Effect of hydrogen sulfide on the proliferation of rabbit vascular smooth muscle cell under high static pressure / 中华普通外科杂志

Objective:To observe the effect of exogenous hydrogen sulfide(H 2S) on the proliferation of rabbit vascular smooth muscle cell(VSMC) under high static pressure. Methods:Rabbit thoracic aorta VSMC were isolated and cultured under high static pressure(100mmHg) and divided into control group [cultured with 0.2%fetal bovine serum(FBS) and no NaHS]、10%FBS group(10%FBS and no NaHS) and NaHS group(10%FBS and 50mmol/L NaHS). VSMC proliferation was analyzed with BUDR. CSE, Calmodulin(p-CaM)and CyclinD1 protein levels of VSMC were measured by Western blotting.Results:Compared with the 10%FBS group, NaHS inhibit the proliferation of rabbit VSMC significantly (0.50±0.03 vs. 0.26±0.03, P<0.05). Compared with control group, CSE protein in the 10%FBS group decreased significantly(1.21±0.10 vs. 0.33±0.04, P<0.05) and p-CaM and CyclinD1 protein increased significantly(0.23±0.04 vs. 0.86±0.04 and 0.22±0.03 vs. 1.19±0.06, P<0.05). Compared with the 10%FBS group, CSE protein in NaHS group increased significantly(0.33±0.04 vs. 1.11±0.11, P<0.05), and the expression of p-CaM and CyclinD1 protein decreased significantly(0.86±0.04 vs. 0.26±0.05 and 1.19±0.06 vs. 0.51±0.03, P<0.05). Conclusion:Exogenous hydrogen sulfide inhibits the proliferation of VSMC under high static pressure by the CSE/H2S pathway which related to the reduction of the expression of p-CaM and CyclinD1.

Effect of NPM1 mutant A on TGF-β1-induced K562 cell proliferation and AKT phos-phorylation / 中国肿瘤临床

Objective: To investigate the effect of nucleophosmin 1 (NPM1) mutant A on TGF-β1-induced K562 cell proliferation and AKT phosphorylation. Methods: K562 cells were infected with Ad5-NPM1 to create an NPM1 over-expression cell model. NPM1 levels were determined by ELISA and Western blot analysis. The levels of AKT and P-AKT were determined by Western blot. MTT was used to measure the proliferation of K562 cells. Results: NPM1 protein levels in K562 cells increased in an Ad5-NPM1-MOI-dependent manner. Cell proliferation and NPM1 levels in the supernatant were significantly increased in K562 cells infected with Ad5-NPM1-30 and Ad5-NPM1-100 compared to those infected with Ad5-vector-100 (P<0.01). Treatment with (10 ng/mL) TGF-β1 increased P-AKT levels, but not total AKT levels in K562 cells. TGF-β1-induced phosphorylation of AKT was significantly increased by infection of K562 cells with Ad5-NPM1-100. No significant differences were found in total AKT levels among all groups. TGF-β1 (10 ng/mL) treatment also in-creased the proliferation of K562 cells. TGF-β1-induced K562 cell proliferation was significantly increased by infection with Ad5-NPM1-100 (P<0.01). Conclusions: NPM1 improves TGF-β1-induced cell proliferation by up-regulating AKT phosphorylation levels.

Effect of D-dimer combined with risk score in screening of acute aortic dissection / 中国中西医结合急救杂志

Objective To discuss the diagnostic value of a diagnostic strategy combining D-dimer and aortic dissection detection risk score (ADDRS) for patients with acute aortic dissection (AAD). Methods The clinical data of 750 patients with suspected AAD in emergency department of Zhongda Hospital Affiliated to Southeast University from January 2016 to January 2018 were retrospectively analyzed, including medical history, gender, age, chief complaint, physical examination, diagnostic imaging data and D-dimer levels on admission. ADDRS = 0 was defined as low risk group, ADDRS = 1 as medium risk group, ADDRS≤1 as non-high risk group,whereas ADDRS > 1 as high risk group. The clinical characteristics of AAD and non-AAD patients, ADDRS, D-dimer, and the diagnostic ability of D-dimer (the cutoff value of 500 μg/L) for AAD in different risk groups were observed. Results AAD was diagnosed in 79 of 750 (10.53%) patients. Of the 256 (34.13%) patients in low risk group, 5 patients were diagnosed with AAD. The medium risk group had 337 (44.93%) patients, including 44 cases with AAD. The high risk group had 157 (20.93%) patients, including 30 cases with AAD. In AAD patients, the proportion of male and hypertension, the incidence of ADDRS risk markers (including abrupt onset of pain, severe pain intensity, ripping or tearing pain, pulse deficit or systolic blood pressure differential of upper limb, focal neurological deficit, recent aortic manipulation, known thoracic aortic aneurysm) and the D-dimer levels in AAD group were significantly higher than those of non-AAD patients [male: 82.28% (65/79) vs. 59.76% (401/671), hypertension: 81.01% (64/79) vs. 41.43% (278/671), abrupt onset of pain: 78.48% (62/79) vs. 39.94% (268/671), severe pain intensity: 78.48% (62/79) vs. 50.52% (339/671), ripping or tearing pain: 32.91% (26/79) vs. 0.75% (5/671), pulse deficit or systolic blood pressure differential of upper limb: 15.19% (12/79) vs. 0.15% (1/671), focal neurological deficit: 7.59% (6/79) vs. 1.64% (11/671), recent aortic manipulation: 6.33% (5/79) vs. 0.30% (2/671), known thoracic aortic aneurysm: 15.19% (12/79) vs. 0.30% (2/671), D-dimer (μg/L): 1 160 (588, 3 340) vs 135 (56, 478), all P < 0.05], the proportion of diabetics was significantly lower than that of non-AAD patients [7.59% (6/79) vs. 18.78% (126/671), P < 0.05]. The positive predictive values of D-dimer for AAD diagnosis in the low risk group and the non-high-risk groups (including low and medium risk groups) were lower than that in the high risk group (8.62%, 26.32% vs. 40.91%), the negative predictive values of D-dimer were higher in the low risk group and non-high-risk groups than that in the high risk group (100.00%, 99.05% vs. 96.70%), missed diagnosis rates were higher than that in high risk group (0, 0.95%, vs. 3.30%). Conclusion In the high risk group, D-dimer≥500 μg/L is helpful for diagnosis of AAD; and in low risk group or non-high-risk group, D-dimer < 500 μg/L can efficiently and accurately exclude AAD.

Protective effect of sodium 4-phenylbutyrate on rats with acute respiratory distress syndrome related right ventricular dysfunction by alleviating endoplasmic reticulum stress / 中华危重病急救医学

Objective@#To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle.@*Methods@#Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α(TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3.@*Results@#Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05).@*Conclusions@#ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.

Protective effect of sodium 4-phenylbutyrate on rats with acute respiratory distress syndrome related right ventricular dysfunction by alleviating endoplasmic reticulum stress / 中华危重病急救医学

Objective To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. Methods Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. Results Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). Conclusions ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.

Protective effect of sodium 4-phenylbutyrate on rats with acute respiratory distress syndrome related right ventricular dysfunction by alleviating endoplasmic reticulum stress / 中华危重病急救医学

Objective To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. Methods Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. Results Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). Conclusions ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.

Epidemiological and clinical characteristics of 109 patients with crayfish-related rhabdomyolysis / 中华内科杂志

A total of 109 in patients with crayfish-related rhabdomyolysis were enrolled in our hospital from July to August 2016,including 31.2％(34/109)males and 68.8％ (75/109)females.The number of home-cooked crayfish accounted for 60.6％ (66/109).Main symptom was back pain 96.3％ (105/109).The misdiagnosis rate was 15.6％ (17/109).On day 1,2,3 after admission and the day before discharge,serum creatine kinase were 1 175(446,2 258)IU/L,3 710(2 137,8 875)IU/L,1 899(1 063,4595)IU/L and 317 (152,532)IU/L,respectively(P＜0.001).Serum myoglobin were (603±484)μg/L,(313±284)μg/L,(104±74)μg/L and (55 ± 20)μg/L,respectively(F=39.1,P＜0.001).Females were more susceptible to cra.crayfish-related rhabdomyolysis.Home-cooked crayfish is prone to induce rhabdomyolysis and easily to be misdiagnosed.Creatine kinase and myoglobin showed characteristic dynamic changes.

Role of the secretory PLA2-IB and PLA2R in human podocyte injury and its possible mechanism / 中华肾脏病杂志

Objective To investigate the role of the group IB secretory phospholipase A2 (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) in human podocyte injury and its possible signal transduction pathway.Methods Differentiated human podocytes were exposed to PBS or different sPLA2-IB concentration conditions (10-9,10-7,10-5 mol/L) for 2 hours.The wound healing assay was used to measure cell migration rate;Apoptosis in cultured human podocytes was assessed by Hoechst 33342 staining and flow cytometry;Western blot was used to analyze the protein expression of p-cPLA2α,p-p38,and p53.Then control siRNA or PLA2R siRNA were transfected to podocytes.Podocytes were divided into normal control group,negative control siRNA group and PLA2R siRNA group.Twenty four hous later,the cells were stimulated by 105 mol/L sPLA2-IB for 2 hours.The protein expression of p-cPLA2α,p-p38,and p53 were detected by Western blot.Results Compared to PBS control group,the migration ability of podocytes decreased when stimulated with sPLA2-IB (10-7mol/L-10-5 mol/L),and the apoptosis of podocytes increased in a concentration-dependent manner,the protein level of p-cPLA2α,p-p38 and p53 protein increased too.After the knockdown of PLA2R by PLA2R siRNA transfection,stimulated the podocytes with the same dosage of sPLA2-IB,the protein expression of p-cPLA2α,p-p38 and p53 all decreased.Conclusion sPLA2-IB stimulation can increase human podocyte apoptosis and decrease its migration ability.The possible mechanism might be through p38-cPLA2α-p53 pathway.

Role of the secretory PLA2-IB and PLA2R in human podocyte injury and its possible mechanism / 中华肾脏病杂志

Objective To investigate the role of the group IB secretory phospholipase A2 (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) in human podocyte injury and its possible signal transduction pathway.Methods Differentiated human podocytes were exposed to PBS or different sPLA2-IB concentration conditions (10-9,10-7,10-5 mol/L) for 2 hours.The wound healing assay was used to measure cell migration rate;Apoptosis in cultured human podocytes was assessed by Hoechst 33342 staining and flow cytometry;Western blot was used to analyze the protein expression of p-cPLA2α,p-p38,and p53.Then control siRNA or PLA2R siRNA were transfected to podocytes.Podocytes were divided into normal control group,negative control siRNA group and PLA2R siRNA group.Twenty four hous later,the cells were stimulated by 105 mol/L sPLA2-IB for 2 hours.The protein expression of p-cPLA2α,p-p38,and p53 were detected by Western blot.Results Compared to PBS control group,the migration ability of podocytes decreased when stimulated with sPLA2-IB (10-7mol/L-10-5 mol/L),and the apoptosis of podocytes increased in a concentration-dependent manner,the protein level of p-cPLA2α,p-p38 and p53 protein increased too.After the knockdown of PLA2R by PLA2R siRNA transfection,stimulated the podocytes with the same dosage of sPLA2-IB,the protein expression of p-cPLA2α,p-p38 and p53 all decreased.Conclusion sPLA2-IB stimulation can increase human podocyte apoptosis and decrease its migration ability.The possible mechanism might be through p38-cPLA2α-p53 pathway.

Epidemiology characteristics of crawfish related rhabdomyolysis in Nanjing, 2016: a multicenter retrospective investigation / 中华危重病急救医学

Objective To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.Methods Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.Results A total of 1183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1124 patients were enrolled. The proportion of men was 36.48% (410/1124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: MoranI = 0.427,Z = 2.646,P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the high-high concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.Conclusion The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.

Anti-oxidant effect of pirfenidone on acute lung injury induced by paraquat poisoning in mice / 中华危重病急救医学

Objective To investigate the anti-oxidant effect of pirfenidone (PD) at different dosage on acute lung injury (ALI) induced by paraquat (PQ) poisoning in mice. Methods 144 ICR mice were randomly divided into four groups: control group (n = 24), PQ poisoned group (n = 24), high and low doses PD treatment groups (n = 48). ALI induced by PQ poisoning model was reproduced by intraperitoneal injection of 25 mg/kg 20% PQ solution in mice, and the mice in control group was given equal volume of normal saline. Intragastric administration with 30 mg/kg and 70 mg/kg PD suspension [PD was dissolved in 0.4% sodium carboxymethyl cellulose sodium (CMC) solution] after PQ poisoning immediately for 3 days in high and low doses PD treatment groups respectively, while the same volume of 0.4% CMC solution was administrated in control group and PQ poisoned group. Then mice in each group were respectively sacrificed at 2, 6, 12, 24, 48 and 72 hours after PD exposure to harvest the lung tissue, nuclear factor-κB (NF-κB) was determined by enzyme linked immunosorbent assay (ELISA), superoxide dismutase (SOD) and malonaldehyde (MDA) were determined by colorimetry, and pulmonary pathological changes were observed with microscope after hematoxylin-ensin (HE) staining. Results Compared with the control group, NF-κB from 2 hours in PQ poisoned group was significantly increased (pg/mg: 106.65±5.96 vs. 79.04±2.40, P 0.05), but no significant difference in NF-κB activity at all time points was found. Under light microscope, a wide range of red blood cells and serous effusion, alveolar septum fracture and pulmonary interstitial inflammatory cell infiltration were shown by pathologic examination in PQ poisoned group. The pathologic changes in high and low doses PD treatment groups were obviously less than those of PQ poisoned group, and no significant difference was found between the two doses groups. Conclusions The early therapeutic effect of PD may relate to the inhibition of NF-κB and reactive oxygen species, then reduce the inflammation of PQ poisoning. The treatment effectiveness of low dose PD seems better than high dose PD.

Retinoid X receptor agonist inhibits TGF-β1-induced collagen synthesis in cardiac fibroblasts by repressing Smad2 activation / 中国病理生理杂志

AIM:To investigate the effect of activation of retinoid X receptor (RXR) on transforming growth factor β1 (TGF-β1) induced collagen synthesis under hypoxic environment in rat cardiac fibroblasts (CFs) and underlying molecular mechanisms .METHODS: CFs were cultured using myocardial tissue with dry method .Hypoxic environment was established for CFs by continuous nitrogen supplement .Type I and type III collagens in supernatants were detected by ELISA.Nuclear and cytoplasmic extractions were prepared using NE-PER nuclear and cytoplasmic extraction reagents .The protein levels of Smad2 and p-Smad2 were determined by Western blot and immunocytochemical staining .RESULTS:Un-der hypoxic condition , TGF-β1 (0.01~10 μg/L) increased the synthesis of type I and type III collagens in a dose-de-pendent manner in the CFs .At the concentration of 5μg/L, the synthesis of collagen I and III was significantly increased as compared with control group (P<0.01).RXR agonist 9-cis-retinoic acid (9-cis-RA;10 -9 ~10 -6 mol/L) decreased TGF-β1 (5μg/L)-induced synthesis of type I and III collagens in a dose-dependent manner in the CFs under hypoxic con-dition.The synthesis of type I and type III collagens was significantly inhibited by 9-cis-RA (P<0.01).Smad2 inhibitor ( 20 nmol/L) showed similar inhibitory effect on the synthesis of type I and III collagens induced by TGF -β1 under hypoxic condition.Compared with TGF-β1 intervention group, the cytoplasmic level of p-Smad2 in the CFs was significantly in-creased in TGF-β1+9-cis-RA group, but the nuclear p-Smad2 level was significantly decreased (P<0.05).CONCLU-SION:Retinoid X receptor agonist 9-cis-RA inhibits TGF-β1-induced synthesis of type I and type III collagens in the CFs by repressing p-Smad2 nuclear translocation under hypoxic condition .

Atorvastatin inhibits atherogenesis by RXRα-mediated depressing oxida-tive stress in STZ-induced diabetic ApoE-/-mice with fat-rich diet / 中国病理生理杂志

AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

A Meta analysis of the effect of enhanced hand hygiene on the morbidity of ventilator-associated pneumonia / 中华危重病急救医学

Objective To determine the effect of enhanced hand hygiene on the morbidity of ventilator-associated pneumonia (VAP).Methods Clinical studies which were related to enhanced hand cleansing to the risk of VAP,which were published between July 1992 and June 2013 in English or Chinese were retrieved via computer and manual screening.Data were extracted according to appropriate inclusion and exclusion criteria and analyzed with RevMan 5.0 software.Results A total of 6 studies,all of which were performed with well controlled protocol,involving 28 461 mechanical ventilator days and 32 428 mechanical ventilator days were analyzed.The morbidity of VAP was 39.5 days per 1 000 mechanical ventilator days and 19.5 days per 1 000 mechanical ventilator days before and after enhanced hand cleaning,respectively.The methods of enhancing hand hygiene included feasible hand hygiene apparatus,long-term education,supervision and feedback,as well as increased hand cleaning compliance.All 6 eligible studies reported that enhanced hand washing lowered the risk of VAP,with risk reduction ranging from 29.8％ to 65.5％ with a mean reduction value of 50.6％.Meta analysis showed that enhanced hand cleaning could protect patients from VAP with odds ratio (OR) varying from 1.43 to 5.82 [pooled OR=2.23,95％ confidence interval (95％CI) 1.62-3.07,P＜0.000 01].It was showed in funnel chart that bias in the published articles was not significant.Conclusions Enhanced hand hygiene has an effect of prevention of VAP morbidity and is associated with lowered morbidity of VAP.However,the reliability of this conclusion is questionable because of poor quality of these studies.

Atorvastatin inhibits platelet aggregation and activation following carotid balloon injury in cholesterol-fed rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of atorvastatin on platelet aggregation and activation in the acute phase following balloon-induced carotid artery injury in rabbits fed cholesterol-enriched diet.</p><p><b>METHODS</b>Thirty rabbits were randomly divided into 5 equal groups, namely control group, high-cholesterol group, model group, low-dose (5 mg/kg daily) atorvastatin group, and high-dose (10 mg/kg daily) atorvastatin group. Platelet aggregation rate was measured in the rabbits by turbidimetric platelet aggregometry, and the changes of serum P-selectin and thromboxane B2 (TXB2) levels were detected with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with those in the control group, serum P-selectin level increased significantly (P<0.01) but platelet aggregation rate and TXB2 level exhibited no obvious changes in high-cholesterol group. After carotid artery balloon injury, P-selectin and TXB2 levels and platelet aggregation significantly increased in cholesterol-fed rabbits, reaching the peak level at 24 h after the injury (P<0.01). Compared with the model group, low-dose atorvastatin treatment significantly decreased P-selectin and TXB2 levels and inhibited platelet aggregation in cholesterol-fed rabbits following carotid artery balloon injury (P<0.01), and such effects of atorvastatin were more prominent at a higher daily dose of 10 mg/kg (P<0.05).</p><p><b>CONCLUSIONS</b>Carotid artery balloon injury in rabbits fed cholesterol-enriched diet can induce platelet activation and aggregation, which reaches the peak level at 24 h after balloon injury and can be dose-dependently inhibited by atorvastatin in the acute phase following the injury.</p>

Effects and related mechanism of retinoid X receptor agonist bexarotene on atherosclerosis progression in diabetic apoE(-/-) mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE(-/-)) mice.</p><p><b>METHODS</b>Eight C57BL/6 mice served as control, 46 apoE(-/-) mice were randomized into 4 groups: apoE(-/-) group (n = 10), STZ+apoE(-/-) group (n = 12), STZ+apoE(-/-)+Bex 10 (10 mg×kg⁻¹×d⁻¹)group (n = 12), STZ+ apoE(-/-)+Bex 30 (30 mg×kg⁻¹×d⁻¹) group (n = 12). Diabetic apoE(-/-) animal model was established by intraperitoneal injection of STZ. Blood glucose was determined by glucose oxidase method. Patch area in thoracic aorta was measured by HE staining. Western blotting was used to determine the RXR and gp91(phox) protein level in thoracic aorta. Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.</p><p><b>RESULTS</b>(1) Patch areas of thoracic aorta were larger in apoE(-/-) group than in C57BL/6 group [(38.40 ± 8.95)µm² vs. (0.10 ± 0.01) µm², P < 0.01], further increased in STZ+apoE(-/-) group [(94.06 ± 8.04)µm², P < 0.05 vs. apoE(-/-) group] and significantly reduced in STZ+apoE(-/-)+Bex 10 group [(78.72 ± 4.62)µm², P < 0.05 vs. STZ+apoE(-/-) group] and further educed in STZ+apoE(-/-)+Bex 30 group [(46.13 ± 7.56)µm², P < 0.05 vs. STZ+apoE(-/-)+Bex 10 group]. (2) Blood glucose level, TG, TC, LDL-C, thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ+apoE(-/-) group than in apoE(-/-) group (all P < 0.05). Blood glucose level and TG, TC, LDL-C levels were similar between STZ+apoE(-/-)+Bex10 and STZ+apoE(-/-) group. Thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ+apoE(-/-)+Bex 10 group than in STZ+apoE(-/-) group (P < 0.05). Blood glucose level, TG, TC, LDL-C levels, gp91(phox) expression in thoracic aorta, ROS level in blood and thoracic in STZ+apoE(-/-)+Bex 30 group were lower than in STZ+apoE(-/-) group (all P < 0.05).</p><p><b>CONCLUSION</b>Bexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE(-/-) mice, the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.</p>

Clinical application of double incision in phacoemulsification combined with trabeculectomy / 局解手术学杂志

Objective Conducting phacoemulsification combined with trabeculectomy through double incision to treat glaucoma and cat-aract,and observing the visual acuity,intraocular pressure before and after the operation and complications of this therapy. Methods Totally 60 patients (78 eyes) with glaucoma and cataract from January 2010 to December 2013 in our hospital were observed. 32 patients (40 eyes) who were given phacoemulsification combined with trabeculectomy through double incision were regarded as the observation group,and the other 28 patients (38 eyes) who were merely given phacoemulsification were regarded as the control group. The visual acuity,intraocular pres-sure and anterior chamber of the two groups were observed and recorded,and they were followed up for 36 months. Results Visual acuity and intraocular pressure of the two groups were improved after operation,but the observation group achieved a better result which showed a significant difference (P< 0. 05). Anterior chamber inflammation occurred in patients of the observation group,and 2 cases were of anterior chamber exudation. The control group,by contrast,has less anterior chamber inflammation. There was no hyphema,shallow anterior chamber, choroidal detachment occurred in both of the two groups. Conclusion Using phacoemulsification combined with trabeculectomy through double incision to treat glaucoma and cataract could receive a good recovery of visual acuity and intraocular pressure. Although,more severe anterior chamber inflammation occurred after operation compared with the control group,it can be alleviated soon after medication. This meth-od is a good therapy which can reduce pain and economic burden of patients from multiple operations. But it requires a strict selection of ap-propriate case.

Regulatory effect of RXR/VDR agonists on atherosclerosis and NF-κB ex-pression in diabetic ApoE knockout mice / 中国病理生理杂志

[ABSTRACT]AIM:ToexploretheeffectofretinoidXreceptor(RXR)agonistbexarotene(Bex)andvitaminD receptor (VDR) agonist calcitriol (Cal) on the expression of nuclear factor-kappa B (NF-κB) and the development of atherosclerosis in streptozotocin-induced diabetic apolipoprotein E knockout ( STZ-ApoE-/-) mice.METHODS: Male mice were treated for 12 weeks as follows:(1) C57+vehicle;(2) ApoE-/-+vehicle;(3) STZ-ApoE-/-+vehicle;(4) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1);(5) STZ-ApoE-/-+Cal (10 μg/kg, twice a week);(6) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1) +Cal (10 μg/kg, twice a week).Intraperitoneal injection of STZ was performed to establish the diabetic animal model .Western blotting and immunohistochemical method was used to detect NF-κB level in the thorac-ic aorta.Plaque area in the thoracic aorta was measured using HE staining .RESULTS:Compared with the C57 mice, the fasting blood glucose in the ApoE-/-mice was not remarkably changed .The levels of total cholesterol ( TC) and low-densi-ty lipoprotein ( LDL) were greatly increased .The fasting blood glucose and lipid levels in STZ-ApoE-/-group were much higher than those in ApoE-/-group.Compared with STZ-ApoE-/-group, the fasting blood glucose and lipid levels in Bex group and Cal group were not significantly changed .Compared with the C57 mice, the protein expression of NF-κB in the ApoE-/-mice and the STZ-ApoE-/-mice was remarkably increased .Compared with STZ-ApoE-/-group, the levels of NF-κB in Bex group, Cal group and combination group were greatly decreased .Compared with STZ-ApoE-/-group, the thoracic artery plaque areas in Bex group and Cal group were inhibited (both P<0.05).Compared with Bex group, the plaque area of the thoracic artery in combination group was significantly decreased (P<0.05).CONCLUSION:Bexaro-tene or calcitriol decreases the development of atherosclerosis in streptozotocin -induced diabetic ApoE-/-mice.Bexarotene combined with calcitriol affords greater protection than monotherapy .The mechanism may be involved in down-regulating the expression of NF-κB.

Effects of human tissue kallikerin gene delivery on proliferation and migration of vascular smooth muscle cells / 中国病理生理杂志

AIM: To investigate the effects of adenovirus-mediated human tissue kallikerin (Ad-hKLK1) gene delivery on the proliferation, migration of VSMC_(SHR) induced by platelet derived growth factor-BB (PDGF-BB). METHODS: The VSMC_(SHR) proliferation induced by PDGF-BB was accessed by cell counting and methyl thiazolyl tetrazoliuin (MTT). The migration was assessed by modified Boyden chamber assay. Western blotting was used to determine the expressions of the cycle-independent kinase inhibitors p27~(Kip1) and p21~(Cip1).RESULTS: Proliferation of VSMC_(SHR) induced by PDGF-BB was inhibited after transfection of Ad-hKLK1 (20-100 MOI) in a MOI-dependent manner. The peak inhibition titer of Ad-hKLK1 fell on 100 MOI, with the peak inhibition rate of 39.3% (cell counting, n=3, P<0.01), 30.2% (MTT, n=3, P<0.01), peak stunning rate of cell-cycle in phase G0/G1 at 36.4%. The inhibitory effects of proliferation and cell-cycle caused by hKLK1 gene delivery were significantly abolished by Hoe140, a bradykinin B2 receptor antagonist. Migration of VSMC_(SHR) induced by PDGF-BB was inhibited after hKLK1 gene delivery, with the peak inhibitory rate of 34.6% (n=6, P<0.01). However the inhibitory effects of migration were not blocked by Hoe140. The protein expression of p27~(Kip1) and p21~(Cip1) increased significantly after the hKLK1 gene delivery, whereas Hoe140 nearly completely blocked these effects (n=3, P<0.01, respectively).CONCLUSION: The hKLK1 gene delivery may inhibit the proliferation and migration of VSMC_(SHR) induced by PDGF-BB. Bradykinin B2 receptor probably mediates the up-regulating expression of p27~(Kip1) and p21~(Cip1) that contributes to the inhibitory effects of proliferation of hKLK1. However, the inhibitory effects of migration by hKLK1 gene delivery may not be mediated by bradykinin B2 receptor.

Effects of rosiglitazone on the atherosclerosis and oxidative stress in diabetic rabbits / 中华内分泌代谢杂志

Rosiglitazone was used for intervention of atherosclerosis in diabetic rabbits.The results showed that the intima/medium thickness ratio,cross section area of plaque,and the expressions of NADPH oxidase p22phox,gp91 phox were decreased;while the total anti-oxidative ability was increased after administration of rosiglitazone as compared with the non-intervention group(all P<0.05).Compared with rosiglitazone treatment group,serum hepatocuprein leveI in rosiglitazone prevention group was increased,while serum malonaldehyde level decreased(both P<0.05).This study suggests that rosiglitazone may have the effect of reducing the oxidative stress and the formation of atherosclerotic plaque in diabetics.