Lead compound optimization plays an important role in new drug discovery and development. The strategies for changing metabolic pathways can modulate pharmacokinetic properties, prolong the half life, improve metabolism stability and bioavailability of lead compounds. The strategies for changing metabolic pathways and improving metabolism stability are reviewed. These methods include blocking metabolic site, reduing lipophilicity, changing ring size, bioisosterism, and prodrug.

Tumor cells and the tumor microenvironment interact through molecular and cellular mechanisms to promote tumorigenesis and tumor migration. The tumor microenvironment is important in tumorigenesis and tumor progression. Tumor-associated macrophages (TAMs), which are ones of the most inflammatory cells in the tumor microenvironment, have significant influence on tumor development. Tumor cells recruit macrophages by releasing chemokines, cytokines, and growth factors, and switch them into M2-type macrophages. Macrophages also release many factors which are important to some stages of tumor development, including tumor growth, angiogenesis, migration, invasion, and distant metastasis. TAM density is associated with treatment failure and poor prognosis in tumor patients. Great progress has recently been made in targeting TAMs for anti-tumor therapy. Strategies of targeting TAMs for anti-tumor therapy include suppression of macrophage recruitment, inhibition of TAM viability, reinstating the TAM phenotype, and transforming M2-type macrophages to M1-type macrophages. This article reviews the latest progress in the field based on TAM functions.

BACKGROUND: Gene microarray data has small sample size and large numbers of variates.Traditional statistical method is not effective.Genetic algorithm(GA)and support vector machine(SVM)are machine learning algorithms developed rapidly in recent years,which can decrease the dimension of features.OBJECTIVE: To combine GA and SVM to classify samples and compare with other two processes in which all genes and difference expression genes are taken as classifiers,respectively.METHODS: We applied golub data set provided by Bioconductor,which included gene expression data of leukaemia samples and normal samples.All genes were used to classify samples with SVM.SAM software was used to extract difference expression genes and estimate False Discovery Rate.Finally,76 difference expression genes were used as feature gene set to classify samples with SVM and GA-SVM respectively.Three classification effects were compared.Additionally,the distribution and function about feature genes in KEGG pathways were also discussed.RESULTS AND CONCLUSION: The accuracy of classification of SVM was improved by decreasing dimension with genetic algorithm.In particular,this process eliminated a great deal of redundant genes and noises,which improves the classification performance.Results show that GA-SVM algorithm is effective in classifying samples.In addition,the pathway analysis shows that signal transmission and amino acid metabolism are two major functions of feature genes.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Bulbar Palsy, Progressive ; etiology ; physiopathology ; therapy ; Cerebral Infarction ; complications ; Female ; Humans ; Male ; Middle Aged ; Pharynx ; physiopathology ; Treatment Outcome

Objective To explore the effects of vecuronium bromide within 24 hours in severe bronchial asthma with acute attack with breathing machine in conventional sedatio.Methods Prospective study,double-blind randomized standard control,where 46 cases of patients of severe bronchial asthma with acute attack transferred to ICU using breathing machine in this year were randomly divided into the vecuronium bromide group (muscle relaxant group) and conventional sedation group (normal group) according to medical record number; Two groups of sample compositions were compared by x test,using two independent samples of t test to compare the effects the treatment and prognosis.Results After mechanical ventilation for 15min and 1-3h in muscle relaxant group,patients' vital signs were statistically analyzed,including respiration; Blood gas analysis parameters were as follows:pH,PaO2,PaCO2,SpO2 of these were improved compared with those in the conventional group (P ＜ 0.05) with statistically significant differences;Compared with the conventional group,in the muscle relaxant group,the retention time in ICU (146.20 ± 17.92) hours,(214.15 ± 22.21) hours,the using time of breathing machine (125.93 ± 16.23) hours,(192.89 ± 22.60) hours,and the dosage of glucocorticoid (2.61 ± 0.17) mg · kg-1 · d-1,(3.55 ± 0.26) mg · kg-1 · d-1,anticholinergic agent(6.25 ±0.51) μg · kg-1 · d-1,(10.64 ±0.75) μg · kg-1 · d-1 and β2 adrenergic receptor agonist (0.06 ±0.01)mg · kg-1 · d-1,(0.15 ±0.04)mg · kg-1 · d-1 were all reduced (all P ＜0.05) with statistically significant differences;The patients were smoothly transferred out of ICU,without the adverse events of mechanical ventilation and cardiovascular diseases.Conclusion The use of vecuronium bromide made the patients with severe bronchial asthma in routine sedation use of breathing machine rapidly correct the clinical symptoms and improve the off-period prognosis.

Objective The aim of the study is to identify the risk factors for infections in cirrhosis patients with hepatocarcinoma.Methods a case control study were employed.a total of 286 patients hospitalized between 1999 and 2003 were included in.Patients who developed infection complication were defined as cases,the remains were controls.the data of possible risk factors,including serum levels of albumin,prothrombin time (PT),total bilirubin(T-Bil),child-pugh score,ascite,Esophageal variceal bleeding,total cholesterol(T-chol),other complication,the total white blood cell (wbc),surgery,and days of hospitalization,were retrospective collected.According multivariate logistic regression model,the potential risk factors were assessed.Result infections developed in 127(43.34%) patients and 100(78%) of these developed infection during hospitalization.There was no significant difference between cirrhosis patients with and without hepatocarcinoma,which infection rate was 41.4%(P=0.25).The mortality rate of cases was 54.3% (69/127),which is significantly higher than control(12.5%,P=0.008). 55 patients(30.7%) had spontaneous bacterial peritonitis (sbp).Bacterial culture of samples were prepared from 97of 127 patients (76.4%),and were positive in 62(63.9%) patients.Although of these culture -positive samples,35(56.4%) samples were Gram-negitive bacterial strains,8 of 15 samples from patients developed sepsis were Gram-positive bacterial.On multivariate analysis,the Alb level and days of hospitalization were the independent risk factors for cirrhosis patients with hepatocarcinoma developed infection complication.the odds ratio was 0.33(95%CI 0.32～0.55),0.23(95%CI 0.14～0.38) respective.Conclusions Cirrhosis patients with hepatocarcinamo with low Alb level and long days of hospitalization should be carefully treated,and administration of broad spectrum antibiotic covering Gram-positive bacterial needs to be considered in treatment of sepsis.

Objective To evaluate the application effect on preventing pressure ulcers of modern medical position pad in orthopaedic. Methods A total of 124 patients with congenital dislocation of the hip, pelvis fractures and femoral fractures were selected between January 2013 and December 2013. They were divided into 2 groups by random digits table method with 62 cases each. The observation group was given modern medical position pad nursing after operation, and the control group was given routine postoperative nursing. Postoperative 2 hours, 4 hours after operation, postoperative 1 day, 2 days, 3 days and before discharge pressure situation, children crushed area skin comfort, families of children with pain on pressure parts skin care satisfaction and turn the situation were analyzed and compared. Results The observation group postoperative 2 hours did not appear the skin red and bruised, there was no crushed in 4 hours, only 4 cases of skin red, no 1 case skin crushed before leaving hospital. Twelve cases of the control group in postoperative 2 hours appeared red skin pressure, 4 hour after crush skin in 4 cases, 6 cases of skin crushed before leaving hospital. The comfortable children for 56 cases, mild discomfort for 6 cases in the observation group,and 31, 23 cases in the control group. The satisfaction was 100.0%(62/62) in the observation group, and 93.5%(58/62) in the control group. The degree of turn the situation pain in the observation group was lower than that in the control group. Conclusions New medical position mat can effectively extend the pediatric orthopaedic congenital dislocation of the hip, pelvis fracture and femoral fracture with roll over time, reduce the stimulation of the skin, sweat for pressure parts effectively prevent the occurrence of pressure sores, improve the crushed area comfort children and families of children with satisfaction, greatly reduce the postoperative pain when rolled over, worth clinical promotion.

Objective To summarize the perioperative experience of nursing recipients undergoing adult-to-adult living donor liver transplantation (A-ALDLT). Method Twenty-five cases of recipients undergoing A-ALDLT were retrospectively analyzed for summarization of perioperative nursing. Results All operations on the patients were successful with an average time of (5.5 ± 0.5)h. Two cases developed with postoperative bile leakage and another two with postoperative pleural effusion, all cured after treatment. Conclusions Perioperative nursing is one important factor of elements to guarantee the success of A-ALDLT. The actively and effectively perioperative nursing measures are the important insurance for the recipients′recovery from graft operation.

Objective To explore the practical new type of patient information sign on the application effect of pediatric surgical ward. Methods Divided 200 cases of patients in our department into the control group and the observation group according to random number table, there were 100 cases in each group. The control group and the observation group in A and B ward respectively, A ward (control group) used the traditional end of the bed, B ward (observation group) used the new information sign. The incidence rate of adverse events, patients′ families health mission efficiently, satisfaction of patients or medical staff were compared between the groups. Results The incidence rate of adverse events in the observation group was significantly lower than that of in the control group [1%(1/100) vs 8%(8/100),χ2=5.701, P < 0.05]. The effectiveness of health education, satisfaction of patients or medical staff and patients′families to health mission satisfaction in the observation group were significantly higher than that of in the control group [91% (91/100) vs 79% (79/100), 97% (97/100)vs 84% (84/100), 98% (98/100)vs 86% (86/100),the value of χ2 was 5.647,9.828 and 9.783 respectively, P < 0.05)]. Conclusions This new utility model patient information sign by the clinical application effect is satisfied, the head of a bed, cue CARDS unification and standardization of management, and reduced the occurrence of nursing adverse events, which can effectively improve the continuity of care services, the effectiveness of health education and medical, nursing, and satisfaction. Should be used widely in clinical.

Hyperlipidemia is one of the most important risk factors of human atherosclerosis and cardiaccerebral vascular disease.The number of hyperlipidemia in China increased year by year and showed a younger trend.The current treatments for hyperlipidemia include drug therapy,physical exercise,diet prevention,liposuction surgery and low-energy laser therapy,etc.Many researches showed that low intensity laser irradiation has a certain curative effect on hyperlipidemia.The aim of this paper is to provide a new idea and method for the future treatment of dyslipidemia by reviewing the anti-hyperlipidemia methods and mechanism of low energy laser irradiation treatment.