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.

Signaling pathways such as MAPK and P13K have been confirmed to be important in the mechanism of tumor genesis, development, prevention and treatment. Thyroid hormone (TH) and its receptor (TR) can affect the pathways resulting in inhibition of tumor growth and metastasis, thus they have gradually become the focus of recent research. However, numerous studies showed that TR gene mutation was often observed in a variety of cancers and resulted in the deregulation of TH/TR mediated downstream pathways, and TR gene mutation became an causative agent to activate downstream proto-oncogene. Recent studies showed that TH/TR might play a role in the regulation of β-catenin degradation, the knowledge of which allows us not only to further understand the function of TR gene in the inhibition of tumor development, but also provide a theoretical basis for the continuous activation of downstream proto-oncogene by TR mutation. To study the downstream pathway of TR gene could eventually guide the clinician and provide a new theoretical basis for cancer prevention and molecular target gene therapy.

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.

In recent years, the incidence of pediatric malignancies has gradually increased. High-risk patients have poor prognosis, and the main effect of treatments such as surgery and radio-chemotherapy has reached a plateau phase. Targeted therapy, with its reliable efficacy and mild toxicity, has become one of the most promising approaches. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, and its abnormal forms include gene fusion, gene mutation, gene amplification, and protein overexpression. These aberrations play important roles in the development of childhood cancer. With the application of ALK inhibitors in clinical anti-tumor therapy, targeted ALK treatment has received increased attention. This article aims to review various studies on the relationship between ALK aberrations and pediatric malignancies.

Objective To analyze the differentially expressed proteomics on T lymphocyte in mice immunized with 14‐3‐3 recom‐bined vaccine and injected with phosphate buffer solution (PBS) .Methods Mice immunized with 14‐3‐3 recombined vaccine were separated in the experiment group and those injected with PBS were selected in the control group .Two weeks after immunization with 14‐3‐3 recombined vaccine ,total protein of T lymphocyte isolated from the two groups was collected and separated by using the two dimensional electrophoresis(2‐DE) .The differentially expressed proteomics were compared .Results The 2‐DE map shown 11 differentially expressed protein plots ,including 7 protein plots spotted in the 2‐DE map of T lymphocyte from 14‐3‐3 recombined vaccine immunized‐mice and 4 protein plots spotted in the 2‐DE map of T lymphocyte from PBS injected‐mice .Conclusion There are differentially expressed proteomics of T lymphocyte in PBS injected‐mice and 14‐3‐3 recombined vaccine immunized‐mice ,which could contribute to clarifing the mechanism on protective immunity of 14‐3‐3 recombined vaccine and optimizing vaccine strategy for improving vaccine effect .

Objective To investigate the relationship between the doses of epidural morphine administered for postoperative analgesia and postoperative urinary retention (POUR). Methods Sixty ASA Ⅰ patients aged < 20-56 yr undergoing atthroscopic knee operation under epidural anesthesia were randomly divided into 3 groups ( n = 20 each) : group Ⅰ and Ⅱ received epidural morphine 1 and 3 mg in 5 ml of normal saline (NS) respectively at the end of operation (group M1, M2 ); group Ⅲ received NS 5 ml instead of morphine (group C). Urinary retention was defined as the patient could not void, when bladder volume was ≥ 600 ml measured using ultrasound. Bladder urine volume was measured before anesthesia and at 4, 6, 8, 10 and 12 h after operation. The occurrence of urinary retention, the first postoperative voiding time, VAS scores and the incidences of vomiting and pruritus were recorded. Results The 3 groups were comparable with respect to age, M/F sex ratio, preoperative bladder urine volume, the amount of local anesthetic used during operation and duration. The incidences of urinary retention, vomiting and pruritus were 65%, 60% and 90% respectively in group M2 and significantly higher than those in the other 2 groups. The first postoperative voiding time was significantly longer in group M2 than in the other 2 groups. VAS scores were significantly lower in group M1 and M2 than in group C. There was no significant difference in VAS scores between group M1 and M2. Conclusion Epidural morphine increases the incidence of POUR in a dose-dependent manner, and 1 mg is the recommended dose.