Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF‐1α‐VEGF pathway in oxygen‐induced retinopathy mice

Retinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti‐VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti‐angiogenic and neuroglial protective in the progression of ROP remains unknown. Thus, this study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen‐induced retinopathy (OIR) mice. The results showed a reduction in retinal vascular leakage in OIR mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen‐induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, HIF‐1α‐VEGF pathway was activated in the retina of OIR mice, yet was suppressed in melatonin‐treated OIR mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti‐inflammation effect via inhibition of HIF‐1α‐VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP.     

单中心乳腺癌术后乳房重建的影响因素

背景与目的：乳腺癌手术方式的选择受到诸多因素影响，本研究旨在分析乳腺癌患者选择乳房重建手术的影响因素，重点探讨居住地距离与乳房重建的关系。方法：回顾性分析了1999年1月—2015年12月复旦大学附属肿瘤医院收治的因单侧或双侧0～Ⅱ期乳腺癌行全乳切除术的女性患者临床资料，分析居住地距离与乳房重建比例的关系。结果：非上海患者选择全乳切除术后乳房重建比例高于上海患者(6.1% vs 4.5%，P<0.001)。居住地距离影响乳房重建比例(P=0.035)。单因素分析显示，居住地距离越远，选择乳房重建手术比例越高，而年龄、体质量指数(body mass index，BMI)、TNM分期与乳房重建的选择呈负相关(P均<0.001)。多因素分析显示，年龄增长、BMI增加、TNM分期较晚是拒绝行乳房重建的独立影响因素(P均<0.001)，而居住地距离不是乳房重建的独立影响因素(P>0.05)，且与具体乳房重建方式无交互作用。年龄与居住地距离呈负相关(P<0.001)。结论：乳腺癌患者的居住地距离与乳房重建比例呈线性相关；年龄、BMI和疾病分期是影响乳房重建的主要因素。     

Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients

We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0?C1). Complete remission (CR) after induction chemotherapy was achieved in 31.8?% of the patients, which increased to 69.6?% after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43?%, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P?<?0.05) in univariate analysis. Using multivariate analysis, we identified serum LDH level, ECOG PS score and local invasiveness to be independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma that shows heterogeneity. The IPI and KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.     

Mechanism of acute lung injury due to phosgene exposition and its protection by cafeic acid phenethyl ester in the rat

The mechanism of phosgene-induced acute lung injury (ALI) remains unclear and it is still lack of effective treatments. Previous study indicated that oxidative stress was involved in phosgene-induced ALI. Caffeic acid phenethyl ester (CAPE) has been proved to be an anti-inflammatory agent and a potent free radical scavenger. The purpose of this study was to investigate the protective effects of CAPE on phosgene-induced ALI and identify the mechanism, in which oxidative stress and inflammation were involved. The phosgene was used to induce ALI in rats. The results showed that after phosgene exposure, total protein content in BALF was not significantly changed. The increase of MDA level and SOD activity induced by phosgene was significantly reduced by CAPE administration, and the decrease of GSH level in BALF and lung were significantly reversed by CAPE. CAPE also partially blocked the translocation of NF-κB p65 to the nucleus, but it had little effect on the phosphorylation of p38 MAPK. In conclusion, CAPE showed protective effects on lung against phosgene-induced ALI, which may be related with a combination of the antioxidant and anti-inflammatory functions of CAPE.