The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective To investigate the effect of preventive nursing on infection of patients with continuous renal replacement therapy (CRRT).Methods A total of 45 patients with CRRT treatment in our department were selected as observation group,given prevention nursing for infection,another 40 CRRT patients during the same period were selected as control group,given routine nursing.The changes of clinical correlated index,APACHE score and the rates of infection and mortality,hospitalization time of two groups were compared.Results The levels of BUN,SCr and CRP after the treatment in the observation group were lower than that in the control group,and the differences were statistically significant (P ＜ 0.05).The APACHE Ⅱ score,the infection rate after treatment in the observation group were lower,and the hospitalization time was shorter than that in the control group,the differences were statistically significant (P ＜ 0.05).Conclusion Preventive nursing can prevent the occurrence of infection in patients with CRRT,promote the improvement of clinical indexes and shorten the hospitalization time of patients.

Objective To investigate the effect of preventive nursing on infection of patients with continuous renal replacement therapy (CRRT).Methods A total of 45 patients with CRRT treatment in our department were selected as observation group,given prevention nursing for infection,another 40 CRRT patients during the same period were selected as control group,given routine nursing.The changes of clinical correlated index,APACHE score and the rates of infection and mortality,hospitalization time of two groups were compared.Results The levels of BUN,SCr and CRP after the treatment in the observation group were lower than that in the control group,and the differences were statistically significant (P ＜ 0.05).The APACHE Ⅱ score,the infection rate after treatment in the observation group were lower,and the hospitalization time was shorter than that in the control group,the differences were statistically significant (P ＜ 0.05).Conclusion Preventive nursing can prevent the occurrence of infection in patients with CRRT,promote the improvement of clinical indexes and shorten the hospitalization time of patients.

Objective To develop a MOSAIQ Integration PlatformCHN (MIP) based on the workflow of radiotherapy (RT) and to meet the actual requirements in China and the special needs for the radiotherapy department.Methods MIP used C/S (client-server) structure mode running on the local network in the hospital and its database was based on the Treatment Planning System (TPS) and MOSAIQ database.Five network servers,as the core hardware,supplied data storage and network service based on cloud services.The core software was developed based on Microsoft Visual Studio Platform using C# network programming language.The MIP server could simultaneously offer network service for about 200 workstations,including entry,query,statistics,and print of data.Results MIP had 15 core function modules,such as Notice,Appointment,Billing,Document Management (application/execution),and System Management,which almost covered the whole workflow of radiotherapy.Up to June 2016,the recorded data in the MIP were as follows:13546 patients,13533 plan application forms,15475 RT records,14656 RT summaries,567048 billing records,and 506612 workload records.Conclusions The MIP based on the RT workflow has been successfully developed and used in clinical practice.It is an important part of radiotherapy information system construction with the advantages of intuitive operation,real-time performance,data security,and stable operation.It is digital,paperless,user-friendly,and convenient for the retrieval and statistics of data as well as information sharing and department management,and can significantly improve the efficiency of the department.More functions can be added or modified to enhance its potentials in research and clinical practice.

Objective To discuss and analyze the clinical effects and value of systemic nursing intervention on constipation in senile patients with multiple fracture of extremities .Methods Retrospective analysis was made on the 360 cases of constipation in se-nile patients with multiple fracture of extremities admitted into hospital for treatment from January 2007 to December 2013.One hundred and eighty patients admitted into hospital from January 2007 to December 2010 were assigned as the control group , while another 180 patients admitted into hospital from January 2011 to December 2013 were assigned as the observation group .The control group was given routine nursing , while the observation group received systemic nursing intervention in addition to routine nursing .Comparison and anal-ysis were made in total satisfaction of nursing on the part of the family dependants , the time of constipation symptom relief , the time of signs relief , the scores of life function and overall life quality , as well as psychological state , were compared between the 2 groups after treatment and nursing .Results Results indicated that total satisfaction of the observation group on the part of family dependents were higher than that of the control group , and statistical significance could be seen , when comparisons were made between the 2 groups ( P<0.05).The time of constipation symptom relief and the time of signs relief of the observation group were shorter , as compared with those of the control group, and there was significant difference, when comparisons were made between the 2 groups (P<0.05).The life function and overall quality of life scores and psychological state as well in the patients of the observation group were significantly su -perior to those of the control group , and significant differences could be noted , when comparisons were made between the 2 groups ( P<0.05).Conclusion Systemic nursing intervention on senile patients with multiple fracture of extremities could effectively increase the clinical efficacy and satisfaction of nursing on the part of family dependents , improve their life quality and psychological state of se-nile patients and relieve symptoms of constipation .With this reason , it was worth further clinical extension .