1.Expression and clinical significance of thymidylate synthase and adenosine triphosphate-binding cassette superfamily G member protein in advanced gastric carcinoma
Hao CHENG ; Xihua JIA ; Shujun ZHENG ; Xiaowei ZHANG ; Jinku ZHANG
Chinese Journal of Digestion 2013;(2):111-114
Objective To investigate the expressions of thymidylate synthase (TS) and adenosine triphosphate (ATP)-binding cassette superfamily G member 2 (ABCG2) in advanced gastric cancer (GC) and to explore their correlation with clinical pathological features.Methods A total of 80surgical specimens of advanced gastric cancer patients were collected.The expressions of TS and ABCG2 in gastric cancer tissues and adjacent normal gastric tissues were detected by immunohistochemical method.The expression of P-glycoprotein in gastric cancer tissues was also examined.The correlations between TS,ABCG2 and clinical pathological features and P-glycoprotein were analyzed.Chi-square test was performed for two groups comparison and Kruskal-Wallis H test were used for multi-groups comparison.Results The positive rates of both TS and ABCG2 in gastric cancer tissues [85.0% (68/80) and 90.0% (72/80)] were higher than those of adjacent normal gastric tissues [62.5 % (50/80) and 78.7 % (63/80)],the differences were statistically significant (x2 =11.466 and 16.463,P=0.009 and 0.001).There were close correlation between the expression of TS,ABCG2 and tumor TNM stage,differentiation status,invasion depth (TS:x2 =30.686,61.470 and 40.545 ; ABCG2:x2=48.192,63.150 and 47.512; all P<0.01).The later the tumor staged,the worse the cells differentiated and the deeper the tumor invaded,the higher level they expressed.Both TS and ABCG2expressions in gastric cancer tissues were correlated with the expression level of P glycoprotein (x2 =43.977and 29.509,both P<0.01).Conclusion TS and ABCG2 may be potential indexes to predict the degree of malignancy,progression,drug resistance and prognosis in gastric cancer.
2.Expression of Apaf-1 and Caspase-9 in prostate cancer and its clinical significance
Bingxin ZHANG ; Xia ZHAO ; Xihua JIA ; Yang LIU ; Jinku ZHANG
Chinese Journal of Clinical and Experimental Pathology 2015;(2):151-153
Purpose To investigate the expression of Apaf-1 and Caspase-9 in prostate cancer ( PCa) and benign prostatic hyperplasia ( BPH) , and to analyze their correlation with clinicopathological parameters of PCa. Methods Immunohistochemistry was used to de-tect Apaf-1 and Caspase-9 protein in 45 cases of PCa and 60 cases of BPH. Results The positive rate of Apaf-1 and Caspase-9 in PCa tissues was significantly lower than that in BPH (P<0. 05). The expression of Apaf-1 and Caspase-9 was not correlated with the age of patients and distant metastasis (P>0. 05), but it was correlated with the pathological grade and clinical stage of PCa (P<0. 05). Conclusion Apaf-1 and Caspase-9 are lowly expressed in PCa. There is positive correlation between the expression of Apaf-1 and Caspase-9 (rs =0. 645, P<0. 01). Apaf-1 and Caspase-9 might be correlated with the carcinogenesis and development of PCa.
3.Expression and clinical significance of apoptotic protease activating factor 1 and bax in prostate cancer
Bingxin ZHANG ; Xia ZHAO ; Jinku ZHANG ; Wenwen JIA ; Jianshu ZHANG ; Jianmei SUN ; Xihua JIA
Cancer Research and Clinic 2016;28(2):116-118
Objective To investigate the expression and clinical significance of apoptotic protease activating factor 1 (Apaf-1) and bax in prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Methods Immunohistochemistry was used to detect the expression of Apaf-1 and bax in the tissues from 45 PCa patients and 60 BPH patients. Results The positive rates of Apaf-1 and bax in PCa tissues were 22.22%(10/45) and 20.00 % (9/45), respectively, while those in BPH tissues were 48.33 % (29/60) and 46.67 % (28/60). There was a statistically significant difference in the expressions of Apaf-1 and bax between two groups (P< 0.05). The expressions of Apaf-1 and bax were not correlated with the age of patients and distant metastasis (P>0.05), but they were correlated with the pathological grade and clinical stage of PCa (P< 0.05). The expressions of Apaf-1 and bax in PCa tissues were lower than those in BPH tissues. There was a positive correlation between the expression of Apaf-1 and bax (r=0.535, P<0.01). Conclusion Apaf-1 and bax might be correlated with the carcinogenesis and development of PCa.
4.Expressions of UHRF1, P53 and their clinical significances in colon carcinoma
Xiaoqing AI ; Xihua JIA ; Xiaobo WANG ; Shujun ZHENG ; Xia ZHAO ; Bingxin ZHANG
Journal of International Oncology 2016;43(5):346-349
Objective To investigate the expression levels and clinical significances of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) and P53 in colon carcinoma.Methods The expressions of UHRF1 and P53 in 70 colon cancer tissues and 30 normal colon ones were detected by means of immunohistochemistry to analyze the correlation of these two proteins in the occurrence and development of colon carcinoma,and the relationship between their expressions and clinico-pathological factors as well as prognosis was discussed.Results The expression levels of UHRF1 and P53 in cancer tissues were significantly higher than those of cancer-adjacent tissues (87.1% vs.56.7%,x2 =11.366,P =0.001;64.3% vs.6.7%,x2 =27.988,P =0.000) and showed a positive correlation between the two proteins (r =0.248,P =0.038).Both UHRF1 and P53 were associated with TNM stages (x2 =4.426,P =0.049;x2 =6.000,P =0.016) and the depth of invasion (x2 =12.553,P =0.002;x2 =4.904,P =0.036).However,they were irrelevant with the age (x2 =0.473,P=0.494;x2 =0.090,P=0.799) and gender (x2 =2.297,P=0.166;x2 =0.512,P=0.617) of patients,as well as the size (x2 =0.638,P =0.481;x2 =2.392,P =0.215) and histological grading of tumors (x2 =2.088,P =0.352;0.303,P =0.859).Kaplan-Meier analysis showed that the median survival time of patients with UHRF1,P53 positive expression was 21.83 months that was lower than patients with UHRF1 positive expression of 24.49 months (Z =-0.624,P =0.533).Both former of which was distinctly lower than that of negative ones of 37.33 months (Z =-2.856,P =0.004;Z =-2.694,P =0.007).Conclusion Both UHRF1 and P53 are highly expressed in colon cancer tissues,which imply that UHRF1 and P53 may be strongly related with colon cancer development and can be a predictor for colon cancer prognosis.
5.Expressions and significances of apoptosis related protein Bcl-2 and Bax in basal-like breast carcinoma
Bingxin ZHANG ; Xia ZHAO ; Xihua JIA ; Xue CHEN ; Hong CHEN ; Qiushuang MA ; Jinku. ZHANG
Journal of International Oncology 2015;(8):569-572
Objective To investigate the expressions and significances of Bcl-2 and Bax in basal-like breast carcinoma (BLBC).Methods The expressions of Bcl-2 and Bax were detected in 43 cases of BLBC, 57 cases of non-BLBC and 60 cases of normal breast tissues by immunohistochemistry,and their relationships with physiological and pathological characteristics of patients were analysized.Results The positive rate of Bcl-2 in BLBC was 69.77%,higher than 43.86% in non-BLBC (χ2 =6.647,P =0.01 0)and 21 .67% in normal breast tissues (χ2 =23.831 ,P =0.001 ).The positive rate of Bax in BLBC was 20.93%,lower than 45.61 % in non-BLBC (χ2 =6.564,P =0.01 0)and 76.67% in normal breast tissues (χ2 =31 .270,P =0.001 ).The expressions of Bcl-2 and Bax were correlated with lymphnode metastasis (χ2 =6.927,P =0.008;χ2 =6.203,P =0.01 3)and pTNMstaging of BLBC (χ2 =6.331 ,P =0.01 2;χ2 =5.972,P =0.01 5).There was negative correlation between the expression of Bcl-2 and Bax in BLBC (r = -0.408,P <0.01 0). Conclusion High expression of Bcl-2 and low expression of Bax interact with each other leading to unbalance of cell deferation and apoptosis,resulting in promoting genesis and progress of BLBC.
6.Expression and clinical significance of Apaf-1 and AEG-1 in colonic carcinoma
Xia ZHAO ; Bingxin ZHANG ; Shujun ZHENG ; Lin LI ; Jianmei GUO ; Xudong MA ; Xihua JIA
Journal of International Oncology 2015;(7):508-511
Objective To study the expressions of apoptotic protease activating factor-1(Apaf-1)and astrocyte elevated gene-1(AEG-1)in colonic carcinoma,and to explore their correlations with the clinical path-ological features. Methods The expressions of Apaf-1 and AEG-1 were detected in 63 colonic carcinoma sam-ples and 30 normal colonic mucosa adjacent to tumor nest by immunohistochemical method,and their correla-tions with clinical features of colonic carcinoma were analyzed. Results The positive expressions of Apaf-1 and AEG-1 in colonic carcinoma were 23. 81%(15 / 63)and 68. 25%(43 / 63),respectively. The positive expre-ssions of Apaf-1 and AEG-1 in normal colonic mucosa were 76. 67%(23 / 30)and 26. 67%(8 / 30),respec-tively. The positive expression rate of AEG-1 was significantly higher in colonic carcinoma than that in normal tissue(χ2 = 14. 192,P = 0. 000). However,the expression of Apaf-1 was signi-ficantly lower in colonic carci-noma than that in normal tissue(χ2 = 23. 497,P = 0. 000). The expression of Apaf-1 was negatively correlated to the expression of AEG-1(r = - 0. 339,P = 0. 007). The expressions of AEG-1 and Apaf-1 were associated with differentiation degree(χ2 = 4. 643,P = 0. 031;χ2 = 12. 034,P = 0. 001)and clinical stage(χ2 = 6. 628, P = 0. 010;χ2 = 8. 246,P = 0. 004),but they were not correlated with age(χ2 = 1. 462,P = 0. 227;χ2 =2. 401,P = 0. 121)and tumor size(χ2 = 0. 333,P = 0. 564;χ2 = 0. 590,P = 0. 442). Conclusion The expression of AEG-1 is up-regulated in colonic carcinoma,but the expression of Apaf-1 is down-regulated,with a significant negative correlation. Apaf-1 and AEG-1 may be closely related to the occurrence and development of colon carcinoma. Therefore,combination detection of Apaf-1 and AEG-1 may be more valuable for the prog-nosis evaluation of colonic carcinoma.
7.Effect of operation duration on pharmacokinetics of desflurane in patients undergoing tumor resection
Yu BAI ; Jia LI ; Yan MI ; Xihua LU ; Yi ZHOU ; Changhong MIAO
Chinese Journal of Anesthesiology 2021;41(2):189-191
Objective:To evaluate the effect of operation duration on the pharmacokinetics of desflurane in the patients undergoing tumor resection.Methods:One hundred and fifty patients of both sexes, aged 18-75 yr, with body mass index of 19-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, in whom abnormal preoperative lung function was not found, undergoing elective surgery with general anesthesia from November 2019 to March 2020, were enrolled in this study.Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, cisatracurium besylate 0.2 mg/kg and propofol 2 mg/kg.The patients were tracheally intubated after mechanical ventilation.Anesthesia was maintained with inhalation of desflurane, the vaporizer dial was adjusted to 6% with fresh gas flow rate of 2 L/min, and sufentanil and cisatracurium besylate were intermittently injected intravenously according to the changes in hemodynamics and degree of muscle relaxation during operation.The duration required for the end-tidal concentration of desflurane reaching 0.5 minimum alveolar concentration (MAC), time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the volatile tank were recorded.The patients were divided into 3 groups according to the operation time: operation time <2 h group (group S), operation time 2-4 h group (group M), and operation time >4 h group (group L). Results:There were no significant differences among the 3 groups in the duration required for the end-tidal concentration of desflurane reaching 0.5 MAC, time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the vaporizer ( P>0.05). Conclusion:Operation duration does not affect the pharmacokinetics of desflurane in the patients undergoing tumor resection.
8.Effect of dexmedetomidine on autophagy during ischemia-reperfusion injury in isolated rat lungs
Jianwei WANG ; Jia LI ; Liyan CAO ; Yan MI ; Xiaofei LIU ; Xihua LU
Chinese Journal of Anesthesiology 2018;38(11):1401-1404
Objective To evaluate the effect of dexmedetomidine on autophagy during ischemiareperfusion (I/R) injury in isolated rat lungs.Methods SPF healthy male Sprague-Dawley rats,weighing 250-320 g,were anesthetized with atropine and pentobarbital sodium,and their lungs were excised to establish the isolated lung perfusion model.Thirty lungs in which isolated lung peffusion models were successfully established were divided into 3 groups (n=10 each) by a random number table method:control group (C group),lung I/R group (I/R group) and dexmedetomidine group (DEX group).The isolated rat lungs were continuously perfused for 150 min in C group.After 15 main of perfusion,the isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in I/R group.In DEX group,the isolated lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetomidine.Pulmonary vascular resistance (PVR) and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min of reperfusion.Lung tissues were collected at 75 min of reperfusion for measurement of lung wet weight (W) and dry weight (D) and for examination of morphological changes of lung tissues (with a light microscope) and autophagic vacuoles of lung cells (under an electron microscope).The W/D ratio and lung injury score were calculated.The expression of mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) in lung tissues was detected by Western blot.Results Compared with C group,the PVR,W/D ratio and lung injury score were significantly increased,the expression of LC3 Ⅱ was up-regulated,and PaO2 was decreased in I/R group and DEX group (P<0.05).Compared with I/R group,the PVR,W/D ratio and lung injury score were significantly decreased,the expression of LC3 Ⅱ was down-regulated,PaO2 was increased,and the expression of mTOR and p-mTOR was up-regulated in DEX group (P<0.05).A lot of autophagic vacuoles of lung cells were found in I/R group,and a few autophagic vacuoles of lung cells were observed in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated lung I/R injury is related to inhibiting autophagy in rats.
9.Effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats
Zhen ZHANG ; Xihua LU ; Qiaorong DENG ; Meng GAO ; Baofeng YANG ; Yaping CUI ; Jia LI
Chinese Journal of Anesthesiology 2018;38(3):376-380
Objective To investigate the effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats. Methods A total of 60 pathogen-free male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-300 g, were divided into 3 groups (n= 20 each) by using a random number table: control group (C group), as-phyxial cardiac arrest-resuscitation group ( CA group) and dexmedetomidine pretreatment group ( Dex group). The anaesthetized rats were intubated with a 16G tracheal catheter which was connected to a rodent ventilator for mechanical ventilation. Cardiac arrest was induced by clamping the tracheal tube at the end of the exhalation until systolic blood pressure decreased to 25 mmHg lasting for 5 min, and then resuscitation was started. At 5 min before cardiac arrest, dexmedetomidine 4. 0 μg∕kg was intravenously injected in group Dex, and the equal volume of normal saline was given instead in C and CA groups. Rats were sacri-ficed at 6 h after successful resuscitation, brain tissues were removed for determination of wet to dry weight ratio ( W∕D ratio), and hippocampal tissues were obtained for examination of the pathological changes (with a light microscope) and ultrastructure (with an electron microscope) and for determination of cell ap-optosis (by TUNEL), expression of CCAAT∕enhancer-binding protein homologous protein (CHOP) and ac-tivated transcription factors (ATF4) and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymer-ase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot). The apoptosis rate was calculated. Results Compared with group C, W∕D ratio of brain tissues was significantly in-creased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was up-regulated, the expression of CHOP, Bax and caspase-3 was up-regulated, and the expression of Bcl-2 was down-regulated in CA and Dex groups (P<0. 05). Compared with group CA, W∕D ratio of brain tissues was significantly decreased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was down-regulated, the expression of CHOP, Bax and caspase-3 was down-regulated, the expression of Bcl-2 was up-regulated (P<0. 05), and the pathological changes were significantly attenuated in group Dex. Conclusion The mechanism by which dexmedetomi-dine pretreatment mitigates brain injury after asphyxial cardiac arrest-resuscitation may be related to inhibi-ting cell apoptosis induced by endoplasmic reticulum stress in rats.
10.Nomogram analysis of risk factors for diabetic neuropathy in primary type 2 diabetic mellitus patients in Zhejiang Province
Shuiya SUN ; Weiwei GUI ; Chengfang JIA ; Qianqian PAN ; Xihua LIN ; Fenping ZHENG ; Hong LI
Chinese Journal of Internal Medicine 2023;62(2):169-175
Objective:To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling.Methods:A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN.Results:DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A 1c (HbA 1c) ( OR=1.159, 95% CI 1.039-1.292), systolic blood pressure ( OR=1.041, 95% CI 1.031-1.051), serum creatinine (Scr) ( OR=1.011, 95% CI 1.004-1.017), serum globulin (GLOB) ( OR=1.072, 95% CI 1.039-1.105), diabetic retinopathy (DR) ( OR=1.463, 95% CI 1.073-1.996), education level of more than junior high school ( OR=2.018, 95% CI 1.466-2.777), and moderate-intensity exercise ( OR=0.751, 95% CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95% CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions:HbA 1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.