Objective Cardiac HERG potassium channel currents can cause long QT syndrome .The function of the cardiac HERG potassium channel is regulated by tyrosine kinase and phosphatase , and protein tyrosine phosphatase non-receptor type 11 ( PTPN11) negatively regulates the HERG potassium channel .This study aimed to investigate the effect of PTPN 11 on the electrophysio-logical characteristics of the HERG channel . Methods The plasmids of pcDNA3.1-PTPN11-EGFP were constructed by PCR technique and transfected or cotransfected with the pcDNA 3.1-PTPN11-EGFP plasmid into HEK293 cells using Lipofectamine 2000.The patch clamp technique was employed to record the HERG channel currents in the control group ( HEK293 cells transfected with pcDNA3.0-HERG-EGFP), PTPN11 overexpression group (pcDNA3.0-HERG and pcDNA3.1-PTPN6-EGFP cotransfected HEK293 cells), and PTPN11 overexpression with PAO group . Results The pcDNA3.1-PTPN11-EGFP plasmid was successfully constructed .Green fluorescence was observed in the HEK293 cells transfected with pcDNA3.0-HERG-EG-FP or cotransfected with pcDNA3.0-HERG and pcDNA3.1-PTPN11.The maximum densities of pulse and tail currents were significantly decreased in the PTPN11 overexpression group as compared with the control ([31.85 ±5.54] vs [45.92 ±3.18] pApF, P<0.05;[73.82 ±11.31] vs [108.43 ±7.98] pApF, P<0.05) but markedly in-creased in the PTPN11 overexpression with PAO group ([48.08 ±4.32] pApF;[120.06 ±8.02] pApF) (P<0.05).The time con-stant of deactivation was significantly higher in the PTPN 11 overexpression group than in the control ([622.16 ±46.49] vs [440.70 ± 49.49] ms, P<0.05). Conclusion The overexpression of PTPN11 decreases HERG potassium channel currents , which can be re-versed by PAO.This finding provides a theoretical basis for the application of certain regulatory enzymes in the HERG channel as a treat -ment of long QT syndrome .

AIM: To study the impacts of the myocardial connexin 43 degradation on conduction velocity during acute myocardial ischemia. METHODS: Studies were carried out in 16 dogs which were randomly divided into control group( n= 4) and ischemia group( n= 12). The acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery. The conduction velocity of ischemic myocardium was determined. The content of Cx43 of the ischemic myocardium was examined by laser confocal microscopy with a double-label immunohistochemistry technique. RESULTS: (1)The Cx43 degraded rapidly during acute myocardial ischemia, and the conduction velocity of ischemic myocardium declined greatly; (2)The conduction velocity correlated positively with the Cx43 pixel density in each small region of ischemic myocardium; (3) The Cx43 pixel density decreased over 50% in the region which occuring permanent conduction block. CONCLUSION: These data suggest the degradation of Cx43 decreases the conduction velocity greatly during acute short time myocardial ischemia, and severe degradation of Cx43 would lead to permanent conduction block.

Objective To evaluate the angiographic findings and the therapeutic effect of thrombolysis in AMI (acute myocardial infarction) patients. Method A retrospective study were carried out in consecutive eighty-four inpatients with AMI treated with intravenous thrombolysis and coronary angiography was taken within a week after illness onset from January 2000 to August 2007. The patients were divided into successful recanalization group and non-recanalization group. Single factor χ2 test and multi-factor logistic regression analysis were applied to observe the relationship among the angiographic features of IRA (infarct-related artery including the number of stnosis, the location of stenosis, the severity of stenosis and the morphological changes) and treatment effect of intravenous urokinase thrombolysis. Results (1) Single factor χ2 test showed that location and the extent of lesion of IRA were eligible to enter the logistic regression formula (P ＜ 0.05),whereas the number of lesions and the severity of IRA's stenosis were not eligible to enter the logistic regression formula (P ＞ 0. 05). (2) Multi-factor logistic regression analysis showed that the extent of lesion of IRA was the only factor that had a negative impact on the therapeutic effect of intravenous thrombolysis.Conclusions The study shows that the extent of lesion of IRA is the only factor that has a negative impact on the therapeutic effect of intravenous thrombolysis; The number, the location of lesion and the severity of stenosis of IRA have no impact on the therapeutic effect of intravenous thrombolysis in AMI.

Objective To discuss the effect and safety of modified XELOX regimen for the treatment of colorectal cancer with he-patic metastases.Methods A retrospective analysis on the clinical data in 18 patients with colorectal cancer with hepatic metastases was performed in our hospital.The diagnosis in all patients was confirmed by biopsy and colonoscopy,and the primary lesion was not resected but with at least 2 courses treatment with modified XELOX regimen (intravenous infusion of oxaliplatin changed into ar-terial perfusion and 1-hour slow perfusion with indwelling catheter).The intrahepatic metastases were detected by CT and/or MRI and the primary focus was examined by enteroscopy every 2 months.A follow-up on survival time was performed and the objective response was evaluated in accordance with RECIST criteria.SPSS 1 9.0 was used for an analysis by Kaplan-Meier method.Results (1)Curative effect was evaluated in all 18 patients and TACE has been used for 1 1 5 times.The median OS was 14.0 months with 95% CI (9.6,18.4),and the median PFS was 8.0 months with 95% CI (5.2,10.8)including CR in 2,PR in 7,SD in 4 and PD in 5.The efficiency rate (RP)was 50.0% and the clinical benefit rate (CBR)was 72.2%;(2)The post-treatment adverse reactions mainly included fever,nausea,emesis,pain,impaired liver function,myelosuppression and peripheral sensory neuropathy,most of which were at Level Ⅰ-Ⅱ without treatment-related death.Fever with different degrees occurred in all patients,and nausea and emesis in 13.Pain and abnormal liver function occurred within 3-5 days after TACE with less than Level 2.Conclusion Modified XELOX regimen is practically effective in treating colorectal cancer with hepatic metastases.With a high objective response rate,it can improve patients'living quality and increase excision rate with tolerable adverse reactions.

Objective To assess the effect of ultrasound-guided percutaneous 125I seed implantation for the treatment of osteolytic metastases. Methods From February 2011 to December 2013, a total of 18 patients with advanced cancer complicated by osteolytic metastases received ultrasound-guided percutaneous implantation of 125I seeds. According to visual analog score (VAS) the pain was estimated before and 3 days as well as one month after the treatment. One month after the treatment follow-up CT scan was performed in all patients to check the tumor size and the distribution of 125I seeds, and the therapy was repeated if necessary. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Results A total of 33 times of procedure were carried out in the 18 patients. Three days after the treatment, local pain was obviously relieved in all cases. Compared with preoperative VAS, the postoperative VAS was significantly improved (P=0.000). The pain was well controlled even one month after the treatment (P=0.000). One month after the last treatment the complete remission (CR) rate was 0% (n=0), partial remission (PR) rate 61.1% (n=11), stable disease (SD) 33.3% (n=6) and progress disease (PD) 5.6% (n=1), and local control rate (CR+PR) was 61.1%. No severe brachytheray-related complications occurred. Conclusion Ultrasound-guided percutaneous 125I seed implantation brachytherapy is technically simple and repeatable, it can safely and effectively guide the performance of percutaneous 125I seed implantation for the treatment of osteolytic metastases. Even in the circumstance of not using TPS, this technique can also obtain satisfactory local control rate and significant pain relief.

Objective To explore the effectiveness,safety and influencing factors of arterial infusion of oxaliplatin for the treatment of colorectal l1iver metastases after surgery.Methods Totally 68 colorectal liver metastases after surgery patients pathologically confirmed received at least two course of arterial infusion of oxaliplatin combined with TACE.According to postoperative intravenous chemotherapy,the patients were divided into group A (no chemotherapy) and group B (chemotherapy).Survival time of patients were followed up.According to the efficacy of solid tumor evaluation criteria the objective effect was evaluated,the adverse reactions were compared between two groups.Cox regression analysis was performed to assess the possible factors influencing survival time.Results The median overall survival (OS) of all the 68 patients was 18 months,with complete remission 16 cases,partial remission 26 cases,stable diseasse 21 cases,stable diseasse 5 cases,the response rate (RR) was 61.76％ (42/68).The median progression-free survival (PFS) was 10 months.The RR,OS and PFS had no statistical difference (all P＞0.05).The variables that eventually entered the Cox regression model were tumor differentiation (P=0.003,hazard ratio 2.202).Conclusion Arterial infusion of oxaliplatin and TACE is effective in treating colorectal liver metastases after surgery,with high objective response rate.

Objective： To study the application of DSA in the diagnosis and treatment of ENT diseases. Methods： The diagnostic and therapeutic roles of DSA in ENT patients admitted from November 1995 to December 1999 were retrospectively studied. Results： Therapeutic vascular embolization using DSA was performed in 9/10 patients with severe epistaxis. The treatment was successful in 8/9 patients with a successful rate of 88.89%; embolization of tumor supplying vessels using DSA as a preoperative measure for reducing operative blood loss in 3 patients with nasopharyngeal fibrohemangioma obtained a total success; diagnosis was clarified in 2 patients using DSA. No patients were with severe complications. Conclusion： DSA is not only a safe and effective measure for diagnosis and therapy, but also effective in differential diagnosis of space occupying lesions. Preoperative selective embolization of tumor supplying arteries can reduce operative blood loss.

Malignant hepatopancreatobiliary tumors are highly malignant and have poor prognosis. 125I seed implantation combined with other minimally invasive therapies for radical treatment of early liver cancer has achieved a good clinical effect in preventing early recurrence after liver cancer surgery. It is also used in the treatment of advanced liver cancer and portal vein tumor thrombosis. 125I seed has achieved a good local control rate in the treatment of tumors with a lack of blood supply, such as intrahepatic cholangiocellular carcinoma and metastatic liver cancer. 125I seed combined with biliary stenting can significantly relieve the symptoms of malignant biliary obstruction and extend the time to restenosis. Comprehensive interventional treatment based on 125I seed can significantly improve quality of life and extend survival time in patients with pancreatic cancer. Therefore, 125I seed implantation is safe and convenient in clinical practice and holds promise for clinical application.

Acetaminophen (APAP) is the most common antipyretic, analgesic and anti-inflammatory drug, but its overdose often leads to acute liver injury, even acute liver failure, and death in some severe cases. At present, there is still a lack of specific treatments. The c-Jun N-terminal kinase (JNK) signal pathway is one of the potential therapeutic targets identified in recent years in overdose APAP-induced acute liver injury. This article reviews the JNK signaling pathway of APAP in liver metabolism, the activation of JNK signaling pathway and the amplification of oxidative stress, other pathways or cellular processes related to JNK signaling pathway, and the possible challenges of drugs targeting JNK, so as to provide direction and feasibility analysis for further research and clinical application of JNK signaling pathway targets in APAP hepatotoxicity, and to provide reference for searching for other targets.
Animals ; Mice ; Acetaminophen/adverse effects* ; Chemical and Drug Induced Liver Injury ; Chemical and Drug Induced Liver Injury, Chronic/metabolism* ; JNK Mitogen-Activated Protein Kinases/metabolism* ; Liver ; Mice, Inbred C57BL ; Signal Transduction

Objective:To investigate the related risk factors of thrombocytopenia grade 2+ G2(+ )] in patients with gastric cancer during chemoradiotherapy.Methods:The pre-treatmentclinical data, hematologic parameters, and the correlation between dose distribution of vertebrae andTPG2(+ ) in non-metastaticgastric adenocarcinoma patients receiving concurrent chemoradiation in Sun Yat-sen University Cancer Center were retrospectively analyzed.Results:A total of 58 patients were included, including 23 cases (40%) in theTPG2(+ ) group and 35(60%) in the TPG2(-) group. There was no statistical difference in baseline clinical data between two groups (all P>0.05). Univariate Logistic regression analysis showed that several baseline parameters including platelet count (PLT), basophil count (BA), lactate dehydrogenase (LDH) and length of CTV (LCTV), the number of vertebrae (VBN), vertebral body volume (VBV), D max, D mean, V 5Gy, V 10Gy, V 20Gy, V 30Gy and V 40Gywere correlated with TPG2(+ )(all P<0.05). However, the multivariate Logistic regressionanalysisshowed that low PLT ( P=0.048), high LDH ( P=0.028), increased LCTV ( P=0.013), high V 20Gy/VBN ( P=0.030) were associated with the risk of TPG2(+ ). Conclusion:In gastric adenocarcinoma patients treated with chemoradiotherapy, correction of PLT reduction before treatment, avoidinglonger CTV and controlled V 20Gy correction for vertebral number may reduce significant thrombocytopenia induced by chemoradiotherapy.