Objective To evaluate the role of spinal phosphatidyl-inositol 3-kinase/Akt (PI3k/Akt) signaling pathway in the maintenance of bone cancer pain (BCP) in rats and its relationship with microglial activation.Methods Forty healthy female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S) ; PI3K inhibitor LY294002 group (group L) ; group BCP; BCP + dimethyl sulfoxide (DMSO) group (group BCP + D) ; BCP + LY294002 group (group BCP + L).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibia.At 7-9 days after inoculation,LY294002 2.5 μg/10 μl was injected intrathecally in L and BCP + L groups,normal saline 10 μl was injected intrathecally in S and BCP groups,and 5％ DMSO 10 μl was injected intrathecally in BCP+ D group once a day.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation and 1,3,5,7,8 and 9 days after inoculation.The rats were sacrificed after MWT was measured on day 9 after inoculation and the L4-6 segments of the spinal cord were removed to determinate the activation of spinal microglia using immunofluorescence.Results Compared with group S,MWT was significantly decreased,and the activation of spinal microglia was increased in BCP,BCP + D and BCP+ L groups.Compared with BCP and BCP + D groups,MWT was significantly increased,and the activation of spinal microglia was decreased in BCP + D group.Conclusion Spinal PI3K/Akt signaling pathway is involved in the maintenance of BCP possibly through activating microglia in spinal dorsal horns of rats.

Objective To evaluate the role of c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) signaling pathway in the spinal cord in the maintenance of bone cancer pain (BCP) in rats.Methods Fifty female Sprague-Dawley rats,weighing 150-180 g,were randomly divided into 5 groups (n =10 each) using a random number table:sham operation group (group S),sham operation + JNK inhibitor SP600125 (group SP),BCP group,BCP + dimethyl sulfoxide (DMSO) group,and BCP+ SP600125 group (group BCP+ SP).BCP was induced by injecting Walker 256 mammary gland cancer cells into the bone marrow of the left tibia.On 10-12 days after BCP,SP600125 10 μg(10 μ1) was injected intrathecally once a day in SP and BCP + SP groups,and 5％ DMSO 10 μl was injected intrathecally once a day in BCP + DMSO group.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before BCP and 3,6,9,10,11 and 12 days after BCP.After measurement of MWT at 12 days after BCP,the rats were sacrificed and L4-6 segments of the spinal cord were removed for determination of MCP-1 expression by using immuno-histochemistry and Western blot.Results Compared with S group,MWT was significantly decreased at 6-12 days after BCP,MCP-1 expression was upregulated in BCP,BCP + DMSO and BCP + SP groups (P ＜ 0.01),and no significant change was found in the parameters mentioned above in SP group (P ＞ 0.05).Compared with BCP group,MWT was significantly increased at 10-12 days after BCP,MCP-1 expression was down-regulated in BCP + SP group (P ＜ 0.01),and no significant change was found in the parameters mentioned above in BCP + DMSO group (P ＞ 0.05).Conclusion JNK/MCP-1 signaling pathway in the spinal cord may be involved in the maintenance of BCP in rats.

Objective To evaluate the role of spinal microglial C-C chemokine receptor type 2 (CCR2) in the maintenance of bone cancer pain (BCP) in rats.Methods Fifty unmated female Sprague-Dawley rats,aged 2 months,weighing 160-180 g,were randomly divided into 5 groups (n =10 each):sham operation group (group Ⅰ),sham operation + RS102895 (CCR2 antagonist) group (group Ⅱ),BCP group (group Ⅲ),BCP + dimethylsulfoxide (DMSO) group (group Ⅳ),and BCP + RS102895 group (group Ⅴ).The rats were anesthetized with intraperitoneal chloral hydrate.BCP was induced by intra-tibial inoculation of 1 × 105 Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibial metaphysis.On 10-12 days after operation,3 μg/μl RS102895 10 μd was injected intrathecally once a day in Ⅱ and Ⅴ groups,10％ DMSO 10 μl was injected intrathecally once a day in Ⅳ group,and normal saline 10 μl was injected intrathecally once a day in Ⅰ and Ⅲ groups.Mechanical paw withdrawal threshold was measured at 1 day before operation and 3,6,9,10,11 and 12 days after operation.After measurement of pain threshold at day 12 after operation,the lumbar segments (L4-6) of the spinal cord were removed for determination of the level of ox-42 (spinal microglial activation marker) (by immuno-histochemistry) and contents of IL1-β,IL-6 and TNF-α (by ELISA).Results Compared with group Ⅰ,mechanical paw withdrawal threshold was significantly decreased at 6-12 days after operation,the number of ox-42 positive cells and contents of IL1-β,IL-6 and TNF-α were increased in Ⅲ,Ⅳ and Ⅴ groups,and no significant change was found in the parameters mentioned above in group Ⅱ.Compared with group Ⅲ,mechanical paw withdrawal threshold was significantly increased at 10-12 days after operation,the number of ox-42 positive cells and contents of IL1-β,IL-6 and TNF-α were decreased in group Ⅴ,and no significant change was found in the parameters mentioned above in group Ⅳ.Conclusion Spinal microglial CCR2 is involved in the maintenance of BCP via activating microglia and promoting the release of inflammatory cytokines of rats.

OBJECTIVETo research the regulation of transmembrane transport activity of paclitaxel influenced by fangchinoline in MDR1-MDCK II cells.

METHODPaclitaxel, one of the substrate of P-gp, was selected as the model drug. Verapamil hydrochloride was adopted as the active control to investigate the bilateral transport activity of paclitaxel regulated by fangchinoline in MDR1-MDCK II cells. RP-HPLC was applied to determine the concentration of paclitaxel in the transporting medium, which was used to calculate apparent permeability coefficient of paclitaxel across MDR1-MDCK I1 monolayer cells.

RESULTThe efflux rate of paclitaxel was faster than the absorption rates across the MDR1-MDCK II monolayer cells with highly expressed P-gp. The absorption rates of paclitaxel combinated with fangchinoline and verapamil hydrochloride respectively were remarkably increased and the efflux rate was decreased. The reversal effect of the fangchinoline was stronger than the verapamil hydrochloride with the same molar concention.

CONCLUSIONFangchinoline can apparently decrease the efflux of paclitaxel and inhibit the multidrug resistance of antitumor drug mediated by P-gp.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Animals ; Benzylisoquinolines ; pharmacology ; Biological Transport ; drug effects ; Cell Line ; Cell Membrane ; drug effects ; metabolism ; Cell Membrane Permeability ; drug effects ; Dogs ; Humans ; Models, Biological ; Paclitaxel ; pharmacokinetics ; Plant Extracts ; pharmacokinetics

This experimental study was designed to investigate the effects and the expressions of microvessel density (MVD), vascular endothelial growth factor (VEGF) on the transplanted tumor in the rat model with Walker-256 after energy controllable steep pulse(ECSP). The experiment revealed that the steep pulse electrical field has better effect on tumor, compared with the control. The positive cell staining intensity of VEGF in the control group was significantly higher than that in ECSP group (P < 0.05). The number of MVD in the tumor tissues of ECSP group was significantly lower than that of tumor control group (P < 0.05). These results showed that ECSP could inhibit the growth and angiogenesis of tumor and its pathway is to down-regulate the expression of VEGF possibly.
Animals ; Carcinoma 256, Walker ; blood supply ; therapy ; Electric Conductivity ; Electric Stimulation Therapy ; methods ; Electromagnetic Fields ; Electroporation ; methods ; Female ; Male ; Neovascularization, Pathologic ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; metabolism

Pulsed electric fields (PEFs) with fixed frequency, width and gradually increased peak value of voltage was applied to 30 healthy rabbit liver tissues. The specific aims were to explore the feasibility of establishing a model of in vivo PEFs distribution in healthy rabbit liver tissues and to provide important references for clinical electrochemotherapy and for electrotransfer. Repeated experiment and self-comparison statistics design were implemented. The rabbit underwent the experiment under intravenous anesthesia and their liver tissues, after exposure to PEFs, were sent for HE staining. Necrotic borderline was visible 3 days after PEFs application, the necrotic shape of concentric circle was evident around the electrodes under optical microscope at lower voltage, as voltage increasing, two necroses in the shape of concentric circle gradually enlarged; nuclei with chromatin condensation, fragmentation and lysis alterations were seen in the middle region between the needles; concentric circles changed into ellipse fusiform and finally overlaped each other forming irregular necrosis contours. Cell cavitation and tissues ischemia were also observed within electric field. The shape of tissue necrosis from the experiment was noted to correlate with theoretic simulation of electric field distribution. Therefore, rabbit liver tissues can be a good carrier for in vivo modeling of electric field distribution when the lethal effects of PEFs in tissues are investigated. PEFs also show safety for the surrounding normal tissue while causing damage or injury to the target area therapeutically.
Animals ; Electricity ; adverse effects ; Electrochemotherapy ; Liver ; pathology ; Male ; Models, Theoretical ; Necrosis ; Rabbits

As a micro-wound and target-aimed technology without special limitation, Electric Pulses have been widely researched in tumor treatment and the effects have been demonstrated by a series of experiments, yet the mechanism has not been explained clearly. In this experiment, energy controllable steep pulse (ECSP) was used to treat nude mice bearing human ovarian tumor, and the result was compared with that of the control group. The expression of an important coagulant factor-tissue factor (TF) was analyzed, as TF was also a tumor indicator of invasion and metastasis, the result may indicate the relationship among ECSP, thrombosis and tumor invasion. In this study, to shed light on the mechanism of tumor treatment in electrical fields, nude mice bearing ovarian tumors were randomly divided into the treated group and the untreated group. We treated the former group and took out the tumor instantly. The thrombosis and necrosis of ovarian tumor were observed under microscope. The expression of TF was analyzed by SP immunohistochemistry and RT-PCR. Lower level of TF expression was noticed in the tumor tissue treated by ECSP, and more apparent thrombosis was also seen in this group. The results make it clear that ECSP can accelerate thrombosis and consume coagulant factors such as TF, and that low expression of TF in tumor tissue can cut out the signal paths of tumor invasion. So it is suggested that ECSP may restrain tumor invasion and metastasis by modulating thrombosis.
Animals ; Electric Stimulation Therapy ; methods ; Electromagnetic Fields ; Electroporation ; methods ; Female ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms ; metabolism ; therapy ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Thromboplastin ; biosynthesis ; genetics

Objective To explore the application effect of concept map teaching of group-discussing mode in standardized nursing training. Methods A total of 80 standardized training nurses in Wuxi No.2 People's Hospital from January 2016 to December 2016 were selected by purposive sampling and randomly divided into the intervention group and the control group, with 40 students in each. The control group was taught according to the conventional teaching method, and the intervention group was taught with the concept map teaching of group-discussing mode. The scores of the independent learning ability assessment scale and the scores of theoretical examination were compared before and after the intervention. The scores of the feedback evaluation scale of concept map teaching of group-discussing mode in the intervention group were observed. Results The score of each dimension and the total score of the independent learning ability assessment scale of the intervention group after intervention were higher than those in the control group, and the difference was statistically significant (P<0.05). The score of theoretical examination in the intervention group was higher than that in the control group with statistical difference (P<0.001). The nurses in the intervention group had a better feedback on the concept map teaching of group-discussing mode. Conclusions The concept map teaching of group-discussing mode obtains good application results in clinical nursing teaching and training, and it can improve the nurses' independent learning ability.

Objective To construct the evaluation index system of the core competence of the nurses in the nuclear medicine department and provide a scientific assessment tool for the core competence evaluation of nurses in the nuclear medicine discipline. Methods Based on the theory of core competence, we selected indexes and determined the weight of them by using literature retrieval, experts interview, Delphi expert consultation and the analytic hierarchy process(AHP) in order to analyze the concentration degree of expert opinion. The coordination degree of expert opinion was analyzed with the coefficient of variation (CV) and coordination coefficient. Finally, the weight of each index was calculated by the AHP. Results Expert enthusiasm: the effective recovery rate of the two rounds of expert consultation was 100%, and a total of 12 experts made personal suggestions. Expert authority analysis: judge coefficient (Ca=0.932) and familiarity degree coefficient (Cs=0.865), the expert's authorities (Cr=0.879). Expert opinion coordination degree: two rounds of expert consultation was CV< 0.25. The expert opinion and modification situation finally formed 5 primary indicators, 18 secondary indicators and 47 tertiary indicators. Conclusions The evaluation index system of core competency of nuclear medicine nurses is highly scientific and reliable, which provides a reference for core competency training of nurses in nuclear medicine.

Objective To observe the clinical effects of auricular plaster therapy combined with acupoint application on preventing postpartum retention of urine. Methods From June 2016 to October 2016, we selected 240 puerpera with full-term pregnancy of Department of Gynaecology and Obstetrics in Hangzhou Red Cross Hospital by random sampling. All of the patients were divided into four groups by the random number table, 60 cases in each group. Patients in control group were treated with routine postpartum care. In this basis, patients in auricular plaster therapy group accepted auricular plaster therapy, patients in acupoint application group accepted acupoint application therapy, patients in auricular plaster therapy & acupoint application group were treated with auricular plaster therapy and acupoint application therapy. Finally, the time of the first micturition, bladder residual urine volume (RUV) and clinical effects of puerpera were compared in four groups. Results The time of the first micturition in auricular plaster therapy & acupoint application group (combined group), auricular plaster therapy group, acupoint application group and control group was (2.45±0.51), (4.28±1.23), (4.25±1.15) and (5.60±1.75) h respectively with significant differences (F= 65.207, P<0.001). The bladder RUV of auricular plaster therapy & acupoint application group was (52.10±12.51) ml less than those of other three groups. The total effective rate of auricular plaster therapy & acupoint application group was 100.00% high than that of other three groups with a significant difference (χ2=179.770, P<0.001). Compared with control group, the time of the first micturition in auricular plaster therapy & acupoint application group was shorter, the bladder RUV was all less, the total effective rate was higher with significant differences (P<0.05). There was no statistically significant difference between auricular plaster therapy group and acupoint application group (P>0.05). Conclusions The auricular plaster therapy combined with acupoint application can effectively prevent postpartum retention of urine which is worth to be spread.