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.

Intracranial atherosclerotic stenosis mostly occurs in Asians,blacks and Hispanicsis,which is the most important reason for the occurrence and recurrence of ischemic stroke.The current studies mainly concentrate on the aspect of the relationship between the intracranial atherosclerotic stenosis and the traditional risk factors.With the development of genetic technology,the relationship between the genetic factors and intracranial atherosclerotic stenosis has also received increasing attention.This article reviews the advances in research on the traditional risk factors for intraeranial atherosclerotic stenosis and genetic research.

[Objective] To compare the clinical cure effects of different operations on myomectomy, and screen out best clinical treatment for hysteromyoma in child-bearing period. [Method] Trace back and analyse 200 cases of such patients, divide them into laparotomy group, laparoscope group, vaginal group and UAE group under different therapies, compare cure effect analysis. [Result] On operation time, operation bleeding and evacuation time, the UAE group ,vaginal and laparoscope groups were successively better than the laparotomy group; but on post-operation medication rate and average in-hospital days, the UAE group was successively less than laparoscope, vaginal and laparotomy groups. On complication rate,the laparoscope was successively less than UAE, vaginal and laparotomy groups.[Conclusion] 4 therapies have respective advantages, UAE and laparoscope myomectomy have little trauma, quick re-covery and reliable cure effect, however, laparotomy can't be completely replaced owing to its wide indications.

ObjectiveTo evaluate the effect of compound oxymatrine injection combination with chemotherapy in patients with advanced ovarian carcinoma.MethodsEighty-six patients with advanced ovarian carcinoma were divided by random digits table method into observation group(43 cases) receiving compound oxymatrine injection plus chemotherapy(paclitaxel plus carboplatin) and control group (43cases) treated with chemotherapy(p aclitaxel plus carboplatin) alone.The change of white blood cell,adverse reaction and effect of the patients were observed.ResultsThe white blood cell of observation group after treatment was obviously higher than that of control group [ (4.7 ± 1.4) × 109/L vs.(3.2 ± 1.6) × 109/L,P ＜ 0.05 ].The rates of nausea and vomiting,transaminase elevating and kidney damage of observation group were obviously lower than those of control group[ 16.3％ (7/43),14.0％ (6/43),20.9％ (9/43) vs.34.9％(15/43),32.6％ (14/43),44.2％ ( 19/43 ),P ＜ 0.05 ].The complete remission rate of observation group was significantly higher than that of control group[55.8％(24/43) vs.27.9％(12/43),P ＜ 0.05].Conclusion Addition of compound oxymatrine injection to chemotherapy for patients with advanced ovarian carcinoma can effectively protect patients against the decreasing of the white blood cell and attenuate the side effects brought by chemotherapy.

ObjectiveTo investigate the effect of humanized nursing in ovarian cancer patients to improve treatment compliance and negative emotional state. Methods120 cases of ovarian cancer patients from October 2009 to October 2010 in our hospital were chosen as the research object.They were divided into the control group and the observation group according to randomization methods with 60 cases in each group.The control group patients were taken routine care.The patients in the observation group were taken humanized nursing on the basis of routine care.The treatment compliances during treatment were compared.The anxiety,depression scores for the two groups of patients before and after treatment were compared.Based on the three indicators,the effect of humanized nursing in ovarian cancer patients to improve treatment compliance and negative emotional state was evaluated. ResultsThe treatment compliance during treatment for the two groups was compared,the full compliance of patients of the observation group was significantly higher than the control group.The difference between the two groups was statistically significant.The anxiety,depression scores before treatment for the two groups were compared.There was no significant difference between the two groups.The anxiety and depression scores showed significant improvement after the treatment,but improvement level of the observation group was significantly higher than the control group.The difference between the two groups was statistically significant. ConclusionsHumanized nursing can improve the treatment compliance and negative mood of ovarian cancer patients effectively,it is conducive to the rehabilitation of patients,and is worthy of clinical application.

Objective To investigate the correlation of serum alpha-fetoprotein (AFP) with clinical pathological factors and prognosis of hepatocellular carcinoma ( HCC ).Methods Two hundred and twenty patients with HCC who hospitalized in our hospital from January 2007 to June 2009 were enrolled in this study.The relationship of AFP levels before operation to clinical pathological factors such as pathological grade,tumor size,tumor encapsulation,tumor numbers,portal vein tumor thrombus,TNM stage and postoperative recurrence were analyzed.Results Serum AFP concentration before operation were related with tumor size ( x2 =11.76,P ＜ 0.05 ),tumor encapsulation ( x2 =17.07,P ＜ 0.05 ),portal vein tumor thrombus ( x2 =8.944,P ＜ 0.05 ),higher TNM stage ( x2 =4.929,P ＜ 0.05 ) and early postoperative recurrence rate ( x2 =5.569,P ＜ 0.05 ).However,it had no correlation with pathological edmondson grade tumor numbers.Conclusion HCC patients with high serum AFP concentration often has greater tumor without encapsulation,high occurrence rate of portal vein tumor thrombus and higher TNM stage,they are more likely to early postoperative recurrence.Serum AFP before operation is useful not only for diagnosis,but also as a prognostic biomarker to predict prognosis and recurrence.

Objective To investigate the correlation between the expression of P-SAPK/JNK and neuronal apoptosis in the striatum during permanent middle cerebral artery occlusion (pMCAO) in rats.Methods Fifty-four male Sprague-Dawley rats were randomly divided into sham operation group and pMCAO 1-,3-,6-,12-,and 24-hour groups (n =9 in each group).Apoptotic neurons in the striatum during cerebral ischemia were detected by TUNEL assay,the nuclear translocation of P-SAPK/JNK in the striatum by immunohistochemical staining expressions of P-SAPK/JNK protein by Western blot.Results The numbers TUNEL- and P-SAPK/JNK-positive cells in the striatum at 1 hour after pMCAO increased significantly (P =0.000 1),and reached the peak at 6 hours.The numbers of TUNEL-positive cells decreased at 12 hours,however,it still higher than the sham operation group (P =0.000 2).Western blot analysis showed that the expression of P-SAPK/JNK after pMCAO increased significantly,and the time-course change was in accord with the result of immunohistochemical staining Neuronal apoptosis in the striatum was significantly positively correlated with the expression of P-SAPK/ JNK (r =0.984,P =0.000 4).Conclusions Cerebral ischemia may induce neuronal apoptosis in the striatum through the activation of P-SAPK/JNK.

Biliary atresia(BA) is a destructive inflammatory obliterative cholangiopathy of neonates affecting both intrahepatic and extrahepatic bile ducts.BA is more common in east Asia.Genetic susceptibility,viral infections,and immune dysregulation may be related to BA,but immune dysregulation may play a key hole in the pathogenesis of BA.A current view of the pathogenesis of BA is that it may involve both a primary perinatal hepatobiliary viral infection and a secondary generation of an autoimmune-mediated bile duct epithelial injury.The etiology of BA is unknown,but there is evidence for the involvement of immunologic dysregulation mechanisms,which will be discussed in this review.

Ageing of population is now a phenomenon of the world and has considerable consequences for public services.Ageing is always accompanied with dysfunction of multiple organs,including hypothalamic-pituitaryadrenal axis.Here,we summarized alterations of hormone secretion of adrenal glands in the elderly and their relationships with Alzheimer' s disease.Moreover,we discussed characteristics of pheochromocytoma,primary aldosteronism,and Cushing's syndrome in the elderly.Lack of typical manifestations usually makes difficulty in diagnosis.

Objective: Through summarizing the main problems and challenges faced in the medical health system reform in China , suggestions are given: the government needs to erhance the health investment and play the role of market mechanism , make the use of electionical information technique, further change the community system of implementing medicine community system, implement the medical service supervision system.