Objective: To explore the expression and distribution of μ-opioid receptors(MOR) in intracardiac ganglia(ICG) and the effect of its agonists on atrial fibrillation(AF). Methods: (1) The chemical anatomical characteristics of ICG in normal SD rats were studied by immunofluorescence single staining. The expression and distribution of MOR in ICG were detected by using immunofluorescence double staining, Western blot, and RT-PCR.(2) Forty male SD rats weighing 250-300 g were randomly divided into 5 groups: normal group, AF model group(AF group), solvent control group(AF-NS group), MOR-specific agonist endomorphin-2(EM2) drug group(AF-EM2 group) and DAMGO drug group(AF-DAMGO group). The AF model was established by tail vein injection of acetylcholine(Ach) and CaCl2, and drug intervention was given during modeling. The duration of AF before and after drug administration was monitored by collecting electrocardiograms. The protein and mRNA expression of MOR in ICG and connexin 43(CX43) in atrial tissue were detected by the method of Western blot and qRT-PCR. Results: (1) Peptide nerve fibers positive for substance P and calcitonin gene-related peptide were found in the ICG, along with parasympathetic neurons positive for acetylcholine transferase and sympathetic neurons positive for tyrosine hydroxylase. The mRNA transcripts and protein of MOR were expressed in the atrial posterior wall tissue. MOR immunoreactive products were mainly distributed in the cell bodies of ICG neurons, primarily in parasympathetic and sympathetic neurons.(2) Compared with the Normal group, the expression ofMORmRNA and protein in ICG of the AF rat decreased(P<0.05). Compared with the AF-NS group, the duration of AF was shortened in the AF-EM2 group and AF-DAMGO group, and the expression of CX43 increased(P<0.05). Conclusion MOR is mainly expressed in sympathetic and parasympathetic neurons in ICG. The expression of MOR decreases in AF rats. MOR agonists alleviate AF.

Objective : To explore the expression of the μ⁃opioid receptor ( MOR) and the effects of intracellular vesicle transport on the MOR expression during endomorphin 2 ( EM2) analgesia. Methods : Adult male SD rats were randomly divided into 3 groups : control (naive) group , neuropathic pain group and drug group. Spared nerve injury (SNI) induced neuropathic pain rats were employed as the pain model. The drug group rats were the SNI pain ones intrathecally injected with EM2. The methods of immunofluorescence single staining and Western blot were used to detect the expression of MOR total protein , phosphorylated protein and Rab7 protein. Immunofluorescence double staining was used to detect the expression of MOR/Rab7 and MOR/LAMP1 co⁃labeled immunoreactivity. Results : Compared with the control group , the expression of total MOR protein and phosphorylated protein in the dorsal root ganglion (DRG) of the SNI pain rats decreased (P < 0. 05) , and the expression of Rab7 significantly increased (P < 0. 05) . The expression of MOR/Rab7 co⁃labeled immunoreactivity in Rab7 and MOR immunoreactive ( Ⅳir) products and MOR/LAMP1 co⁃labeled immunoreactivity in MOR and LAMP1 ⁃ir products both increased (P < 0. 05) . Multiple intrathecal injection of EM2 significantly increased paw withdrawal threshold in the SNI neuropathic pain rats (P < 0. 01) , the expression of MOR protein and phosphorylated protein in DRG was increased (P < 0. 05) , while the expression of Rab7 decreased (P < 0. 05) . Compared with the control group , the expression of MOR/Rab7 positive products in Rab7 and MOR positive ones decreased , and the expression of MOR/LAMP1 positive products in LAMP1 and MOR positive markers decreased ( P < 0. 05 ) . Conclusion In the process of analgesia , EM2 inhibits the expression of Rab7 in the DRG of SNI neuropathic pain rats , reduces the transport of MOR to lysosomes , and promotes the re⁃sensitization of MOR.

OBJECTIVE To investigate the effect and mechanism of Pinggan huoxue powder on cerebral ischemia-reperfusion injury （CIRI） in rats. METHODS CIRI model was induced by suture-occluded method. SD rats were divided into sham operation group， model group， positive control group （Tongxinluo capsule 0.325 g/kg）， Pinggan huoxue powder low-dose， medium-dose and high-dose groups （3.02， 6.04， 12.08 g/kg）， with 12 rats in each group. Each group was given constant volume of water or drug intragastrically， once a day， for consecutive 14 d. Longa score was used to evaluate neurological function of rats on the 1st， 7th and 14th day of intervention. After the last administration， the percentage of cerebral infarction volume in rats was measured， and neuronal injury （neuronal density） and neuronal apoptosis were observed； the protein expressions of p53， B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3 and activated Caspase-3 （Cleaved caspase-3） in brain tissue were detected. RESULTS Compared with sham operation group， Longa score at the 1st， 7th and 14th day of intervention and the percentage of cerebral infarction volume in model group significantly increased （P＜0.05）， and the arrangement of cortical cells in ischemic side was disordered， Nissl bodies were absent and vacuolated， and a large number of cell apoptosis occurred. The neuronal density and protein expression of Bcl-2 at the lesion side were significantly decreased （P＜0.05）， while the protein expressions of p53， Bax， Caspase-3 and Cleaved Caspase-3 were significantly increased （P＜0.05 or P＜0.01）. Compared with model group， the expressions of Bcl-2 in cerebral ischemia cortex of rats in Pinggan huoxue powder high-dose group were significantly increased （P＜0.05）. Longa scores of rats in Pinggan huoxue powder medium-dose and high-dose groups on the 7th and 14th day of intervention were significantly decreased （P＜0.05）， and other indexes were also significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Pinggan huoxue powder can protect cerebral nerves and inhibit apoptosis of CIRI model rats， the mechanism of which may be related to down-regulating the protein expressions of p53， Bax and Caspase-3 and up-regulating the protein expression of Bcl-2.

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).
Adult ; Anti-Asthmatic Agents ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; Disease Progression ; Dose-Response Relationship, Drug ; Eosinophils ; Forced Expiratory Volume ; Humans ; Leukocyte Count ; Quality of Life ; Randomized Controlled Trials as Topic

Objective To observe the blood vessels distribution in iliac blood velles triangular area of the lumbosacral vertebrae and confirm the range of safety working area,so as to provide anatomic data for anterior lumbosacral interbody fusion.Methods CTA imaging da-ta of abdominal vessels were randomly collected from 32 adult patients.Observed the distribution and intersection features of lumbosacral ver-tebral ventral blood vessels.Measured the distance from the bifurcation or confluence to the L5 dise,level interval of iliaca vessels in the infe-rior boundary of L5 ,and width of L5 /S1 intervertebral space.And then computed the range of safety working area and conducted a preliminary classification.Results The lumbosacral vertebral ventral operation space is mainly (87.4%)composed of left iliac vein and right common iliac artery.In this study,patients of type A accounted for 87.4%,vascular clearance of the L5 dise was (3.8 ±1.1)cm,safety working area was (5.2 ±1.2)cm2 ,and the display ratio of L5 /S1 was 73.2%.Patients of type B accounted for 6.3%,vascular clearance of the L5 dise was (4.2 ±0.5)cm,safety working area was (7.1 ±0.2)cm2 ,and the display ratio of L5 /S1 was 81.0%.Patients of type C accounted for 6.3%,vascular clearance of the L5 dise was (1.0 ±0.7)cm,safety working area was (1.3 ±0.7)cm2 ,and the display ratio of L5 /S1 was 31.2%.The differences of anatomical parameters among the three types were statistically significant (P <0.05).Conclusion The study showed that most ordinary people have enough operation space in the lumbosacral vertebral ventral,which is suitable for anterior lumbosacral interbody fusion,but it is necessary to take preoperative imaging screening.

Objective To investigate the clinical value of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the treatment and therapeutic effect evaluation of patients with an exacerbation of chronic obstructive pulmonary disease.Methods The levels of serum sTREM-1,procalcitonin (PCT) and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA) in 49 exacerbation of chronic obstructive pulmonary disease (COPD) subjects [acute exacerbation of chronic obstructive pulmonary disease (AECOPD) group],49 stable COPD subjects(sCOPD group) after treatment and 49 healthy volunteers as healthy control group.The levels of sTREM-1,PCT and CRP in different groups were compared and the relationship between the level of sTREM-1 in AECOPD and sCOPD groups,and PCT,and CRP was analyzed,respectively.Results The content of sTREM-1,PCT and CRP between different groups had significant difference(P ＜0.05).The level of sTREM-1 in both AECOPD and sCOPD groups was significantly positive correlated with PCT (P ＜ 0.05) and negative correlated with CRP (P ＞ 0.05).Conclusions For guiding the treatment and curative effect evaluation of patients with AECOPD,sTREM-1 has important clinical reference value.

Objective To explore the effects of anti-tumor immunity induced by dendritic cells (DCs) vaccine pulsed with PEP3-KLH (keyhole limpet hemocyanin) on induction of specific immunity against prostate cancers.Methods DCs were propagated from bone marrow of C57BL/6 mice in vitro with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4).On day 5 of culture, DCs were harvested and incubated with PEP3-KLH or KLH.Then the DC vaccine was inoculated into C57BL/6 mice by subcutaneous injection for three times with an interval of two weeks.One week after the last vaccination, the levels of IL-2, IL-12, and interferon (IFN)-γwere measured with enzyme-linked immunosorbent assay (ELISA) kit.The aforementioned immunized mice with DC vaccines were challenged with transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 tumor cells, the tumor growth curve was drawn, and survival rate was checked and compared.The cytotoxic T lymphocyte (CTL) activity induced by DCs was tested with lactate dehydrogenase (LDH) release method.The percentages of CD3 + , CD4+ ,or CD8 + T cells in tumor-infiltrating lymphocytes (TILs) were determined with flow cytometry.Results PEP3-KLH-DC group stimulated the body and induced higher levels of secreted IL-2, IL-12, and IFN-γ compared to DCs control and KLH-DC groups (P ＜ 0.01).The tumor of mice vaccinated with PEP3-KLHDC grew significantly slower than that injected with DCs or KLH-DC (P ＜0.01).Compared to the others, the survival rate in PEP3-KLH-DC group raised remarkably (P ＜ 0.01).PEP3-KLH-DC group induced more outstanding specific CTL activities of killing tumor cells than DCs control group and KLH-DC group (P ＜ 0.01), and the cytotoxicities of TILs in PEP3-KLH-DC group was significantly enhanced (P ＜0.01).The percentages of CD3 + , CD4 + , or CD8 + T cells in TILs (40.9％, 34.1％) in PEP3-KLH-DC group were significantly higher than those in DC-KLH (27.3％, 5.2％) or DCs (26.2％, 5.1％) group.Conclusions PEP3-KLH-DC vaccine can inhibit effectively tumor growth, enhance long-term survival in mice,intensify the local immunologic function of tumor, and elicit and promote profound specific anti-prostate cancer cellular immune responses.

Objective To study the relation between the levels of protein C(PC),protein S(PS),antithrombin Ⅲ(AT-Ⅲ)with cerebral infarction.Methods 126 patients with cerebral infarction were divided into the groups according to the age,onset time and infarction area and contemporaneous 30 individuals with healthy physical examination were selected as the control group.The levels of PC,PS and AT-Ⅲ were detected.The relation between the change of these indicator levels with the age,onset time and infarction area was analyzed Results The levels of AT-Ⅲ,PC and PS in the acute stage youth group were lower than those in the acute stage middle age and elderly group with statistical differences between them (P <0.05).The level of the AT-Ⅲ,PC and PS in the acute stage group were lower than those in the recovery stage group and the control group,difference had statistical significance(P <0.05).The levels of AT-Ⅲ and PS in the recovery stage group were lower than those in the control group with statistical difference (P <0.05),but the level of PC had no statistical difference between the recovery stage group and the control group.The further study found that the level of AT-Ⅲ,PC and PS in the small infarction group,middle infarction group and large infarction group showed the gradually decreasing trend,the differences had statistical significance (P <0.05).Conclusion The decrease of AT-Ⅲ, PC and PS levels is the importan factor of cerebral infarction occurrence and is closely correlated with cerebral infarction ocurrence especially in the patients less than 45 years old.Observing the change of PC,PS and AT-Ⅲ levels has the important significance for judging the cerebral infarction progression.

OBJECTIVETo study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation.

METHODSNinety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded.

RESULTSThere was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation.

CONCLUSIONSUrapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

Extracorporeal Circulation ; Heart Rate ; Humans ; Hypertension ; prevention & control ; Interleukin-6 ; blood ; Phentolamine ; therapeutic use ; Piperazines ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

Proteomics is an emerging discipline and has been widely used in a variety of fields despite of having very short history in comparison with other disciplines. In Chongqing Medical Univer-sity, the course contents were adjusted to fulfill the most effective integration of proteomics research with postgraduate training program for medical university. Diverse teaching was advocated here and af-ter-school communications were greatly encouraged in teaching. Traditional multimedia teaching plat-form remained the main teaching way and students were organized to visit the research platform as supplementing teaching way. The overall quality and effectiveness of teaching were effectively improved by successful implementation of the above initiatives.