Expression and effect of sodium-potassium-chloride cotransporter on dorsal root ganglion neurons in a rat model of chronic constriction injury

Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons.To this aim,rats with persistent hyperalgesia were randomly divided into four groups.Rats in the control group received no treatment,and the rat sciatic nerve was only exposed in the sham group.Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide,an inhibitor of NKCC1,based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group.In the experiment measuring thermal withdrawal latency,bumetanide (15 mg/kg) was intravenously administered.In the patch clamp experiment,bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour,or bumetanide (5 μg/μL) was intrathecally injected.The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats.We found that the thermal withdrawal latency of rats was significantly decreased on days 7,14,and 21 after model establishment.After intravenous injection of bumetanide,the reduction in thermal retraction latency caused by model establishment was significantly inhibited.Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7,14,and 21 after model establishment.No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment.The Cl^– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl^– concentration in dorsal root ganglion neurons of chronic constriction injury model rats.We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl^– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment.The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased,and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment.After bumetanide administration,the above indicators were significantly suppressed.These results confirm that CCI can induce abnormal overexpression of NKCC1,thereby increasing the Cl^– concentration in dorsal root ganglion neurons;this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia.In addition,bumetanide can achieve analgesic effects.All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital,College of Medicine,Shihezi University,China on February 22,2017 (approval No.A2017-169-01).     

路径式营养管理在食管癌患者围术期的应用研究

目的 探讨路径式营养管理在食管癌围术期患者中的应用效果。方法 选取2018年1月至2018年7月在四川省肿瘤医院胸外科接受食管癌根治手术治疗的患者156例，随机分为干预组（n=78）和对照组（n=78），干预组采用路径式营养管理，对照组采用常规营养管理，比较两组患者在术后7d血红蛋白、前白蛋白、体质指数（BMI）、预后营养指数（PNI）等营养指标、术后并发症发生率及术后住院时间。结果 干预组患者术后7d血红蛋白（126.09±16.69）g/L、前白蛋白（208.74±38.51）mg/L、BMI（22.28±2.05）kg/m2、PNI（46.62±4.03）优于对照组，差异有统计学意义（P<0.05）；干预组患者胸腔积液发生率低于对照组，差异有统计学意义（t=4.02，P=0.04）；干预组患者住院时间短于对照组，差异有统计学意义（t=6.53，P=0.03）。结论 路径式营养管理能有效改善食管癌围术期患者营养状况、降低并发症发生率、缩短术后住院时间。     

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center,Cohort Study

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres^® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size 5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres^® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.     

大体积肺癌IMRT初次及二次计划剂量学变化研究

目的 采用刚性配准和形变配准方法获得大体积非小细胞肺癌(NSCLC) IMRT中靶区和危及器官(OAR)的累加剂量,并与初次计划的剂量进行比较。方法 选择 30例采用IMRT的大体积NSCLC患者,每位患者分别在放疗前和放疗20分次时进行4DCT模拟定位,基于初次4DCT的平均密度投影CT1-avg制定放疗计划为Plan1,基于二次4DCT的平均密度投影CT2-avg修改放疗计划为Plan2,分别采用刚性配准和形变配准方法将两次计划进行剂量累加得到Plan刚性和Plan形变。比较初次定位和二次定位之间大体肿瘤体积(GTV,以吸气末时相图像CT50%上的勾画为准)和OAR (OAR,以平均密度投影图像CTavg上的勾画为准)的体积变化,以及Plan2、Plan刚性、Plan形变的剂量体积指标相比Plan1的差异。结果 二次定位和初次定位相比,GTV、心脏体积分别缩小44.2%、5.5%,患侧肺、健侧肺、全肺体积分别增大5.2%、6.2%、5.8%(P<0.05);对于内GTV (IGTV,10个4DCT时相的GTV融合而来)和计划靶体积(PTV)的D95%、D98%、V100%,Plan2与Plan1相近(P>0.05),Plan刚性、Plan形变较Plan1均略有下降(P<0.05);对于脊髓、心脏、患侧肺、双肺剂量,Plan2、Plan刚性、Plan形变较Plan1均降低(P<0.05),其中心 脏V30Gy和 Dmean分别降低27.3%、16.5%、15.3%和15.2%、6.6%、5.6%,双 肺V20Gy和 Dmean分别降低15.6%、4.5%、3.7%和15.7%、6.2%、5.1%;Plan形变的IGTV和PTV的D95%、D98%,心 脏V40Gy,患侧肺和全肺 的V20Gy、Dmean高于Plan刚性(P<0.05)。形变配准后OAR相似指数明显高于刚性配准(P<0.05)。结论 Plan2中OAR剂量体积指标相比Plan1差别很大,因此它们在预测OAR放射性损伤方面均有较大偏差,而形变配准得到的剂量体积指标可以提高预测精度。     

基于TCGA数据库探究肾透明细胞癌关键基因的表达及预后作用

目的:探究肾透明细胞癌中关键基因的表达及预后作用，寻找潜在治疗靶点。方法:从TCGA数据库下载肾透明细胞癌mRNA的表达数据，通过Rstudio软件分析肿瘤与正常组织间差异表达基因，对差异表达基因进行富集分析、蛋白-蛋白相互作用网络构建，并分析出关键基因，最后对关键基因进行预后分析。结果:得到1 855个差异表达基因，其中有1 207个是上调的，648个是下调的，富集分析发现差异基因主要与信号转导、物质代谢、免疫反应等信号通路相关。筛选出10个关键基因中有6个存在预后价值。结论:筛选出的差异基因及信号通路可以帮助我们探索肾透明细胞癌发病的分子机制，同时为靶向治疗的研究提供潜在的理论依据。