Discovery of novel α2A adrenergic receptor agonists coupling to Gαi/o proteins by virtual screening / 中国药理学与毒理学杂志

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Caspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism. @*Materials and Methods@#Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation. @*Results@#CARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9. @*Conclusion@#We demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

Verticalization of frontal P axis on electrocardiography in patients with acute exacerbation of chronic obstructive pulmonary disease and asthma / 中华全科医师杂志

Objective@#To investigate the clinical significance of verticalization of frontal P axis on electrocardiagraphy (ECG) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and asthma.@*Methods@#Thirty five COPD patients and 20 asthma patients with acute exacerbation admitted in Jing′an District Central Hospital were enrolled and 20 health subjects served as a control group. The 12 lead ECG examination, pulmonary function test and high resolution CT (HRCT) scan of lung were performed. The P axis in ECG, pulmonary function and CT emphysema score were compared among three groups. The correlation of P axis verticalization with pulmonary function and CT emphysema score was analyzed.@*Results@#There were significant differences in P axis(F=24.36), FEV1/FVC(F=39.36), FEV1(F=28.82), FEV1%(F=30.64), FVC%(F=3.45), PEF%(F=13.22), RV/TLC(F=10.46) and total emphysema score (F=50.60) among the three groups (all P<0.01). P axis was positively correlated with age(r=0.229), total emphysema score(r=0.567), upper lung emphysema score(r=0.542), middle lung emphysema score(r=0.507), lower lung emphysema score(r=0.572)(all P<0.01), and negative correlation with body mass index(r=-0.491), cardiothoracic ratio (r=-0.396), FEV1/FVC(r=-0.609), FEV1(r=-0.389), FEV1%(r=-0.460), and PEF% (r=-0.419)(all P<0.01). Taking P axis>60 ° as cut-off value for screening COPD, the sensitivity was 0.933, specificity was 0.667, positive predictive value was 0.833 and negative predictive value was 0.857.@*Conclusion@#The verticalization of frontal P axis on ECG is significantly associated with obstructive ventilation disorder and CT emphysema score, which can be used as a preliminary screening index for COPD.

Verticalization of frontal P axis on electrocardiography in patients with acute exacerbation of chronic obstructive pulmonary disease and asthma / 中华全科医师杂志

Objective:To investigate the clinical significance of verticalization of frontal P axis on electrocardiagraphy (ECG) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and asthma.Methods:Thirty five COPD patients and 20 asthma patients with acute exacerbation admitted in Jing′an District Central Hospital were enrolled and 20 health subjects served as a control group. The 12 lead ECG examination, pulmonary function test and high resolution CT (HRCT) scan of lung were performed. The P axis in ECG, pulmonary function and CT emphysema score were compared among three groups. The correlation of P axis verticalization with pulmonary function and CT emphysema score was analyzed.Results:There were significant differences in P axis( F=24.36), FEV 1/FVC( F=39.36), FEV 1( F=28.82), FEV 1%( F=30.64), FVC%( F=3.45), PEF%( F=13.22), RV/TLC( F=10.46) and total emphysema score ( F=50.60) among the three groups (all P<0.01). P axis was positively correlated with age( r=0.229), total emphysema score( r=0.567), upper lung emphysema score( r=0.542), middle lung emphysema score( r=0.507), lower lung emphysema score( r=0.572)(all P<0.01), and negative correlation with body mass index( r=-0.491), cardiothoracic ratio ( r=-0.396), FEV 1/FVC( r=-0.609), FEV 1( r=-0.389), FEV 1%( r=-0.460), and PEF% ( r=-0.419)(all P<0.01). Taking P axis>60 ° as cut-off value for screening COPD, the sensitivity was 0.933, specificity was 0.667, positive predictive value was 0.833 and negative predictive value was 0.857. Conclusion:The verticalization of frontal P axis on ECG is significantly associated with obstructive ventilation disorder and CT emphysema score, which can be used as a preliminary screening index for COPD.

Comparison of effects of allogeneic blood transfusion and hemodiluted autotransfusion on cellular immune function in patients undergoing cesarean section / 中华麻醉学杂志

Objective To compare the effects of allogeneic blood transfusion and hemodiluted autotransfusion on cellular immune function in the patients undergoing cesarean section.Methods Sixty patients,aged 20-35 yr,weighing 50-80 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective cesarean section,were randomly divided into 2 groups (n =30 each) using a random number table:hemodiluted autotransfusion group (group HAT) and allogeneic blood transfusion group (group ABT).Both groups received epidural anesthesia.The radial artery was cannulated after epidural anesthesia,and the autologous blood was collected in group HAT.The autologous blood transfusion timing:intraoperative blood loss was expected to exceed 20％ of blood volume.For the patients in whom intraoperative blood loss was not expected to exceed 20％ of blood volume,bleeding was stopped,and autologous blood was infused intravenously after peritoneum closure.The allogeneic blood transfusion timing:when hemoglobin ＜ 70 g/L,packed red blood cells 1-5 U were infused intravenously;when prothrombin time,or activated partial thromboplastin time ＞ 1.5 times of the normal value,the fresh frozen plasma 100-400 ml was infused intravenously;when platelet count＜50× 109/L,platelets 10-40 U were infused intravenously.When entering the operating room (T0),on 1st day after operation (T1),and on 5th day after operation (T2),blood samples were collected to detect the levels of T lymphocyte subsets CD3+,CD4+ and CD8+ (using FACScan flow cytometer),and serum interleukin-2 (IL-2) and IL-6 concentrations (by enzyme-linked immunosorbent assay).CD4+/CD8+ ratio was calculated.Results Compared with the values at T0,the levels of CD3+ and CD4+,CD4+/CD8+ ratio,and serum IL-2 concentrations were significantly decreased,and the serum IL-6 concentrations were increased at T1,2 in group ABT,and at T1 in group HAT (P＜0.05).Compared with group ABT,the CD3+ and CD4+ levels,CD4+/CD8+ ratio and serum IL-6 concentrations were significantly increased at T1,and the serum IL-2 concentrations were increased at T1,2 in group HAT (P＜0.05).Conclusion Compared with allogeneic transfusion,hemodiluted autotransfusion has less inhibitory effect on cellular immune function in the patients undergoing cesarean section.

Clinical study of endoscopic intratumor injection of recombinant human adenovirus p53 (rAd-p53) combined with esophageal stent implantation in the treatment of advanced esophageal cancer / 中国基层医药

Objective To compare the efficacy and incidence of complications of stenting alone and intratumoral injection of recombinant human adenovirus p53 combined with stent implantation in the treatment of advanced esophageal cancer patients.Methods 2 4 cases with advanced esophageal cancer,who could only eat semi liquid,liquid food or could not eat,were randomly divided into control group(A group) and treatment group (B group).12 cases in A group were treated with esophageal stent implantation,12 cases in B group were given endoscopic intratumor injection of recombinant human adenovirus p53 combined with food tract stent implantation.Results The rate of improvement of dysphasia had no significant difference in survival period:the treatment group survival time of 3.2-38 months,mean (27.0 ± 2.3) months,while the control group survival time of 2.8-27months,an average of (14.7 ± 8.0) months,the difference between the two groups was significant (t =3.521,P ＜ 0.05).The incidence rate of restenosis in treatrnent group was 8.3％,that in control group was 41.7％.There was significant difference (x2 =7.532,P ＜0.05).Conclusion Endoscopic intratumor injection of recombinant human adenovirus p53 combined with esophageal stent implantation in the treatment of advanced esophageal carcinoma can prolong the survival time of patients with esophageal stent implantation,and to reduce the incidence of restenosis.

Effect of different concentrations of sevoflurane combined with propofol on CPR and complement in patients with laparoscopic hysterectomy / 中国生化药物杂志

Objective To explore the effect of different concentrations of sevoflurane combined with propofol on CPR and complement in patients with laparoscopic hysterectomy.Methods 80 patients with hysteromyoma were randomly divided into A group with 27 cases, B group with 27 cases and C group with 26 cases.3 groups of patients were underwent laparoscopic hysterectomy surgery, and preoperative anesthesia with different concentrations of sevoflurane, A group with 2.5% sevoflurane anesthesia, B group with 3% sevoflurane anesthesia, C group with 3.5%.The clinical efficacy, CRP, complement levels and adverse reactions were compared among 3 groups.Results Compared with A group, the Karnofsky score of group B and group C was higher(P<0.05), there was no significant difference in Karnofsky score between the two groups of B and C, and the level of CRP in 3 groups increased and C3 and C4 decreased(P<0.05).Compared with group A, the level of CPR in group B and C were lower(P<0.05), C4 and C3 were higher( P<0.05 ) .There was no significant difference in the incidence of adverse reactions among 3 groups.Conclusion 3% concentration of sevoflurane combined with propofol in the induction of anesthesia in laparoscopic hysterectomy has better anesthetic effect, and has little effect on the CRP and the complement of the body .

Allogeneic hematopoietic stem cell transplantation for hemophagocytic syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the conditioning regimen, efficacy and side effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hemophagocytic lymphohistiocytosis (HLH).</p><p><b>METHOD</b>From 2010 to 2012, a total of 11 cases after allo-HSCT were evaluated including 8 cases with familial hemophagocytic lymphohistiocytosis (FHL) and 3 cases with Epstein-Barr virus (EBV) related HLH. Allo-HSCT from HLA haploidentical HSCT was performed for 3 cases and unrelated allo-HSCT for 8 cases; 7 cases underwent allo-HSCT with conditioning regimen of etoposide (VP16), busulphan (Bu), fludarabine (Flu) and antilymphocyte globulin (ATG) and 4 cases with Flu, melphalan (Mel) and ATG. Cyclosporine (CsA) or tacrolimus, mycophenolate (MMF) and methorexate (MTX) were used for prevention of graft versus host disease (GVHD). Four cases received anti-CD25 MoAbs, 7 cases received cord blood and 1 of them received haploidentical bone marrow to prevent GVHD.</p><p><b>RESULT</b>Three cases died after allo-HSCT. The median overall survival time of the 8 cases evaluated was 585 days (154-1 115 d). All the patients were successfully engrafted. Acute GVHD (aGVHD) occurred in 8 cases, including 3 cases of gradeI/II and 5 cases of grade III/IV. Chronic GVHD (cGVHD) occurred in 4 cases. Seven cases had cytomegalovirus (CMV) reactivation.</p><p><b>CONCLUSION</b>The allo-HSCT was successful in treating primary and refractory hemophagocytic syndrome.</p>

Efficacy of continuous incision analgesia with 0.2 ％ levobupivacaine for postoperative analgesia in parturients undergoing cesarean section / 中华麻醉学杂志

Objective To evaluate the efficacy of continuous incision analgesia with 0.2％ levobupivacaine for postoperative analgesia in parturients undergoing cesarean section.Methods Thirty ASA physical status Ⅰ or Ⅱ parturients who were at full term,aged 20-30 yr,weighing 60-80 kg,undergoing elective cesarean section,were enrolled in the study.The parturients received 0.2％ levobupivacaine 2 ml/h via a continuous incision analgesia device at the end of surgery.Pain was evaluated by visual analogue scale (VAS).Additional tramadol 50 mg was given when VAS score was above 3 and the consumption was recorded.The effective analgesia within 48 h after surgery (no addition of tramadol,VAS score ≤3) was recorded.The serum prolactin level was measured at 30 min before cesarean section and 24 and 48 h after cesarean section.The colostrum time was recorded.The toxic reaction and side effects were recorded.Results The effective analgesia rate was 80 ％.The consumption of tramadol was (95 ± 15) mg.The colostrum time was (24 ± 6) h.No toxic reaction was found.The serum prolactin level was significantly higher at 24 and 48 h after surgery than that at 30 min before surgery (P ＜ 0.05).Conclusion Continuous incision analgesia with 0.2％ levobupivacaine provides better efficacy,earlier colostrum time and fewer side effects for postoperative analgesia in parturients undergoing cesarean section.

Glucagon-like peptide-1 regulates lipometabolism by down-regulating adipose triglyceride lipase in 3T3-L1 adipocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of glucagon-like peptide-1 (GLP-1) on glycolipid metabolism in 3T3-L1 adipocytes and explore the mechanism.</p><p><b>METHODS</b>3T3-L1 adipocytes were treated with GLP-1, insulin, or both for 24 h, and Western blotting was used to analyze the expression levels of adipose triglyceride lipase (ATGL), glucose transporter type 4 (GLUT4), Akt1, Akt2 and phosphorylated Akt in the cells. Immunofluorescence was used to observe lipid content in 3T3-L1 adipocytes.</p><p><b>RESULTS</b>Akt1 and Akt2 were not activated by insulin stimulation in 3T3-L1 adipocytes. Akt was phosphorylated by GLP-1 stimulation, which inhibited the expression of ATGL and increased the translocation of GLUT4 from the intracellular membranes to plasma membranes. These changes were more obvious under the synergistic effect of insulin in 3T3-L1 adipocytes.</p><p><b>CONCLUSION</b>GLP-1 decreases lipolysis by inhibiting the expression of ATGL and improves insulin resistance by increasing the translocation of GLUT4 in 3T3-L1 adipocytes.</p>

Development of medical supplies management system / 中国医疗器械杂志

<p><b>OBJECTIVE</b>This paper adopts advanced information technology to manage medical supplies, in order to improve the medical supplies management level and reduce material cost.</p><p><b>METHODS</b>It develops a Medical Supplies Management System with B/S and C/S mixed structure, optimizing material management process, building large equipment performance evaluation model, providing interface solution with HIS, and realizing real-time information briefing of high value material's consumption.</p><p><b>CONCLUSION</b>The medical materials are managed during its full life-cycle. The material consumption of the clinical departments is monitored real-timely. Through the closed-loop management with pre-event budget, mid-event control and after-event analysis, it realizes the final purpose of management yielding benefit.</p>

Clinical analysis of caspofungin treatment for invasive fungal disease in advanced age patients / 中华老年医学杂志

Objective To evaluate the efficacy and safety of caspofungin in the treatment of invasive fungal disease (IFD) in advanced age patients. Methods A retrospective analysis of the clinical data was conducted. IFD patients who had received caspofungin treatment in elderly wards were included. Results From January 2007 to August 2009, 29 IFD patients aged 80-100 years (mean 89 ) were treated with caspofungin. Except that one patient dead on the first drug administration day, there were 28 evaluable patients, 13 were cured (46.4%), 6 were markedly improved (21.4%), 3 progressed (10.8%) and 6 dead (21.4%). The overall effective rate was 67. 8%. Of 13cured patients, 12 were Candida bacreremia, 1 was Candida albicans disease of lung. Of 6 dead patients, 2 were Candida bacteremia, 1 was Candida albicans disease of lung and 3 was suspected of lung IFD. One patient performed that alanine aminotransferase was increased, considering drug-related impairment of liver function. Conclusions Caspofungin is effective and safe in the treatment of IFD in advanced age patients.

A clinical studv of 49 cases of invasive pulmonary aspergillosis / 中华内科杂志

Objective studyring the proven and probable invasive pulmonary aspergillosis(IPA) eases of some hospitals in Shanghai to provide evidence fur the improvement of IPA clinical diagnosis and therapy.Methotis Fortv-nine IPA cases were retrospectively analyzed for demography data,host tactors,underlying conditions.chest CT,microorganism and histopathology examination,as well as therapy and clinical outcome.ResultsOf 49 subjects including 19(38.8%)proven and 30(61.2%)probable IPA,3 pailents(6.1%)had no host factors,25 patients(51.0%)had IPA associated host factors and underlying conditions.while 21 patients(42.9%)had uncertained fundamental diseases.Chest CT evaluation demonstrated that radiological lesions include nodules in 29 patients,patching in 15,mass in 12,consolidation in 10.cavitation in 34,Halo sign in 19,air bronchogram in 18,crescentic sign in 6,bilateral in 33 and multifocal lesions in 38.The yielding rate of fungus culture in sputum was 26.5%(13/49),and in bronchoalveolar lavage fluid was 66.7%(10/15).Eleven of thirty-six patients(30.6%)had positive results of serum galactomannan antigen tests.Nineteen of twenty-one patients(90.5%)were proven as IPA by lung histologic examinations.Aspergillus fumigatus was the most common pathogen 81.0%(17/21).The responding rate to initial anti-fugus therapy wag 50%(21/42).Conclusion Our study suggests that in IPA patients,bilateral,muhifocal and nodular lesion could be the most common radiological characteristic,while Halo and crescentic sign occar occasionally.Invasive technologies are more valuable to IPA diagnosis.

Preliminary observation on proliferation and apoptosis of HSC-T6 and L02 induced by sulfasalazine / 重庆医科大学学报

Objective:To investigate the effect of sulfasalazine on proliferation and apoptosis of HSC-T6 and L02 in culture. Methods:HSC-T6 and L02 were incubated with different concentration of sulfasalazine.Cell proliferation was assessed by CCK-8 assay,cell apoptosis was analyzed by annexin Ⅴ FITC/PI flow cytometry;and apoptotic morphology was examined by vital staining of acridine orange/ethidium bromide(AO/EB). Results:Compared with the control group,the proliferation of HSC-T6 was significantly inhibited by sulfasalazine in a time and dose-dependant manner,when the concentration of sulfasalazine in the medium reached a certain level range. The HSC-T6 apoptotic induced by sulfasalazine was confirmed by AO/EB and annexin Ⅴ FITC/PI.compared with the control group,the proliferation and apoptosis rate of L02 treated by group had no statistical significance,and AO/EB staining showed no apoptosis. Conclusion:Sulfasazinea at the same concentration can specifically inhibit the proliferation of HSC and induce HSC apoptosis.

Observation of the efficacy and safety of panipenem and betamipron in the treatment of serious in-hospital infection in elderly patients / 中华老年医学杂志

0. 05). Conclusions Panipenem and betamipron are effective and safe drugs in the treatment of serious in-hospital infection in elderly patients.

Apoptosis of hepatic stellate cells induced by sulfasalazine / 第三军医大学学报

Objective To determine whether sulfasalazine stimulates hepatic stellate cell (HSC-T6) apoptosis and its possible mechanism. Methods CCK-8 assay, acridine orange/ethidium bromide(AO/EB) and Annexin Ⅴ FITC/PI were used to determine cell growth and cell apoptosis. The expression of NF-?B P65, phospho-IKK and phospho-I?B was detected by Western blotting. The nuclear translocation of HSC-T6 P65 was observed with laser confocal microscopy. Results Sulfasalazine displayed a strong growth inhibition and promoting apoptosis effect on HSC-T6 cells in a dose and time-dependent manner. Sulfasalazine, but not 5-aminosalicylic acid or sulfapyridine, inhibited the activation of NF-?B by down-regulating the expressions of P-IKK, P-I?B and the nuclear translocation of P65. Conclusion Sulfasalazine can inhibit NF-?B activity and promote apoptosis in HSC-T6 cells, where the Rel/NF-?B/I?B/IKK pathway plays an important role in HSC survival.