OBJECTIVETo investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines.

METHODSWe treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively.

RESULTSThe proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P <0.05). At 24 hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/- 1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control group (P <0.05) , and the DU145 cells showed an even higher sensitivity to bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay manifested that the apoptosis rates of DU145 and LNCaP cells after treated with 20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% , respectively, significantly higher

CONCLUSIONBortezomib enhances the sensitivity of than those after treated with either bortezomib or NK cells alone (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of current cancer therapies, and it is more efficacious for androgen-independent prostate cancer.

Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; drug effects ; Humans ; Killer Cells, Natural ; drug effects ; Male ; Prostatic Neoplasms ; pathology ; Pyrazines ; pharmacology

Objective To explore the clinical efficacy and the influence of one-port,three-port and four-port laparoscopic cholecystectomy on quality of life in patients with laparoscopic cholecystectomy.Methods The clinical data of 60 patients with laparoscopic cholecystectomy were reviewed,and to compare the general condition,the influence of postoperative recovery and complications,disease of digestive system and the quality of life index in patients treated by one-port laparoscopic cholecystectomy(one-port group),three-port laparoscopic cholecystectomy(three-port group) and four-port laparoscopic cholecystectomy(four-port group).Results Although the time of operation in oneport group was longer than the other two groups (t =3.82,P ＜ 0.05 ; t =4.04,P ＜ 0.05),there were significant differ ences in the volume of the inoperative blood loss,hospital stay time,hospital costs in one-port group compared with the other two groups (P ＜ 0.05).There was no difference among the three groups in the incidence of postoperative complications (P ＞ 0.05).And when leaving hospital,the score of all dimensionalitis in the scale of Gastrointestinal quality of life index (CIQLI),containing the state of physiological function,state of daily life and social activities,psychological emotional state and quality of life of the total score were all higher than those in the other two groups (t =2.22,1.87,2.31,2.43,all P ＜ 0.05),and there was no difference between three-port group and four-port group(P ＞ 0.05).Conclusion Compared with the three-port laparoscopic cholecystectomy and four-port laparoscopic cholecystectomy,one-port laparoscopic cholecystectomy can reduce the inoperative blood loss,shorten hospitalization time and reduce their fee in hospital,and it also can effectively improve patients'quality of life,restore the patients'normal work and life in the shortest possible time.

Objective To examine the circulating glucose and body weight in the transgenic MKR mouse model who expressed dominant-negative IGF-1 receptor and insulin receptor in skeletal muscle leading to systemic insulin resistance and diabetes. Methods MKR mice were genotyped by PCR analysis of tail DNA.And in these mice we examined the circulating glucose and body weight once a week from 1 to 16 weeks of age, and the circulating insulin and glucose tolerance at age of two-month-old by using C57 mice as controls. Results The descendents of MKR mice kept hereditary feature. And these mice had hyperglycaemia from 3 weeks of age,and an increasing body weight slowly(P

[Objective] To study the inhibitory effect of bcl-2 antisense oligonucleotide(ASODN)combined with radiation on lung carcinoma cells NCI-H446.[Method]The cultured NCI-H446 lung carcinoma cells were divided into 5 groups:control,pure radiation,nonsense+radiation,lipofectin+radiation,ASODN+radiation.Every group except for control were assayed by MTT on the inhibition rates,24h,48h,72h after 10Gy irradiation respectively.[Results]The inhibitions of lung carcinoma cells NCI-H446 were observed in ASODN+radiation,lipofectin+radiation,nonsense+radiation and pure radiation groups.The differences between the ASODN+radiation group and the other three groups were significant(P

The significance and method of green chemistry teaching are expounded in detail during the course of medical chemistry experiment,and a new experiment system of green chemistry suiting with medicine is designed in the paper.

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

Objective To study the expression of microtubule-associated protein-2 (MAP-2) in the CA3 region of the hippocampus and any effect of acupuncture combined with exercise training on the recovery of learning and memory after experimental cerebral infarction.Methods Eighty Wistar rats were randomly divided into a sham-operation group (n = 8 ) and an operation group (n = 72 ) subdivided randomly and equally into a model group, an exercisetraining group and an acupuncture plus exercise training group, with 24 rats in each group. After right middle cerebral artery occlusion or a mock operation, the expression of MAP-2 in the CA3 region of the hippocampus was detected with immunohistochemistry 1, 3 and 5 weeks after the operation. Learning and memory function was assessed at the 5th week post operation.Results MAP-2- positive fibers were arranged in an orderly way and distributed densely in the shamoperation group. After cerebral infarction, number of MAP-2 positive neurons and dendrite fibers decreased in the CA3 region of the affected side. A week after the operation, MAP-2 positive fibers had increased significantly in the acupuncture plus exercise group compared with the model group and the exercise group. At the 3rd and 5th week post operation, expression of MAP-2 and optical density had increased significantly compared with the model group and the exercise training group. At the 5th week post operation, Y maze discrimination and learning tests showed that learning and memory had improved significantly more in the acupuncture plus exercise training group compared with the model group and the exercise training group.Conclusions Exercise training combined with acupuncture can promote changes in dendritic plasticity and increase MAP-2 expression in the CA3 region after cerebral infarction. This may be correlated positively with the recovery of learning and memory after cerebral infarction, at least in rats.

Melanin is a kind of biopolymer, composed of a complex quinine/indole-quinone derived mixture which is produced in melanocytes from tyrosine. More than 100 genes related to melanin deposition have been found in mouse. Slc24a5 (solute carrier family 24, member 5) is a novel gene first cloned in zebrafish. And it has been confirmed that the Slc24a5 is involved in controlling the melanin deposition in zebrafish. Here the full length of the chicken slc24a5 mRNA sequence, its expression profile and a discussion of its relationship to melanin deposition in chicken were reported. Chicken Slc254a5 has a CDS of 1 269bp, predicting a protein of 423 amino acids which is about 80 amino acids shorter than in human and mouse. It has 9 exons and 8 introns and spans more than 1lkb of genome sequence. The quantitative real-time PCR confirmed that the chicken Slc24a5 was highly expressed in the eye of White Leghorn and Beijing Fatty Chickens, and in the eye, skin and muscle of Silky. The relative expression in Silky eye is more than two times that of White Leghorn. The relative expression in Silky skin is about 70 times that of White Leghorn and about 15 times that of Beijing Fatty Chickens. The relative expression in Silky muscle is about 15 times that of White Leghorn and about 3 times that of Beijing Fatty Chickens. And the expression result is in accordance with the melanocyte and melanin deposition in these tissues.

BACKGROUND: Delirium is an acute organic brain syndrome caused by various reasons, and it is common in elderly patients. Antipsychotics treatment is an important method to control delirium.OBJECTIVE: To observe the efficacy of new antipsychotic agent of olanzapine and the traditional antipsychotic agent of haloperidol in treating senile delirium.DESIGN: A randomized controlled observation. SETTING: Mental Health Center, the First Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 175 inpatients with senile delirium were selected from the First Affiliated Hospital of Chongqing University of Medical Sciences from September 2001 to September 2003, they were randomly divided into olanzapine treatment group (n=74), haloperidol treatment group (n=72) and a control group(n=29). There were 111 males (63.4%) and 64 females (36.6%). Delirium had occurred for a duration of 30 minutes to 17 days, with an average of (3.02±2.71) days. The enrolled patients were classified according to the etiological factors of delirium: metabolic (n=68), toxic (n=47), structural (n=25) and infectious (n=35).METHODS: Different treatments were used in different groups. Control group (n=29): The patients were only given somatic treatment aiming at delirium, and not any drug for central nervous system was used. Olanzapine group (n=74): Besides the somatic treatment aiming at delirium, the patients were given olanzapine (Zyprexa, produced by Eli Lilly and Company,5 mg/tablet) taken orally or sublingually (fasted patients), the initial dosage was 1.25-2.5 mg per day, and then adjusted to 1.25-20 mg per day. Haloperidol group (n=72): Besides the somatic treatment aiming at delirium, they were treated with intramuscular injection of haloperidol (2.5-10 mg per day). The effects were prospectively observed for 1 week.The scores were observed before enrollment and at 1-7 days respectively,the severity of mental disorder and amelioration were evaluated by the clinical global impression scale-severity of illness (CGI-SI) and global improvement item of clinical global impression scale (CGI-GI). The dosage and time of administration was taken as the dosage and time to take effect when the CGI-SI baseline scores decreased by more than 1 point.MAIN OUTCOME MEASURES: The severity of mental disorder and amelioration were observed.RESULTS: ① The scores of CGI-SI after treatment were significantly decreased in the olanzapine group, haloperidol group and control group, and there were significant differences (P ＜ 0.01). ② The rates of marked effect in the three groups were 82.4%, 87.5% and 31.0%, respectively, and those in the two treatment groups were significantly different from that in the control group (P ＜ 0.01). ③ Both olanzapine and haloperidol began to take effect at small dosages, and it was the fasted in the olanzapine group, followed by the haloperidol group, and slowest in the control group.CONCLUSION: Olanzapine and haloperidol have similar effects in treating senile delirium. However, olanzapine is faster to take effect than haloperidol.

ObjectiveTo study the technique and therapeutic effect of percutaneous cannulate screw fixation to treat the traumatic diastasis of the pubic symphysis.MethodsFrom February 2003 to December 2010,46 patients (27 men and 19 women,mean age of 34.6 years) with unstable pelvic fractures and diastasis of the pubic symphysis were admitted.All the patients were treated by closed reduction and percutaneous cannulate screw fixation of the symphysis pubis.Then to complete the fixation of posterior ring,by percutaneous screw inserted through the sacroiliac joint or posterior iliac wing.According to Tile's classification,the patients were classified into type B1.1 in 4 cases,B1.2 in 7,B2 in 2,B3 in 2,C1.1 in 7,C1.2 in 7,C1.3 in 10,C2 in 5 and C3 in 2.All patients were performed posterior ring fixation except 4 cases of type B1.1.Anteroposterior,inlet and outlet X-ray radiographs and CT scans of the pelvis were taken preoperatively to evaluate the stability and deformities,and after surgery the plain radiographs and CT scans were taken to evaluate the reduction and the location of screws.ResultsThe average operative time was 45 min (range,15-65 min),and the average intraoperative blood loss was 25 ml (range,15-50 ml).Each patient was inserted one screw in the symphysis pubis.Thirty-five patients underwent postoperative pelvic CT scan and 3screws of them penetrated the wall of symphysis pubis.The average follow-up period was 23.5 months (range,5-48 months).In the follow-up period,no infection and displacement were found.The last follow-up result:according to Matta and Tornetta's standard,the result was excellent in 43 cases and good in 3.Among all patients,31 cases (67.39％) had returned to their original works,6 were to give up their original works as complicating injuries; 28 cases had no pain,13 cases had slight pain of the symphysis pubis while to make an effort,5 cases had pain of sacroiliac joint.There were no iatrogenic injury of nerve.ConclusionClosed reduction and percutaneous cannulate screw fixation of the traumatic diastasis of the pubic symphysis is a safe,feasible and easy manipulated method.The operative injuries is small and the clinical outcome is satisfactory.