The best characterized methotrexate (MTX) transporter is the reduced folate carrier (RFC),whose gene polymorphism is one of the reasons causing MTX resistance. Based on the studies in rencent years,we have known that synthesis of mutant RFC or loss of RFC transcripts and proteins results in antifolate resistance due to incomplete inhibition of cellular enzyme targets and insufficient substrate for polyglutamate synthesis. So additional human RFC structural and mechanistic studies are absolutely essential. This paper summarizes an association between the polymorphisms of RFC and MTX resistance, which can provide a basis for clinical treatment.

Objective To investigate the effect of controlled intensive blood pressure reduction on acute cerebral hemorrhage.Methods Eighty-eight patients with acute cerebral hemorrhage were divided into controlled blood pressure reduction group (controlled group,48 cases) and general blood pressure reduction group(general group,40 cases) by random number table method.Respectively given positive blood pressure reduction and according to the guidelines for treatment.The intracranial hematoma volume after admission,Glasgow coma scale (GCS) score,the United States national institutes of health stroke scale (NIHSS) score,surgery rate within 24 h after admission and fatality rate within 30 d after admission in two groups were compared.Results The initial blood loss between two groups had no significant difference(P ＞0.05).The intracranial hematoma volume,growth rate of intracranial hematoma,intracranial hematoma enlargement ratio in controlled group on 24 h after admission were lower than those in general group,there were significant differences [(19.3 ± 11.6) ml vs.(30.5 ± 10.9) ml,(17.8 ± 12.7)％ vs.(37.1 ±25.7)％,16.7％ (8/48) vs.47.5％ (19/40)] (P ＜ 0.05 or ＜ 0.01).The GCS and NIHSS score between two groups on admission and 1,7,14 d after admission had no significant difference(P ＞ 0.05).The surgery rate within 24 h after admission in controlled group was lower than that in general group [8.3％ (4/48) vs.25.0％ (10/40)],there was significant difference (P ＜ 0.01).The fatality rate within 30 d after admission between two groups had no significant difference (P ＞ 0.05).Conclusion Cerebral hemorrhage early control of blood pressure can not change its recent neural functional recovery and reduce the fatality rate,but may be significantly delayed hematoma enlargement and reduce the rate of surgery.

The breast cancer stem cell theory provides a theoretical basis for explaining phenotypic and functional heterogeneity of breast cancer. These breast cancer stem cells(CSCs)promote tumor growth and are closely related to breast cancer intrinsic drug resistance. Therefore,targeted therapy of breast CSCs has become a hot area in basic and clinical research. There is growing evidence that nanoparticles can kill cancer by targeting breast CSCs ,such as targeted tumor stem cell-specific expressed surface markers(AL-DH1,CD44,and CD90),tumor stem cell stemness-related NOTCH,Hedgehog and TGF-βsignaling pathways. In this review,we summarized the characteristics and research status of breast CSCs ,and the application of nanotechnology in the treatment of breast cancer.In addition,we also summarized the research status of epigenetic drugs aimed to restrain the reprogramming of breast cancer cells.

Objective To investigate a sonic wave device including micro-oscillator and microphone for real-time monitoring the situation of the esophageal motility of lower esophageal sphincter (LES). Methods A micro-oscillator that can actively send sound waves was located at one side of LES, and a microphone located at the other side can be to capture the sound generated from the oscillator. This device was tested in vitro by utilizing a LES simulator in quiet and noisy environment, as well as in vivo in a pilot model corresponding to moments A-D. Results In the in vitro test, the sound can be captured by the microphone, and its power strength was correlated with closing and opening of LES. The measurements showed statistically significant Pearson correlation coefficients. In the in vivo test, the LES was open and closed by an endoscope, which was monitored in real-time by another endoscope inserted into the distal stomach from the duodenum. The sound power strength corresponding to moments A-D were (-89.63 ± 0.79) dB, (-84.74 ± 0.97) dB, (-82.37 ± 1.93) dB and (-89.86 ± 0.75) dB. Conclusion The LES dynamics can be monitored by the acoustic interrogation device, which has the potential to become an effective minimally-invasive technique for studying LES dysfunction.

Objective To perform the research on the domestic hospital marketing. Methods Through deep discussion,data analysis and marketing survey,we conducted a research on the market positioning and marketing strategies for Shanghai Ruijin-Harvard Heart Center which is a Sino-foreign joint venture. Results The demand is much bigger than the current supply in the market for cardiovascular diseases.The establishment of the center meets the demands of the market. Conclusion The center will focus on the adult patients in Shanghai and Yangtze Delta,and combine the external,internal and interactive marketing strategies.It may provide some useful experience for the Chinese hospital management,especially for hospital marketing.

Objective To compare the clinical curative effect between transjugular intrahepatic portosystemic stent-shunt (TIPS) and TIPS together with gastric coronary vein embolization (GCVE) in treating cirrhosis portal hypertension (PHT) associated with upper gastrointestinal hemorrhage (UGH),and to discuss the necessity,feasibility and clinical curative effect of TIPS plus GCVE.Methods The clinical data of 38 PHT patients with UGH,who were admitted to authors' hospital during the period from April 2010 to May 2012,were retrospectively analyzed.Only TIPS was employed in 15 patients (group A),and TIPS plus GCVE was adopted in 23 patients (group B).Before and after operation,the indexes,hemodynamics of portal vein and spleen,the morphology of spleen,and the degree of gastrointestinal varices were determined and analyzed.The patients were followed up to observe the occurrence of postoperative complications.Results In both groups,the postoperative portal vein pressure showed an obvious reduction with accelerated velocity of flow,and the splenic venous congestion index was decreased,these changes were statistically significant when compared with the preoperative ones (P＜0.05),and which was more obvious in group B than in group A (P＜0.05).After the treatment,the esophagogastric varices (EGV) was obviously improved,the improvement rates of group B and group A were 94.7％ and 66.6％ respectively,the emergency hemostasis rates of group B and group A were 100％ and 75.0％ respectively,The rates of re-bleeding were 4.3％ and 28.5％ respectively;the above results of group B were statistically better than those of group A (P＜0.05).No statistically significant differences in liver function indexes existed between preoperative values and postoperative ones in the same group as well as in group comparison (P＞0.05).The differences in the postoperative hepatic encephalopathy (HE) occurrence and in primary patency rate of stent between the two groups were not statistically significant (P＞0.05).In both groups,the re-intervention patency rate was 100％.The incidence rate of HE in patients in whom the distal end of stent was located in the left branch of portal vein was strikingly lower than that in patients in whom the distal end of stent was located in the right branch of portal vein (P＜0.05).Conclusion For the treatment of PHT associated with UGH,TIPS combined with GCVE carries reliable curative effect,this therapy is superior to simple use of TIPS.

Objective To investigate the dynamic changes of IL-2, IFN-γ, TNF-α, IL-4, IL-5 and IL-10 in mice immunized with Eg14-3-3 and then challenged by Echinococcus granulosus protoscoleces.Methods ICR mice were subcutaneously immunized every two weeks for altogether three times with rEg14-3-3, followed by the challenge with Echinococcus granulosus protoscoleces intraperitoneally four weeks after the third immunization.The PBS control group mice were operated in the same way.We collected mouse serum from tail vessel at different time points after immunization and challenge.The serum levels of IL-2, IFN-γ, TNF-α, IL-4, IL-5 and IL-10 were examined with enzyme-linked immunosorbent assay.Results The levels of the six cytokines were higher after immunization and challenge infection in rEg14-3-3 group than in PBS control group.The immunized mice generated a great deal of Th1 cells, namely, IL-2, IFN-γ and TNF-α, after immunization and showed a peak at week 10 (acute infection phase), then the level decreased rapidly at week 30 (chronic infection phase), and maintained a high level for a long time.In contrast, Th2 cells like IL-4, IL-5 and IL-10 kept a low level until week 18, peaked at week 30, and then decreased gradually but maintained a relatively high level for a long time.For PBS control group, IL-2, IFN-γ and TNF-α did not increase obviously before infection, but increased rapidly after challenge infection and peaked at week 18;then the level decreased gradually and maintained a high level for a long time.On the other hand, IL-4, IL-5 and IL-10 kept a low level, but increased gradually after challenge infection.IL-4 peaked at week 18 while IL-5 and IL-10 peaked at week 30, and then they all decreased slowly but maintained a relatively high level for a long time.Conclusion Eg14-3-3 can induce significant antibody response by Th2 cells and cell-mediated immunity response by Th1 cells.Both Th1 and Th2 cells participate in the anti-echinococcusis protective immunity.

Angiogenidiseaseof the retinare the common reasonof several visual loss.Vasculaendothelial growth facto(VEGF) playan importanrole in pathologiangiogenesis.In recenyears,the developmenof anti-VEGF therapiehatransformed the prognosiof these conditions.The treatmenof angiogenidisease had entered an erof anti-VEGF therapy,especially in the treatmenof choroidal neovascularization (CNV) caused by age-related maculadegeneration (AMD).Abreakthrough,anti-VEGF therapy changethe photodynamitherapy (PDT) based weAMD (wAMD) treatmenmode.In thipaper,we describe thaeven though relegated to background,PDstill haclinical therapeutivalue fospecial circumstanceand certain type of CNV lesion,awell ain certain retindisease.

Alport syndrome (AS) is a hereditary glomerular basement membrane disease characterized by hematuria, progressive renal hypofunction, usually with nervous deafness and ocular lesions, and its pathogenesis is the mutation in genes encoding the type Ⅳ collagen. Diagnosis of AS should combine with clinical manifestations, renal pathologic changes, immunofluorescence examination and gene diagnosis. At present, AS hasn t had any cure measure yet. As the pathogenesis of AS is much clearer in recent years, the researches of gene diagnosis and gene therapy have got some gratifying achievements.

Notch signaling pathway plays a vital role in cell fate decisions. Notch signals are transferred among adjacent cells through Notch receptors and their ligands, which can regulate differentiation, proliferation and apoptosis of many cell types including stem cells. They can also influence organ formation and morphopoiesis. Genetic mutations in the Notch signaling pathway are related to the emergence and development of many diseases. Notch signaling pathway is increasingly becoming important drug targets for cancer, hereditary disease such as CADASIL and other related diseases. It is also used to develop stem cell therapeutics to treat age or trauma related degenerative diseases such as Alzheimer's disease, Parkinson disease and diabetes.