Male breast cancer (MBC)is one of rare malignant carcinomas,of which the pathogenesis and biological characteristics remain elusive.Recently,it has been reported that breast cancer susceptibility gene (BRCA)1 ,BRCA2,checkpoint kinase 2 (CHEK2)and partner and localizer of BRCA2 (PALB2)play important roles in the pathogenesis of MBC.Whereas the relationship between BRCA1 -interacting protein 1 (BRIP1 )and MBC is still controversial.

Objective To evaluate the therapeutic effects,acute and late side-effects of cisplatin plus 5-fluorouracil (PF) schemed chronomodulated chemotherapy combined with concurrent intensitymodulated radiotherapy(IMRT) for nasopharyngeal carcinoma.Methods A total of 48 nasopharyngeal carcinoma patients treated with chronomodulated chemotherapy plus concurrent IMRT were retrospectively studied.The radiation doses prescribed to the gross target volume GTVnx of nasopharyngeal,to the positive neck lymphnodes GTVnd,to the clinical target volume CTV1,and to CTV2 were 73.92-77.88,69.96,60.06-66.00 and 50.96-56.00 Gy respectively.The Kaplan-Meier survival analysis was used to calculate the local-regional progression-free rate.The acute and late side-effects were graded according to RTOG radiation morbidity scoring criteria.Results The complete remission (CR) rate was 41.6％(20/48) ; the partial remission (PR) rate was 47.9％ (23/48) ; the stable disease (SD) rate was 4.2％(2/48) ; and the local tumor control rate was 89.6％.Most of the patients had grade 1 to 2 acute side effects and grade 0 to 1 late side-effects.No grade 4 acute and late toxicity was observed.1,2,4-year survival rates were 93.8％,79.2％ and 64.5％,respectively.The DVH analysis showed that IMRT improved the total dose and dose per-fraction to the target volume with considerable dose reduction of the normal structures at the same time.Conclusions PF chronomodulated chemotherapy plus concurrent intensity-modulated radiotherapy for NPC could improve therapeutic effects with satisfactory tolerance of the side effects.

Aim To investage the regulatory effect of alizarin on renal interlobar arterial smooth muscle cells. Method The effect of alizarin on BKCa channels was observed by whole-cell patch clamp recording tech-nique. Results Selective BKCa channel blocker ibTX inhibited alizarin-induced outward current(P<0. 05);single smooth muscle cells were incubated in extracel-lular fluid with no Ca2+ 30 minutes, selective L-Ca2+channel blocker nimodipine, selective calcium ion che-lating agent BAPTA-AM and ryanodine inhibited the a-lizarin-induced BKCa channels current, too ( P <0. 05 ) . Conclusion Alizarin relaxes renales interlobar arterial smooth muscle via activation of L-Ca2+ channel firstly, which lead to Ca2+ flowed into cytoplam, and rising of Ca2+ in cytoplam ryanodine receptor indirect-ly, and BKCa is activated at last.

AIM:To investigate the influence and mechanisms of human pancreatic cancer tumor microenvironments on T-cell immunoglobulin mucin-3 (TIM-3) expression and function of dendritic cells (DCs).METHODS:Tumor-infiltrating dendritic cells (TIDC) and para-carcinoma tissue DCs were isolated by Ficoll-Hypaque density centrifugation from trypsinized pancreatic carcinoma tissues, and the peripheral blood mononuclear cells were isolated from pancre-atic cancer patients or healthy people.The expression of TIM-3 on DCs was detected by flow cytometry.DCs isolated from healthy people peripheral blood mononuclear cells were induced by rhGM-CSF and IL-4.The expression of TIM-3 in the DCs treated with the culture supernatants of Capan-2, SW1990 and Panc-1 pancreatic cancer cells or human skin fibroblast (Hs27) cells for 48 h, and in the DCs treated with supernatants of Capan-2 cells, anti-VEGF-R2, anti-IL-10 and EP2 re-ceptor blocking peptide were evaluated by flow cytometry.The releases of IFN-βand IL-12 in the culture supernatants of DCs pretreated with monoclonal antibody ( mAb) to TIM-3 or DNase+RNase, followed by stimulation with apoptotic Ca-pan-2 cells, were detected by ELISA.RESULTS:DCs in tumor microenvironments had higher expression of TIM-3 than the DCs from para-carcinoma tissues and pancreatic cancer patient or healthy people peripheral blood ( P<0.01 ) .TIM-3 expression in the DCs treated with the culture supernatants of Capan-2, SW1990 and Panc-1 pancreatic cancer cells for 48 h was much higher than that in Hs27 cells (P<0.05).Treatment with a combination of anti-VEGF-R2, anti-IL-10 and EP2 receptor blocking peptide largely diminished the upregulation of TIM-3 on the DCs mediated by Capan-2 cell superna-tants (P<0.05).The concentrations of IFN-βand IL-12 in the DCs with high expression level of TIM-3 were lower than those in the DCs with low TIM-3 expression level.Treatment with mAb to TIM-3 resulted in much more IFN-βand IL-12 releases (P<0.01), but DNase+RNase made this effect disappear.CONCLUSION:TIM-3 serves as a negative regula-tor of DCs innate immune responses in the pancreatic cancer microenvironments.The secretion of soluble factors to tumor microenvironment by pancreatic cancer cells, including IL-10, VEGF and PGE2 , may contribute to the regulation of TIM-3 expression.

ObjectiveTo investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better.MethodsBetween Mar 2010 to Jan 2011,11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy,target volumes were delineated based on fused CT imaging before and after IC following project determination.Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTVnx in order to ensure radical doses for the imaging tumor volume before IC,the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test.ResultsBefore and after IC,the average volumes of GTVnx were respectively 44.72 cm3 and 28.87 ( t =3.89,P =0.003 ),the average volumes of GTVnd were respectively 32.76 cm3 and 19.82 cm3 ( t =2.47,P =0.033 ),the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased ( t =2.93-4.59,all P ＜0.05).ConclusionsLANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy showes significant shrinkage of tumor volume.The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC.

Objective To explore the effect of telephone intervention on discharged patients after total hip replacement. Methods 214 participants were assigned to the intervention group including 104cases receiving 6 months of telephone intervention and the control group including 110 cases receiving routine nursing by random number table method. The intervention were taken at 1,2 week and 1,2,3,6 month after patients discharged. The outcome measurements were the self-designed questionnaire of functional exercise compliance and Harris scale at 1, 3, 6 month patients discharged. Results The scores of self-designed questionnaire of functional exercise compliance were (42.24±4.58), (38.55±5.84), (36.98±5.41) at 1, 3, 6 month discharge from hospital in the intervention group, while in the control group was (38.79 ± 5.98), (35.45 ± 6.44), (32.45 ± 6.04) respectively. There were significant between two groups, t value was 3.290, 2.567 and 4.024 respectiveliy, P<0.05. There was no significant of Harris scale′s scores between two groups when they discharged. The scores of Harris scale were (66.51±6.64), (75.30± 6.65), (89.44±4.98) at 1, 3, 6 month discharge from hospital in the intervention group, while in the control group was (61.31 ± 6.68), (70.56 ± 8.01), (81.18 ± 6.13) respectively, and it has significant between two groups, t value was 4.232, 3.509 and 8.076, P<0.05. Besides, the scores of self-designed questionnaire of functional exercise compliance were decline and the scores of Harris scale were up along the time patients discharged in two groups(P < 0.05). Conclusions Telephone as a simple, convenient, efficient tool could enhance patients functional exercise compliance and hip function after total hip replacement.

Background and purpose:To perform whole mount technique in the diagnosis of the prostate cancer could provide orientation to the specimen. Whole mount technique has great value in pathologic diagnosis and morphological research. However, limited by the specimen-making technique, shortage of equipment and heavy workload, this technique has not been generally accepted in China. The aim of this study was to evaluate the signiifcance of whole mount technique in the diagnosis of the prostate cancer by comparing the clinical and pathological variables between whole mount patients and conventional ones after radical prostatectomy (RP).Methods:A total number of 229 patients’ whole mount RP specimens were recruited in the study from Dec. 2012 to Feb. 2014. The control group included 393 patients’ specimens which underwent conventional sampling from Jan. 2010 to Jun. 2012. We compared the clinical and pathological variables between the groups, including age, preoperative PSA level, methods of diagnosis, preliminary diagnostic Gleason score, clinical T stage, postoperative Gleason score, pathological T stage, positive surgical margin, extraprostatic extension, seminal vesicle invasion and pelvic lymph node metastasis.Results:Two groups shared similar preoperative parameters. Also there was no signiifcant difference between the whole mount and the conventional sampling groups in postoperative Gleason score, pathological T stage, extraprostatic extension and pelvic lymph node metastasis. However, positive surgical margin and seminal vesicle invasion rates were much higher in the whole mount group than the control one and both of the differences reached statistical signiifcance (26.2%vs 17.6%, 23.1%vs 17.0%;P=0.010, 0.025)Conclusion:After compared the clinical and pathological variables, we could conclude that whole mount technique has prevalence in the diagnosis of the positive surgical margin and seminal vesicle invasion compared with the conventional sampling technique. Thus, whole mount technique should be strongly recommended in the diagnosis of prostate cancer.

Objective To evaluate the differences of toxicities,therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin (DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods Seventy patients with biopsydiagnosed stages Ⅲ and Ⅳ B NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital.The TPF chemotherapy regimen was administered as follows:The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day,the 5-FU with 750 mg · m-2 · d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h).The induction chemotherapy was 21 days per cycle,for two cycles.After that all patients were randomly treated with 2-3 cycles of sinusoidal chronomodulated infusion or flat intermittent constant rate infusion of DDP with IMRT.Using a multi-channel programmed pump,the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one,repeated every 3 weeks for 2-3 cycles.DDP was administered from 10:00 am to 10:00 pm.Concurrent radiotherapy regimen was administered as follows:GTVnx 69.96-73.92 Gy/33 f,PTVnx 69.96 Gy/33 f,PTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f.Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression:leukocytes,and then nausea,oral mucositis and hemoglobin.The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression:hemoglobin,leukocytes,and then nausea,oral mucositis.No significant differences were observed for toxicities(P ＞ 0.05).After concurrent chemoradiotherapy,the complete response rate (CR),partial response rate (PR),stable disease rate(SD),progressive disease rate (PD) and overall response rate (ORR) were 11.4％,85.7％,2.9％,0 and 97.1％ in the group of sinusoidal chrono-modulated infusion.The CR,PR,SD,PD,ORR in the group of flat intermittent constant rate infusion were 22.9％,74.2％,2.9％,0,97.1％,respectively.However,there was no significant differences of effect in the two Arms (P ＞ 0.05).For sinusoidal ehrono-modulated infusion and flat intermittent infusion group,the 2-year overall survival(OS) were 82.9％ and 94.3％ respectively,the 2-year progression-free survival(PFS) were 77.1％,91.4％ respectively,and the 2-year distant metastasis free survival (DMFS) were 82.9％,91.4％ respectively.The value of CD3 + in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy (Z =3.254,P ＜ 0.05).The value of CD4 +,CD8 +,CD16 + CD56 +,CD19 +,and CD4 +/CD8 + had no differences in two Arms (P ＞ 0.05).Conclusions No significance differences on the toxicities,therapeutic efficacy and survival were observed between the two groups,but immune function might be improved in the sinusoidal chrono-modulated infusion group.

Objective To investigate the effect of alizarin on BKCa channel beta subunit and electrophysiological characteristics in interlobar renal artery of SHR.Methods Tail artery pressure measurement instrument,pressure myograph system,whole cell patch clamp technique and Western blot were used to measure the change of systolic pressure of SHR,renal interlobar arterial diameter,single vascular smooth muscle cell electrophysiological characteristics and expression of the BKCa channel beta subunit before and after alizarin intervention,respectively.Results (1) SHR systolic pressure was decreased after alizarin intervention (P ＜ 0.01).(2) ibTX inhibited alizarin-mediated renal interlobar arterial relaxation (P ＜ 0.01).(3) Alizarin enhanced BKCa channel-mediated outward currents (P ＜ 0.05).(4) Alizarin up-regulated BKCa channel beta subunits after alizarin intervention (P ＜ 0.01).Conclusion Alizarin reduced SHR systolic pressure and relaxed interlobar renal artery by enhancement BKCa currents via mediation of the function of beta subunits.

Objective To establish and evaluate anxiety and depression like behaviors in MPTP-in-duced chronic Parkinsonism cynomolgus monkey. Methods Ten cynomolgus monkeys ( 15. 0 ± 1. 5 years old) were divided into normal group and MPTP-induced parkinsonism group(PD group),5 animals in each group. The behavioral methods for evaluating the anxiety and depression like behaviors in non-human prima-tes included Apathy Feeding Test (AFT),Human Intruder Test (HIT),Novel Fruit Test (NFT) and Preda-tor Confrontation Test (PCT). The changes in behavioral indicators between the two groups were analyzed. Results In AFT,PD group spent more time in observing food on both sides,and significantly higher than that in normal group (left:0. 73(0. 49) s,0. 50(0. 28) s,P<0. 01;right:0. 75(0. 60) s,0. 53(0. 16) s,P<0. 01),moreover PD group had limb disorder on the right side,and spent more time in taking food which sig-nificantly more than normal group (0. 83(0. 20) s,0. 57(0. 14) s,P<0. 01). In HIT,PD group moved and stood better than that in normal group,and occurred abnormal behaviors,such as climbed,grinded,scratched and shook cages (P>0. 05),while normal group spent more time in the back of cage during Stare and Back period( Stare:0(64. 70)s,111. 27(38. 94)s,P=0. 033; Back:0(25. 84) s,120(114. 69) s; H=17. 397). Finally,PD group had lower take-up rate and higher withdrawal rate than normal group in PCT(P>0. 05). Conclusion This study establishes a multi-angle evaluation of behavioral methods for anxiety and depres-sion in non-human primates. The analysis confirmed that chronic Parkinson's disease cynomolgus monkeys has different degrees of anxiety and depression,which provides a new method for preclinical intervention in Parkinson's disease.