Evaluation of Intraductal Ultrasonography,Endoscopic Brush Cytology and K-ras,P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture

Background:In qualitative diagnosis of bile duct stenosis,single diagnostic measure is difficult to make a correct diagnosis,to combine several diagnostic techniques may be helpful to make an accurate ...     

Diagnostic Utility of Diffusion-weighted Magnetic Resonance Imaging in Differentiating Small Solid Renal Tumors (≤4 cm) at 3.0T Magnetic Resonance Imaging

Background:

The aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤4 cm).

Methods:

In this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm² and values compared via the Kruskal–Wallis and Mann–Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.

Results:

The tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10⁻³ mm²/s), ccRCCs ([1.53 ± 0.31] × 10⁻³ mm²/s) and the normal renal parenchyma ([2.22 ± 0.12] × 10⁻³ mm²/s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10⁻³ mm²/s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.

Conclusions:

DW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.     

右美托咪定对大鼠移植肝缺血/再灌注所致急性肺损伤中细胞凋亡及CCAAT增强子结合蛋白同源蛋白的影响

目的 探讨右美托咪定预处理对大鼠原位移植肝缺血/再灌注(I/R)所致急性肺损伤(ALI)中细胞凋亡及CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)的作用.方法 选择雄性SD大鼠40只,按随机数字表法分为假手术组、I/R模型组、右美托咪定低剂量组和右美托咪定高剂量组,每组10只.采用二袖套法结扎并切断肝动脉,供体肝脏移植入后即可完全开放门静脉复制肝I/R模型;假手术组开腹后只游离肝周韧带,不进行其他特殊处理;右美托咪定低剂量组和高剂量组分别于I/R前1 h静脉泵注右美托咪定 2.5μg·kg-1·h-1和5.0μg·kg-1·h-1,1 h内完成.实验结束后留取肺组织,检测肺组织湿/干质量(W/D)比值;光镜下观察肺组织病理学变化并进行肺泡损伤定量评估(IQA),电镜下观察肺组织超微结构变化;反转录-聚合酶链反应(RT-PCR)检测CHOP mRNA表达水平;蛋白质免疫印迹法(Western Blot)检测CHOP的蛋白表达水平;原位末端缺刻标记法(TUNEL)检测肺组织细胞凋亡情况,并计算凋亡指数(AI).结果 与假手术组比较,I/R模型组肺W/D比值(4.94±0.84比2.29±0.54)、IQA〔(40.52±5.15)%比(4.55±1.85)%〕和AI〔(36.57±5.85)%比(2.85±0.95)%〕均明显升高(均P<0.0l);光镜和电镜下均显示肺组织结构发生明显的损伤.与I/R模型组比较,右美托咪定低剂量组和右美托咪定高剂量组肺W/D比值(3.29±0.85,2.68±0.78比4.94±0.84)、IQA〔(23.69±2.62)%,(15.86±3.61)%比(40.52±5.15)%〕 和AI〔(25.73±3.71)%,(14.66±2.61)%比(36.57±5.85)%〕均明显降低(均P<0.01),光镜和电镜下可见肺组织结构损伤明显减轻.I/R模型组有大量肺血管内皮细胞和肺泡上皮细胞发生凋亡,而右美托咪定低剂量组和高剂量组细胞凋亡则明显减少.与假手术组比较,I/R模型组CHOP mRNA〔吸光度(A)值:0.96±0.18比0.43±0.08〕及蛋白(灰度值:2.79±0.74比1.02±0.27)表达水平均明显升高(均P<0.01).与I/R模型组比较,右美托咪定低剂量组和高剂量组CHOP mRNA(A值:0.69±0.13、0.56±0.12比0.96±0.18)及蛋白(灰度值:1.96±0.58、1.34±0.49比2.79±0.74)表达水平均明显降低,且以高剂量组的降低更显著(均P<0.01).结论 右美托咪定对移植肝I/R肺组织具有保护作用,该作用可能与其抑制CHOP的活化、减少肺组织细胞凋亡有关.     

Pokemon和p53在乳腺癌组织中的表达及其生物学意义

目的 探讨乳腺癌组织中Pokemon和p53蛋白的表达及其相关性,并分析其与乳腺癌患者临床病理特征的关系。方法 采用免疫组化En Vision 法检测90 例乳腺癌和相应癌旁组织中Pokemon 和p53 蛋白的表达情况。结果 乳腺癌组织中Pokemon和p53蛋白表达阳性率均明显高于癌旁组织（均P＜0.01）;Pokemon 和p53蛋白的表达与乳腺癌患者临床分期及淋巴结转移均有关（均P＜0.01）,而与患者年龄、肿瘤大小、组织学类型及分级均无关（均P ＞0.05）。Spearman相关分析显示在乳腺癌组织中,Pokemon 和p53 蛋白表达呈正相关（P＜0.01）。结论 Pokemon 和p53蛋白异常表达可能与乳腺癌的发生、发展有关,联合检测两者对评估乳腺癌生物学行为及预后具有较重要的临床意义。     

不同扫描仪构建的结直肠癌全切片数字病理图像中人工标注迁移的研究

目的研究结直肠癌人工智能病理诊断模型构建过程中,病理医师对数字切片癌组织的人工标注在不同扫描仪构建的全切片图像（WSI）中准确迁移的方法。 方法在本研究中,我们提出了一种基于图像配准的标注迁移方法,在来自不同扫描仪的WSI之间建立仿射映射。通过多分辨率最小化两个WSI缩略图之间的互信息来估计最佳仿射映射参数,以避免和改变扫描仪特定特性的影响,减少计算时间。我们使用了181张结直肠癌病理切片,使用两个品牌的扫描仪获得相应的WSI,对上述标注迁移方法进行测试。 结果181张HE切片的扫描结果表明,同一张切片由不同扫描仪构建的WSI在颜色、位置、大小等属性上都有不同的表现。使用我们提出的标注迁移方法,其中179张图像的人工标注成功地在不同扫描仪构建的WSI中迁移,其中125对使用单个CPU核心的计算时间不到1分钟。 结论我们提出了一种快速、准确的全自动的标注迁移方法,用于在不同扫描仪构建的WSI之间传递人工标注。在准备深度学习训练数据过程中,既可以避免病理医师对新图像的重新标注,也可以避免病理医师之间在标注上的差异。     

稳定期慢性阻塞性肺疾病患者的气道阻力与运动相关呼吸困难肺功能参数的关系

目的观察稳定期慢性阻塞性肺疾病(COPD)患者的各项气道阻力(Raw)参数与运动相关呼吸困难肺功能参数的相关关系。方法前瞻性纳入上海交通大学附属胸科医院和第一人民医院门诊稳定期COPD患者180例,根据慢性阻塞性肺疾病全球倡议(GOLD 2017版)制订的肺功能诊断标准分为Ⅰ-Ⅳ级4组,受试前8 h内均未应用支气管舒张剂。所有患者在吸入沙丁胺醇400μg后接受常规肺功能和气道阻力测试。同期选择42例成年健康体检者作为对照组。结果Ⅱ级以上COPD患者的第1秒用力呼气容积和呼出50%肺活量时流量均显著低于健康成年人和Ⅰ级COPD患者,总气道阻力、有效气道阻力、吸气阻力和呼气阻力则呈进行性增高。Ⅲ-Ⅳ级COPD患者的深吸气量占预计值百分比(IC%pred)<80%,同时改良英国医学研究委员会呼吸困难量表评分超过2分;7例Ⅲ级(13.2%)和14例Ⅳ级COPD患者(33.3%)的吸气分数(IC/TLC)≤25%,而仅有1例Ⅱ级COPD患者的IC/TLC≤25%(1.9%)。结论稳定期中重度COPD患者呼出气流受限趋于加重,Raw各项参数中呼气阻力增高尤为显著。Ⅲ-Ⅳ级COPD患者更易出现运动相关呼吸困难症状,且IC/TLC≤25%。     

Safety and efficacy of coblopasvir and sofosbuvir in patients with genotypes 1, 2, 3 and 6 HCV infections without or with compensated cirrhosis

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention‐to‐treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow‐up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.     

Antimycobacterial activity of Pichia pastoris-derived mature bovine neutrophil β-defensins 5

Tuberculosis (TB) is an ongoing threat to global health, and the lack of effective therapies for treating it is also a global problem. Previous studies have shown that human cathelicidin and defensins have effective antimicrobial activity against Mycobacterium spp. To our knowledge, there are no reports on the antimycobacterial effects of bovine neutrophil β-defensins so far. Here, we identified the antimicrobial effect of mature bovine neutrophil β-defensins (mBNBD) 5 against Mycobacterium infection both in vitro and in vivo. The mBNBD5 protein was expressed in Pichia pastoris. To increase the yield of β-defensins, a purification method was employed by adding a 6-His·tag to the C-terminus of the mBNBD5 gene. Our results indicated that recombinant mBNBD5 protein was successfully expressed and purified from Pichia pastoris with intact antimicrobial activity. The recombinant protein exhibited potent bactericidal activity in vitro against M. smegmatis and M. bovis, with a dose-dependent manner and a time-dependent manner. The electron microscope results showed that the bacterial cell wall of M. bovis was disrupted when incubated with mBNBD5 for 72 h. Our data also indicated that the exogenous addition of mBNBD5 could reduce the survival of Mycobacterium spp., especially M. tuberculosis and M. bovis in RAW 264.7 macrophages. These results provide foundations for the development of mBNBD5 as a potential new therapeutic agent for TB treatment.     

胰腺分裂内镜治疗价值

目的探讨内镜下治疗胰腺分裂的疗效和安全性。方法收集2006年6月至2013年6月在南京大学医学院附属鼓楼医院消化科就诊的8例胰腺分裂患者的临床资料,对术中及术后情况进行回顾性分析。结果8例胰腺分裂患者共行经内镜逆行胰胆管造影术28例次,均置入胰管支架,其中7例同时行副乳头括约肌切开术,6例行内镜下扩张术,1例行胰管取石术。术后出现1例次轻度胰腺炎。随访2～47个月,1例死于胰腺癌,3例已拔出支架,3例定期复查,1例失访。患者术后慢性胰腺炎急性发作频率及腹痛程度均较术前明显降低。结论内镜下治疗胰腺分裂安全有效,可减少胰腺炎发作频率,减轻术后腹痛程度,术后并发症发生率低。