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.

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 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.

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 select antiplatelet regimen according to the results of CYP2C19 gene polymorphism,and then compare the major adverse cardiac events,bleeding events and the incidence of adverse reactions between two antiplatelet regimens. Methods Two hundred and seven patients who were diagnosed with acute coronary syndrome(ACS)and underwent elective PCI were tested for CYP2C19 genetic polymorphism,and 94 cases with CYP2C19 intermediate metabolism were randomly divided into high-dose clopidogrel group and ticagrelor group(47 cases each).High-dose clopidogrel group was given clopidogrel 150 mg once daily,and ticagrelor group ticagrelor 180 mg twice daily.Major adverse cardiac events,bleeding events and the incidence of adverse reactions were observed between two groups one month later. Results The average declined platelet aggregation rate was significantly different between the two groups[(6.27±5.65)% and(12.30±10.23)%,P<0.01];Adverse drug reactions ,the incidence of bleeding events and major adverse cardiac events of two groups were not significantly different. Conclusion Ticagrelor has stronger antiplatelet aggregation effects than high-dose clopidogrel.There is no difference in short-term clinical outcomes between the two groups.

With the rapid growth of incidence of non-small cell lung cancer (NSCLC),more and more studies have been made about its occurrence,development and metastatic mechanism m recent years.Researches about Fas/FasL protein expression and Fas/FasL-mediated apoptosis,immune escape mechanism and their roles in the pathogenesis,progression and prognosis of lung cancer are constantly emerging.Discussion about the roles of Fas/ FasL system in NSCLC could provide evidence for early diagnosis,prognosis prediction and new treatment of NSCLC.

Splenic radiofrequency ablation (RFA) is a safe, effective and minimally-invasive approach for the management of hypersplenism due to portal hypertension. After RFA, the remnant volume of the spleen will be decreased, the hypersplenism can be corrected, and the hepatic artery blood flow can be significantly increased with resultant marked improvement of liver function; in addition, hypertrophy and regeneration of the liver can be induced. However, many factors can affect the therapeutic results of RFA,therefore, further studies are necessary to clarify the underlying mechanisms.

Objective To investigate the value of transvaginal ultrasound in the diagnosis of endometrial polyps. Methods One hundred and ten patients diagnosed as endometrial polyps by transvaginal ultrasound and undergone operative hysteroscopy and histologic examination, were analyzed retrospectively.Results Among 110 cases 75 cases (68.2%) were accurately diagnosed by transvaginal ultrasound,while 35 cases (31.8%) were misdiagnosed.The diseases misdiagnosed included endometrium hyperplasia,intrauterine adhesions and submucousmyoma.Conclusions Combining clinical symptoms with ultrasonogram characters and optimal time of detection can reduce the misdiagnostic rate of endometrial polyps.

Objective To study the incidence, spreading path, prognosis and treatment of the umbilical metastasis Sister Mary Joseph nodule (SMJN) from malignancies Methods To analyse the clinical feature from 3 cases of SMJN and to review pertinent literatures Results Three cases SMJN were come from advanced primary peritoneal carcinoma in case 1, recurrent mucinous ovarian papillary adenocarcinoma in case 2 after primary cytoreductive surgery and systemic chemotherapy and case 3 with recurrent endometrial carcinoma All patients received umbilical resection and the umbilical metastasis was comfirmed pathologically, while case 3 was diagnosed adenocarcinoma spreading by fine needle respiration before the surgery The mean survival was 63 months following surgery or chemotherapy or radiotherapy, case 1 died of advanced malignancy, while case 2 and case 3 were still alive 58 and 44 months, respectively Conclusions Although the incidence being low, SMJN was the important sign of one of the vast metastatic malignancy and has grave prognosis Umbilical resection should be performed on some patients of SMJN with relative good condition, and chemotherapy or radiotherapy should also performed accordingly