膀胱癌患者尿NMP22测定的临床意义

目的：评价尿核基质蛋白22（NMP22）在膀胱癌诊断和预后判定中的应用价值。方法：采用ELISA法测定18例膀胱癌和20例泌尿系良性疾病患者尿液中NMP22值,及10例膀胱移行细胞癌患者术后尿NMP22值。结果：18例膀胱癌患者尿NMP22的中位值为44．3IU／L,20例泌尿系良性疾病患者尿NMP22的中位值为5．8IU／L,二者相比判别有显著性意义（P＜0．02）。以10IU／L为临界值,诊断膀胱癌的敏感性为83％,特异性为70％,阴性预测值为82％。10例膀胱移行细胞癌患者术后尿NMP22中位值为7．8IU／L,与术前相比明显下降（P＜0．01）。尿NMP22在肿瘤分级间的差别无显著性意义。结论：尿NMP22作为一种灵敏、简便的早期诊断膀胱癌的瘤标,对于预后判断可能具有应用价值。     

彩色多普勒超声在眼眶病诊断中的价值

目的 探讨彩色超声多普勒（color Doppler imaging,CDI）在眼眶病诊断及鉴别诊断中的应用价值。方法 应用CDI技术对288例眼眶病患者眼眶病病变内部的彩色血流显像和脉冲多普勒频谱进行检测。结果 288例眼眶病中,恶性肿瘤38例,炎性假瘤23例,泪腺混合瘤（血流信号不丰富）18例,神经鞘瘤22例,脑膜瘤7例,良性血管内皮瘤及血管外皮瘤各2例,视神经胶质瘤及神经纤维瘤各1例,瘤体内CDI均可检测出血流信号;海绵状血管瘤62便,皮样囊肿16例及脂肪瘤1例瘤体内CDI检测均无血流信号;静脉性血管瘤29例中,CDI检测出静脉血流信号16例;动静脉血管瘤3例CDI检测出动脉血流信号;静脉曲张15例在颈静脉加压和压力解除过程中示动态血流变化;婴儿性血管瘤6例应用糖皮质激素治疗后内部血流信号明显减少;颈动脉海绵窦瘘13例,其中颈内动脉海绵窦瘘（internal carotid cavernous sinus fistula,CCF)8例和硬脑膜海绵窦瘘（dural cavernous sinus fistula,DCF）5例CDI检测均显示眼上静脉扩张动脉化,同时CCF的眼上静脉的血流速度和每分血流量高于DCF,而阻力指数低于DCF。1例眼上静脉血栓性静脉炎显示眼上静脉扩张但无血流信号。结论 CDI对于多血管性肿瘤和眼眶血管性疾病有其特征性的表现。CDI检测在协助B超、CT或MRI检查眼眶病确定疾病的诊断和鉴别诊断中的重要意义。     

Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded,Placebo-Controlled,Randomized Phase III Trial (ALTER0703)

Background

Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC.

Materials and Methods

This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1–14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety.

Results

A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4–4.5) over placebo group (1.5 months; 95% CI, 1.4–1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27–0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8–9.7 vs. 7.2 months; 95% CI, 6.2–8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%).

Conclusion

Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients.

Implications for Practice

In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

     

儿科人群临床试验中对受试者疼痛管理的伦理考虑

作为“临床试验中对受试者疼痛管理的伦理考虑”系列标准之一，主要论述《儿科人群临床试验中对受试者疼痛管理的伦理考虑》的起草背景、制定依据和适用范围，以及儿科人群临床试验中受试者疼痛等负担的来源和识别、在儿科人群临床试验方案设计和临床试验执行过程时使受试者疼痛最小化的措施，以期从伦理角度对儿科人群临床试验中受试者疼痛管理提出指导意见。其适用于伦理审查中对于儿科人群临床试验中受试者疼痛管理的伦理考虑，以及研究者制定临床试验方案和试验流程对儿科人群疼痛管理的关注。对临床试验中儿科人群疼痛予以更多关注，是保护儿科受试者权益的措施之一，有助于保障儿科临床试验顺利开展。     

T-Wave Indices and Atherosclerosis

Tpeak-Tend interval, the time difference between the peak and the end of the T-wave, reflects the degree of dispersion of repolarization. Its prolongation has been associated with higher risks of developing ventricular arrhythmias and sudden cardiac death in different pro-arrhythmic conditions such as Brugada and long QT syndromes. In this review, we will provide a comprehensive overview on how Tpeak-Tend is altered in different atherosclerotic conditions such as hypertension, stable coronary artery disease, acute coronary obstruction, and coronary slow flow as well as inflammatory diseases affecting the arterial tree. We will explore its relationship with arterial function and dysfunction, ventricular remodeling, and arrhythmic and mortality outcomes. The published literature shows that patients with coronary atherosclerosis, whether in the form of stable coronary artery disease, chronic total occlusion, slow flow, or acute coronary obstruction, have prolonged Tpeak-Tend intervals and Tpeak-Tend/QT ratios. These can be used to predict the occurrence of ventricular arrhythmias and sudden cardiac death. They also correlate with the extent and severity of arterial stenosis and structural remodeling of the ventricles as well as arterial function and dysfunction. Finally, they can be normalized following revascularization and may therefore be used as a surrogate measure of treatment success.     

Sevoflurane postconditioning attenuates cerebral ischemia-reperfusion injury via protein kinase B/nuclear factor-erythroid 2-related factor 2 pathway activation

Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of sevoflurane against experimental stroke. Focal cerebral ischemia was performed via 1 h of middle cerebral artery occlusion followed by reperfusion. At the onset of reperfusion, rats were subjected to postconditioning with sevoflurane or without sevoflurane for 1 h. Neurological deficit score was assessed at different time points after reperfusion. Cerebral infarct volume, oxidative stress level and the binding activity of Nrf2 to antioxidant response element were assessed, meanwhile the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), quinine oxidoreductase 1 (NQO1), protein kinase B (Akt) and phosphor-Akt was examined by Western blot at 72 h after reperfusion. Sevoflurane postconditioning administration significantly reduced neurological deficit score, infarct volume and oxidative stress levels, while increased the expression of phosphorylation Akt, NQO1, Nrf2 and the binding activity of Nrf2 to ARE in middle cerebral artery occlusion rats. These neuroprotective effects were all suppressed by LY294002, a selective PI3K blocker. Taken together, these findings provided evidence that sevoflurane postconditioning protects brain against ischemic/reperfusion injury, and this neuroprotective effect involves the Akt/Nrf2 pathway.     

Autophagy Enhances the Aggressiveness of Human Colorectal Cancer Cells and Their Ability to Adapt to Apoptotic Stimulus

Objective To investigate LC3B-Ⅱand active caspase-3 expression in human colorectal cancer to elucidate the role of autophagy and to explore the relationship of autophagy with apoptosis in human colorectal cancer. Methods LC3B expression was detected by immunohistochemistry in 53 human colorectal cancer tissues and 20 normal colon tissues.The protein levels of LC3B-Ⅱand active caspase-3 were also determined by Western blot analysis in 23 human colorectal cancer tissues and 10 normal colon tissues. Results LC3B was expressed both in cancer cells and normal epithelial cells.LC3B expression in the peripheral area of cancer tissues was correlated with several clinicopathological factors,including tumor differentiation(P=0.002),growth pattern of the tumor margin (P=0.028),pN(P=0.002),pStage(P=0.032),as well as vessel and nerve plexus invasion(P=0.002).The protein level of LC3B-Ⅱin cancer tissue was significantly higher than in normal tissue(P=0.038),but the expression of active forms of procaspase-3 in cancer tissue was lower(P=0.041).There was a statistically significant positive correlation between the expression levels of LC3B-Ⅱand the active forms of procaspase-3(r=0.537,P=0.008). Conclusions Autophagy has a prosurvival role in human colorectal cancer.Autophagy enhances the aggressiveness of colorectal cancer cells and their ability to adapt to apoptotic stimulus.