Numb,one of the important cell fate determinants,plays a key role in regulation of nerve system development,and it is closely related to the occurrence of tumors.It is proven that Numb is implicated in the processes of occurrence,invasion and metastasis of tumors through regulating the way of cell division,cell polarity,epithelial-mesenchymal transitions and several signal pathways,e.g.,Notch,Hh,p53.The expression levels of Numb in cells are related to the malignant degree and prognosis of tumors.It is vital to explore the role of Numb in tumors for treating tumors at the standpoint of Numb.

BACKGROUND: Nitric oxide synthase(NOS) is the key factor for the synthesis of nitric oxide (NO) . Because NO combines with oxygen, hemoglobin and other substances in vivo easily and deactivates quickly, and it is not exactly determined, so determining the activity of NOS is the important link for further studying the pathogenesis of NO in cerebral ischemia/reperfusion (I/R)injury.OBJECTIVE: To study the effect of different types of NOS in the process of cerebral I/R injury.DESIGN: Randomized and controlled animal experiment.SETTING: Instituteof Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: This experiment was carried out in the Shandong Key Laboratory of Prevention and Treatment for Encephalopathy from May to December 2005. Twenty-eight adult healthy male Wistar rats, of clean grade, weighing from 220 to 260 g, were provided by the Experimental Animal Center of Shandong University. The involved rats were randomly divided into sham-operation group (n =4) and cerebral ischemia group (n =24). Six time points were set in cerebral ischemia group: ischemia 1 hour reperfusion 6 hours, 12 hours, 1 day, 3 days, 7 days and 14 days, 4 rats at each time point.METHODS: Rat models of middle cerebral artery occlusion/reperfusion were established by suture-occluded method through inserting a suture into the left internal-external carotid artery. The expressions of different types of NOS at different time points after cerebral I/R were detected by immunohistochemical technique.MAIN OUTCOME MEASURES: ①Toluidine blue-stained two groups of nerve cells; ② The expression and distribution of neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS(iNOS) at different time points.RESULTS: ①Karyopyknosis and cell debris appeared in the nerve cells of the injured region of cerebral ischemia group,and there were no significant differences of cells among different time points. ② Six hours after reperfusion, the expressions of nNOS, eNOS and iNOS were found in the neurons of brain tissue and increased with the elongation of time of reperfusion. The regions in which different types of NOS in neurons of brain tissue were expressed were cortical area and corpora striata. nNOS and iNOS were highly expressed within 12 hours to 7 days after reperfusion in the brain, and eNOS was highly expressed within a short time period, i.e. 6 hours to 3 days after reperfusion. eNOS expression increasing and decreasing occurred earlier than nNOS and iNOS. But the expressions of three kinds of NOS all reached peak on the first day after reperfusion. The changing tendencies of the expression of three kinds of NOS in the cortical area and corpora striata were the same basically.CONCLUSION: After cerebral I/R injury, the high expression of eNOS occurs early and lasts for a short time, while that of nNOS and iNOS occurs late and lasts for a long time.

Community rehabilitation of cardiovascular disease is of great significance. Exercise therapy of cardiovascular disease in communities is necessary and feasible. At present, the main problems China faced to carry out community exercise therapy of cardiovascular disease include: cardiovascular patients with a weak sense of community exercise therapy, lack of professional rehabilitation personnel, inadequate community-based exercise therapy practice and lack of community rehabilitation funding. To solve above problems, we should strengthen the community exercise therapy practice of cardiovascular disease, and promote the cooperation between community rehabilitation and hospital rehabilitation. In all, comprehensive efforts should be made in order to solve the problems.

Objective To investigate the effect of high mobility group box chromosomal protein 1 (HMGB1) knockdown on improving renal function and decreasing cell proliferation of glomeruli in lupus nephritis (LN) MRL/Faslpr mice.Methods Twenty-four MRL/Faslpr mice were randomly divided into 3 groups:LN model group,shHMGB1 group and empty plasmid group.Besides,eight MRL/MpJ mice,age and mass matched to the MRL/Faslpr mice,were chosen as normal control group (shNC group).Electroporation technology was used for in vivo transfection in treatment group.shHMGB1 group and empty plasmid group were transfected by electroporation technology for shHMGB1 plasmids and empty plasmid,LN model group and normal control group were transfected only with saline.Automatic biochemical analyzer was used to detect serum urea nitrogen (BUN) and creatinine (Scr) levels and 24 h urinary protein (UP) was tested.HE staining was used to detect the pathological change of renal tissues; real-time PCR,immunofluorence staining and Western blotting were used to detect the mRNA and protein expression of HMGB1 and PCNA.Results (1) The HMGB1 mRNA and protein expression in LN group increased compared with those in control group,HMGB1 mRNA and protein expression in shHMGB1 group reduced compared with those in LN model group (all P ＜ 0.05).(2) 24 h UP of MRL/Faslpr mice in shHMGB1 group significantly reduced compared with those in LN group (P ＜ 0.05).(3) Immunofluorence and Western blotting showed that positive signal of proliferating cell nuclear antigen (PCNA) was mainly located in nuclei,PCNA mRNA and protein in glomeruli of LN model group increased compared with those of control mice (P ＜ 0.05).Interestingly,PCNA expression in glomeruli of shHMGB1 group remarkably reduced (P ＜ 0.05).Conclusions shHMGB1 significantly improves renal function and decreases cell proliferation of glomeruli in LN MRL/Faslpr mice.

Objective To assess the effect and influencing factors on 131I treatment for cervical lymph node metastasis (LNM) after operation in patients with PTC.Methods PTC patients (n =117;45 males,72 females;average age (45.17± 15.50) years) with postoperative cervical LNM from January 2010 to December 2014 were analyzed retrospectively.LNM was diagnosed by surgical pathology,imaging results and clinical follow-up.Single factor analysis was performed in age,gender,operation mode,TNM stage,131I treatment time and other factors.The results for 131I treatment effect included CR,PR,NC.Two-sample t test and x2 test were used.Results Among the 117 PTC patients with postoperative LNM,53 (45.3％) cases had non-131 I-avid metastasis.Fifty of the 64 (54.7％) patients with 131I-avid metastasis were treated with 131I.Nineteen patients (38.0％) achieved CR,22 (44.0％) achieved PR,and 9 (18.0％) showed invalid results.Fourteen of the 64 patients underwent another cervical lymph node dissection.Nine patients achieved CR,5 patients achieved PR,and 4 PR patients were then treated with 131I and finally achieved CR.Single factor analysis showed that the influencing factors of non-131I-avid lymph node included patients' age (t =3.459),serum Tg level (x2 =6.698) and metastasis with 1s F-FDG uptake (x2 =26.928;all P＜0.05).The influencing factors of 131I treatment effect included lymph node dissection procedure (x2 =6.487),unilateral or bilateral lesion (x2=5.187) and LNM size (x2=8.099;all P＜0.05).Conclusions 131I treatment is ineffective for nearly 50％ of patients with non-131I-avid LNM.The influencing factors of 131I treatment effect include the lymph node dissection procedure,unilateral or bilateral lesions and LNM size.

Objective:Three-dimensional (3D) ultrasound (US) is increasingly being introduced in the clinic,both for diagnostics and image guidance.Although dedicated 3D US probes exist,because of its expensive cost,3D US can also be acquired with the still frequently used two-dimensional (2D) US probes.Methods:Obtaining 3D volumes with 2D US probes is a two-step process.First,a positioning sensor must be attached to the probe for 2D image matching;second,a reconstruction of a 3D volume can be performed into a regular voxel grid.Results:This paper presents a way to realize the 3D US in irled-based Image Guided Radiotherapy using a homemade 2D US.Conclusions:The experiments demonstrate a method of saving costs and having advantages in clinic application.

Objective To investigate the relationship of expressions of cylooxygenase-2(COX-2) and hypoxia-inducible factor-1?(HIF-1?) in hepatocelluar carcinoma(HCC) and the possible antineoplastic mechanism of selective COX-2 inhibitor.Methods The expressions of COX-2 and HIF-1? in 53 cases of HCC tissues were detected immunohistochemically.Western blot was employed to evaluate the effects of variant concentration of COX-2 inhibitor meloxicam on expression of HIF-1? in Cobaltchloride-stimulated SMMC-7721 cell.Results Of 53 tumor tissues,the expression of COX-2 was 22/53(41.5%) strongly positive stained,11/53(20.8%) positive stained,and 20/53(37.7%) negative stained.Meanwhile the expression of HIF-1? was 18/53(34.0%) strongly positive stained,18/53(34.0%)positive stained,17/53((32.1%)) negative stained.The expression of COX-2 was correlated positively with HIF-1? in HCC(r=0.440,P

Objective To observe the effect of daidzein on extracellular matrix of uremic rats and to discuss its mechanism.Methods Uremic rat model were established by 5/6 nephrectomized. Model rats were devided into daidzein group, control group. Rats with sham-operation were regarded as the normal control. At time of baseline, 4th and 8th week after operation, urinary protein and biochemical detection were measured. The pathologic changes, fibronectin (FN) and typeⅣcollagen (ColⅣ) were investigated at 8th week. The Western-Blot and RT-PCR were used to measure protein expression and mRNA transcription of TGF-β1. Results At 8th week after operation, the urinary protein (12.35 ± 2.13 mg/24 hvs. 19.93 ± 3.19 mg/24 h), serum urea (10.11 ± 0.65 mmol/Lvs.12.09 ± 0.78 mmol/L) and creatinine (68.10 ± 2.51μmol/Lvs.77.63 ± 3.20μmol/L) in the daidzein group decreased significantly than those in the control group (P<0.01). The deposition of ColⅣ (16.33% ± 2.14%vs. 24.68% ± 3.97%) and FN (19.17 ± 2.68 vs. 29.35 ± 4.15) in the daidzein group decreased significantly than those in the control group (P<0.01). Compared with control group, the pathological lesion in the daidzein group was less serious. The mRNA transcription (0.37 ± 0.06vs. 0.64 ± 0.08) and protein expression of TGF-β1 (0.28 ± 0.09vs. 1.40 ± 0.13) in the daidzein group were attenuated significantly than those in the control group (P<0.05). ConclusionsDaidzein had a beneficial effect on uremic rats. It may be associated with a decrease of extracellular matrix accumulation.

Objective To investigate the effect of genistein on deposition of extracellular matrix(ECM) in uremic rats and its mechanism.Methods The uremic rat model was established by 5/6 nephrectomy.The model rats were divided into the genistein group(G) and control group (C).The sham-operation group served as the normal control(S).Urinary protein and biochemical indexes before operation,at postoperative 4,8 weeks were measured in various groups.The pathologic changes of renal tissue were observed.The glomerular sclerosis index(GSI) was evaluated by the semi-quantitative method.fibronectin(FN) and type Ⅳ collagen (ColⅣ) deposition situation were detected by using the immunohistochemical method.Western blot and RT-PCR were used to measure the protein expression and mRNA transcription of TGF-β1.Results Comparing postoperative 4 weeks with the group C,the urinary protein excretion amount was decreased[(11.63 ± 2.07) mg/d vs.(19.93 ± 3.19) mg/d,all P＜ 0.01],serum urea nitrogen and creatinine levels of the group G were decreased[(9.39±0.59)mmol/L vs.(12.09±0.78)mmol/L,(65.11±3.79)mmol/L vs.(77.63±3.20)μmol/L,all P＜0.01].Until postoperative 8 weeks,the urinary protein excretion amount was decreased and the decrease of serum urea nitrogen and creatinine levels was more obvious.The deposition of ColⅣ and FN in renal glomerulus was lower than that of the control group[(17.30±1.96)％ vs.(24.68±3.97)％;(18.26±2.31)％ vs.(29.35±4.15)％,all P＜ 0.01].Glomerular sclerosis was significantly alleviated.The TGF-β1mRNA and protein expression were attenuated (P＜0.05).Conclusion Genistein can reduce the deposition of ECM in uremic rats and has a protective effect on kidney.

OBJECTIVE:To investigate the efficacy and safety of Xiaojin pill combined with docetaxel,epirubicin and cyclo-phosphamide in the treatment of breast cancer in stage Ⅲ and its effect on immune functions. METHODS:102 patients with breast cancer in stage Ⅲ were randomly divided into control group (51 cases) and observation group(51 cases). All patients were given symptomatic treatments as hydration,alkalization and antiemetic treatments in the duration of chemotherapy,and were given conven-tional treatments as 0.75 mg Dexamethasome oral tablets in 12 and 6 hours before the chemotherapy lespectively. Control group was given 75 mg/m2 Docetaxel injection,d1,intravenous infusion+60 mg/m2 Epirubicin hyclrochloride for injection,d1,intravenous in-fusion+600 mg/m2 Cyclophosphamide for injection,d1,intravenous infusion;observation group was additionally given 6 g Xiaojin pill,orally,twice a day. 21 d was regarded as a treatment course. Short-term clinical efficacy,immunoglobulin,T lymphocyte sub-sets(CD4+/CD3+,CD8+/CD3+,CD4+/CD8+)and the incidence of adverse reactions before and after chemotherapy in 2 groups after 2 courses were observed. RESULTS:There were no significant differences in the short-term effective rate and incidence of adverse reactions between 2 groups (P>0.05). Before chemotherapy,there were no significant differences in the immunoglobulin and T lymphocyte subsets between 2 groups(P>0.05). After chemotherapy,immunoglobulin levels in 2 groups were significantly lower than before,the differences were statistically significant (P<0.05);but there were no significant differences between 2 groups (P>0.05);CD4+/CD3+,CD8+/CD3+,CD4+/CD8+ in control group and CD8+/CD3+ in observation group were significantly lower than before,and CD4+/CD3+ and CD4+/CD8+ in observation group were higher than control group,the differences were statistically significant (P<0.05),but there was no significant difference in the CD8+/CD3+ between 2 groups (P>0.05). CONCLUSIONS:Based on the conventional treatment,Xiaojin pill combined with docetaxel,epirubicin and cyclophosphamide shows significant effi-cacy in the treatment of breast cancer in stageⅢ,and can improve immune functions,with good safety.