Objective To analyze the surgical technique of extraperitoneal laparoseopic radical prostatectomy with neurovascular bundle preservation and its effect on micturition control and sexual function in patients with prostate cancer. Methods Twenty-two patients with a median age of 66. 9 years underwent extraperitoneal laparoscopic radical prostatectomy with neurovascular bundle preservation from October 2005 to March 2009 in our hospital and Shanghai Changzheng hospital. All patients had no erectile dysfunction. According to the pathology, there were 2 cases of PIN high grade, 4 cases of Tla-b, 9 cases of Tlc, 4 cases of T2a-b, 2 cases of T2e and 1 case of T3a. Results All operation were successful and no case was conversed to open surgery. The average operation time was 225 min and the mean blood loss was 850ml. The amount of blood loss in 1 case was 1200 ml because of injuring deep dorsal vein of penis. 4 cases received blood transfusion, gatheters of all patients were removed 2 weeks after operation, and three cases with mild incontinence regained continence of urine after 6 months follow-up. No patient occurred postoperative vesicourethral anastomotic leakage of urine. The surgical margin of 1 case was positive. No biochemical index of prostatl cancer recurred during postoperative follow-up of 10-24 months (with an average of 16 months). 20 cases had sexual function recovery after operation. Conclusions The extraperitoneal laparoscopie radical prostatectomy with neurovascular bundle preservation for prostate cancer is a safe and effective treatment method with less bleeding, small damage and less complications. It can guarantee the maximum of micturition control and sexual function, which is worthy to be popularized in the clinic.

Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.

OBJECTIVE: To prepare zedoary turmeric oil compound liposomes (ZTOC-LPS) and evaluate its quality.METHODS: The preparation method of liposome, the addition amount of soybean phosphatidylcholine (SPC), ratio of SPC to cholesterol (CH) in lipid, drug-lipid ratio of zedoary turmeric oil (ZTO), drug-lipid ratio of tretinoin in formulation, and water bath temperature were screened using encapsulation efficiency and drug-loading amount of ZTO (represented by germacrone) and tretinoin as investigation indexes. Quality evaluation and primary stability investigation were conducted for liposomes prepared by optimal preparation technology. RESULTS: The optimal preparation method was ethanol injection method; The optimal preparation technology were SPC 4 mg in 1 mL lipid, the mass ratio of SPC to CH 3:1, the ratio of ZTO to lipid 1:9, the ratio of tretinoin to lipid 1:70, water bath temperature of 55 ℃. Encapsulation efficiencies of ZTO and tretinoin were (64. 63 ± 1. 00)％ and (90. 33 土 0. 72)％ in 3 batches of ZTOC-LPS, respectively. Drug-loading amount of ZTO and tretinoin were (9. 09 ± 0. 14)％ and (1. 43 ± 0. 02)％, respectively. Particle size was (257. 41 ± 7. 58) nm, Zeta potential was (-38. 77 ± 0. 81) mV,PDI was 0. 10 ± 0. 04; the results of centrifugal acceleration test showed that the liposomes had good physical stability. No obvious change was found in each investigation index of ZTOC-LPS that stored at (4 ± 2) ℃ for 1 month. CONCLUSIONS: Established preparation technology is simple and feasible, the quality of the prepared ZTOC-LPS conforms to the requirements, and it can provide reference for the following research of ZTOC-LPS.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.