Objective To investigate the effect of bortezomib on proliferation and apoptosis of pancreatic cancer cell lines BxPC3,SW1990 and explore possible mechanisms of bortezomib's killing effect on cancer cells.Methods BxPC3,SW1990 cells were treated by using 1,10,50,100,500 nmol/L and 1,10 μmol/L of bortezomib,and cells without bortezomib treatment were considered as control group.The cell proliferation was determined by MTF assay,and apoptosis was determined by flow cytometry.Bak,Bax,Bcl2,Bcl-xl,survivin mRNA expressions were measured by RT-PCR,and Western blot was applied to determine the expressions of pro-caspase-3,cleaved-caspase-3,Bax,Bcl-2,surviving protein.Results When bortezomib concentration was higher than 50 nmol/L,it inhibited the proliferation of two cell lines in a dose and time-dependent manner.And with the same treatment the rate of proliferation inhibition of BxPC3 cells by bortezomib was greater than that of SW1990 cells,and the difference between the two cell lines was statistically significant (P ＜0.05).Apoptosis rates in the groups of BxPC-3 and SW1990 cells treated by 100 nmol/L bortezomib were (22.56 ± 4.23) ％ and (12.71 ± 2.23) ％,which were significantly higher than those in control group (2.15 ± 0.47) ％ and (2.32 ± 0.54) ％,P ＜ 0.05).In addition,apoptosis rate of BxPC3 cells was significantly higher than that of SW1990 cells (P＜0.05).Bak mRNA expression of BxPC3 and SW1990 cells after 100 nmol/L bortezomib treatment were not significantly changed,but the expression of Bax mRNA and protein was significantly increased (P ＜0.05).Bcl-2 mRNA and protein,as well as Bcl-xl mRNA expressions was significantly decreased (P ＜0.05).The expression of survivin mRNA and protein in BxPC3 cells were decreased,but were increased in SW1990 cells(P ＜0.05).The expression of pro-caspase-3 protein in the two cell lines was decreased,while the expression of cleaved-caspase-3 protein was increased (P ＜0.05).Conclusions Bortezomib can inhibit the proliferation of pancreatic cancer cell Iines BxPC-3 and SW1990 and induce apoptosis,and the effect on BxPC3 cells is more than that on SW1990 cells.The mechanism may depend on activation of the mitochondrial pathway of apoptosis,and be related to survivin-involved drug-resistance.

Objective To explore the roles and related mechanisms of Protein Phosphatase 2A(PP2A) in cognitive dysfunction after the chronic cerebral ischemia.Methods 70 male Sprague Dawley rats in clean degree were divided into sham group,chronic cerebral ischemia group (Bilateral carotid arteries occlusion,2VO),and chronic cerebral ischemia group with PP2A activation group(2VO+aPP2A).The rats were injected intraperitoneally with 1.88 μmol/ml sodium selenate(15 μmol · kg-1 · d-1) or equal volume of saline for 4 weeks.After one month,the chronic cerebral ischemia models were reproduced by the occlusion of bilateral common caroid artery.Then the abilities of learning and memory were tested by Morris water maze,electrophysiological indices were recorded to analyze the LTP changes,and destribution of synaptic vesicles was observed by electron microscope.Results Morris water maze test showed that the 2VO group had significantly longer latent time than sham group in searching platform(P＜0.05),and the 2VO+aPP2A group had dramatically shorter latent time (P＜0.01) than that of 2VO group.Then removing platform to test the rats memory,the data showed that 2VO group spent markedly longer time than sham group to reach the location of the former platform (sham group:(14.50±1.98)s ; 2VO group:(17.30±2.11) s) (P＜0.01),and the 2VO+aPP2A group((15.09± 1.45) s) spent dramatically shorter latent time(P＜0.05) than that of 2VO group.The electrophysiological data showed that 2VO group had the noticeably smaller field excitable postsynaptic potential slope (fEPSP) slope ratio between pre and post of the high frequency stimulations (Long-term potential,LTP) than sham group(sham group:1.69±0.27; 2VO group:2.02±0.137) (P＜0.01),and the 2VO+aPP2A group(1.86±0.19) had strikingly higher ratio than that of 2VO group(P＜0.01).The electromicroscope observation showed that presynaptic vesicles density of 2VO was remarkably lower than that of sham group (sham group:(4.51±0.29) /μm2 ; 2VO group:(2.02±0.14) /μm2) (P＜0.01),and presynaptic vesicles density of 2VO+aPP2A group((3.58±0.50) /μm2) was noticeably higher than that of 2VO group(P＜0.01).Conclusion Activating PP2A can prevent the cognitive dysfunction after chronic cerebral ischemia through regulating LTP and synaptic vesicle density.And PP2A is probably a potential target for preventing and treating the cognitive dysfunction after chronic cerebral ischemia.

Objective To observe the principles of cell proliferation and apoptosis in the developing mouse cochlear sensory epithelium, and investigate correlation with differentiation of hair cells.Methods The developing inner ears of C57BL/6 embryonic mice,aged from eighth embryonic day (E8) to just natal mice (P0), were observed by transmission electron microscope.Results Cochlear primordium arose at E10. After E14, sensory epithelia began to differentiate. Corti primordium arose at E16, and shapes of supporting and hair cells tend to mature. But the organ of Corti was still poorly developed at P0. Meanwhile Cell karyokinesis of the cochlea arose at E11 ,then gradually increased. But it began to decrease from E14. Cell apoptosis arose at E13.It reached its peak from E14 to E15,then it began to decrease gradually.Conclusion Cell proliferation and apoptosis were inevitable in the developing mouse cochlea.Cell proliferation, cell apoptosis and differentiation of hair cells consequently arose and overlapped each other. Homeostasis between cell proliferation and apoptosis has an important role in the developing mouse cochlear sensory epithelium.

Objective: To investigate the plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer (D-D) and fibrinogen (Fib) among patients with pneumoconiosis, so as to provide insights into the prevention of thrombosis among patients with pneumoconiosis. Methods: Ninety-six male coal workers with stable-stage pneumoconiosis admitted to China Pingmei Shenma Group Occupational Disease Prevention and Control Hospital from February 2019 to February 2021 were included in the pneumoconiosis group, and 43 male healthy volunteers in the hospital during the same period were selected as the control group. The plasma D-D, Fib, IL-6 and CRP levels were detected from subjects in the two groups. The associations of plasma D-D and Fib levels with IL-6 and CRP levels were examined using Pearson correlation analysis among pneumoconiosis patients. Results: Participants in the pneumoconiosis group and the control group had a mean age of (52.91±3.89) and (52.64±4.12) years, D-D of (1.28±0.91) and (0.44±0.11) mg/L, Fib of (4.41±0.98) and (2.88±0.61) g/L, IL-6 of (0.63±0.19) and (0.42±0.06) ng/L and CRP of (3.30±1.65) and (1.35±0.12) mg/L, respectively. Higher plasma D-D, Fib, IL-6 and CRP levels were detected in the pneumoconiosis group than in the control group (all P<0.05). The plasma D-D level correlated positively with IL-6 level among pneumoconiosis patients (r=0.347, P<0.001). Conclusion High plasma IL-6, CRP, D-D and Fib levels are detected among patients with pneumoconiosis, and the plasma D-D level correlates positively with IL-6 level among patients with pneumoconiosis.

Background and purpose:The occurrence of endometrial cancer may be related to the persistent stimulus of endogenous and exogenous estrogen without progesterone antagonist. But how does estrogen regulate cell proliferation is still unknown. AKT pathway is the most important signal transduction way to mediate proliferation in the cells. The main aim was to study whether estradiol induces the expression of VEGF, bFGF and IL-8 in the endometrial cancer HEC-1A cells by activating AKT, and its effect on proliferation. Methods:Western blot was used to detect the expression of AKT protein in HEC-1A cells after estradiol stimulation, AKT inhibitor or ER inhibitor stimulation followed by estradiol. Real-time PCR and ELISA were used to detect the gene and protein expression of VEGF, bFGF and IL-8 in different inhibitors. Cell colony formation assay, lfow cytometry and CFSE assay were used to examine the proliferation in HEC-1A cells. Results:The expression of p-AKT protein in HEC-1A cells after stimulation with estradiol was markedly higher than that in the control group (P=0.006 2);the expression of p-AKT protein in AKT inhibitor group and ER inhibitor group were signiifcantly decreased than that in estradiol group (P=0.006 0, P=0.006 4). qPCR and ELISA showed the mRNA and protein expression of VEGF, bFGF, IL-8 in estradiol group were signiifcantly increased than that in control group (P<0.05);The expressions of VEGF, bFGF, IL-8 in AKT inhibitor group and ER inhibitor group were signiifcantly decreased than that in estradiol group (P<0.01). The abilities of proliferation and cell cycle were signiifcantly increased in HEC-1A cells after estradiol stimulation. Conclusion:Estrogen induces the production of VEGF, bFGF and IL-8 through activating AKT signal pathway.

BACKGROUND: The osteoinduction by biomaterials has been proven in various animal experiments. OBJECTIVE: To investigate the osteoinduction of porous calcium phosphate cement on bone marrow mesenchymal stem cel s. METHODS: Bone marrow mesenchymal stem cel s were isolated from rabbits aged 1 week in vitro and labeled by PKH-67 or PKH-26, respectively. Forty-eight adult New Zealand white rabbits were randomized into four groups and porous calcium phosphate cement was implanted into both sides of gluteus maximus in each rabbit. Then, 1 mL PKH-26-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into the superior gluteal artery branch at each side of gluteus maximus near the femur, and 1 mL PKH-67-labeled bone barrow mesenchymal stem cel s (1×1010/L) injected into tissues around the cement (group A); 1 mL PKH-26-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into the each side of superior gluteal artery branch (group B); 1 mL PKH-67-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into tissues around the cement (group C); the same amount of normal saline was injected into tissues around the cement (group D). At 3, 7 and 12 weeks after implantation, the cement and its surrounding tissues were extracted and detected by fluorescence microscope and Massion staining. Expression of bone morphogenetic protein 2 was analyzed by RT-PCR. RESULTS AND CONCLUSION: Under fluorescence microscope, PKH-26-labeled bone barrow mesenchymal stem cel s attached fast and distributed homogeneously; however, PKH-67-labeled bone barrow mesenchymal stem cel s attached slowly and exhibited a gradual y homogeneous distribution. Massion staining showed that ectopic new bone formation appeared to have an upward trend in al groups, and the area of new bones in groups A, B and C were larger than that of group D at different time points after implantation. There was a significantly higher expression of bone morphogenetic protein 2 in groups A, B and C compared with the group D at different time points after implantation (P < 0.05), and the expression was the highest in the group A (P < 0.05). In conclusion, the porous calcium phosphate cement can induce bone barrow mesenchymal stem cel s chemotaxis and osteogenetic differentiation. Besides, osteoblasts are differentiated from both the surrounding capil aries and body fluid, and capil ary-derived mesenchymal stem cel s occupy the important position.

The early of nutritional support (parenteral and enteral) in the very/extremely low birth weight infants improve the survival rate and avoid extrauterine growth restriction.The practice of early nutritional strategy,appropriate enteral feeding and the individualized care and assessment program can result in catch-up growth and avoid growth and development deficits.

Objective To evaluate the morbidity of the post-prostatectomy incontinence of supra-pubic transvesical prostatectomy(SPP) and transurethral resection of prostate(TURP). Methods One hundred and thirtyfive patients were divided into two groups. 82 patients underwent SPP and 53 patients underwent TURP. We ob-served the morbidity and the time lasting of post-prostatectomy incontinence, the severity of post-prostatectomy in-continence as evaluated by Stamey incontinence grading system,patients who had more than one week postoperativeincontinence were received urodynamic tests,then we got the information of their incontinence types. Results We found that patients who underwent SPP had higher morbidity, severity and time lasting than those who underwent TURP. SPP group had much more morbidity of stress incontinence than TURP group, but the same morbidity of ur-gent incontinence after operation as the later. Conclusion TURP may be better than SPP in consideration of the post-prostateetomy incontinence. SPP group has more stress incontinence and it may be caused by complete resection of prostate and damnifieation of the mucous membrane of membranous urethra.

Objective To probe into the effect of nursing intervention on complications and compliance of cancer patients with PICC. Methods 86 tumor patients selected from June 2007 to June 2010were randomly divided into the intervention group and the control group with 43 patients in each group. After the two groups of patients were diagnosed they were treated with routine care, the intervention group wasgiven additional comprehensive nursing interventions aiming at PICC complications and compliance. The complications and treatment compliance of the patients were analyzed. Results Compared with the control group, the rate of full compliance significantly improved and the rate of partial compliance significantly decreased in the intervention group. At the same time, compared with the control group, the incidence rate of phlebitis, catheter-related bloodstream infection and catheter blockage and catheter off of the intervention group were significantly lower. Conclusions Nursing intervention for cancer patients with PICC can reduce complications and improve treatment compliance of them and is of great clinical significance.

Objective To investigate the effect of vitamin D supplementation on biochemical imdexes and compliations in patients with type 2 diabetes(T2DM).Methods Two hundred and ten patients with type 2 diabetes of the People's Hospital of Chongli County were selected from January 2001 to January 2002.According to the envelope sampling method they were divided into vitamin D supplementation group of 105 people and not supplemented group of 105 people,and 105 healthy people at the same period as control group.Compared the biochemical baseline indicators differences.After 10 years of follow-up,the biochemical indexes and the complications were detected and compared again.Results After ten years follow-up,82 cases of supplementation group were followed up,78 cases of not supplemented group were followed up.The level of FPG and HbA1c of supplementation group and not supplementation group were higher than that of control group,the differernce was significant(P＜0.05).In supplement group,TG levels,25(OH) D3 concentrations and BMD values were (2.11±0.41) mmol/L,(16.88±5.02) μg/L and-1.15±(-0.25) respectively,and equal to the control group ((2.12 ± 0.38) mmol/L,(44.83 ± 21.25) mmol/L,-0.94 ± (-0.21)),and TG levels were lower than not supplemented group,25 (OH) D3 concentrations and high bone density higher than not supplemented group((24.53±15.61) mmol/L,-3.15±(-0.33),P＜0.05).FPG,Cr,BUN,UA,FIB,and BNP in supplement group were(10.00±2.32) mmol/L,(64.77±9.31) μmol/L,(6.41± 1.24) mmol/L,(339.83±43.74) mmol/L,(2.41±0.46) g/L and (588.92±73.69) ng/L,in not supplemented group were (15.60±2.51) mmol/L,(92.69±11.68).μmol/L,(8.70±2.35) mmol/L,(398.94±49.13) mmol/L,(2.89±0.54) g/L and (761.09±91.52) ng/L,all higher than those in control group ((5.01 ±0.59) mmol/L,(57.81±6.61) μmol/L,(4.52±1.11) mmol/L,(311.83±49.51) mmol/L,(2.00±0.31) g/L,(434.31 ± ±71.03) ng/L),and those indexes in supplement group all higher than in not supplemented group(P＜0.05).The level of HbA1c of supplement group and not supplemented group both higher than control group((11.32 ± ±2.03) ％,(13.22±4.17) ％ and (5.34±1.99) ％,P＜0.05).There were 45 cases in supplement group occurred diabetic nephropathy and cardiovascular complications,and 65 cases of not supplemented group (x2 =15.07,P＜0.05).Conclusion The relationship of Vitamin D and various complications of diabetes mellitus are closely,and supplementing vitamin D can reduce the complications of diabetes.