1.Effects of minute quantity of endogenous endotoxin from the lung on ventilator-induced lung injury in rats
Xiaolei WANG ; Haiou LI ; Kezhong LI
Chinese Journal of Anesthesiology 2010;30(1):79-82
Objective To investigate the effects of minute quantity of endogenous endotoxin originating from the lung on ventilator-induced lung injury in rats. Methods Thirty-two pathogen-free male adult SD rats weighing 370-390 g were randomly divided into 4 groups ( n = 8 each): group I spontaneous breathing (group C) ; group Ⅱ spontaneous breathing + IPS (group CL) ; group IE mechanical ventilation (group M) and group IV mechanical ventilation + LPS (group ML). The animals were anesthetized with intraperitoneal 20% urethane 0.8 ml/100 g. Right common carotid artery and left femoral vein were cannulated for BP monitoring and fluid and drug administration. The animals were tracheostomized. In group CL and ML LPS 100μg /kg was instilled into trachea. In group M and ML the animals were mechanically ventilated (V_T 20 ml/kg, PEEP=0, I = E = 1:1). P_(ET) CO_2 was maintained at 35-45 nun Hg by adjusting respiratory rate. The animals were breathing or ventilated with room air,and ECG, BP, HR and P_(ET)CO_2 were continuously monitored. Blood gases were analyzed at the beginning and 1, 2 and 3 h of experiment. The animals were sacrificed at 3 h of experiment. The lungs were removed for microscopic examination. The pathological changes of the lung were scored (0 = normal,3 = severe change) . Wet/dry lung weight ratio was determined. The left lung was lavaged. The broncho-alveolar lavage fluid (BALF) was collected. WBCs in BALF were counted. Pulmonary albumin permeability (PAP) (BALF protein concentration/plasma protein concentration) was determined. Plasma TNF-a and macrophage inflammatory protein 2 (MIP-2) concentrations were detected with ELISA. The endotoxin receptor CD14 mRNA expression in lung tissue was determined by RT-PCR and the macrophage CD14 expression in BALF was determined by immuno histochemistry in group C and M. Results Wet/dry lung weight ratio and PAP were significantly higher in group ML than in group M and C. WBC count in BALF, the pathological score and plasma MIP-2 concentration were significantly higher in group M and ML than in group C and were significantly higher in group ML than in group M. TNF-a concentration was significantly higher in group CL and ML and was not detected in group C and M. CD14mRNA expression in the lung tissue and CD14 expression in BALF macrophage were significantly higher in group M than in group C. Conclusion Minute amount of endogenous endotoxin from the lung can aggravate ventilator-induced lung injury in rats. Mechanical ventilation with large tidal volume sensitizes the lung to LPS stimulation through up-regulation of CD14 exexpression.
2.Long-term follow-up of two interventional procedures for achalasia
Yingsheng CHENG ; Minghua LI ; Kezhong SHANG
Journal of Interventional Radiology 2005;14(2):171-174
Objective To observed the long-term follow-up of the two types of interventional procedure for achalasia. Methods The study cohort was comprised of 140 patients of achalasia including 70 patients treated under fluoroscopy with pneumatic dilation (group A) and 70 with temporary partially covered metal stent dilation (group B). Results One hundred and forty dilations were performed on the 70 patients of group A with complications of chest pain (n=35), reflux (n=18), and bleeding (n=8); 38 atients of relapsing dysphagia during a 12-month follow-up, and 50 patients out of 60 of recurrent dysphagia during a 36-month follow-up. Seventy partially covered expandable metal stents were temporarily placed in the 70 patients of group B and withdrawn after 3-7 days via gastroscopy with complications of chest pain (n=28), reflux (n=15), and bleeding (n=9); 7 patients out of 70 exhibited dysphagia relapse during a 12-month follow-up, and 9 out of 58 patients exhibited dysphagia relapse during a 36-month follow-up. All the stents were inserted and withdrawn successfully. The follow-up in groups A-B lasted for 12-96 months. Conclusion Temporary partially covered metal stent dilation is one of the best methods of interventional procedure for achalasia in long-term follow-up. (J Intervent Radiol,2005,14:171-174)
3.Clinical verification and application of mathematical models for predicting the probability of malignant or benign in patients with solitary pulmonary nodules
Desong YANG ; Yun LI ; Guanchao JIANG ; Kezhong CHEN ; Jun WANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(2):82-85
Objective Based on the mathematical models established in Department of Thoracic Surgery of Peking University People's Hospital for predicting malignant probability for solitary pulmonary nodules ( SPN),another continuous 145 patients with SPN were assessed to verify the accuracy of the model comparing with foreign models (Mayo model and VA model).Methods A retrospective cohort study in our institution included 145 patients with definite pathological diagnosis of SPN from Oct 2009 to Aug 2011,72 males and 73 females,average age (59.4 ± 12.2 ) years old.Clinical data included age,gender,course of disease,symptoms,history and quantity of smoking,time of smoking cessation,history of tumor,family history of tumor,tumor site,diameter,calcification,speculation,border,lobulation,traction of pleural,vascular convergence sign,and cavity.These raw data were incorporated into our model,Mayo model and VA model,the probability of malignant in every patient was calculated separately according to methods described before.The sensitivity and specificity of these 3 models were evaluated then.Afterwards,calibration of the 3 models was assessed by the Hosmer-Lemeshow (H-L) test.Discrimination was tested by calculating the area under curve ( AUC ) after the receiver operating characteristic (ROC) curve was drawn.Results 32.4% (47 in 145 patients) of the nodules were malignant,and 67.6% (98 in 145 patients) were benign in this group.Verified the accuracy of our model with sensitivity of 94.9%,specificity of 66.0%,positive predictive value of 85.3% and negative predictive value of 86.1%.The H-L test showed good fitting in all models ( P >0.05 ).The AUC for our model was 0.874 ±0.035,and 0.784 ± 0.041 in Mayo model (P =0.004 compared to our model),0.754 ± 0.041 in VA model (P =0.002 compare to our model).And,there was not significant statistical difference between Mayo model and VA model (P >0.05 ).Our model has the best precision indexed by AUC,which were statistically significant differential compared with Mayo model and VA model.Conclusion The model established by our center has superior value than foreign counterparts in predicting the probability of malignant or benign in patients with SPN.
4.Effect of isoflurane on expression of p-GSK-3β and β-catenin in neural stem cells in hippocampus of developing rats
Yue SUN ; Manyi SUN ; Lining SUN ; Guoyong SUN ; Kezhong LI
Chinese Journal of Anesthesiology 2017;37(1):66-69
Objective To evaluate the effect of isoflurane on the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and β-catenin in neural stem cells (NSCs) in the hippocampus of developing rats.Methods Twenty-four 7-day-old Sprague-Dawley rats,weighing 15-20 g,were divided into 2 groups (n =12 each) using a random number table:control group (group C) and 2% isoflurane group (group Ⅰ).Group C inhaled 30% oxygen for 4 h.Group Ⅰ inhaled 2% isoflurane in 30% oxygen for 4 h.Six rats were randomly selected from each group,and 5-bromodeoxyuridine (BrdU) 200 mg/kg was intraperitoneally injected immediately before anesthesia to assess the proliferation of NSCs in the hippocampal dentate gyrus.The rats were sacrificed at 6 h after the end of anesthesia,and hippocampi were isolated for determination of the number of BrdU positive cells in the dentate gyrus (by immunohistochemistry) and expression of p-GSK-3β and β-catenin in hippocampal tissues (by Western blot analysis).Results Compared with group C,the number of BrdU positive cells was significantly decreased,and the expression of p-GSK-3β and β-catenin was down-regulated in group Ⅰ (P<0.05).Conclusion Isoflurane can inhibit the proliferation of NSCs in the hippocampal dentate gyrus of developing rats,and the mechanism may be related to down-regulation of the expression of p-GSK-3β and β-catenin.
5.Effect of isoflurane anesthesia on Wnt3a expression in hippocampus of developing rats
Lining SUN ; Yue SUN ; Jun QI ; Xueqin WANG ; Kezhong LI
Chinese Journal of Anesthesiology 2016;36(5):551-553
Objective To evaluate the effect of isoflurane anesthesia on Wnt3a expression in the hippocampus of developing rats.Methods Twenty-four 7-day-old male Sprague-Dawley rats,weighing 125-155 g,were randomly divided into 3 groups (n=8 each) using a random number table:control group (group C),4 h inhalation of 2% isoflurane group (group I4),and 6 h inhalation of 2% isoflurane group (group I6).The rats were sacrificed at 6 h after the end of treatment in each group,and the hippocampi were removed for determination of Wnt3a mRNA expression (by real-time reverse transcriptase polymerase chain reaction) and Wnt3a expression (by Western blot).Results Compared with group C,the expression of Wnt3a and Wnt3a mRNA in hippocampi was significantly up-regulated in I4 and I6 groups (P<0.05).Compared with group I4,the expression of Wnt3a in hippocampi was significantly up-regulated (P<0.05),and no significant change was found in the expression of Wnt3a mRNA in hippocampi in group I6 (P>0.05).Conclusion The mechanism of isoflurane-induced neurotoxicity is probably related to upregulation of Wnt3a expression in the hippocampal tissues of developing rats.
6.A clinical prediction model for N2 lymph node metastasis in clinical stageⅠnon-small cell lung cancer
Kezhong CHEN ; Fan YANG ; Xun WANG ; Guanchao JIANG ; Jianfeng LI ; Jun WANG
Journal of Peking University(Health Sciences) 2015;(2):295-301
Objective:To estimate the probability of N2 lymph node metastasis and to assist physicians in making diagnosis and treatment decisions.Methods:We reviewed the medical records of 739 patients with computed tomography-defined stage Ⅰ non-small cell lung cancer ( NSCLC ) that had an exact tumor-node-metastasis stage after surgery.A random subset of three fourths of the patients ( n =554 ) were selected to develop the prediction model.Logistic regression analysis of the clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis.A prediction model was then built and externally validated by the remaining one fourth ( n=185 ) patients which made up the validation data set.The model was also compared with 2 previously described models.Results:We iden-tified 4 independent predictors of N2 disease:a younger age, larger tumor size, central tumor location, and adenocarcinoma or adenosquamous carcinoma pathology.The model showed good calibration ( Hos-mer-Lemeshow test:P=0.923) with an area under the receiver operating characteristic curve (AUC) of 0.748 (95%confidence interval, 0.710-0.784) .When validated with all the patients of group B, the AUC of our model was 0.781 (95% CI: 0.715 -0.839) and the VA model was 0.677 (95% CI:0.604-0.744) (P =0.04).When validated with T1 patients of group B, the AUC of our model was 0.837 (95%CI:0.760 -0.897) and Fudan model was 0.766 (95% CI: 0.681 -0.837) (P <0.01) .Conclusion:Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined stageⅠNSCLC and was more accurate than the existing models.Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.
7.The plasma levels of glutamate and γ-aminobutyric acid in Parkinson’s disease patients with depression and their clinical significance
Qing TONG ; Yongsheng YUAN ; Qinrong XU ; Li ZHANG ; Siming JIANG ; Kezhong ZHANG
Chinese Journal of Nervous and Mental Diseases 2015;(4):224-228
Objective To investigate the plasma levels of glutamate (Glu) andγ-aminobutyric acid (GABA) in Par?kinson’s disease patients with depression (PDD) and their clinical significance. Methods Plasma levels of Glu and GA?BA were measured in 88 PD patients including 43 PDD patients and 45 PD patients without depression, and 68 healthy controls by using high performance liquid chromatography (HPLC-RF). Depression was assessed in enrolled subjects by using the Hamilton Depression Scale (HAMD). The plasma levels of Glu and GABA were compared among different groups and their associations with HAMD scores were subsequently evaluated by correlation analysis. Results The plas?ma levels of Glu and GABA were significantly lower in PD group(49.81±22.79,249.17±62.57)than in normal control group(149.59±50.08,276.66±85.43)(all P<0.05). In addition, PD patients with depression exhibited significantly low?er plasma levels of Glu and GABA(40.34±15.77 and 233.63±53.56)compared to PD patients without depression(58.86± 24.87 and 264.02±67.39)and healthy controls (all P<0.05). Correlation analysis indicated that HAMD scores were nega?tively associated with plasma levels of Glu ( r=-0.366,P=0.000 ) and GABA ( r=-0.217,P=0.043 ). Conclusion The decrease in plasma levels of Glu and GABA may be implicated in the pathogenesis of depression in PD patients.
8.The application value of susceptibility weighted imaging in measuring brain iron deposition in the clinical assessment of Parkinson’s disease
Jianwei WANG ; Min WANG ; Dehang WANG ; Xunning HONG ; Li ZHANG ; Kezhong ZHANG
Journal of Practical Radiology 2016;32(4):493-496
Objective To explore the application value of susceptibility weighted imaging(SWI)in measuring brain iron deposition in the diagnosis and the assessment of Parkinson’s disease(PD).Methods Thirty cases with PD underwent head routine magnetic resonance imaging and SWI scanning.The unified PD rating scale(UPDRS)was used to assess the severity of PD.The phase values of substantia nigra (SN),red nucleus(RN),caudate nucleus (CA),globus pallidus(GP)and putamen (PUT)were measured manually on the phase map.The correlation between the phase values of the region of interest(ROI)and the UPDRS scores of PD was analyzed.Results There were no significant differences between the phase values of the less severe body side and those of the more severe body side (SN,P=0.120;RN, P=0.402;CA,P=0.196;GP,P=0.616;PUT,P =0.985).Significant negative correlations were found between the phase values of SN, CA,GP and the UPDRS Ⅲ scores,respectively (SN-UPDRS Ⅲ:r=-0.407,P =0.026;CA-UPDRS Ⅲ:r =-0.424,P =0.02;GP-UPDRS Ⅲ:r=-0.363,P =0.048).Significant negative correlation was found between the phase values of SN and the UPDRSⅤranks (r=-0.373 ,P =0.043 ),while the similar correlation was found between the phase values of CA and the UPDRSⅠ scores (r=-0.367,P =0.046)and the medium negative correlation was found between the phase values of GP and the gait disorder scores of UPDRS Ⅲ(r=-0.41 1,P =0.024).But no correlation was found between the phase values of other ROIs and the UPDRS scores. Conclusion SWI could quantitatively assess the brain iron deposition of the PD patient,which provided reference for clinical diagnosis and assessment of PD.
9.miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1.
Xiaoling ZHAO ; Yue SUN ; Yongbo DING ; Jun ZHANG ; Kezhong LI
Yonsei Medical Journal 2018;59(10):1205-1213
PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.
Anesthesia
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Animals
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Apoptosis*
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Blotting, Western
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Brain
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Flow Cytometry
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Fluorescent Antibody Technique
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Hippocampus
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Immunoprecipitation
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In Situ Nick-End Labeling
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Lentivirus
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Luciferases
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Lymphoma, B-Cell
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Memory
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Mice
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Neurons
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Repression, Psychology
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RNA
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Spatial Memory
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Water
10.The clinical application of endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer
Hui ZHAO ; Jun WANG ; Jianfeng LI ; Yun LI ; Zuli ZHOU ; Liang BU ; Xizhao SUI ; Kezhong CHEN ; Xiao LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(2):105-107
Objective To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer. Methods The study was retrospective, a total of 52 patients underwent EBUSTBNA for known or suspected lung cancer. All patients were detected enlarged mediastinal lymph nodes on CT scan ( ≥ 1.0cm). Results Of the 52 patients, 41 patients were found with N2 or N3 disease on EBUS-TBNA. 11 patients with negative EBUS-TBNA underwent thoracoscopy or thoracotomy for pulmonary resection and mediastinal lymph node dissection, 9 patients were confirmed N0 by pathology, whereas 2 patients had metastatic lymph node. The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EBUS-TBNA for the mediastinal staging of lung cancer were 95.3%, 100%, 96.2%, 100%, and 81.8%, respectively. The procedure was uneventful, and there were no postoperative complications. Conclusion EBUS-TBNA is an effective and safe technique for mediastinal staging in lung cancer patients.