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.

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 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 The study is mainly on the effect and outcome of 131 I treatment for children and adolescents with differentiated thyroid cancer .Methods We compared the difference between rhTSH -aided ra-dioiodine treatment and L -thyroxin withdrawal .Our study collected 87 patients in a retrospective study .In order to analysis the effect,we divided into two groups.The experimental group has 46 patients,and control check has 41 patients.We compared the basic characteristics and mortality in different groups by χ2 -test,t-test and F-test based on data type .Results The thyroid stimulating hormone concentrations of experimental group patients have significant differences in the first ,the third and the sixth day after the injected of rhTSH ,the third day is the highest.The TSH concentration has significant difference between the two groups before 131I treatment(t=2.362, P=0.023).For the Tg(thyrobolulin)negative patients,Tg concentration in control check is higher than the third day after injected of rhTSH in the experiment group (1.5 ±1.2 vs.0.7 ±1.4,P=0.034).Whole body image has been done by scintigraphic after 3~8 months of 131I treatment.Thirty four(84%)patients have no radioiodine up-take in experiment group,and 40(87%)patients have no radioiodine uptake in control check ,there is no differ-ence between the two groups (χ2 =0.277,P=0.599).There is no difference between the two groups on the rea-son for retreatment(P=0.875).Conclusion The outcome of rhTSH -aided radioiodine treatment is similar to L-thyroxin withdrawal in short -term recurrences ,and rhTSH-aided radioiodine treatment with 131 I therapy for children and adolescents with DTC is a better method .

Objective To explore the clinical features of sentinel polyps (rectal polyps with proximal colon carcinoma) and its correlation with proximal colon carcinoma.Methods From January 2011 to June 2015,the clinical features of 331 hospitalized patients with rectal polyps were retrospectively analyzed.According to whether the patient with colon carcinoma,the clinical data of rectal polyps patients were divided into pure polyps group (n =294) and sentinel polyps group (n =37).The characteristics under endoscopy,clinical pathological features,treatment and prognosis of two groups were observed.Results The positive rate of tumor marker of sentinel polyps group was higher (67.6 ％,25/37) than that of pure polyps group (6.8 ％,20/294;x2 =32.174,P ＜ 0.01).When compared to pure polyps group,most polyps of sentinel polyps group were in maximum diameter over 1 cm [62.2％ (23/37) vs 46.9 ％ (138/294)],multi-polyps [n ＞5,43.2％ (16/37)vs11.6％ (34/294)] and adenomatous polyp [83.8 ％ (31/37) vs 35.7 ％ (105/294)] (x2 =10.863,15.686,and 22.653,P ＜0.01).Majority of the proximal colon carcinoma with rectal polyps was papillary adenoearcinoma and tubular adenocarcinoma which was account for 75.7 ％ (28/37);Duke A,29.7％ (11/37),Duke B,29.7％ (11/37),Duke C,24.3％ (9/37) and Duke D,16.2％ (6/37).96.6 ％ (282/294) of patients with pure polyps underwent endoscopic treatment and all of them were cured and discharged.40.5％ (15/37) of patients of sentinel polyps group accepted the radical operation and 24.3％ (9/37) received endoscopic submucosal dissection.Conclusions If multiple,maximum diameter over 1 cm and adenomatous rectal polyps were detected under colon endoscope,the possibility of carcinogenesis of the polyps or the proximal colon should be aware.The patient should be followed up in short-term and complete the whole colon examination.

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.