificity (95 % CI, 86.0-97.0 %). The area under the receiver-operating characteristic curve on per-patient and per-vessel levels was 0.949 and 0.913. Mean effective dose was 0.58?±?0.17 mSv. Mean size-specific dose estimate was 3.14?±?1.15 mGy.

Conclusions

High-pitch prospectively ECG-triggered cCTA combined with iterative image reconstruction provides high diagnostic accuracy with a radiation dose below 1 mSv for detection of coronary artery stenosis.

Key Points

? Cardiac CT with sub-milliSievert radiation dose is feasible in many patients ? High-pitch spiral CT acquisition with iterative reconstruction detects coronary stenosis accurately. ? Iterative reconstruction increases who can benefit from low-radiation cardiac CT.     

消化道类癌三种内镜治疗方法的比较

目的比较普通圈套器电切、内镜黏膜切除术(EMR)和内镜黏膜下剥离术(ESD)治疗消化道类癌的有效性和安全性。 方法回顾性分析2006年1月至2015年6月病理符合消化道类癌患者的临床资料,比较普通圈套器电切治疗(普通圈套器电切组,12例)、内镜黏膜切除术治疗(EMR组,47例)和内镜黏膜下剥离术治疗(ESD组,39例)的组织学完全切除率、并发症,以及术后随访6～36个月观察其疗效。 结果内镜治疗消化道类癌的组织学完全切除率为78.57%(77/98)。普通圈套器电切组的组织完全切除率为66.67% (8/12),EMR组为82.98% (39/47),ESD组为76.92% (30/39),差异均无统计学意义 (P＝0.463)。仅1例ESD治疗后发生穿孔,其他患者未出现并发症。所有患者随访6～36个月,均未复发。 结论内镜治疗对病变未超过黏膜下层的小的消化道类癌是一种安全有效的方法。     

Sclerostin Antibody Treatment Increases Bone Formation,Bone Mass,and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

The development of bone‐rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl‐AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six‐month‐old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency‐induced bone loss, at which point Scl‐AbII was administered for 5 wk. Scl‐AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency‐induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non‐ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody‐mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone‐related disorders, such as postmenopausal osteoporosis.     

Increased RANK ligand in bone marrow of orchiectomized rats and prevention of their bone loss by the RANK ligand inhibitor osteoprotegerin

Orchiectomized (ORX) rats were used to examine the extent to which their increased bone resorption and decreased bone density might relate to increases in RANKL, an essential cytokine for bone resorption.Serum testosterone declined by > 95% in ORX rats 1 and 2 weeks after surgery (p < 0.05 versus sham controls), with no observed changes in serum RANKL. In contrast, RANKL in bone marrow plasma and bone marrow cell extracts was significantly increased (by  100%) 1 and 2 weeks after ORX. Regression analyses of ORX and sham controls revealed a significant inverse correlation between testosterone and RANKL levels measured in marrow cell extracts (R = − 0.58), while marrow plasma RANKL correlated positively with marrow plasma TRACP-5b, an osteoclast marker (R = 0.63). The effects of RANKL inhibition were then studied by treating ORX rats for 6 weeks with OPG-Fc (10 mg/kg, twice/week SC) or with PBS, beginning immediately after surgery. Sham controls were treated with PBS. Vehicle-treated ORX rats showed significant deficits in BMD of the femur/tibia and lower trabecular bone volume in the distal femur (p < 0.05 versus sham). OPG-Fc treatment of ORX rats increased femur/tibia BMD and trabecular bone volume to levels that significantly exceeded values for ORX or sham controls. OPG-Fc reduced trabecular osteoclast surfaces in ORX rats by 99%, and OPG-Fc also prevented ORX-related increases in endocortical eroded surface and ORX-related reductions in periosteal bone formation rate. Micro-CT of lumbar vertebrae from OPG-Fc-treated ORX rats demonstrated significantly greater cortical and trabecular bone volume and density versus ORX-vehicle controls. In summary, ORX rats exhibited increased RANKL protein in bone marrow plasma and in bone marrow cells, with no changes in serum RANKL. Data from regression analyses were consistent with a potential role for testosterone in suppressing RANKL production in bone marrow, and also suggested that soluble RANKL in bone marrow might promote bone resorption. RANKL inhibition prevented ORX-related deficits in trabecular BMD, trabecular architecture, and periosteal bone formation while increasing cortical and trabecular bone volume and density. These results support the investigation of RANKL inhibition as a strategy for preventing bone loss associated with androgen ablation or deficiency.