DNA damage repair gene mutations are prevalent in advanced prostate cancer. Among these, mutations in homologous recombination repair genes could impair the ability of cell to restore the DNA double-strand break, which can be exploited by Poly-ADP-ribose polymerase (PARP) inhibitors through synthetic lethality and result in cell death. The phase Ⅲ study " PROfound" showed that the PAPR inhibitor Olaparib could significantly improve the survival of patients with homologous recombination repair gene mutations compared with novel hormone agents, starting the era of targeted, precise and individualized treatment based on genetic profile detection for prostate cancer treatment.

To meet the challenge of the clinical teaching,the"Regulations on the Management of Clinical Teaching Practice in Medical Education"has been made and implemented, which establish the definitude responsibilities,rights and profit relations among doctors,students and the patients. Related organizations and persons should fully realize its normative significance,implementation obstacles and deepen the study of clinical teaching research,thus facilitating the enhancement of the teaching effect,and building a harmonious triangular relationship among the concerned parties.

Dioscin is the main raw material for the synthesis of steroid hormone drugs. Currently, the direct acid hydrolysis is the mainly industrial production method for dioscin. However, the use of strong acid can not only destroy the structure of dioscin resulting in very low yield, but also produce a large amount of waste water and residues, which seriously pollute the environment. So the clean production of dioscin is the urgent demand of water conservation and environmental protection. In the paper, the recent research pro-gresses in the clean production technology and process of dioscin were summarized, and the advantages and problems were discussed in order to provide reference for the improvement and application of the new technology and process.

Objective To recognize the CT manifestations of benign metastasizing leiomyoma (BML).Methods Four cases of BML proved by pathology were retrospectively analysed.Among these, 2 cases were pulmonary BML,1 ease was leiomyomatosis peritonealis diseminata(LPD),and 1 case was combined with pulmonary BML and LPD.All of them were female,and had a history of hysterectomy,the average age were 45.The CT findings of them were analyzed.Results The CT of pulmonary BML in three cases showed multiple rounded,well-defined discrete nodules,0.2—2.0cm in diameter,random distribution,and no calcification in the nodules.No hilum or mediastinum lymphadenopathy,and no pleural effusion.There were no enhancement after intravenous contrast examination.The CT findings of LPD in two cases were many masses around the vena cava,abdominal aorta and/or iliac artery.The masses were 4— 5cm in diameter with smooth margin and homogeneous density.No lymph node or ascites were found.One case who got intravenous contrast enhanced CT scan showed significant enhancement of the lesions;another case who got PET CT study showed no significant tracer concentration.Conclusion When multiple metastasizing nodular lesions with sharp margin and homogeneous density were found in the lungs or abdomen,they should be considered the possibility of BML in women with hysterectomy history.

Objective To identify the risk factors of Burkholderia cenocepacia associated nosocomial lower respiratory tract infections (NLRTIs),and to investigate the drug resistance of Burkholderia cenocepacia strains.Methods A total of 138 patients with Burkholderia cenocepacia associated NLRTIs and 40 patients with non-Burkholderia cenocepacia associated NLRTIs were enrolled in the study.All patients were collected from the Second Affiliated Hospital of Wenzhou Medical University during January 2009 and December 2012.Clinical data and results of drug sensitivity tests were retrospectively reviewed.Chi-square test and Logistic regression analysis were performed to identify the risk factors of Burkholderia cenocepacia associated NLRTIs.Results Logistic regression analvsis showed that combination use of 2 or more antimicrobial agents,mechanical ventilation,stay in intensive care unit (ICU) for more than two weeks,use of antacid H2 antagonist and deep venous puncture were the independent risk factors of Burkholderia cenocepacia associated NLRTIs (OR =6.315,5.957,5.254,4.585 and 2.017,P ＜0.05).Burkholderia cenocepacia strains were sensitive to levofloxacin,ceftazidime and sulfamethoxazole; More than 40％ strains were resistant to cefotaxime,ceftriaxone,cefepime,aztreonam and tetracycline; And nearly 100％ strains were resistant to gentamicin,amikacin and tobramycin.Conclusion Burkholderia cenocepacia associated NLRTIs are more likely to occur in patients with combination use of 2 or more antimicrobial agents,mechanical ventilation,and those who stay in ICU for more than two weeks,or received antacid and deep venous punctures,and most Burkholderia cenocepacia strains are multiple drug resistant.

Objective To investigate the role of autophagy in radiation-induced death response of human nasopharyngeal carcinoma cells.Methods MTT method was used to detect cell viability of CNE-2 cells in different time after irradiation.Clonogenic survival assay was used to evaluate the effect of autophagy inhibitor (chloroquine phosphate) and autophagy inductor (rapamycin) on radiosensitivity of nasopharyngeal carcinoma cells.Cell apoptosis was assessed by flow cytometry.The expressions of LC3 and P62 were measured with Western blot.Cell ultrastructural analysis was performed under an electron microscope.Results Irradiation with 10 Gy induced a massive accumulation of autophagosomes accompanied with up-regulation of LC3-Ⅱ expression in CNE-2 cells.Compared with radiation alone,chloroquine phosphate (CDP) enhanced radiosensitivity significantly by decreasing cell viability (F =25.88,P ＜ 0.05),autophagic ratio (F =105.15,P ＜ 0.05),and LC3-Ⅱ protein level(F =231.68,P ＜0.05),while up-regulating the expression of P62 (F =117.52,P ＜ 0.05).Inhibition of autophagy increased radiation-induced apoptosis (F =143.72,P ＜ 0.05).Rapamycin (RAPA) also significantly decreased cell viability,but increased autophagic ratio and LC3-Ⅱ protein level while down-regulated the expression of P62.Induction of autophagy increased radiation-induced apoptosis(F =167.32,P ＜ 0.05).Conclusions Blockage of autophagy with CDP could enhance radiosensitivity in human nasopharyngeal carcinoma cells,suggesting that inhibition of autophagy could be used as an adjuvant treatment to nasopharyngeal carcinoma.

Objective To compare the myocardial protective effects of isoflurane versus sevoflurane in patients undergoing off-pump coronary artery bypass grafting (OPCABG). Methods Forty ASA Ⅱ or Ⅲ patients (NYHA Ⅱ or Ⅲ ) of both sexes, aged 40-55 yr, weighing 55-94 kg, scheduled for elective OPCABG, were randomly divided into 2 groups ( n = 20 each): isoflurane group ( group Ⅰ) and sevoflurane group ( group S). Anesthesia was induced with midazolam, sufentanil and vecuronium. Patients were tracheal intubated and mechanically ventilated. Anesthesia was maintained with inhalation of isoflurane or sevoflurane and infusion of sufentanil and vecuronium. In group Ⅰ, the initial end-tidal concentration of isoflurane was 1.2%. In group S, the initial end-tidal concentration of sevoflurane was 1.7 %. BIS value was maintained at 40-50 by adjusting the end-tidal concentration of isoflurane or sevoflurane. The central venous blood samples were collected immediately before skin incision, at the end of surgery, 2 and 24 h after surgery for determination of plasma creatine kinase-MB (CK-MB) activity and cardiac troponin Ⅰ (cTnI) concentration. The adverse cardiovascular events were recorded. Results The incidences of ventricular premature beat, tachycardia, bradycardia, ventricular fibrillation and S-T segment elevation ( ＞0.1 mV) during surgery and the plasma CK-MB activity and cTnI concentration after surgery were significantly higher in group S than in group Ⅰ ( P ＜ 0.05). Conclusion Isoflurane has better myocardial protective effect than sevoflurane in patients undergoing OPCABG.

Objective To investigate the correlations of extracellular matrix and hepatic ultramicrostructural changes with clinical manifestations in patients with mild chronic hepatitis B (CHB).Methods Patients with chronic HBV infections were enrolled and were divided into mild CHB group (n=66) and HBV carrier group (n=10).Serum samples were collected from patients, and serum HBV markers, HBV DNA load and liver fibrosis indexes were measured.All subjects received liver biopsy, and the tissue samples were observed by light microscope and electron microscope.T test and χ2 test were performed for measurement data and enumeration data, respectively.Spearman test was used for ranked data.Results The differences on ALT and AST levels between mild CHB group and HBV carrier group were significant (t=12.42, 7.06, P＜0.05), but there was no significant difference on HBV DNA load between two groups (t=0.24, P ＞ 0.05).Serum liver fibrosis indexes (hyaluronic acid, type Ⅲ collagen,type Ⅳ collagen and laminin protein) in mild CHB group were not significantly higher than those in HBV carrier group (t=0.45, 0.95, 0.76 and 1.21, P ＞0.05).In mild CHB group, there were 33 patients with ≥G2 and ≥S2, but in HBV carrier group were only 2 patients (χ2=4.17, P ＜ 0.05).Seventeen patients in mild CHB group were with S3-4, while that was not observed in HBV carrier group (χ2=4.75, P ＜0.05).In mild CHB group, hepatic ultramicrostrutural changes on fat storing cell, collagen protein and portal area were correlated with fibrosis grades, and the correlation coefficients were 0.351, 0.675 and 0.301, respectively (P=0.004, 0.000 and 0.014).Conclusion Electron microscope is of higher sensitivity than light microscope in observing hepatic ultramicrostructural changes, which is effective in evaluating the severity of mild CHB.

Objective To compare the clinical efficacy and safety of isotretinoin erythromycin gel, a gel containing isotretinoin (0.05%) and erythromycin (2%), versus adapalene gel in the treatment of mild to moderate acne vulgaris. Methods A multicenter, randomized, open, parallel-controlled clinical study was conducted. A total of 192 patients with mild to moderate (Grade Ⅰ -Ⅲ ) acne vulgaris were enrolled in this study according to the grading criteria for acne severity in guidelines for the treatment of acne in China. Efficacy analysis was carried out in 169 patients and safety analysis in 190 patients. The patients were classified into trial group (n = 86) and control group (n = 83 ) to be treated with isotretinoin erythromycin gel or adapalene gel once a night for 6 weeks. Patients were evaluated at the baseline, on week 2, 4 and 6 during the treatment for the count of comedones (both open and closed), inflammatory papules and pustules, severity of acne and local or general adverse effects. Results After the start of treatment, the response rate gradually increased and severity of acne decreased in both groups. On week 6, the total response rate was 51.16% in the trial group and 40.96% in the control group (P ＞ 0.05), while a greater reduction in the count of pustules and inflammatory lesions was observed on week 4 and 6 in the trial group with a lower severity grade of acne compared with the control group (P ＜ 0.05 or 0.01 ). Adverse reactions were similar in both groups and manifested as tolerable local irritation. Conclusions The efficacy of isotretinoin erythromycin gel is similar to that of adapalene gel in the treatment of mild to moderate acne vulgaris, however, isotretinoin erythromycin gel seems superior to adapalene gel in reducing inflammatory lesions and rapidly improving severity of acne vulgaris.

Objective To study the surgical techniques of the extended subfrontal epidual approach to resect chordoma in skull base.Methods 18 cases of chordoma in skull base treated mierosurgically were analyzed retrospectively.Results Total resection were achieved in 15 patients(83%),gross resection in 3 patients(17%).There was no complication in all cases.Conclusion The microsurgery for chordoma in skull base via the extended subfrontal epidual approach is of the benefits such as clear and wide fields of vision,and minimize brain trauma.Lumber drain placement and the skull base reconstruction could improve the rate of total tumor removal and reduce complications.