In the treatment of human epidermal growth factor receptor 2 (Her-2) overexpressing breast cancer,some patients have drug resistance to trastuzumab.Potential mechanisms of resistance to trastuzumab include impaired access of trastuzumab to Her-2 ; alternative signaling from insulin-like growth factor-1 receptor (IGF-1R),hepatocyte growth factor receptor (HGFR) and so on; aberrant downstream signaling caused by loss of phosphatase and tensin homologs deleted from chromosome 10 (PTEN);phosphatidylinositol 3-kinase catalytic alpha polypeptide gene (PIK3CA) mutation; over-expression of heat shock protein 90 (HSP90) and CD44. Additionally,potential strategies for overcoming resistance to trastuzumab include using new targeted medicines,such as pertuzumab,lapatinib and trastuzumab-DM1.

Imatinib,a small-molecule kinase inhibitor,has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumors ,However,resistance to imatinib is a more and more serious problem.This review summarizes the existing knowledge of the imatinib resistance mechanism in gastrointestinal stromal tumors and describes the treatment directions in further.

Objective To investigate the changes of umbilical cord and the vasoactive substance in umbilical vein in intrahepatic cholestasis of pregnancy.MethodsBy HE staining method we analyzed the pathologic change of umbilical cord of 25 women with intrahepatic cholestasis of pregnancy(ICP)and fetal distress(ICP fetal distress group),25 ICP women without fetal distress group(ICP control group)and 27 normal pregnancies(control group).The nitric oxide synthase(NOS)and endothelin-1(ET-1)were detected in human umbilical vein endothelial cells(HUVEC)by immunohistochemistry method.Umbilical vein total bile acid(TBA)and NOS and ET-1 were measured.Resuits(1)A remarkable high TBA level was found in umbilical vein in ICP,and it was higher in ICP fetal distress group(19.0±2.3)μmol/L than in ICP control group(9.0±1.7)μmol/L(P＜0.05);it was higher in ICP control group than the control group(4.4±1.5)μmol/L(P＜0.05).(2)A significant difference was found in the endotheliocytes of umbilical vein in ICP fetal distress group compared with ICP control group.The ratio of cells with pathological changes in ICP fetal distress group(92％,23/25)was higher than ICP control group(68％,17/25;P＜0.05).The occurrence of the pathological changes was associated with TBA.(3)The expression of eNOS in ICP fetal distress group 0.09±0.06 was lower than in ICP control group 0.21±0.08(P＜0.05),and it was lower in ICP control group than in control group 0.47±0.07(P＜0.05).In contrast.the expression of ET-1 in ICP fetal distress group 0.49±0.08 was higher than in ICP control group 0.32±0.07(P＜0.05),and it was higher in ICP control group than control group 0.14±0.06(P＜0.05).The expression of inducible nitric oxide synthase(iNOS)in ICP fetal distress group 0.20±0.04 and ICP control group 0.21±0.05 was lower than in control group 0.26±0.04(P＜0.05),but no significant difference was found in ICP fetal distress group and ICP control group(P＞0.05).(4)The expression of eNOS,iNOS and ET-1 was correlated with umbilical vein TBA in ICP(r1=-0.88,r2=-0.45,r3=0.79;P＜0.01),respectively.Conclusions High level of TBA in ICP is harmful to the umbilical vein endothelium,which is correlated with the raised expression of ET-1.and the decreased expression of eNOS,and iNOS in human umbilical cord endothelium cells.All these changes of umbilical vein may be associated with the occurrence of fetal distress in ICP.

Objective To explore the pathologic feature of children with kidney disease.Methods A retrospective analysis on renal bio-psy findings in 246 cases of children patients.Pathological classification was made according to the modified WHO criteria of 1995 for renal pathology.Results Of the 246 children,104 cases were diagnosed as primary glomerulonephritis,accounting for 42.28% of the total cases,136 cases as secondary glomerulonephritis,accounting for 42.28%,3 cases as hereditary nephritis,accounting for 1.22%,and 3 cases as unclassified renal disease,accounting for 1.22%.In primary glomerulonephritis,66 cases were diagnosed as nephrotic syndrome,23 cases as persistent glomeruloneplritis,8 cases as acute nephritis syndrome,3 cases as chronic nephritis syndrome,2 cases as isolated proteinuria,1 case as rapidly progressive glomerulonephritis,1 case as isolated hematuria.IgA nephropathy was the most frequent pathological type,accounting for 15.85%(39 cases),followed by mesangial proliferative glomerulonephritis,minimal change disease,endocapillary proliferative glomerulinephritis,IgM nephropathy,membranous nephropathy,focal segmental glomerulosclerosis,and minor lesion nephropathy.In secondary glomerulonephritis,Henoch-Schonlein purpura nephritis accounting for 48.37%(119 cases),followed by hepatitis B virus associated nephritis(11 cases) and lupus nephritis(6 cases).In hereditary nephritis,there were 2 cases with thin glomerular basement disease and 1 case with Alport syndrome.Conclusions Among the 246 cases of renal biopsy data,the secondary glomerulonephritis,especially Henoch-Schonlein purpura nephritis,is more common than primary glomerulonephritis.In primary glomerular diseases,IgA nephropathy is the most frequent pathological type.

Objective: To explore the effect of resveratrol on the chemosensitivity of cervical cancer cells and its regulatory mechanism. Methods: Hela/DDP cells were divided into four groups: Hela/DDP group, resveratrol group, CDDP group, and resveratrol+CDDP group. Cell viability and proliferation were detected by CCK-8. Cell cycle and apoptosis were tested by flow cytometry. The expressions of p21, CDK2, cyclinD1, caspase-9, caspase-3, Bcl 2 and Bax were measured by Western blot. Results: The sensitivity of Hela/DDP cells to cisplatin was lower than that of Hela cells (P<0.01). Resveratrol significantly enhanced Hela/DDP cells' sensitivity to cisplatin (P<0.01). The inhibition of CDDP on the proliferation of Hela/DDP cells was increased by resveratrol (P<0.01). The G1 phase arrest of CDDP on Hela/DDP cells was enhanced by resveratrol (P<0.01). The expression of p21 was higher in resveratrol group and CDDP group than in Hela/DDP group, and the expressions of CDK2 and CyclinD1 were lower than in Hela/DDP group (P<0.01). Compared with CDDP group, the expression of p21 in resveratrol+CDDP group was elevated with the decrease in CDK2 and cyclinD1 expressions (P<0.01). The induction of CDDP on the apoptosis of Hela/DDP cells was elevated by resveratrol (P<0.01). The expressions of caspase-3, caspase-9 and Bax were higher in resveratrol group and CDDP group than in Hela/DDP group, and the expression of Bcl-2 was lower than in Hela/DDP group (P<0.01). Compared with CDDP group, apoptosis in resveratrol+CDDP group was increased with the reduced expression of Bcl-2 (P<0.01). Conclusion: Resveratrol enhances the chemosensitivity of cervical cancer cells by inducing cell cycle arrest and apoptosis.

Objective To investigate the effect of sequential method in the training of primary anesthesia nurses. Methods A phased, gradual sequential method was used to train 11 primary anesthesia nurses. One-year full-course training was divided in 4 stages, each lasting 3 months. The theory and operational examination were held at the end of each stage and the tutoring teachers reported their comments. Result The mean scores of 11 primary anesthesia nurses were more than 90 points in both theory and operations examination, and the mean scores of tutor′s evaluation more than 85 points in each stage. Conclusion The sequential method can help primary anesthesia nurses to get better anesthesia-related knowledge, skill and clinical comprehensive ability, which set a solid foundation for their work of anesthesia care.

Cardiovascular disease is a severe threat to human health and life. Among many risk factors of cardiovascular disease, genetic or gene-based ones are drawing more and more attention in recent years. Accumulated evidence has demonstrated that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant capacity, insulin resistance, increased lipid levels, etc., and thus can promote the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and metabolic syndrome. In this review, we discusses the possible mechanisms between ATM gene and cardiovascular risk factors, which could be helpful to the related research and clinical application.
Aging ; Ataxia Telangiectasia Mutated Proteins ; genetics ; Cardiovascular Diseases ; genetics ; DNA Damage ; DNA Repair ; Humans ; Mutation ; Risk Factors

The complement system, the chief component of innate immunity, is not only required for host defense against pathogens and homeostasis, but also related to the pathogenesis and development of various kidney diseases. Recent study has shown that tissue-derived complement and immune cell-derived complement can each mediate local inlfammation. The comple-ment system acts as a bridge between innate and adaptive immunity. Furthermore it’s also a functional bridge between pathogenic humoral and cellular immune responses in an array of kidney diseases. Increasing evidence links inappropriate complement acti-vation and deifciencies of complement proteins to the pathogenesis of kidney autoimmune disease, ischemia-reperfusion injury, transplant rejection and complications in hemodialysis. The development of pharmacologic agents that target complement in pa-tients with this assortment of immune and/or inlfammatory kidney diseases has the potential to abrogate disease progression and improve patient health.

Animals ; Heart ; growth & development ; Myocardium ; metabolism ; Nerve Growth Factors ; genetics ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley