1.Administration of sirolimus affects vein graft neointima hyperplasia
Feng XIAO ; Lufeng ZHANG ; Zhihui SHI
Journal of Peking University(Health Sciences) 2003;0(05):-
Objective: To investigate the effect of Sirolimus on vein graft neointima hyperplasia via oral administration compared with local delivery, and find out an effective and safe way to provide support for clinical application. Methods: A rabbit external jugular vein-to-common carotid artery model was established. Twenty-four healthy rabbits were divided into 4 groups at random: blank-control group, F-127 control group, group 3 that received locally applied slow-releasing Sirolimus with F-127, group 4 that received oral Sirolimus (the commercial name Rapamune). The ratio of intima to medium thickness and re-stenosis rate (ratio of lumina to lumina plus intima area) were measured, PCNA positive cells by immunohistochemical staining were detected to indicate the degree of cell proliferation, and apoptosis cells detected by TUNEL. Results: Compared with blank-control group, neointima hyperplasia was inhibited significantly in group 3 and group 4 intima thickness were (90.11?10.99)?m versus (29.38?10.45) ?m, (18.29?9.03)?m, respectively. Re-stenosis rate was reduced (lumina area/ total area ratio were 0. 58?0.11 versus 0.80?0.16, 0.77?0.16, respectively). Proliferation of VSMC was inhibited (cell proliferation indexes were 31.03%?6.80% versus 20.32%?9.19%, 16.22%?5.85%, respectively) and cell apoptosis level raised (cell apoptosis indexes were 16.27%?6.49% versus 33.39%? 7.05%, 33.42%?7.11%, respectively). There was no significant difference between group 3 and group 4. Conclusion: Both locally applied slow-releasing Sirolimus and oral Rapamune could inhibit vein graft neointima hyperplasia; Administration via local delivery was preferred for little side-effect on the whole body. This conclusion provides support for clinical application.
2.Cilia Toxicity and Mucosal Irritation of Gastrodin Nasal Temperature-sensitive in situ Gel
Zhihui YAN ; Yi TAN ; Miao XIAO
China Pharmacist 2017;20(2):253-255
Objective:To evaluate the nasal safety of gastrodin nasal temperature-sensitive in situ gel through the studies on cilia toxicity in toads and mucosal irritation in rats. Methods:The toads were randomly divided into four groups, saline group, gastrodin in situ gel group, blank gel matrix group and sodium deoxycholate group, and the cilia toxicity was observed in vivo by a toad palate meth-od. The rats were randomly divided into three groups, saline group, gastrodin in situ gel group and blank gel matrix group, and the mucosal irritation was studied in rats through the observation of nasal mucosal pathological changes and behavioral indices. Results:Compared with the saline group, gastrodin in situ and blank gel matrix showed no notable effect on the cilia movement function in toads, and the effect on cilia movement of sodium deoxycholate showed statistically significant difference when compared with that of sa-line, gastrodin in situ gel and blank gel matrix (P<0. 01). During and after the treatment, no sneezing appeared in the rats. Com-pared with that in the saline group, the number of scratching nose in the gastrodin in situ gel group and blank gel matrix group in-creased (P<0. 05) without difference between the groups (P>0. 05), and after the 2-day withdrawal, that in the gastrodin in situ gel group and blank gel matrix group decreased significantly when compared with that at the last administration (P<0. 05) and showed no notable difference when compared with that in the saline group (P>0. 05). The number of inflammatory cells in the nasal mucosa in the gastrodin in situ gel group and blank gel matrix group increased complicated with congestion and cilia falling off, and after the with-drawal, the mucosal morphology in the three groups showed no significant difference. Conclusion:The local application of gastrodin in situ gel has high security, which is valuable to be studied further.
4.Clinical study of cerebral arteriovenous malformation associated with hemodynamics correlative aneurysms
Yiyou LI ; Zhihui ZHU ; Zhaowei QIN ; Jianguo XIAO ; Xiaodong WANG
Chinese Journal of Postgraduates of Medicine 2013;36(32):26-28
Objective To investigate the classification of cerebral arteriovenous malformation (AVM) associated with hemodynamics correlative aneurysms and its efficiency treated by endovascular treatment.Methods The clinical data of 17 patients of AVM associated with hemodynamics correlative aneurysms undergoing endovascular treatment were analyzed retrospectively.Results Eleven cases of aneurysms with great divergence between the aneurysm and arteriovenous malformation were embolized,6 cases of aneurysms without a great divergence between the aneurysm and arteriovenous malformation,1 case of aneurysm was treated with stent,other 5 cases of aneurysms were not treated.Eleven cases of arteriovenous malformations were embolized completely,4 cases were embolized 71%-90% and 2 cases were embolized 50%-70%.Six cases with residual were given radiotherapy.Follow-up 3 months to 3 years,there were no cases of cerebral hemorrhage or death.Unhandled 5 cases of aneurysm and 1 case of stent implantation with the follow-up by using digital subtraction angiography,laneurysm with a stent was closed.Three aneurysms were disappeared and 2 aneurysms were reduced significantly among the 5 cases of aneurysms without treatment.One case of aneurysm occlusion in patients with stent implantation.Conclusions Classification based on a great divergence artery or not between the aneurysm and arteriovenous malformation is more instructive for clinical treatmen of cerebral arteriovenous malformation associated with hemodynamics correlative aneurysm.If it has not a great divergence artery between aneurysm and arteriovenous malformation,arteriovenous malformation after a thorough treatment,aneurysms need not be treated.The endovascular treatment for cerebral arteriovenous malformation associated with hemodynamics correlative aneurysms has a good efficiency and can be treated as a priority.
5.Endovenous radiofrequency ablation in combination with TriVex for treatment of chronic venous insufficiency of the lower extremity
Zhihui ZHANG ; Shaomang LIN ; Yandan YAO ; Jianbin XIAO ; Baigen ZHANG
Chinese Journal of General Surgery 2008;23(3):179-182
objective To evaluate the therapeutic efficacy of endovenous radiofrequency ablation in combination with TriVex for the treatment of chronic venous insufficiency (CVI)of the lower extremity.Methods One hundred and fifty CVI cases(150 limbs)were randomly assigned to Group A(75 limbs)and Group B(75 limbs).Patients in Group A were treated with greater saphenous vein radiofrequency ablation procedures in combination with TriVex.Patients in Grpup B were treated with greater saphenous vein traditional stripping operation in combination with TriVex.The short-term results in hospital and patient self-assessment for the operation at postoperative 4 week were compared with each other:The changes of CEAP classification and venous clinical severity score(VCSS)were compared. Results Operation time was(67±11)min in Group A versus(69-4-9)min in Group B(P>0.05).Postoperative pain,average hospital stay in Group A were significantly less and shorter than in Group B(P <0.05).The scores of selfassessment for the operation were(11.21±2.00)in Group A versus(10.52±2.08)in Group B(P<0.05).The change of CEAP classification and VCSS were statistically significant after operation in both groups(P<0.01).The VCSS decreased 4.6 ±2.5 in Group A versus 4.3±2.7 in Grpup B(P>0.05).Conclusions Endovenous radiofrequency ablation in combination with TriVex for treatment of CVI are effective,less traumatic,of fast recovery.CEAP classification and VCSS are useful tools for assessing outcomes after the operation.
6.Regulation of Nrf2 pathway to protect ventilator induce lung injury in vivo via inhibition of caveolin ;phosphorylation
Rong ZHONG ; Jun XIAO ; Chunguang DAI ; Zhihui YU ; Ji ZHOU
Chinese Critical Care Medicine 2016;28(6):547-552
Objective To investigate whether the inhibition of caveolin-1 (Cav-1) phosphorylation will regulate effectively nuclear factor-erythroid 2-related factor (Nrf2) signal pathway and downstream effector molecules and protest against ventilation induced lung injury (VILI) in an animal model in vivo. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n = 10): sham group in which rats did not receive ventilation but received tracheotomy; lung protective ventilation (PV) for 1 hour or 2 hours group; mechanical ventilation (MV) at high volume tidal (VT, 40 mL/kg) for 1 hour or 2 hours group; protein tyrosine kinase inhibitor PP2 or rosiglitazone (Rsg) pretreatment + high VT ventilation for 1 hour or 2 hours groups. The two pretreatment groups were given intraperitoneal injection PP2 15 mg/kg or intragastric administration of Rsg 5 mg/kg 1 hour before ventilation respectively. The rats were sacrificed after model reproduction, and bronchoalveolar lavage fluid (BALF) was collected. Pulmonary vascular permeability was measured by Evans blue (EB). The levels of tumor necrosis factor-α (TNF-α), activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) in BALF were determined by enzyme linked immunosorbent assay (ELISA). Then the lung tissues were collected, the lung wet/dry ratio (W/D) was calculated, the changes in pathology was observed with light microscope, and myeloperoxidase (MPO) activity was determined by colorimetric analysis. Nrf2 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of Cav-1 tyrosine residues 14 phosphorylation (pCav-1-Y14), Cav-1, peroxisome proliferators-activated receptor γ (PPARγ) and claudin-5 as well as Nrf2 in cytoplasm and nucleus were determined by Western Blot. The positive expressions of PPARγ and claudin-5 in lung tissues were assayed with immunohistochemistry staining. Results There were no obvious pathological changes in the lung tissue in sham group and PV groups, and there were no significant differences in all the parameters between the two groups either. However, the injury in lung tissue was severe in the high VT groups in which W/D ratio, EB contents, MPO activity, and TNF-α, AP-1, IL-8, NF-κB levels in BALF as well as the protein expressions of Cav-1 and pCav-1-Y14 were significantly higher than those of sham group and PV groups, and the protein expressions of PPARγ and claudin-5 were significant lower than those of sham group and PV groups with a dose-dependent manner; but Nrf2 expressions in cytoplasm and nucleus did not show a statistical increase. After pretreatment of PP2 or Rsg, W/D ratio, MPO activity, EB contents, TNF-α, AP-1, IL-8, and NF-κB in BALF were significantly decreased as compared with those of high VT group, and RT-PCR showed significant up-regulation of Nrf2 mRNA in lung tissues too. Moreover, there was a statistically significant increase in expressed Nrf2 proteins in nucleus in PP2 or Rsg groups as compared with those of high VT groups [Nrf2 in nucleus (gray value): 0.61±0.06, 0.56±0.06 vs. 0.31±0.02 at 1 hour, 0.38±0.06, 0.43±0.07 vs. 0.22±0.03 at 2 hours; all P < 0.05], but no significant difference was found in the expression of Nrf2 protein in the cytoplasm among all groups. The protein expressions of pCav-1-Y14 in PP2 pretreatment groups were significantly lower than those of high VT groups (gray value: 0.89±0.04 vs. 1.48±0.02 at 1 hour, 0.86±0.02 vs. 1.31±0.01 at 2 hours; both P < 0.05); but expressed PPARγ proteins and expressed claudin-5 proteins in PP2 or Rsg pretreatment groups were significantly higher than those of high VT groups [PPARγ (gray value): 0.34±0.07, 0.42±0.13 vs. 0.17±0.07 at 1 hour, 0.38±0.09, 0.33±0.07 vs. 0.16±0.03 at 2 hours; claudin-5 (gray value): 0.33±0.05, 0.38±0.07 vs. 0.14±0.03 at 1 hour; 0.30±0.06, 0.31±0.04 vs. 0.17±0.04 at 2 hours; all P < 0.05]. Conclusions The inhibition of Cav-1-Y14 phosphorylation can increase the expression of Nrf2 in the nucleus, then result in an increase in the protein expressions of PPARγ and claudin-5 of its effector molecules. This effect can reduce the inflammation and capillary permeability of lung tissue in the model of VILI.
7.Evaluation of the outpatients risk pooling of capitation payment under basic medical insurance in China
Ronghai WU ; Liyang WANG ; Zhihui CAO ; Li XIAO ; Zhiguo ZHANG
Chinese Journal of Hospital Administration 2015;(4):266-270
An analysis is made according to policy documents of localities on capitation payment, and by means of literature review and the analysis framework of the World Bank,this paper reviewed studied the following:definition of service package,per capita rate,designated institutions,design of financial regulations,and service supervision.Given the attempts made at localities,most of the schemes are incomplete in design,and defective in capitation measurement methods and dynamic adjustment mechanisms.The authors recommend a systematic design of the capitation payment scheme for better outcomes.
8.Effect of amikacin and prulifloxacin alternate application in the treatment of lung infections in ICU resistant acinetobacter bauman
Lingmin ZHOU ; Zhihui GUAN ; Feifei SHAO ; Xiaorong XIAO
Chinese Journal of Biochemical Pharmaceutics 2016;36(12):99-102
Objective To investigate the effect of Amikacin and prulifloxacin alternate application in the treatment of Lung infections in ICU resistant Acinetobacter Bauman.Methods 82 cases of Lung infections in ICU resistant Acinetobacter Bauman from August 2014 to August 2016 in our hospital were selected and randomLy divided into two groups, 41 cases in control group were given routine treatment, 41 cases in the experimental group were treated with Amikacin and prulifloxacin alternate application, and patients were treated continuous for two weeks.Levels of serum CRP, PCT, WBC, N%, SCR, BUN, AST, ALT, scores of APACHE II and CPIS and clinical efficacy were observed pre-and post-treatment.Results After two weeks, levels of serum CRP, PCT, WBC and N% in experimental group were significantly lower than control group, scores of APACHE II and CPIS were significantly lower than the control group, the total clinical efficiency was higher than the control group(P<0.05), and the levels of serum SCR, BUN, ALT, AST were lower, but had no statistically difference.Conclusion Amikacin and prulifloxacin alternate application in the treatment of Lung infections in ICU resistant Acinetobacter Bauman can reduce the patient's inflammatory reaction and the degree of infection.
9.Regulation of paxillin tyrosine phosphorylation via inhibition of c-Abl kinase to protect ventilator induce lung injury in vivo in rats
Rong ZHONG ; Jun XIAO ; Chunguang DAI ; Zhihui YU
Chinese Critical Care Medicine 2017;29(7):596-601
Objective To determine whether the inhibition of paxillin tyrosine residues 31 and tyrosine residues 118 (Pxn Y31 and Pxn Y118) phosphorylation via inhibition of c-Abl kinase will effectively block its downstream effector molecules vessel endothelium-cadherin (VE-cad), and whether Rho/Rho kinase activation which will induce the vascular barrier dysfunction. Methods Ninety healthy male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n =10). Only tracheotomy was undergone in the sham group. Groups of protective ventilation were set at a volume tidal (VT) of 6 mL/kg, a positive end-expiratory pressure (PEEP) of 5 cmH2O (1 cmH2O =0.098 kPa) for 1 hour or 2 hours (namely group PVT 1 h and group PVT 2 h), respectively. Groups of high VT were put on mechanical ventilation (MV) at high VT 30 mL/kg, PEEP 0 for 1 hour or 2 hours (namely group HVT 1 h and group HVT 2 h), respectively. Groups UO126 and AG957 pretreatment were set on MV at HVT for 1 hour or 2 hour respectively, but they were given p42/44 mitogen-activated protein kinase (p42/44MAPK) inhibitor UO1261 mg/kg by intraperitoneal injection or c-Abl kinase inhibitor AG95710 mL/kg by intragastric injection 1 hour before HVT ventilation. All the animals were sacrificed after experiments and specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Pulmonary vascular permeability was measured by Evans blue (EB). The levels of tumor necrosis factor-α(TNF-α) in BALF were measured by enzyme linked immunosorbent assay (ELISA). Then the change of lung tissue pathology was observed with light microscope, diffuse alveolar damage system (DAD) score and lung wet/dry ratio (W/D) were estimated. The myeloperoxidase (MPO) activity was measured by colorimetric analysis, phosphorylations of c-Abl Y245, Pxn Y31, Pxn Y118, VE-cad Y658, p42/44MAPK Y202/Y204, myosin light chain (MLC) and myosin-associated phosphatasetype Y696 (MYPT Y696) were determined by Western Blot. Results ① There were no obvious pathological changes in the lung tissue in the sham group and PVT 1 h or 2 h group, and also there were no significant differences in all the parameters between above groups. However, the injury in lung tissue was severe in the HVT groups. In addition, DAD score, lung W/D ratio, EB content, the activity of MPO, and TNF-α in BALF in HVT groups were significantly higher than those in sham group and PVT groups. After pretreatment with AG957 or UO126, all the parameters were significantly decreased as compared with those of groups HVT. ② The levels of phosphorylation of the proteins in lung tissue in HVT groups were increased as compared with those of group sham and groups PVT, especially at 2 hours of MV. However, compared with groups HVT, the level of p-VE-cad Y658 in lung tissue decreased significantly in group AG957 and group UO126 at 2 hours after HVT. However, the levels of all phosphorylated proteins at 2 hours were significantly lowered in the AG957 group compared with those of the HVT group [p-c-Abl Y245 (gray value): 0.29±0.04 vs. 0.42±0.04, p-Pxn Y31 (gray value): 0.51±0.03 vs. 0.70±0.05, p-Pxn Y118 (gray value):0.65±0.04 vs. 0.91±0.04, p-VE-cad Y658 (gray value): 0.77±0.07 vs. 1.32±0.07, p-p42/44MAPK Y202/Y204 (gray value): 0.38±0.06 vs. 0.61±0.03, p-MLC (gray value): 0.37±0.04 vs. 0.77±0.05, p-MYPT Y696 (gray value):0.54±0.05 vs. 0.87±0.06, all P < 0.05]. After pretreatment with UO126, the phosphorylation level of VE-cad in lung tissue at 2 hours was significantly lower than that of HVT group (gray value: 0.74±0.04 vs. 1.32±0.07), and the phosphorylation levels of p42/44MAPK and its downstream effector molecules MLC and MYPT Y696 were also significantly decreased [p-p42/44MAPK Y202/Y204 (gray value): 0.38±0.07 vs. 0.61±0.03, p-MLC (gray value):0.37±0.04 vs. 0.77±0.05, p-MYPT Y696 (gray value): 0.55±0.05 vs. 0.87±0.06, all P < 0.05]. Conclusions Pxn Y31 and Pxn Y118 phosphorylation could be blocked by inhibition of c-Abl kinase, which could strengthen VE-cad at attachment junction and might block formation of Pxn-guanine nucleotide-exchange factor H1 (GEF-H1)-p44/42MAPK signalosome which induce activation local Rho signaling, lead to activation of MLC phosphorylation, actomyosin contraction, and increase endothelial permeability.
10.Research on the effect of protection against ventilator-induced lung injury via regulation of caveolin-1/heme oxygenase-1 signaling
Rong ZHONG ; Jun XIAO ; Zhihui YU ; Ji ZHOU ; Chunguang DAI
Chinese Critical Care Medicine 2015;(7):568-573
ObjectiveTo determine whether the inhibition of caveolin-1 tyrosine residues 14 (Cav-1-Y14) phosphorylation with protein tyrosine kinase inhibitors (PP2) will upregulate heme oxygenase-1 (HO-1) activity to protect against ventilation induced lung injury in vivo of an animal model.Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into nine groups (eachn = 6). Group A served as normal control group, in which rats did not receive ventilation but tracheotomy. Groups B1 and B2 received lung protective ventilation respectively for 1 hour or 2 hours. Groups C1 and C2 received high tidal volume (40 mL/kg) ventilation for 1 hour or 2 hours, respectively. The group D1 or D2 also received high tidal volume ventilation for 1 hour or 2 hour respectively, but they were given PP2 1 hour before high tidal volume ventilation. The groups E1 and E2 also received high tidal volume ventilation respectively for 1 hour or 2 hours, but tyrosine kinase inhibitor PP2 and HO-1 inhibitor zinc protoporphyrinⅨ(ZnPPⅨ) were given to animals 18 hours before high tidal volume ventilation. All the animals were sacrificed after ventilation, and the specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Then the changes in pathology of lung tissue was observed, and diffuse alveolar damage scores (DAD) were calculated, myeloperoxidase (MPO) activity was measured by colorimetric analysis, lung wet/dry ratio (W/D) was estimated. The expressions of phosphorylated caveolin-1 (P-Cav-1-Y14), caveolin-1 (Cav-1) and HO-1 were determined by Western Blot. The expressions of high mobility group B1 (HMGB1) and advanced glycation end product receptor (RAGE) in lung tissues were assayed with immunohistochemistry staining. The levels of tumor necrosis factor-α(TNF-α) in BALF were measured by enzyme linked immunosorbent assay (ELISA).Results There was no significant difference in all the parameters between group A and groups B. Compared with group B1, DAD score, W/D ratio, the activity of MPO and the concentration of TNF-α in BALF in group C1 were significantly increased [DAD score:7.97±0.59 vs. 0.55±0.13, W/D ratio: 5.70±1.61 vs. 5.04±0.63, MPO (U/g): 1.82±0.14 vs. 0.77±0.26, TNF-α(ng/L): 370.10±29.61 vs. 54.38±8.18, allP< 0.05], and the injury in ventilation 2 hours group was more serious than that in ventilation 1 hour group. Compared with groups C, all the parameters in groups D were significantly decreased. The parameters in groups E were significantly higher than those in groups A, B, and D, but no significant difference was found as compared with groups C. Compared with groups B, the protein expressions of Cav-1 and P-Cav-1-Y14 (gray value) in groups C were significantly increased (1 hour: 1.49±0.02 vs. 1.26±0.13, 1.34±0.02 vs. 0.87±0.04;2 hours: 1.58±0.02 vs. 1.27±0.27, 1.31±0.01 vs. 0.95±0.02, allP< 0.05), and the expression of HO-1 protein (gray value) was significantly decreased (1 hour: 0.59±0.02 vs. 1.10±0.01, 2 hours: 0.49±0.01 vs. 1.20±0.02, both P< 0.05). No significant difference in Cav-1 protein expression between groups D as well as groups E and groups C. The protein expression of P-Cav-1-Y14 in groups D and E was significantly lower than that in groups C. The protein expression of HO-1 in groups D was significantly higher than that in groups C, but the phenomenon was not found in groups E as compared with groups C. Compared with group A, the positive expression of HMGB1 and RAGE in lung tissue in groups C and E was significantly increased, but no significant difference was found between groups B as well as groups D and group A.Conclusion Cav-1-Y14 phosphorylation is the key factor for ventilator induced lung injury, which can not only lead to a decrease in vascular barrier function, but also inhibit the activity of HO-1 enzyme, thus further aggravates inflammatory injury of the lung as induced by mechanical ventilation.