Neoadjuvant chemotherapy is one of the common means in multidisciplinary treatment of locally advanced breast cancer,with anthracyclines and taxanes as main chemotherapeutic drugs.In recent years,molecular target agents have significantly improved the efficacy of chemotherapy,as well as have provided more choices and ideas for clinical treatment.Currently,the widely studied molecular targeted drugs include trastuzumab,lapatinib,pertuzumab,T-DM1 and bevacizumab.

Protein kinase C (PKC) is a group of phospholipid-dependent serine/threonine protein kinases, which togeth-er with protein kinase A (PKA) and protein kinase G (PKG) constitute a superfamily of serine/threonine protein kinase AGC. PKC includes classic PKC, novel PKC, atypical PKC and some members of kinase associated with PKC (PRK). PKC is wide-ly distributed in mammalian tissues and cells, which plays an important biological role in growth and metabolism, prolifera-tion and differentiation of cells. A series of studies have demonstrated that variations of multiple cells, occurrence and devel-opment of diseases are related to the abnormal expression of PKC. Therefore, designing and searching for efficient PKC inhib-itors have very important implications for synthesis of many kinds of effective drugs and treatment of a variety of clinical dis-eases including cancer, cardiovascular, and hypertension, et al. In recent years, the research on PKC inhibitors has become the focus of domestic and foreign research. A large number of literatures have reported many kinds of effective PKC inhibi-tors, and analyzed their function site, mechanism, clinical trial data and so on. The discovery of these PKC inhibitors has im-portant implications for structural analysis of PKC and the treatment of diseases. So in this paper, the efficient PKC inhibi-tors are summarized.

Tumor multidrug resistance (MDR) is the leading cause of clinical chemotherapy failure and death.Researches show that the occurrence of MDR is related to P-glycoprotein,multidrug resistance-associated proteins,breast cancer resistance-associated proteins,lung resistance-related proteins and other factors.Now the reversal strategies of MDR include chemical drugs reversal,gene reversal,immune reversal,traditional Chinese medicine reversal and drug-loaded nano-system reversal,which make some progress and help to improve the effect of cancer chemotherapy.

Objective To observe the pharmacokinetic feature of Radix Acanthopanacis Senticosis suspension(RASS). Methods The research was conducted with pharmacodynamic endpoint approach and pharmacodynamic approach and adopted with phagocytic index as pharmacological parameter. Results Pharmacodynamic endpoint approach: K_(el)=0.2d~(-1), K_a=2.5 d~(-1), AUC(S_0)=10.4g?kg~(-1)?d, VRT=19.3d~2.Pharmacodynamic approach: K_(el(ef))=0.1d~(-1), K_(a(ef))=2.9d~(-1), AUC(S_0)_((ef))=62.7(%)?d, VRT_((ef))=43.2d~2. The data obtained by pharmacodynamic approach differed from that by pharmacodynamic endpoint approach, indicating the delay of drug effect. Conclusion Pharmacokinetic Data of RASS are first obtained in this article, which show that pharmacodynamic endpoint approach and pharmacodynamic approach is feasible.

Objective To evaluate the effects of continuous quality improvement (CQI) management on nutritional status,renal function progression,and compliance of low protein diet in patients with chronic kidney disease (CKD).Methods Totally 115 CKD patients who were regularly followed up in CKD clinic services were recruited in this study.Plan,Do,Check,and Act (PDCA) method was adopted to manage the dietary of these patients for 12 months.The clinical indicators and diet compliance before and after receiving CQI management were compared.Results After receiving the CQI management,the nutritional status of patients was well maintained;meanwhile,the average hand strength and the hemoglobin,serum albumin,total cholesterol,and triglyceride levels showed no significant changes (all P ＞ 0.05).Subjective feelings of patients were improved.The modified Subjective Global Assessment of Nutrition (mSGA) score was decreased from 7.0 (7.0,8.0) to 7.0 (7.0,7.0) (P =0.000).The estimated glomerular filtration rate (eGFR) calculated by formula of modified MDRD was decreased from (40.74 ± 14.49) to (37.94 ± 16.86) ml/(min · 1.73 m2) (P =0.000),and the average descended speed was (2.81 ±7.42) ml/(min · 1.73 m2) per year.The creatinine clearance rate had no statistical difference between pre-and post management (P =0.910),and the average descended speed was (0.19 ± 17.01) ml/min per year.The daily protein intake (DPI) and protein equivalent of nitrogen appearance rate (PNA) were both significandy descended:DPI/kg decreased from (0.79 ± 0.27) to (0.64 ± 0.15) g/ (24 h · kg) (P =0.000),and PNA/kg dropped from (1.02 ± 0.32) to (0.82 ± 0.24) g/ (24 h · kg) (P =0.000).The scores of awareness and compliance of patients on low protein diet were significantly increased after CQI management (P =0.000).Conculsion Applying CQI on dietary and nutrition management in CKD patients can maintain the good nutritional status and improve the compliance of low protein diet.

Objective To explore the value of ectopic gastic mucosa imaging in diagnosis of Meckel′s diverticulum.Methods Twenty-five cases suspected of gastrointestinal bleeding underwent conventional ectopic gastic mucosa imaging with 99mT_cO_4-.The diagnostic criteria Meckel′s diverticulum was that abnormal radio active accumulation in the abdomen observed.Results Three cases of ectopic gastic mucosa imaging was positive,and the diagnosis was all confirmed by surgery and pathology examination.The rest 22 cases were caused by other reasons confirmed by affirmative examinations.Conclusions Ectopic gastic mucosa imaging is easy to conduct,safe with no injury to the patients.It can be the first choice of examination in the diagnosis of gastrointestinal bleeding in children.

ObjectiveTo investigate the effect of remifentanil on hepatic ischemia-reperfusion (I/R) injury in rats with liver cirrhosis.MethodsThirty male SD rats weighing 260-300 g were randomly divided into 3 groups (n =10 each):group liver cirrhosis (group C); group liver cirrhosis + hepatic I/R (group I/R) and group remifentanil (group R).Liver cirrhosis was produced in all animals in the 3 goups.I/R injury was induced by 20 min occlusion of the hepatic artery and portal vein entering the middle and left lobes of the liver followed by 4 h reperfusion at 1 week after establishment of hepatic cirrhosis in I/R and R groups.In group R remifentanil was infused iv at 1 μg·kg-1 ·min-1 starting from 10 min before ischemia until the end of 4 h reperfusion.Venous blood samples were taken from inferior vena cava at the end of 4 h reperfusion for measurement of serum ALT and AST activities.The animals were then sacrificed and liver specimens were taken from middle lobe for determination of Bcl-2 and Bax expression (by immuno-histochemistry) and hepatocyte apoptosis (by TUNEL) and microscopic examination.Apoptosis index (percentage of apoptotic cells) was calculated.ResultsI/R significantly increased serum ALT and AST activities,Bax expression and apoptosis index and decreased Bcl-2 expression in group I/R as compared with group C.Remifentanil significantly attenuated the I/R-induced changes in serum ALT and AST activities,Bax and Bcl-2 expression and apoptosis in group R as compared with group I/R.Remifentanil also ameliorated I/R-induced liver damage.ConclusionRemifentanil can auenuate hepatic I/R injury in rats with liver cirrhosis by up-regulating Bcl-2 expression and down-regulating Bax expression and inhibiting apoptosis.

Objective: To explore the related factors of quality of life(QOL) among rural elderly population in Shandong Province and explore the relationship among these factors.Methods: In this cross-sectional study,a sample of 451 elderly peple(aged from 60 to 92,without hearing or mental problems) was selected by a stratified cluster random sampling method.The 36-item Short Form Health Survey(SF-36) was used to measure QOL,and the AMOS 5.0 was used to carry out path analysis.Results: The QOL average score of all subjects was(78.5?15.4);QOL scores of males was higher than that of females [(81.2?13.0) vs.(77.5?16.3),P=0.003].There was a significant decrease of the QOL score with increasing age [60-69 years,(82.2?13.3);70-79 years,(77.0?16.0);≥ 80 years,(71.4?16.4);P

Aim To investigate the effect of Sirt1 activator SRT1720 on high glucose(HG)-induced apoptosis in mouse mesangial cells(MMCs).Methods Cultured mouse MMCs were divided into normal glucose group(NG),NG plus mannitol group(M),high glucose group(HG),HG plus SRT1720 group(HG+SRT).Apoptosis of MMCs was analyzed by DeadEndTM Fluorometric TUNEL System and flow cytometry.Reactive oxygen species(ROS)production was observed by flow cytometry.The expression levels of caspase-3,cleaved caspase-3,Bax,Bcl-2,p38 MAPK,p-p38 MAPK,p53,acetylated p53 and cytochrome C protein were observed by Western blot.The mRNA levels of Bax and Bcl-2 were detected by real-time PCR.Results Compared with normal glucose group,the production of ROS,the number of cell apoptosis,the expression of cleaved caspase-3,p-p38 MAPK and acetylated p53 and ratio of Bax/Bcl-2 were significantly increased,the expression of Sirt1 was decreased,meanwhile,the release of cytochrome C from mitochondria to cytoplasm was significantly increased in MMCs in high glucose group.Treatment with SRT1720 inhibited HG-induced increase of ROS production,cell apoptosis,expression of cleaved caspase-3,acetylated p53 and p-p38 MAPK,ratio of Bax/Bcl-2 and release of cytochrome C,and reversed HG-induced Sirt1 expression.Conclusion SRT1720 could prevent HG-induced apoptosis maybe by decreasing ROS production,preserving mitochondrial function and inhibiting p53 acetylation and activation of p38 MAPK in MMCs.

Objective To explore the association between acute ischemic stroke and albumin to creatinine ratio (ACR).Methods A case-control study.During January to December in 2013, 127 acute ischemic stroke patients as case group and 150 controls who were similar with case group in age and gender were recruited in Tianjin Union Medicine Center . According to diabetes , hypertension , cardiovascular diseases and patients without these three diseases , case group was divided into A1, B1, C1 and D1 subgroups, control group was divided into A2, B2, C2 and D2 subgroups in the same way.The first morning urine from participants were collected .Urinary albumin concentration was tested by nephelometry , urinary creatinine was examined by using enzymic method , ACR were calculated(≥30 mg/g as the cutoff value). Then difference of ACR between case and control group was compared , the cutoff value of albuminuria for ischemic stroke patients was analyzed by ROC , and the risk factor of ischemic stroke were analyzed by logistic regression analysis.Results The prevalence of albuminuria in ischemic stroke patients was 38.58%(49).According to analysis of covariance, after adjustment for age, gender, cardiac-disease, diabetes, hypertension, lnACR in case group was significantly higher than control group (3.18 mg/g vs 2.78 mg/g, t=2.13 P=0.03), especially D1 was significantly higher than D2 subgroup (3.01 mg/g vs 2.51 mg/g,t=5.56,P=0.009) .If 19.82 mg/g from ROC analysis was used as the cut-off value, the sensitivity and specificity are 68.5% and 61.7%.The odds ratio ( OR ) of ACR >19.82 mg/g was about 2-fold when compared with ACR<19.82 mg/g adjusted for stroke risk factors , and the OR value is 2.43 in comparison of patients without diabetes , hypertension and cardiovascular diseases .Conclusions Urinary albumin excretion is the independent risk factor of ischemic stroke .The increased urinary albumin has important clinical significance to predict the risk of ischemic stroke for the patients without diabetes , hypertension and cardiovascular diseases.