OBJECTIVE: To construct a VEGFR1 and VEGFR2 bi-targeting oligopeptide-based fusion protein A7/G6-LDP and investigate its anti-angiogenic activity and the mechanism of action. METHODS: PCR and overlap PCR were used to construct the fusion protein A7/G6-LDP expression vector that consists of the gene encoding G6, A7, LDP, and the linker peptide. The product was purified by affinity chromatography and analyzed by SDS-PAGE and HPLC. The binding activity to endothelial cells was examined by ELISA and immunocytochemical staining. The inhibition of HMEC-1 proliferation was determined with CCK-8 assays. The phosphorylation of AKT and c-Raf was detected by Western blotting. HMEC-1 migration was determined using a wound healing assay and tube formation was measured after incubation on Matrigel. RESULTS: The data of DNA sequence confirmed that the A7/G6-LDP fusion protein was correctly constructed. The fusion protein was recovered in high yield (up to 20 mg·L-1) and high purity after His-tag purification. A7/G6-LDP bound to HMEC-1 and HUVEC, respectively; in addition, it inhibited endothelial cell proliferation more effectively than LDP alone when used higher concentration. Moreover, A7/G6-LDP disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. The mechanistic study showed that A7/G6-LDP decreased the phosphorylation of AKT in HMEC. CONCLUSION: The engineered VEGFR1 and VEGFR2 bi-targeting oligopeptide-based fusion protein A7/G6-LDP effectively inhibits anti-angiogenesis. It might serve as a drug delivery carrier in targeted cancer therapy.

Objective To study the diagnosis and treatment of neuroendocrine carcinoma of the nasal cavity and paranasal sinuses, and analyse the influencing factors of suvival and prognosis. Methods We retrospectively analyzed the diagnosis and treatment process of 14 patients with sinonasal neuroendocrine carcinoma (SNEC) admitted in The First Affiliated Hospital of Kunming Medical University from 2007 to 2011. All patients were followed up to learn the survival status of them.Results All patients were followed up for one year up to six years except 2 patients who gave up treatment. Five patients died and six survived with good tumor control in the followed up period. Two patients received only endoscopy surgery, and one of them died from lung metastasis in 21 months after operation, and the other one survived with good tumor control, the disease free survival (DFS) was 9 months . Eight patients were treated by endscopy surgery and /or chemo-radiotherapy, three cases died in following-up period, and five of them survivied with good tumor control, and the disease free survival was 20.25 months.Two patients with transcatheter arterial infusion chemotherapy survivied with good tumor control within the follow up period,and the DFS was 25.5 months.Five patients had moderately differentiated SNEC and DFS was 25.5 months. Seven patients had poorly differentiated SNEC with DFS 14.6 months. Six patients were T4N0M0, four patients were T3N0M0, two patients T2N0M0, and their DFS were 19 months, 12.8 months and 33 month, respectively. Conclusions Surgery with radiotherapy and/or chemotherapy is the current treatment method for sinonasal neuroendocrine carcinoma. Small cell neuroendocrine carcinoma with poor differiation displays highly aggressive and poor prognosis. Diagnosis and treatment in early stage is important for good prognosis.

OBJECTIVE:To ensure the stability of electronic data capture(EDC)system in drug clinical trials and to improve the quality of drug clinical trials. METHODS:The quality control system for EDC system was established and introduced from the formulation of quality control process,establishment of data standard,trial project management,daily management,trial project design,system operation,system function,etc. RESULTS & CONCLUSIONS:Data standard have been achieved through estab-lishing EDC quality control system by our hospital based on attributable,legible,contemporaneous,original and accurate principle. The management of trial project and daily management are conducted through data registration,staff training,the formulation of da-ta management plan,fault emergency treatment,database backup;multiple verification of support data,data lock and export,trial report autogeneration and other functions have been realized by formulating related standard operation instruction,program file,op-eration manual and quality record. Those aspects improve facticity,accuracy and integrality of data in clinical trials,and lay a foun-dation for further data mining.

OBJECTIVE:To promote the supervision and management of clinical trial by institution. METHODS:The structure and function of clinical trial management system(CTMS)developed by our hospital and other enterprise together were analyzed to evaluate the application and operation result of CTMS. RESULTS & CONCLUSIONS:CTMS of our hospital is made up of foun-dation,efficiency and strategy. It is equipped with role allocation,information exchange and report,information warning,drug tracking,clinical trial process control,quality control of electronic record,electronic signature and integration and connection with other system,etc. Relevant operation procedure is established to promote standardization and institutionalization of CTMS. Due to the application of CTMS,the cooperation among departments become smoother,and management level have been enhanced in dai-ly management,pharmacy management,subjects and document administration. It also simplifies the work of researcher and reduc-es the human error by the autogeneration of trial records and tables with the system. Consequently,the monitor coveraged through-out all the trial process.

Objective To assess the efficacy and safety of nimotuzumab in combination with radiochemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods 42 patients with locoregionally advanced NPC were retrospectively analyzed.They all received the treatment of nimotuzumab in combination with radiochemotherapy.Intensity modulated radiationtherapy (IMRT) was applied and the prescribed radiation dose administered to the primary tumor was between 70 to 79.2 Gy in 32-37 fractions and 41-49 days.The dose administered to lymph nodes was between 65 to 76 Gy in 32-37 fractions and 41-49 days.Nimotuzumab was given weekly during irradiation.All patients received chemotherapy.Results The main adverse events were mucositis,bone marrow suppression,dermatitis and xerostomia.Grade 1 or 2 oropharyngeal mucositis occurred in 29 (69.0 ％) patients,and grade 3 in 2 (4.8 ％).Grade 1 or 2,3 or 4 leucopemia occurred in 25 cases (59.5 ％),16 cases (38.1％),respectively,without occurrence of febrile neutropenia.There was no treatment related death.Complete response (CR) rate was 90.5 ％ (38/42),partial response (PR) rate was 9.5 ％ (4/42) and the total efficiency was 100 ％.After a median follow-up of 22.5 months,the 1-year local control rate was 100 ％.1-year distant metastasis-free survival rate was 92.7 ％.1-year overall survival rate was 95.2 ％.Conclusion Nimotuzumab combined with radiochemotherapy was efficient and safe for locoregionally advanced NPC.

Objective To analyze the use of multidisciplinary team approach (MDT) for advanced and refractory hepatic alveolar echinococcosis in individualized treatment.Methods A retrospective study was conducted on the use of multidisciplinary team approach in individualized diagnosis and treatment for 137 patients with advanced and refractory hepatic alveolar echinococcosis (with invasion of major blood vessels and bile ducts,and/or with lung and brain metastasis) in our hospital from January 2005 to December 2013.The patients were divided into two groups:The MDT group (n =49) and the non-MDT group (n =88).The MDT group was further divided into two subgroups:subgroup A was the surgical treatment group (n =26),and subgroup B was the non-surgical treatment group (n =26).In the subgroup B,13 patients underwent late radical surgery.The non-MDT group was also further divided into two subgroups:subgroup a was the surgical treatment group (n =61),and subgroup b was the non-surgical treatment group (n =27).In subgroup b,5 patients underwent late radical surgery.The time taken to confirm the diagnosis,perioperative hospital stay,operation time,blood loss,postoperative drainage time,postoperative hospital stay,early postoperative complications (pleural and peritoneal effusions,bile leak,anastomotic leak),late postoperative complications (jaundice,anastomotic stenosis,recurrence),and rates of radical surgery were compared between subgroup A and subgroup a.The rates of late radical resection were compared between subgroup B with subgroup b.All data were analyzed using the Mann-Whitney rank sum test or the Chi-square test.Results Subgroup A had significantly shorter perioperative hospital stay,postoperative hospital stay,and total length of hospital stay than subgroup a (P ＜ 0.05).The incidence of late postoperative complications (jaundice,anastomotic stenosis,recurrence) was also significantly less than subgroup a (P ＜ 0.05),and the radical surgery rate was significantly higher than subgroup a (P ＜ 0.05).There was no significant difference in the time taken to confirm the diagnosis,operation time,blood loss,postoperative drainage time,early postoperative complications (pleural and peritoneal effusions,bile leak,anastomotic leak) (P ＜ 0.05) between subgroup A and subgroup a.The ratio of subgroup B receiving chemotherapy alone or drainage + chemotherapy,and the rate of late implement of radical resection were significantly higher than subgroup b (P ＜0.05).Conclusions A multidisciplinary team approach in individualized treatment comprehensively combined the advantages of the effects of drugs,intervention,surgery and systemic nutritional support.The best individualized treatment plan could be used which improved the rates of radical surgery in advanced and refractory hepatic alveolar echinococcosis,reduced postoperative complications,improved quality of life,and offered chances of radical resection in the patients who had lost the opportunities for surgery.

Objective To analyze the efficacy of different treatment methods for end-stage hepatic alveolar echinococcosis combined with obstructive jaundice.Methods A retrospective study was conducted on the diagnosis and treatment of 55 patients with end-stage hepatic alveolar echinococcosis combined with obstructive jaundice managed from January 2000 to January 2013 at the First Affiliated Hospital of Xinjiang Medical University.The patients were divided into two groups according to the treatment options:group A,the palliative surgery group (n =38,69.1％) using palliative resection and biliary decompression ; and group B,the interventional group (n =17,30.9％) using percutaneous transhepatic cholangial drainage (PTCD).We analyzd the general data,preoperative and postoperative liver function,operation time,blood loss,average hospital stay,duration of postoperative tube drainage of abscess cavity,degree of lesion with invasion into the first porta hepatis,progressive lesion,continuous invasion and/or distant metastasis,biliary complications,mortality,and cumulative survival rates.The t-test or t'-test was used to analyze continuous data and the chi-square test was used to analyze categorical data.Parallel log rank test and Kaplan-meier method were used to calculate survival rates in survival analysis.Results When compared with group B,group A had significantly longer operative time,more blood loss,and longer average hospital stay (P ＜0.05).The postoperative total bilirubin,direct bilirubin,γ-glutamyl transpeptidase and alkaline phosphatase,aspartate aminotransferase,alanine aminotransferase were significantly higher than in group B (P ＜0.05).The level of post operative albumin was lower in group A than in group B.The two groups of patients (A and B) had similar background including general data (gender,age,nation),preoperative liver function,duration of postoperative tube-drainage of abscess cavity,degree of lesion-invasion into first porta hepa tis,progressive lesion-invasion and/or distant metastasis,biliary complications,mortality,cumulative survival rates and survival curves.Conclusions Interventional treatment is an effective treatment for end-stage hepatic alveolar echinococcosis combined with obstructive jaundice.It has the advantages of minimal invasiveness,simplicity,safety and repeatability.It may replace traditional palliative surgery in the future.

Objective:To investigate the changes of cyclooxygenase-2 (COX-2) expression in the spinal cord dorsal horn atfer intrathecal a speciifc p38MAPK inhibitor-SB203580 on neuropathic pain in rats induced by chronic constrictive injury (CCI) to the sciatic nerve. Methods:Twenty-four male SD rats atfer intrathecal catheter placement were randomly divided into 4 groups:a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2%DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of chronic constrictive injury was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day atfer the surgery. hTen all rats were sacriifced and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry. Results:Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was signiifcantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 atfer the sugery, the threshold to mechanical on the surgery side was signiifcantly lower in the SB group than in the NS group and the DMSO group. hTe expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group. Conclusion:Intrathecal administration of SB203580 has signiifcant analgesic effect in the CCI rat model. Expression of COX-2 is signiifcantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.

0.05).Compared with control group,the GK activity of liver cell,the expression of PEPCK and the expression of GLUT4 in model group decreased signifi cantly(P

Objective To evaluate the effectiveness and safety of radical versus conservative surgery for hydatid liver cysts.Methods The Pubmed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedicine Database, CNKI, Wan Fang Databases, VIP Databases, Chinese scientific and technical journals full-text database and Chinese Journal of full text database were searched for randomized clinical trials or none-randomized clinical trials from January 2000 to January 2015.A Meta-analysis was performed with RevMan5.1.Results 10 studies with 2 123 patients were included into the final analysis.Meta-analysis demonstrated that the radical group was significantly longer in operation time [weighted mean difference (WMD) =25.11;95％ CI: 16.18-34.05;P ＜ 0.05], was significantly shorter in the length of hospital stay (WMD =-3.94;95％CI:-7.57-0.32;P ＜0.05), was significantly lower in the incidence of bile leak (OR =0.19;95％ CI: 0.07-0.49;P ＜ 0.05), was significantly lower in the incidence of residual cavity infection (OR =0.08;95 ％ CI: 0.04-0.15;P ＜ 0.05), and in the incidence of local recurrence (OR =0.10;95 ％ CI: 0.05-0.18;P ＜ 0.05) when compared with the conservative surgery group.Conclusions For hydatid liver cysts, radical surgical procedures had significantly lower rates of complications and recurrence.Thus, they are better treatments for hepatic cystic echinococcosis.