Decreased expression levels of DAL-1 and TOB1 are associated with clinicopathological features and poor prognosis in gastric cancer

PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer

Gastric cancer, one of the most common disease, has become a major public health problem worldwide. Cisplatin (DDP) has been a widely used drug for the treatment of cancer, also usually applied in gastric cancer in clinic. However, the side effects including toxicity and drug-resistance restricted the usage of DDP in clinic, so we prepared a DDP-complexed hydrogel (DDP-Gel) and investigated its efficacy in gastric cancer. For in vivo studies, MKN45-Luc cells were injected into BLAB/C node mice subcutaneously to establish gastric cancer with orthotopically grown tumors. Mice bearing tumors were treated with normal saline, DDP and DDP-Gel. Body weight and survival condition were observed and recorded. The treatment efficacy in vivo was detected by luciferase imaging and histological evaluation was performed by H&E staining of different organs. Additionally, normal ICR mice were treated with different doses of DDP/DDP-Gel to calculate their LD₅₀ in vivo. The results showed that DDP-Gel prolonged survival time and ameliorated body weight changes of mice bearing tumors. DDP-Gel exhibited higher efficacy to inhibit tumor growth and metastasis, compared to DDP. Besides, LD₅₀ of DDP-Gel was 166.0?mg/kg, 13.2 folds higher than DDP. As a conclusion, DDP-Gel showed a more effective and safer function than DDP in gastric cancer, which indicating that DDP-Gel might be a novel strategy for gastric cancer therapy.     

Cognitive Impairments in Patients with Bipolar Affective Disorder in Remission

Neuroscience and Behavioral Physiology - Objective. To determine the frequency, structure, and severity of cognitive impairments in patients with bipolar affective disorder (BAD) in remission....     

Liguzinediol对阿霉素诱导的慢性心衰大鼠心功能的影响

目的 通过阿霉素（Dox）复制大鼠慢性心力衰竭（CHF）模型，观察Liguzinediol对CHF大鼠心功能的影响。方法 通过血流动力学观察Liguzinediol对Dox（腹腔注射，2 mg/kg）诱导的CHF大鼠左心室内压最大上升/下降速率(±dp/dt_max)、左心室内压(LVSP)、动脉收缩压(ASP)、动脉舒张压(ADP)和心率(HR)的变化；观察Liguzinediol对血清一氧化氮（NO）、一氧化氮合成酶（NOS）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）以及血浆中丙二醛（MDA）的影响。结果 Liguzinediol能增加LVSP、+dp/dt_max、ASP、ADP、AP、HR，降低-dp/dt_max(P<0.05~0.01)；降低NO、iNOS以及MDA的浓度，同时增强了SOD的活性(P<0.05~0.01)；抑制IL-6和TNF-α的生成(P<0.05~0.01)。结论 Liguzinediol可明显改善Dox诱导的CHF大鼠血流动力学指标，减少模型大鼠炎症因子的释放以及抑制氧自由基的生成。      

甲状腺癌根治术中不同途径显露喉返神经的应用效果评价

目的 探讨甲状腺癌根治术中不同途径显露喉返神经的应用情况.方法 根据随机数字表法将92例进行甲状腺癌根治术的患者随机分为对照组和观察组,每组46例.对照组采用甲状腺下动脉途径法显露喉返神经,观察组采用甲状腺最下动脉途径法显露喉返神经.比较两组患者寻找喉返神经的时间、术中出血量、手术时间、术后声音嘶哑和喉返神经损伤的发生率.结果 观察组患者寻找喉返神经的时间和手术时间均明显短于对照组患者,差异均有统计学意义(P﹤0.01).观察组患者的术中出血量明显少于对照组患者,差异有统计学意义(P﹤0.01).观察组患者术后声音嘶哑和喉返神经损伤的发生率均低于对照组患者,差异均有统计学意义(P﹤0.05).结论 甲状腺癌根治术中应用不同途径显露喉返神经,其效果存在差异.与甲状腺下动脉途径法相比,甲状腺最下动脉途径法能够明显缩短寻找喉返神经的时间和手术时间,减少术中出血量,降低术后声音嘶哑和喉返神经损伤的发生率,值得临床推广应用.     

黑色素瘤缺乏因子2在肿瘤发生发展中作用的研究进展

黑色素瘤缺乏因子2（AIM2）作为AIM2样受体（ALR）家族成员之一，其和胞质中异常存在的双链DNA进一步组装成 AIM2炎症小体而引起炎症及其相关的包括肿瘤在内的多种疾病。关于AIM2对肿瘤的作用机制，较为明确的是其作为炎症小体 发挥作用，然而AIM2在结肠癌、宫颈癌、肾癌、肝癌等肿瘤中均有差异表达，并且还通过不依赖于AIM2炎症小体的途径发挥促 进或抑制肿瘤的作用，该途径包括PI3K/AKT、EMT、NF-κB以及MAPK/ERK等信号通路。加深基于AIM2对肿瘤发生发展中作 用机制的认识可为肿瘤诊治研究提供新的思路。     

经胫骨隧道前交叉韧带双束八股解剖重建的临床研究

目的观察关节镜下采用自体腘绳肌腱经胫骨隧道前交叉韧带（anterior cruciate ligament, ACL）双束八股解剖重建的临床效果。方法随访上海交通大学附属第六人民医院运动医学科2018年12月—2020年1月收治的103例ACL断裂患者资料，其中男78例，女25例，年龄18~45岁，平均（26.8±5.86）岁；左侧47例，右侧56例，均采用关节镜下自体腘绳肌腱经胫骨隧道打股骨骨隧道，ACL双束八股解剖重建。按照Lysholm评分、国际膝关节评分委员会（IKDC）膝关节评分、Tegner膝关节评分标准和膝关节自我效能量表K-SES评价疗效。结果所有患者术后获随访12～42个月，平均（24±8.18）个月；手术前、末次随访评分比较，Lysholm评分分别为（48.41±4.44）分和（95.34±1.91）分，2组比较差异有统计学意义（P<0.001)；IKDC评分分别为（44.05±4.36）分和（95.66±1.89）分，2组比较差异有统计学意义（P<0.001)；Tegner评分分别为（2.84±0.95）分和（6.15±0.89）分，2组比较差异有统计学意义（P<0.001)；膝关节自我效能量表K-SES量表（3.10±0.83）分和（7.12±1.10）分，2组比较差异有统计学意义（P<0.001)。末次随访103例患者前抽屉试验阴性，轴移试验阴性。98例（95.1%）Lachman试验阴性，5例（4.9%）Lachman试验1°阳性。结论关节镜下采用自体腘绳肌腱经胫骨隧道双束八股解剖重建前交叉韧带是一种恢复膝关节稳定性，恢复伤前活动水平的有效方法。