1.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.
2.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.
3.Prevention and treatment of short-term complications in 8 heart transplantations and 1 heart lung transplantation
Ji-Ming SHA ; Zhong-Ya YAN ; Yi-Jun WU ;
Chinese Journal of Organ Transplantation 2005;0(08):-
Objective To summary the experience of management for orthotopic homologous heart transplantation,heart-lung co-transplantation and to discuss the postoperative treatment of short-term complications.Methods Orthotopic homologous heart transplantation and heart-lung co- transplantation on 9 cases were performed from May 2004 to February 2006.The patients were traced closely and all complications were treated in time.Results During hospital stay,hypertension oc- curred in one case,right heart insufficiency in one case,infection of mycetes and cytomegalovirus in 2 cases after the heart transplantation,and in the patient undergoing heart-lung co-transplantation,renal inadequacy,bronchial anastomosis stenosis and fungus infection occurred.All patients obtained symp- tomatic relief before discharge.Conclusion Proper perioperative management,immunosuppressive therapy and management of postoperative complications could reduce mortality and obtain satisfactory therapeutic effect in the near future.
4.Expression of survivin and P53 detected by tissue microarray and its significance in gastric adenocarcinoma
Qi-Chang YANG ; Yi-Zhong FENG ; Chong-Jun ZHONG ; Ping WANG ; Xiaohua JI ; Yi SHEN ;
Chinese Journal of Digestion 2001;0(11):-
Objective To investigate the role of survivin and P53 in apoptosis of gastric adeno- carcinoma,as well as its relationship with the clinicopathologic features and the prognosis.Methods The gas- tric tissue microarrays were composed of those from 100 cases of gastric cancer and 30 controls.At these tissue microarrays,expressions of survivin and P53 were investigated immunohistochemically,and tumor cell apoptosis index was examined by TUNEL method.Of the 100 cases,47 cases were followed-up from 14 months to 13 years,in which the survival was analyzed.Results Two paraffin-embedded gastric carcinoma tissue micro- arrays were successfully constructed,including 114 and 116 tissue spots,respectively.Immunohistochemical analysis showed that survivin was expressed in 78 cases (78%).No expression of survivin was detected in control tissue (P0.05).In the 47 cases with followed-up data,univariant analysis revealed that the survival was correlated with invading of vessel and nerve,TNM stages,and expression of survivin.The histological grades and expression of P53 were not related to prognosis.However,Cox stepwise proportional hazards analysis showed that only TNM staging and survivin status retained significant independently in prospecting prognosis.Conclusions The expression of survivin was associated with the pathologic features,TNM stages and prognosis in gastric carcinoma,indicating that overex- pression of survivin may be a poor prognosis factor for gastric carcinoma.
5.Risk factors for aortic and mitral Valve calcification in maintenance hemodialysis patients
Xuesen CAO ; Jianzhou ZHOU ; Jie TENG ; Yihong ZHONG ; Jun JI ; Zhonghua LIU ; Bo SHEN ; Xiaoqiang DING
Chinese Journal of Nephrology 2011;27(4):259-265
Objective To explore the potential risk factors for aortic and mitral valve calcification in maintenance hemodialysis(MHD)patients. Methods Patients on MHD for at least 6 months.aged≥1 8 years without history of surgery or catheter for heart valve disease were enrolled in the study.Echocardiographic examination was performed to detect the calcification.The risk factors for aortic and mitral valve calcification were analyzed by Logistic regression. Results One hundred and eighty-one MHD patients(98 men and 83 women)were enrolled in the study.Of all the patients,aortic or mitral valve calcification was found in 94 patients(5 1.9%),aortic valve calcification in 90 patients(49.7%),mitral valve calcification in 30 patients(16.6%),aortic and valve calcification in 26 patients(14.4%).Multivariate Logistic regression showed that age(β=5.52,P=0.007),dialysis duration(β=6.99,P=0.039)and pre-albumin(β=-12.616,P=0.004)were independently correlated with aortic valve calcification.Mitral valve calcification was independently correlated with dialysis duration(β=6.057,P=0.002),history of primary hypertension(β=3.054,P=0.008),hemoglobin(β=-0.061,P=0.035)and β2 microglobulin(β=7.63,P=0.01).While the correlation between mitral valve calcification and age was borderline significant(β=0.085,P=0.05).Conclusions Valve calcification is prevalent in MHD patients,and aortic valve calcification is more common than mitral valve calcification.Age,dialysis duration and low serum pre-albumin are independent risk factors for aortic valve calcification.The risk factors for mitral valve calcification include age,dialysis duration,history of primary hypertension,anemia and high serum β2 microglobulin.
6.Cross-sectional study on hypertension in patients with chronic kidney disease
Jing LIN ; Xiaoqiang DING ; Jun JI ; Chensheng FU ; Yihong ZHONG ; Jianzhou ZOU ; Jie TENG ; Yi FANG
Chinese Journal of Nephrology 2009;25(11):827-831
Objective To investigate the situation of prevalence,treatment and control of hypertension in patients with chronic kidney disease(CKD)by CROSS-sectional study. Methods Nine hundred out-patients with CKD in our department from November 2006 to March 2007 were enrolled in the study,including 480 male and 420 female.Among 900 CKD cases,354 patients underwent maintenance dialysis,including 228 on hemodialysis and 126 on peritoneal dialysis.Results The prevalence of hypertension in CKD patients was 80.2%(nude 83.5%vs female 76.4%,P<0.01).The prevalence of hypertension in patients on dialysis was significantly higher than that in non-dialysis patients(90.1%vs 73.8%,P<0.01),but there was no significant difference between hemodialysis and peritoneal dialysis cases.Antihypertensive treatment rate was 92.4%in CKD patients with hypertension.and was significantly higher in patients on dialysis than that in non-dialysis patients(95.6%vs 89.8%.P<0.01).The control rate according to current recommendations for CKD patients (BP<130/80 mm Hg) was very low. Control of both SBP and DBP was only achieved in 20.4% of non- dialysis patients. The control rate of hypertension (BP< 125/75 mm Hg) in patients with proteinuria >1 g/24 h was 8.4%. The proportion of dialysis patients with BP<140/90 mm Hg was significantly lower than that of non-dialysis patients (45.2% vs 55.5%, P<0.01). The percentage of hemodialysis patients with BP < 140/90 mm Hg was significantly higher than that of peritoneal dialysis patients (49.8% vs 36.5%, P<0.05). The prevalence of hypertension was associated with the decrease of renal function and the increase of age. The prevalence of hypertension in diabetic nephropathy was higher than that in primary glomerular diseases. Patients received 1, 2, 3 and 4 or more kinds of antihypertensive drugs accounted for 37.2%, 37.5%, 19.3% and 5.9% respectively. The combination of calcium channel blocker (CCB) and renin-angiotensin-aldosterone system (RAAS) inhibitors was more frequently used in CKD patients. The CCB was the most frequently prescribed drug (74.1% ), followed by angiotensin Ⅱ receptor blockers (ARB) (48.4%), angiotensin-converting enzyme inhibitors (ACEI) (25.6%) and alpha, beta-blockers (24.7%). Conclusions The prevalence of hypertension in CKD patients is quite high, which is associated with the progression of renal function, increase of age, the type of underlying kidney disease, obesity and diabetes mellitus. The control of hypertension is unsatisfied in CKD patients, especially in dialysis patients and those with overt proteinuria.
7.Surgical repair and reconstruction of male external genitals.
Zhong WANG ; Hai-jun YAO ; Da-chao ZHENG ; Wen-ji LI
National Journal of Andrology 2015;21(7):579-586
One of the challenges in andrology nowadays is the diagnosis and treatment of external genital abnormalities and defects along with the consequent voiding, sexual, and reproductive dysfunctions, for which no guidelines are yet available. Hitherto, surgical repair and reconstruction are efficient for these diseases. The key to these operations is to individualize surgical strategies according to the specific local lesion and dysfunction, usually involving flap and graft techniques. This article presents our experience in the surgical treatment of penile and scrotal abnormalities and defects with urological and andrological techniques and microsurgical strategies, focusing on the external repair and functional reconstruction. Satisfactory treatment outcomes pivot on a precise evaluation of the disease, a rational design of surgical procedures, and an earnest communication with the patient. Some cases are rather complicated and challenging, usually with complications, and therefore deserve further researches for more effective treatment strategies in clinical practice.
Andrology
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Genitalia, Male
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abnormalities
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surgery
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Humans
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Male
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Penis
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abnormalities
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surgery
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Reconstructive Surgical Procedures
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methods
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Scrotum
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abnormalities
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surgery
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Surgical Flaps
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Treatment Outcome
8.Regulation effects of electroacupuncture with different acupoint combinations on blood lipid in rats with hyperlipemia.
Guo-xin ZHANG ; Jin-ling MIAO ; Zhong-Yuan ZHANG ; Hai-Jun WANG ; Lai-xi JI
Chinese Acupuncture & Moxibustion 2014;34(9):894-897
OBJECTIVETo observe the regulatory effects of electroacupuncture with different acupoints combinations on blood lipid and atherosclerosis index (AI) in rats with hyperlipemia, so as to make a preliminary screening for the optimal acupoints combination for hyperlipemia.
METHODSOne hundred and five clean-grade SD male rats were randomly divided into 9 groups, including a normal group, a model group, a Quchi group, a Zhongwan group, a Fenglong group, a Quchi+Zhongwan group, a Quchi+Fenglong group, a Zhongwan+Fenglong group and a Quchi+Zhongwan+Fenglong group (three acupoints group), 17 rats in the normal group and 11 rats in the rest groups. The normal group was fed with normal diet, while the rest groups were fed with high-fat diet for 3 weeks to prepare the hyperlipemia model. All the rats were given unlimited water. After the establishment of model, the normal group was fed freely without any treatment; the model group was bundled and immobilized everyday; the rest groups were bundled, immobilized and treated with electroacupuncture at corresponding acupoints with disperse-dense wave, 20 min per time, once a day. After 4 weeks, the blood examples were collected from abdominal aorta to measure the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and analyzed the AI in each group.
RESULTSAfter the treatment, TC, TG, HDL-C, LDL-C and AI in each acupuncture group were all lower than those in the model group (P<0.05, P<0.01). Compared with single acupoint group and the Quchi+Zhongwan group, the content of TC in the three acupoints group was lower (P<0.01). The differences of content of TG among each acupuncture group were not significant (all P>0.05). Compared with the rest 6 acupuncture groups, the content of HDL-C and AI in the three acupoints group were significantly different (all P<0.05). The content of LDL-C in the three acupoints group was decreased as compared with the Quchi group and the Zhong-wan group.
CONCLUSIONThe electroacupuncture at "Quchi" (LI 11), "Zhongwan" (CV 12) and "Fenglong" (ST 40) has more advantages on regulating the content of HDL-C and LDL-C as well as improving AI in hyperlipemia rats, and it has superior effects on blood lipid metabolism.
Acupuncture Points ; Animals ; Electroacupuncture ; Humans ; Hyperlipidemias ; blood ; therapy ; Lipids ; blood ; Male ; Rats ; Rats, Sprague-Dawley
9.Treatment of dens fracture with cannulated screw fixation under locational guidance
Zhaowan XU ; Feng LI ; Bingwu WANG ; Guoxia SUI ; Jun ZHONG ; Weiqiang LIU ; Xuwu JI ; Qingshan ZHUANG
Chinese Journal of Trauma 2011;27(6):509-512
Objective To evaluate the clinical effect of the cannulated screw fixation in treatment of the dens fracture under locational guidance. Methods The study involved 27 patients treated with the cannulated screw fixation under locational guidance from January 2005 to January 2009.There were 19 patients with type II fracture and eight with type light m fracture.The lateral and open mouth position X-ray examination of the cervical ventebrae was done to observe the fracture healing. Results The operation lasted for a range of 40 minutes to 1.3 hour (average 1.0 hour),which showed no any complications.The patients were followed up for average 6.5 months(3-12 months),which showed sound fracture healing in 26 patients but nonhealing in one. Conclusion The cannulated screw fixation for treatment of the dens fracture under locational guidance is characterized by easy operation,minor trauma and satisfactory outcome.
10.Effect of Daidzein intravitreal injection on optic nerve injury in rats
Zhong-Jun, TANG ; Zhen-Ping, HUANG ; Wen-Jing, YANG ; Yong-Xiang, ZOU ; Ji-Ping, CAI
International Eye Science 2014;(8):1378-1381
AIM:To discuss Daidzein intravitreal injection whether has protective and recovery effects on acute nerve damages.
METHODS:After the crush models of acute optic nerve were set up, 72 males SD rats were divided into 4 groups randomly as common group without surgery, FBS negative control group, Daidzein treatment group ( 10μmol/L, 100μmol/L, 1000μmol/L ) and positive control group using rats nerve growth factor ( mNGF, 100ng/mL ). Three days after interference, all experimental animals were executed. HE staining was used to evaluate morphologic change of the retina, immunohisochemical staining and western-blot tests for identifying and quantifying the distinct expression of Caspase-3 and GAP-43 among the groups.
RESULTS: Compared with the normal group and negative control group, retinal morphology of different concentrations of each Daidzein treatment group and positive control group was more complete, the expression of Caspase-3 protein was relatively lower, the expression of GAP-43 protein was relatively higher, the differences have statistically significance (P<0. 05).CONCLUSION: Daizein injection in the vitreous cavity has the capacity of protection and restoration in rat's acute nerve damages.