Therapies targeting endocrine receptors and human epidermal growth factor receptor 2 have become important treat-ment modes for patients with hormone receptor breast cancer. Despite the availability of these options, however, development of prima-ry or secondary drug resistance and subsequent disease progression in patients with advanced disease continue to occur. Mammalian tar-get of rapamycin (mTOR), a key regulator of cell growth and proliferation, has been implicated in the induction of cellular processes leading to the uncontrolled growth of cancer cells. Recent studies have suggested that overactivation of the mTOR pathway may be in-volved in the development of endocrine resistance. Interrupting this signaling cascade may alleviate such resistance and help restore drug sensitivity. A number of agents targeting the mTOR pathway have shown potent anti-tumorigenic effects in vitro, and several agents show great potential for treating breast cancer patients. Many clinical studies have shown that combining endocrine therapy with mTOR inhibitors could significantly increase the survival rate of breast cancer patients. In this study, we focus on recent research prog-ress on mTOR and its inhibitors in endocrine therapy resistance in breast cancer.

Objective To explore the effects of simvastatin in the treatment of hyperlipidemia fatty liver. Methods Animal models were set up by feeding high caloric diet. Liver index (liver weight/body weight), liver function, blood lipid, liver lipid, the content of MDA in serum and liver were assayed before and after therapy with simvastatin. Results Liver index, blood lipid, liver lipid, and the content of MDA in liver as well as in serum increased significantly ( P

Objective To evaluate the protective effects of oral administration of D-methionine tablets on noise-induced hearing loss.Methods A total of 203 volunteers were recruited and randomly divided into two groups:experimental group (n=113)and control group (n=90).The subjects in the experimental group received oral administration of D-methionine tablets(1 500 mg/day)and those in the control group received placebo for 3 days before impulse noise exposure.The routine audiometric evaluation and ABR testing were performed and recor-ded 1 day and 7 days post- noise exposure.The statistical analysis was carried out with SPSS 11.0.ResuIts The changes of hearing in all participators were observed after noise exposure.The results were as follow:The hearing thresh-olds at three time points were 40.5±9.3,51.7±12.3,44.1±11.4 dB nHL in experimental group and 41.5±8.9,62.4± 13.7,47.6±12.5 dB nHL in control group,respectlvely;the ABR I-V IPLs at three time points were 3.72±0.21 ms, 3.99±0.36 ms,3.82±0.25 ms in experimental group,while 3.71±0.22 ms,4.45±0.37 ms,3.85±0.34 ms in control group,respectively.There were statistically significant differences between the two groups.ConcIusion The oral adminis-tration of D-methionine tablets pre noise exposure can protect against noise-induced hearing loss.

AIM: To investigate the alteration of serum free fatty acids in the carbon tetrachloride-induced fatty liver. METHODS: Drug-induced fatty liver rat models were built by injection 40% CCl_4. Serum free fatty acids were analyzed by gas chromatography. RESULTS: In the composition of serun free fatty acids, polyunsaturated fatty acids [oleic acid C18∶1,(28.672?7.332 ?/mg?L~(-1) vs 41.373?2.180 ?/mg?L~(-1)), linoleic acid C18∶2(16.739?0.871 ?/mg?L~(-1) vs 24.959?5.325 ?/mg?L~(-1)), arachidonic acid C20∶4(6.105?2.656 ?/mg?L~(-1) vs 9.802?0.779 ?/mg?L~(-1)),P

Cultured smooth muscle cells from bovine aortic media were incubated with hyperlipemic serum for 14 days. Lipid peroxides in the cells were higher than controls (P

Programmed death-1(PD-1)is a major co-suppression receptor expressed on T cells.Binding with its ligands (PD-L1 and PD-L2),PD-1 can inhibit T cell proliferation,activation and cytokine secretion.In normal organs,PD-1 /PD-Ls signaling pathway plays an important role in maintaining immune tolerance,while during tumorigenesis,it can suppress T cell immune response and promote tumor immune escape.This article reviewed the research progress on PD-1 /PD-Ls signaling pathway,comprised of structure and expression of PD-1 /PD-Ls, mechanism of the signaling pathway,as well as the expression characteristics of soluble form of PD-1 /PD-L1 (sPD-1 /sPD-L1),and summarized the categories of anti-PD-1 /PD-Ls antibodies and their clinical trials in canc-er immunotherapy.

Objective:To establish an HPLC method for the determination of thymol in thymol alcoholic solutions. Methods: An Agilent Eclipse XDB-C18(250 mm ×4.6 mm,5μm) column was used with the mobile phase of methanol-water (65∶35), the flow rate was 1. 0 ml·min-1 . the detection wavelength was 275nm, the injection volume was 10μl, and the column tenperature was 25℃. Re-sults:A good linear correlation of thymol was observed within the range of 60-160 μg·ml-1(r=0. 999 5). The average recovery was 101. 59% with RSD of 1. 39%(n=9). Conclusion:The method is quick, simple and accurate, which can be used in the determina-tion of thymol alcoholic solutions with good selectivity and sensitivity.

Objective To determine the value of complexed prostate-specific antigen (cPSA) in predicting metastasis in patients with prostate cancer.Methods From January 2012 to April 2014,the clinical data of 74 patients with newly diagnosed prostate cancer in our hospital was retrospective reviewed.The prostate cancer was diagnosed by transrectal ultrasound guided biopsy and postoperative pathologic diagnosis.The patients were divided to 2 groups according to metastases status.There were 38 patients in the group of metastasis and 36 patients in the group of without metastasis.In metastasis group,the bone metastasis was found in 36 cases.There is only one case with lung metastasis and one case with lymph node metastasis.In the group without metastasis,the T stages classification were T1-T2 in 17 cases and T3-T4 in 19 cases.While,10 cases with T1-T2 stage and 28 cases with T3-T4 stage were confirmed in the group with metastasis.There was no statistical significance of T stages and mean age in two groups (P＞0.05).The level of cPSA in the serum was detected by chemiluminescent immunoassay,the level of tPSA,fPSA were detected by electro-chemiluminescent immunoassay,fPSA/tPSA,cPSA/tPSA were evaluated and the corresponding specificity were calculated.The correlation of age with tPSA,cPSA were analysed.The differences in PSA,fPSA/tPSA,cPSA/tPSA were compared between metastasis and non-metastasis group.ROC curve analysis was used to determine the diagnostic value of cPSA and tPSA,In the meantime,area of ROC curves were compared by Z test.Results The age was not related to the value of tPSA (r=-0.09,P=0.12) and cPSA(r=-0.38,P=0.14).The median levels of tPSA,fPSA,and cPSA are 29.88μg/L,2.18 μg/L and 18.86 μg/L in the group without metastasis,respectively.The median levels of tPSA,fPSA,and cPSA were 410.05 μg/L,51.50 μ.g/L and 290.40 μg/L in the group with metastasis,respectively.Significant differences of those results could be found in two groups (P＜0.05).fPSA/tPSA was 0.07 and cPSA/tPSA was 0.79 in the group without metastasis.fPSA/tPSA was 0.08 and cPSA/tPSA was 0.80 in the group of metastasis.fPSA/tPSA (P=0.77),cPSA/tPSA (P=0.64) in patients with metastasis were not greater than in those without metastasis (P＞0.05).The area under the curve of tPSA and cPSA were 0.83 (95％ CI 0.73-0.93) and 0.82 (95％CI 0.73-0.92) respectively.Analysis of ROC curves showed that the AUC for cPSA is not significant different from tPSA (Z=1.64,P=0.10).The specificity of cPSA was 22.2％ which is higher than that of tPSA (19.4％) at a sensitivity of 92.1％ in predicting metastasis comparing with the patients without metastasis.The sensitivity could reach to 90.0％ when the cut off value of tPSA was 9μg/L or the cut off value of cPSA was 7 μg/L.Conclusions In our study,a preliminary validation that cPSA is useful for predicting the metastasis in patients with prostate cancer was made.

OBJECTIVE: To evaluate the protective effects of oral administration of D-methionine tablets on noise-induced hearing impairment. METHOD: Two hundred and three volunteers were recruited and randomly divided into two groups: experimental group (n= 113) and control group (n=90). The subjects received oral administration of D-methionine tablets in the experimental group and placebo in the control group before noise exposure. Routine audiometric evaluation and ABR testing were performed and recorded before and after noise exposure. The statistical analysis was carried out with SPSS 11.0. RESULT: There were no differences in auditory threshold and I-V interpeak latency pre-noise exposure (P>0.05), however, there were statistically significant differences between two groups 1 d, 7 d after noise exposure (P<0.01 and P<0.05). In-respective-group, there were statistically significant differences between before and 1 d after noise exposure (P<0.05 and P<0.01), however, no difference was noted between before and 7 d after noise exposure in the experimental group (P>0.05). CONCLUSION The protective effects of D-methionine tablets were prominent on the noise-induced hearing impairment. Further studies regarding the optimal time of D-methionine administration will be recommended in the future.
Administration, Oral ; Adult ; Hearing Loss, Noise-Induced ; drug therapy ; Humans ; Male ; Methionine ; therapeutic use ; Young Adult

Objective To investigate the effect of flurbiprofen axetil on perioperative plasma levels of prostaglandin E2 (PGE2) and β-endorphine (β-EP) in patients after remifentanil-based anesthesia.Methods Sixty ASA Ⅱ patients of both sexes,aged 40-64 yr,weighing 50-75 kg,undergoing resection of esophageal cancer,were randomly divided into 3 groups (n =20 each):intralipid group (group A),flurbiprofen axetil pretreatment + postoperative analgesia with flurbiprofen axetil group (group B) and flurbiprofen axetil pretreatment group (group C).Anesthesia was induced with propofol,remifentanil and rocuronium and maintained with propofol,remifentanil and intermittent iv boluses of rocuronium.In group A,intralipid 0.2 ml/kg was injected intravenously at 30 min before operation and patient-controlled intravenous analgesia (PCIA) with fentanyl 15μg/kg + intralipid 0.2 ml/kg was used for postoperative analgesia.In group B,flurbiprofen axetil 2 mg/kg was injected intravenously at 30 min before operation and PCIA with fentanyl 15 μg/kg + flurbiprofen axetil 2 mg/kg was used for postoperative analgesia.In group C,flurbiprofen axetil 2 mg/kg was injected intravenously at 30 min before operation and PCIA with fentanyl 15 μg/kg + intralipid 0.2 ml/kg was used for postoperative analgesia.PCIA solution contained fentanyl 15 μg/kg,flurbiprofen axetil 2 mg/kg and intralipid 0.2 ml/kg in 100 ml of normal saline.The PCA pump was set up with a 0.5 ml bolus dose,a 10 min lockout interval and background infusion at a rate of 2 ml/h after a loading dose of 5 ml starting from 30 min before the end of operation.VAS score was maintained ＜ 3 after operation,and tramadol 50 mg was injected intravenously when VAS ≥ 4 after operation.The amount of remifentanil used during operation and the number of successfully delivered doses and the number of attempts,requirement for tramadol,apnea and severer hypotension were recorded within 48 h after operation.Blood samples were taken immediately before induction of anesthesia,at the end of operation,24 and 48 h after operation (T1-4) for determination of plasma β-EP and PGE2 concentrations.Results There was no significant difference in the amount of remifentanil used among the three groups (P ＞ 0.05).Compared with group A,the number of successfully delivered doses,the number of attempts and the requirement for tramadol were decreased,and the concentration of plasma PGE2 at T2,3 were significantly decreased in groups B and C,and the concentrations of plasma β-EP at T3,4 in group B and at T4 in group C were significantly increased (P ＜ 0.05).Compared with group B,the number of successfully delivered doses,the number of attempts and requirement for tramadol were significantly increased,and the concentration of plasma β-EP at T3,4 wassignificantly decreased in group C (P ＜ 0.05).Compared with the baseline value at T1,the concentrations of PGE2 were significantly increased at T2,3,and the concentration of plasma β-EP was significantly increased at T2,but decreased at T4 in group A,and the concentrations of β-EP at T3,4 were significantly increased in group B (P ＜ 0.05).There was no significant difference in the concentrations of PGE2 and β-EP between the four time points in group C (P ＞ 0.05).Apnea and severer hypotension were not found in the three groups.Conclusion The mechanism by which flurbiprofen axetil reduces postoperative opioid tolerance in patients after remifentanil-based anesthesia may be related to the decrease in PGE2 levels and increase in β-EP levels.