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).     

清化方治疗重症肺炎(痰热壅肺证)的临床研究

目的观察自拟清化方治疗重症肺炎(痰热壅肺证)患者的疗效。方法患者74例随机分为观察组与对照组各37例,对照组予西医常规治疗,观察组在对照组的基础上加用清化方治疗,分别于5、10 d后比较两组疗效。结果治疗5 d后,两组炎症指标、临床肺部感染评分(CPIS)、序贯器官功能衰竭评分(SOFA评分)、急性生理与慢性健康评分Ⅱ(APACHⅡ评分)、中医证候评分与治疗前比较,均显著改善(P<0.05);观察组在APACHⅡ评分、中医证候评分等方面与对照组比较,差异均有统计学意义(P<0.05)。治疗10 d后,两组炎症指标、CPIS评分、SOFA评分、APACHⅡ评分、中医证候评分与治疗前比较,差异均有统计学意义(P<0.05);观察组在降钙素原(PCT)、APACHⅡ评分、中医证候评分等方面与治疗5 d后及对照组比较,差异均有统计学意义(P<0.05);观察组总有效率为80.00%,显著高于对照组的68.97%(P<0.05)。结论清化方对重症肺炎实证患者有较好的疗效,能有效改善患者的炎症反应,调整脏器功能,减轻患者症状,改善预后。     

Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin‐bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.     

Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Immunotherapy has revolutionized cancer treatment for several hematologic and solid organ malignancies; however, pancreatic cancer remains unresponsive to conventional immunotherapies. Several characteristics of pancreatic cancer present challenges to successful treatment with immunotherapy, including its aggressive biology, poor immunogenicity, and abundant desmoplastic stroma which can impede effector T cell infiltration and promote an immunosuppressive microenvironment. In this review, we evaluate the current understanding of the immune and stromal landscapes of pancreatic cancer, discuss the successes and failures of stroma-targeted therapies, and highlight how stroma-directed therapies may be synergistic with immunotherapy.     

基于手机应用程序的居家用药管理对肺移植受者依从性及生存质量的影响

目的探讨"肺病与移植管理"App结合1日药盒用药法居家用药管理方案对肺移植受者自我管理、用药依从性及生存质量的影响。 方法选取2019年1至6月无锡市人民医院肺移植中心门诊随访的73例肺移植受者进行自我管理、用药依从性及生存质量的问卷调查。成立用药随访管理小组，制订肺移植受者居家用药管理方案。予肺移植受者"肺病与移植管理"APP结合1日药盒用药法居家用药管理方案干预3个月后再次对其进行问卷调查，比较干预前后受者自我管理、自我效能、用药依从性及生存质量差异。采用配对t检验比较"肺病与移植管理"App结合1日药盒用药法居家用药管理方案干预前后肺移植受者自我管理、自我效能、用药依从性和生存质量得分，P<0.05为差异有统计学意义。 结果干预3个月后，受者自我管理、认知性症状管理实践、用药依从性、生存质量及生理方面生存质量得分分别为(37±7)、(16±3)、(7.0±1.0)、(154±26)和(77±14)分，均高于干预前[(33±9)、(13±6)、(6.5±1.1)、(141±30)和(67±17)分]，差异均有统计学意义(t＝-0.609、-3.383、-12.864、-2.818和3.586，P均<0.05)。干预前后受者自我效能、运动锻炼、与医师的沟通、症状管理、疾病共性管理和心理方面生存质量得分差异均无统计学意义(t＝-1.972、-0.609、-1.486、-1.747、-1.746和1.487，P均>0.05)。干预前用药依从性好、中和差受者分别有16、41和16例，干预后分别为27、40和6例。 结论基于移动健康平台制订的居家用药管理方案可提高肺移植受者自我管理、用药依从性及生理方面的生存质量。     

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.     

Antiviral Properties of Traditional Chinese Medicine against Coronavirus: Research Clues for Coronavirus Disease-2019

The objective of this study was to provide research clues for the prevention and treatment of coronavirus disease?2019 (COVID?19) and coronavirus (CoV) infection using Traditional Chinese Medicine (TCM). A review on research and clinical trials that using TCM extracts and active ingredients against CoV was performed, and a table of TCM agents and their effects on CoV were summarized. Relevant analysis was performed and visual expression of the data included summarizing the types of TCM and treatment methods for COVID?19. TCM fighting against CoV is mainly used in the lung and heart channels, and its medicinal properties are mainly cold and mild, while its taste is mainly bitter and sweet. The majority of research focused on treatments that clear away heat and toxic materials and those that strengthen body resistance and tonify deficiencies. TCM has unique advantages to fight against CoV. The development of new anti?CoV therapy using TCM is of great significance for the prevention and treatment of COVID?19 pneumonia and various viral infectious diseases.