Objective To explore the appropriate time to block adrenal androgens in endocrine therapy of prostate cancer.Methods An human androgen-dependent prostate carcinoma xenograft model in SCID mice was established with LNCaP cells.Firstly,the serum PSA and tumor volume of 2 groups (castrated and not castrated) were measured on the 1,4,7,10,14,17,21,28,35,42,49 and 56 day to determine the recurrent time of prostate cancer after castration.Secondly,3 different groups of castration and adrenalectomy at the same time,adrenalectomy in recurrence after castration and sham adrenalectomy in recurrent after castration,were set to measure the serum PSA and tumor volume on the 1,4,7,10,14,17,21,28,35,42,49 and 56 day.The tumor tissues of 5 groups were harvested to measure testosterone concentration,and tumor progress in these groups was compared.Results The recurrence time was 14 days in castrated group,21 days in group with castration and adrenalectomy at the same time and 35 days in group with adrenalectomy in recurrence after castration.The testosterone concentration in tumor tissues was (2.69± 0.21) pmol/g in the group with castration and adrenalectomy at the same time,and (2.16±0.13) pmol/g in the group with adrenalectomy in recurrence after castration,and the difference was significant (P＜0.05).Conclusion Compared with the therapy of castration and adrenalectomy at the same time,the therapy of adrenalectomy in recurrence after castration may have slower progress course in prostate cancer.

Objective To investigate the mechanism of body weight support treadmill training (BWSTT) and electroacupuncture (EA)for spinal cord injury. Methods 56 adult SD rats were divided into control group (n=16), EA group (n=16), BWSTT-EA group (n=16) andblank group (n=8). They were treated 3 d after operation, and assessed with Basso-Beattie-Bresnahan (BBB) scale and the brain-derived neurotrophicfactor (BDNF) was measured in injured tissue with real time immunohistochemisty assay 1 d, 7 d, 14 d, 21 d after treatment. ResultsThe score of BBB was significantly higher in the BWSTT- EA group than in control group and EA group 1 d, 7 d, 14 d, 21 d after treatment(P<0.05), as well as the expression of BDNF (P<0.05). Conclusion BWSTT and EA can promote the recovery of spinal cord injury,which may associate with the expression of BDNF in injured tissue.

In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.

Objective To study the relevance of 1iver fibrosis at Kasai procedure with age, degree of pathological changes of liver tissue, header bile ductuler proliferation and pathological feature of portal fibrous tissue in biliary atresia patients. Methods From January 2013 to June 2016, 48 biliary atresia patients accepted Kasai procedure, and liver tissue biopsy and portal fibrous tissue excision was done. Level of liver fibrosis was evaluated under microscope using Masson trichrome staining and HE staining, and extent of ductular reaction was evaluated using CKl9 immunohistochemistry staining with image analysis technology. Based on classification of Okamoto severity degree of liver fibrosis, forty eight patients were divided into two groups:low-grade liver fibrosis group (23 patients)and severe liver fibrosis group (25 patients). The relevance of age at Kasai procedure, liver pathological changes, header bile ductuler proliferation, portal fibrous tissue in volume and bile ductuler proliferation, inflammation reaction with severity degree of liver fibrosis was analyzed with SPSSl6.0 software statistically. Results Age of severe 1iver fibrosis group at Kasai procedure were 38- 89 d, and the mean age was (62.64 ± 14.92) d. Age of low-grade 1iver fibrosis group were 18- 92 d, and the mean age was (53.13 ± 16.89) d. There was significant difference (t=2.071, P=0.044). Mean number of patients with header bile ductuler proliferation at Kasai procedure in severe 1iver fibrosis group and low-grade 1iver fibrosis group were (17.28 ± 4.31) cases and (11.39 ± 4.00) cases, and there was significant difference (t=4.900, P=0.000). There was significant difference in degree of hepatocellular pathological changes at Kasai procedure between groups (χ2 =4.691, P=0.030). There were no significant differences in the volume of portal fibrous tissue in volume (t=0.276, P=0.784), portal bile ducts proliferation (t=0.53, P=0.60) and inflammation reaction (χ2=3.074, P=0.080) between groups. Conclusions There is significant relevance between the degree of 1iver fibrosis in biliary atresia patients at Kasai procedure and age, level of hepatocellular pathological change and degree of header bile ductuler proliferation , The more older the age, the more sever the hepatocellular pathological change and the bile ductuler proliferation, the more sever the liver fibrous.

Objective To analyze the characteristics and prognosis of intra-aortic balloown pump (IABP) supported percutaneous coronary intervention (PCI) in patients with Acute Coronary Syndrome (ACS) complicated with cardiogenic shock (CS).Methods 197 ACS patients complicated with CS patients received IABP supported PCI in Beijing Anzhen hospital from January 2014 to December 2015 were involved.According to the clinical results, all patients were divided into survival group and non-survival group.The clinical and laboratory parameters were compared between groups.Results Among the 197 patients enrolled, there were 162 patients in the survival group and 35 patients in the non-survival group.The mean age was (57.3±14.7) year-old, mean arterial blood pressure (MAP) on admission was (53.3±14.6) mmHg (1 mmHg=0.133 kPa).Percentage of diabetes comorbidity, cTnI level, oxygen index and MAP were significantly different between the survival and the non-survival groups (P<0.05).The symptom onset to balloon time and door-to-balloon time intervals were found delayed with significant difference in the non-survival group compared to the survival group (P<0.05).IABP improved hemodynamic parameters including blood pressure, cardiac function and oxygen index (P<0.05) in both groups.Duration of vasopressor usage, IABP implantation, percentage of invasive mechanical ventilation, length of stay in intensive care unit, acute kidney injury (AKI) and re-infarction were also significantly different between the two groups (P<0.05).Conclusions Adverse events risk is higher in ACS patients complicated with cordiogenic shock requiring IABP support for PCI.Patients with mortal outcomes are older, comorbid with diabetes mellitus and history of myocardial infarction and higher event rates of re-infarction and acute kidney injury during hospitalization.Intensive care should be implemented to reduce the incidence of adverse events.

Objective To report a case of pulmonary alveolar microlithiasis ( PAM) in Peking Union Medical Col-lege Hospital and to summarize the clinical features and genetic characters .Methods The clinical features , ima-ging results , pathology findings and SLC34 A2 gene mutation was analyzed and reported .Results The patient was a 35 years old male, presenting with cough and sputum for 10 years and worsen with short of breath for 3 weeks. Computed tomography of lung and pathology findings support the diagnose of pulmonary alveolar microlithiasis .And a heterozygous mutation c .A910 T in exon 8 of SLE34 A2 gene was discovered through genetic testing .Conclusions Since to the treatment is non-specific in this rare disease , it's significantly important to recognize this disease through early non-specific clinical features but typical imaging findings .And the finding that c .A910 T is more common in Asia population may provide us a potential target for screening and possible genetic engineering therapy .

Aim To investigate the effect of hesperidin on human lung cancer cell A549 and the possible mechanism.Methods The cell apoptosis and necrosis of A549 treated with hesperidin were measured by the Hoechst 33342/PI fluorescent dye based on microfluidic chip technology.Cell cycle and apoptosis rate were evaluated by flow cytometry(FCM).The expressions of the related genes were detected through the real-time fluorescent quantitative PCR technology(RT-PCR) including VEGF, PI3K and PTEN.The protein expressions of Bcl-2, Cyclin B1, PI3K, Akt and PTEN were detected by Western blot after hesperidin intervention.Results The proliferation of A549 cells was significantly inhibited by hesperidin in a dose-dependent manner.FCM results showed that hesperidin could not only influence the G0/G1 phase and S phase, but also promote the apoptosis of lung cancer cells.Meanwhile, the apoptosis and necrosis rate was increased from(6.7±0.6)% to(27.9±1.1)% compared with that of control group(P<0.05).From the level of molecular, the gene expressions of VEGF and PI3K were decreased, while the PTEN was increased after hesperidin stimulation.Western blot results showed that the expression of protein Bcl-2, Cyclin B1 and Akt were decreased, which all showed close relationship with cell apoptosis, cell cycle and PI3K-Akt signaling pathway.The expression of PI3K was increased, but the change of PTEN was not statistically significant compared with that of control group.Conclusion Hesperidin induces lung cancer cell apoptosis through PI3K-Akt signaling pathway, which blocks cancer cell division and destroys the balance of related protein expression.

Objective To study the effect of dexmedetomidine (DEX) on postoperative cognitive function and preoperative inflammation in the elderly patients undergoing general anesthesia. Methods 70 elderly patients undergoing general anesthesia operation were chosen and divided into observation group and control group randomly. DEX and physiological saline were applied in observation group on the basis of routine general anesthesia. The cognitive function of patients in both groups were tested by mini-mental state examination (MMSE) and the incidence rate of cognitive dysfunction (POCD) were measured at 1 day before surgery, 1 day, 3 days, 5 days, and 7 days after surgery. The level of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) were tested before anesthesia, during skin incision, rightly after operation and 1h after operation. Results MMSE scores were significantly higher and the incident rates of POCD were lower in observation group than those in control group at 1 day and 3 days after surgery (P<0.05). The levels of IL-6 and TNF-αincreased obviously during skin incision and postoperative period, and they were significantly lower in observation group (P<0.05). The levels of IL-6 and TNF-αdecreased to the levels before anesthesia in observation group, and were still much higher in control group than that of preanesthesia (P < 0.05). Conclusions DEX infusion intraoperatively may effectively decrease the incidence of early POCD, whose mechanism could be reducing inflammation response.

Objective To observe the level of autophagy induced by TRAIL in TT cell line and identify the role of autophagy in TRAIL-inducing apoptosis of TT cell line.Methods The growth inhibition of TT cells was measured by MTT assay.MDC staining was used to identify the happening of autophagy.Annexin V/PI double staining was used to analyze the apoptosis rate of TT cells by flowcytometry.The protein expression of caspase-8 and Beclin1 was detected by Western blot.Results ① The growth inhibition ratio of TT cells induced by TRAIL at the concentration of 250,500,1000 and 2000 ng/ml was (3.02 ± 1.82)％,(4.87 ± 1.45)％,(7.51 ± 1.57) ％,(12.76 ± 3.23) ％ respectively,which suggested significant resistance of TT cells to TRAIL.② MDC-labeled green light vesicles was significantly increased after the treatment of TRAIL for 48 h.③ The apoptosis rate of TT cells induced by TRAIL at the concentration of 500 ng/ml and 1000 ng/ml after the pretreat ment of 3-MA for 4 h was(17.83 ± 1.54) ％ and(27.81 ± 1.79) ％ respectively,which was significantly higher than the apoptosis rate induced by TRAIL(3.70 ± 0.34) ％,(6.55 ± 0.59) ％ alone and that induced by 3-MA(7.71 ± 0.64) ％ (t =3.282,P ＜ 0.05 ; t =7.830,P ＜ 0.01).④ The combination treatment of TRAIL and 3-MA increased the cleavage of caspase-8 and down-regulated the expression of Beclin 1.Conclusion Autophagy induced by TRAIL may contributes to the resistance of TT cells to TRAIL,which can be reversed by the inhibition of autophagy.