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.

The abnormal changes of tumor suppressor genes such as deletion mutant,transcription inactivation or silence on human chromosome 3p (pter) are considered as a key step which is closely related to the tumorigenesis of several kinds of cancers,especially clear cell renal cell carcinoma,one kind of renal cancer.And on this basis,it has been confirmed that the deletion and downregulation of multiple 3p genes such as VHL,RASSF1A,SEMA3B,SETD2,PBRM1,NPRL2 and so on,play a vital important role in the tumorigenesis and development of clear cell renal cell carcinoma.And they provide a further way to explain the molecular mechanism of the tumorigenesis of kidney cancer.However,when the regulatory pathway and mechanism research of some genes are known to us,the other genes,especially those newly founded,which are still not clear and need to be further investigated.

Objective To investigated the relationship between serum matrix metalloproteinase-9(MMP-9) and carotid atherosclerosis(AS) in type 2 diabetes mellitus(T2DM).Methods A total of 93 patients with T2DM were recruited to our study.The intima-media thickness(IMT) and plaques of carotid artery were measured.These patients were divided into 3 groups according to their IMT values: diabetes mellitus(DM) group(n=32),carotid artery intima thicken group(n=31) and carotid artery intima plaque group(n=30).At the same time,30 healthy individuals were selected as control.Serum level of MMP-9 were determined and analyzed.Results The serum MMP-9 in DM group was significantly higher than that in healthy controls([550.26±269.28]μg/L vs.[359.70±215.62]μg/L,t=2.23,P＜0.05).The serum MMP-9 level of intima thicken group(712.15±340.47)μg/L was significantly higher than that in healthy controls(t=4.53,P＜0.01) and DM group(t=2.40,P＜0.05).The serum MMP-9 level of plaque group([889.08±247.80]μg/L) was even more significantly higher than DM group(t=4.89,P＜0.01),IMT group(t=2.53,P＜0.05) and healthy controls(t=7.01,P＜0.01).Conclusion The severity of carotid atherosclerosis in T2DM is closely associated with the serum MMP-9 level.

Objective To investigate the incidence, risk factors and drug-resistance of Pseudomonas aeruginosa infection in intensive care unit (ICU). Methods Totally 171 patients with sepsis admitted in ICU were enrolled. Pathogenic bacteria culture and antimicrobial susceptibility tests were performed. SPSS10. 0 software was used for Logistic regression analysis of the risk factors. Results Pseudomonas aeruginosa infection was confirmed in 37 patients, and 45 strains of Pseudomonas aeruginosa were isolated. Logistic regression revealed that recent antibiotics use ( OR = 4. 291 , 95% CI: 1. 727-10. 662) , length of ICU stay (OR = 1.117, 95% CI: 1.058-1. 181) , mechanical ventilation (OR = 3.400, 95% CI: 1.348-8.579) and central venous catheterization (OR =3. 339, 95% CI: 1.322-8.434) were independent risk factors of Pseudomonas aeruginosa infection. The resistance rate of cefotaxime was the highest (68.9%) and 18 strains (40%) were multidrug-resistant. Conclusions Pseudomonas aeruginosa infection is common in ICU and it is usually multidrug resistant. The rational use of antibiotics and aseptic technique of invasive catheterization are important for the prevention of Pseudomonas aeruginosa infection.

Objective To investigate the pathological changes of ultrastructure of mucosa in various bronchial segments from type 2 diabetic patients. Methods Sixteen cases of type 2 diabetic patients were selected,2-3 pieces of bronchial mucosa and submucosal tissue of the lesion were taken from various bronchi during bronchoscopy and these samples were observed under a transmission electron microscope. Results The basal lamina of bronchial capillary were diffusely thickened and mostly showed onion-skin like change,protein deposited around and mixed with basal menbrance;irregular highly electron dense materials were found to deposite around capillary,capillary lumen became narrow or even collapsed,neutrophilic leucocyte marginated in lumen and adhered with endothelium;protein deposited in the interstitial;endothelial cells and pericytes had dark cell changes.The cistern of rough endoplasmic reticulum dilated and vesicle formed.Conclusion Bronchial mucosa and its surrounding tissues show characteristic pathological changes of diabetes,bronchial is also the target organ of chronic diabetic damage.

Objective To study the effects of strontium (Sr) on proliferation and osteogenic differentiation of human marrow mesenchymal stem cells (hMSCs) in vitro,and to determine its optimal concentration.Methods Six milliliter of bone marrow was obtained from a healthy adult volunteer,the hMSCs were then isolated and cultured in vitro,and the cell phenotype was identified by flow cytometry.The 4th passage cells were used for experiment,and they were randomly divided into 5 groups:the osteogenic agents (10-8mol/L dexamethasone,50?g/ml ascorbic acid and 10mmol/L beta-sodium glycerophosphate) were used alone in the control group (group A),and the combination of osteogenic agents and different doses of strontium chloride (3.75?10-3,3.75?10-2,3.75?10-1 and 3.75mmol/L) were used in group B,C,D and E.The proliferation level,alkaline phosphatase (ALP) activity and osteocalcin (OCN) content of MSCs were determined by MTT colorimetric assay,enzyme-labeled method and radioimmunological method,respectively.The amount and area of calcium nodules in each group were observed by alizarin red staining.Results The proliferation and osteogenic differentiation rate of each group increased significantly with the lapse of culture time(P