1.Association between EGFR mutation status and efficacy of first-line EGFR-TKI in patients with ;advanced non-small cell lung cancer
Haiying JIANG ; Yanfang LI ; Mei ZHU ; Qian LI ; Jiao LYU
Journal of International Oncology 2017;44(1):19-23
Objective To evaluated the effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)on advanced non-small cell lung cancer (NSCLC)patients with different EGFR mutation status (exon 1 9 deletion and exon 21 mutation).Methods Seventy-two advanced NSCLC patients with EGFR mutation confirmed by histopathology were enrolled.All of the patients received first-line EGFR-TKI.The relationships between EGFR mutation status and objective response rate (ORR),disease control rate (DCR),progression free survival (PFS ) and overall survival (OS ) were analyzed.Results Of the 72 patients,37 patients expressed exon 1 9 deletion,35 patients expressed exon 21 mutation,and all of them could be evaluated.The ORR and DCR of patients with exon 1 9 deletion were higher than those of patients with exon 21 mutation (75.7%vs.51 .4%,χ2 =4.583,P=0.032;89.2%vs.68.6%,χ2 =4.636,P=0.031 ).The modified median PFS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (1 3.2 month vs.1 0.8 month,χ2 =4.700,P=0.030).The median OS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (30.2 month vs.25.6 month,χ2 =4.686,P=0.030).The side effects were similar between the two groups.The most common adverse reaction was rash,and the incidence had no significant difference between the two groups (48.7% vs.48.6%,χ2 =0.000,P=0.995 ).Conclusion EGFR mutation status is a predictor for PFS,OS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.NSCLC patients with EGFR exon 1 9 deletion are associated with longer survival time and better response rate compared with those with exon 21 mutation.
2.Differentiation of Pc and P2 variants in class 1 integron by high-resolution melting analysis
Quhao WEI ; Gang LI ; Xiaofei JIANG ; Qingfeng HU ; Huoyang LYU ; Yonglie ZHOU ; Ming GUAN ; Yuan LYU
Chinese Journal of Laboratory Medicine 2017;40(2):95-100
Objective To develop a simple high-resolution melting ( HRM) analysis method for differentiation of Pc and P2 variants in class 1 integron.Methods DNA fragments containing Pc and P2 variants were amplified from plasmids pACW ( PcW ) and pACWP2 ( PcW-P2 ) respectively , then these purified PCR products and P 2 promoters were analyed full-length amplicon by HRM .Eight DNA fragments containing different Pc promoters were amplified and site-specific mutated from plasmids pACS ( PcS ) , pACH2 ( PcH2 ) , pACH1 ( PcH1 ) , pACW ( PcW ) , genomic DNA of Klebsiellar pneumonia HS07-68 (PcWTGN-10)and HS05-1792(PcH2TGN-10)respectively.The purified PCR products and eight Pc variants were characterized by HRM analyses of an unlabeled probe and full-length amplicon.This assay was applied to the differentiate Pc and P2 variants in 109 class 1 integrons from 95 urine clinical Escherichia coli isolates in Huashan Hospital during 2004 -2007.The differentiation results were compared with that determined by direct sequencing .Results P2 promoter with a significant higher melting temperature ( Tm ) can be identified by HRM analysis clearly .P2 promoters were identified in 2 class 1 integrons and consistent with direct sequencing results .Eight Pc variants were classified into three groups: PcS, PcSTGN-10 , PcW, PcWTGN-10, PcH1, PcH1TGN-10.Using direct HRM analysis.PcH2, PcH2TGN-10 were classified into four groups:PcS, PcH1, PcH2, PcW, PcSTGN-10 , PcH1TGN-10 , PcH2TGN-10 , PcWTGN-10 according to the melting curves of the unlabeled probe .Combined the HRM analyses of the whole amplicon and unlabeled probe , the eight Pc variants can be differentiated from each other .Five different Pc variants, PcS, PcW, PcH1, PcH2TGN-10 and PcWTGN-10 , were identified and consistent with direct sequencing results .Conclusions This developed a simple Pc and P 2 variants differentiation method via simultaneous HRM analyses of an unlabeled probe and full-length amplicon .This method is cost-effective and accurate , could be used in differentiation of Pc and P2 variants of class 1 integrons in clinical isolates .
3.Effects and mechanism of peroxiredoxin-6 on uItravioIet induced corneaI injury in rats
Jiahui LYU ; Minmin JIANG ; Hui SHI ; Jianyuan LI ; Zhenning DU
Journal of China Pharmaceutical University 2016;(1):84-89
To investigate the therapeutic effect of peroxiredoxin-6(PRDX6)on ultraviolet-induced corneal injury in rats and explore the mechanism.The rat model of corneal injury was established by exposing to ultravio-let.Male wister rats were randomly divided into control groups,dexamethasone (DXM)groups and PRDX6 groups,the rats were administered four times a day and for 12 days.The corneal opacity was observed with a slit-lamp microscope.Histopathologic changes were observed with light microscopy.The content of corneal malonalde-hyde(MDA)was determined by thiobarbituric acid test and the total antioxidative capacity(TAOC)was detected by chemical colorimetric test.P38 MAPK signal pathway was detected with the method of Western blot and the gene expression of cytokines were measured by RT-PCR method.Compared with the control group,PRDX6 treat-ment significantly reduced corneal opacity,improved corneal pathology injury,decreased the MDA content and in-creased the TAOC.In the PRDX6 group the level of phosphorylated p38 protein was significantly lower than that in the control group.The gene expression of cytokine were different between control and PRDX6 groups(P <0.05).PRDX6 showed therapeutic effect in the rat model of ultraviolet-induced corneal injury.This maybe be concerned with that it could alleviated the oxidative damage,suppressed p38 MAPK phosphorylation and regulate the gene expression of cytokine.
4.The value of endorectal elastography in the diagnosis of malignant rectal adenoma
Guangxi, ZHONG ; Ke, LYU ; Qing, DAI ; Jianchu, LI ; Yuxin, JIANG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2015;(3):211-217
Objective To assess the value of endorectal elastography in the diagnosis of malignant rectal adenoma. Methods Sixty patients referred to the department of basic surgery of Peking Union Medical College Hospital for the evaluation of rectal adenoma from January 2011 to May 2013 were included in this prospective cohort. All patients underwent elasticity score (ES) and strain ratio(SR) examine before operation. To evaluate the reproducibility of the strain-ratio measurements, the intraclass correlation coefficient (ICC) was calculated. Compared with final operational pathological results,the diagnostic values of elasticity score and strain ratio method were assessed. Results Histopathological result showed there were 20 adenomas and 40 adenocarcinomas. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ERUS was 68%(27/40), 40%(8/20), 58%(35/60), 69%(27/39), 38%(8/21), respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of elasticity score was 85%(34/40), 70%(14/20), 80%(48/60), 85%(34/40), 70%(14/20), respectively. The SR of adenocarcinomas was significantly higher than that of adenomas(2.82±1.81 vs 1.23±0.57, t=3.333, P < 0.05). The differences among the SR of benign adenoma, benign adenoma with severe atypical hyperplasia and completely malignant lesions were statistically significant (1.26±0.84 vs 2.94±1.95, 1.42±0.55 vs 2.94±1.95, t=2.619, 2.415, P=0.013, 0.021). When 1.240 was chosen as the best cut-off value of SR, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of strain ratio was 82%(33/40), 75%(15/20), 80%(48/60), 87%(33/38), 68%(15/22), respectively. Conclusion Endorectal elasotgraphy can accurately diagnose the malignant rectal adenoma, which can provide reliable preoperative imaging evidence for clinical operation mode.
5.Relation between the gene status of epidermal growth factor receptor and efficacy of the first-line tyrosine kinase inhibitor in patients with advanced non-small cell lung cancer
Haiying JIANG ; Mei ZHU ; Yanfang LI ; Qian LI ; Jiao LYU ; Jing LI
Cancer Research and Clinic 2016;28(6):373-377
Objective To explore the relationship between mutation status of epidermal growth factor receptor (EGFR) and efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced nonsmall ccll lung cancer (NSCLC).Methods The data of 72 outpatients and inpatients with stage Ⅲ b/ⅣNSCLC diagnosed by histopathology and harbored EGFR-activating mutations (exon 19 and exon 21) from January 2008 to December 2013 in Xuzhou Cancer Hospital were collected.All of them received first-line EGFR-TKI.The relationships between EGFR gene status and response rate or progression-free survival (PFS)were analyzed.Results Of the 72 patients with EGFR mutation,37 patients harbored exon 19 deletion,and 35 patients harbored exon 21 L858R point mutation.The efficacies of all patients were assessable.The objective response rate (ORR) was 63.9 % (46/72) and disease control rate (DCR) was 79.2 % (57/72) in all patients,including 2 cases of complete remission (CR),44 cases of partial remission (PR),1 1 cases stable disease (SD) and 15 cases of disease progression (PD).Patients with exon 19 deletion had a higher ORR [75.7 % (28/37) vs 51.4 % (18/35),P =0.032] and a higher DCR [89.2 % (33/37) vs 68.6 % (24/35),P =0.031]than patients with exon 21 L858R mutation.The PFS of patients with exon 19 deletion was significantly longer than that of patients with exon 21 L858R mutation (12.0 months vs 9.5 months,P =0.030).Cox multivariate analysis indicated that the gender,histological type,smoking history were the major influence factors of PFS.The differences of toxicity between the two groups were not significant.Conclusion EGFR-activating mutation is a predictor for PFS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.
6.Efficacy assessment of 33 cases of peroral endoscopic myotomy in different achalasia subtypes by esophageal high-resolution manometry
Meng LI ; Bin LYU ; Lu ZHANG ; Haibiao BAO ; Ning JIANG ; Li CHU
Chinese Journal of Digestion 2016;36(4):254-258
Objective To explore the symptomatic improvement of different achalasia (AC)subtypes after peroral endoscopic myotomy (POEM) procedure.Methods A total of 33 patients received POEM for the first time were enrolled.Patients were evaluated by high-resolution manometry (HRM)and subtyped by Chicago classification criteria.The total scores of symptoms were evaluated by Eckardt scale before and after POEM.Solid food dysphagia,liquid dysphagia,reflux and chest pain were scored by five-point Likert scales and compared by Wilcoxon paired test.Multiple linear regression analysis was performed to analyze key factors affecting the prognosis of symptoms.Results Among 33 AC patients,there were 20 females and the mean age was (44.0± 13.3) years.According to Chicago criteria,four patients had subtype Ⅰ AC,25 patients had subtype Ⅱ AC,and four patients with subtype Ⅲ achalasia.Before operation,the total Eckardt score was 7.5(6.3,10.0),which declined to 1.5 (1.0,3.0) after operation,and the difference was statistically significant (Z=-4.795,P < 0.01).There was no statistically significant difference in the incidence of solid food/liquid dysphagia,reflux and chest pain among subtypies.Solid food dysphagia was the main symptom of each AC subtypes.POEM could improve all the symptoms of subtype Ⅱ AC except for chest pain.Before and after POEM,solid food dysphagia score was 16.0 (12.0,16.0) and 2.0 (1.0,12.0),liquid dysphagia score was 2.0 (0.0,5.0) and 0.0(0.0,0.0),reflux score was 9.0 (6.0,9.0) and 0.0 (0.0,1.0),respectively,and the differences were statistically significant (Z =-3.929,-3.470,1.841;all P< 0.01).The results of multiple linear regression analysis indicated that female and 4 s integrated relaxation pressure (4 s IRP) of 10 mL continuous swallows were positively correlated with symptom scores of solid food dysphagia (β 3.950,P=0.048;β=0.376,P=0.005);While 4 sIRP in solid food swallow was negatively correlated with symptom scores of solid food and liquid dysphagia (β=-0.244,P =0.008;β=-0.118,P =0.037).Conclusion For patients with AC,clinical symptoms could be significantly improved by single treatment of POEM,but there are certain differences in the symptomatic improvement among different subtypes.
7.Maintenance treatment of advanced non-small cell lung cancer
Kunxiang LYU ; Wenhui LI ; Yu HOU ; Ming ZHANG ; Li WANG ; Jiang XI
Journal of International Oncology 2014;41(4):283-285
Currently platinum-based double chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC).When the disease is under control,the next step after a standard course of chemotherapy is controversial,and maintenance treatment is used in the treatment of advanced NSCLC increasingly.Maintenance treatment of advanced NSCLC includes continue maintenance treatment and medication changed maintenance therapy.currently used for maintenance therapy with pemetrexed and erlotinib are shown to improve overall survival,which are usually used for maintenance treatment.
8.Expression of miR-520d-3p in X-rays irradiated A549 cells and serum samples of non-small cell lung cancer patients and its significance
Xiujun SONG ; Qisheng JIANG ; Sinian WANG ; Huijie YU ; Xiao LI ; Zhenyuan LI ; Jin LYU
Cancer Research and Clinic 2017;29(7):433-436,441
Objective To investigate the expression of miR-520d-3p in 2 and 4 Gy X-ray irradiated A549 cells, serum samples of non-small cell lung cancer (NSCLC) patients and its significance. Methods Real time quantitative PCR (RT-qPCR) was employed to detect the expression miR-520d-3p in 2 and 4 Gy X-ray irradiated A549 cells in vitro. Besides, 0, 2 and 4 Gy X-ray irradiated A549 cells were used to prepare animal model of nude mice lung metastasis through mainline. The expressions of miR-520d-3p and lung tissue of nude mice were detected, and the serum samples of NSCLC patients were collected to test the expression of miR-520d-3p . Results Compared with the control group ( 0 Gy ) , the expression of miR-520d-3p was up-regulated significantly in 2 and 4 Gy X-ray irradiated A549 cells after 48 hours (1.00±0.03, 1.47±0.10, 1.84 ±0.09 respectively), and there was a significant difference (F= 94.350, P= 0.000). Furthermore, compared the control group with injection after 10 weeks, the expressions of miR-520d-3p in nude mice lung tissue in 0, 2 and 4 Gy X-ray irradiated groups were increased (2.33 ±0.13, 8.24 ±0.25, 3.46 ±0.14, respectively) (F=1.787, P= 0.227), and the expressions in serum were increased (11.43±2.30, 10.22±4.62, 8.99 ±3.67, respectively) (F= 1.547, P= 0.246). Out of 20 serum samples of NSCLC patients (including 10 cases of adenocarcinoma, 10 cases of squamous carcinoma ), 11 cases (55%) were detected with up-regulated miR-520d-3p expression. Conclusions 2 and 4 Gy X-ray could increase the expression of miR-520d-3p of A549 cells in vitro and in vivo, which might be correlated with the enhanced invasion and metastasis of A549 cells induced by X-ray in vitro and in vivo. Furthermore, the expressions of miR-520d-3p were increased significantly in over 50%serum samples of NSCLC patients, which might be a new marker for the diagnosis of NSCLC.
9.Applying percentile method combined with ROC curve to determine the reference values for 11 amino acids in newborns measured by non-derivatized tandem mass spectrometry
Yanyun WANG ; Ling LYU ; Yun SUN ; Bing YANG ; Yahong LI ; Tao JIANG
Chinese Journal of Laboratory Medicine 2016;39(10):756-760
Objective To determine the reference values of 11 amino acids measured by non-derivatized tandem mass spectrometry ( MS/MS).Methods 22 430 healthy newborns and 14 children with metabolic dysfunction in Nanjing were enrolled in this study.The levels of the 11 amino acids, including Ala, Arg, Cit, Gly, Leu +Ile, Met, Orn, Phe, Pro, Tyr and Val, were measured by non-derivatized tandem mass spectrometry using dry blood spots.After pre-setting up different cutoff values according to the amino acid levels of the newborns, reference value ranges of the 11 amino acids were determined by using the method of percentile combined with ROC curves.Results According to the results of frequency distribution histogram, the levels of the 11 amino acids of newborns belong to approximate normal distribution.By analysis of ROC curves, the cut-off values for amino acids were 0.2%-99.8%.Conclusion It established reference values of 11 amino acids in newborn and provided basis for the other screening center to make the cut-off value.
10.Practice of standardized question library based separation of teaching from testing system in integrated life sciences curriculum
Jiao LI ; Lixia LYU ; Wenxia JIANG ; Lei XU ; Qiaoling CAI ; Guotong XU
Chinese Journal of Medical Education Research 2015;(5):486-488
Department of Regenerative Medicine of Tongji University School of Medicine intro-duced the standardized question library construction-based separation of teaching from testing system into integrated life science course. By establishing the question library, professional teachers in the assessment center are responsible for making and correcting test papers of final exam for students. In addition to the separation of teaching and testing, regular quiz during the semester is also involved in the final grades of students. The results show that high-quality question library effectively promotes implementation of separation of teaching from testing. The question library construction is a dynamic and long-term task that requires real-time updates along with knowledge updates. This preliminary practice of separation of teaching from testing system in the integrated life sciences curriculum has proved to be useful for improving teaching style and the style of study significantly.