Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

Objective To analyze the miss rates of colorectal adenomas during colonoscopy as well as risk factors influencing the adenoma miss rates and to take corresponding measures. Methods A total of 432 patients who underwent index and follow-up colonoscopy in 18 months were randomized and investigated. The results of two colonoscopies were compared and the missed adenomas were defined as the adenomas de-tected only during the second colonoscopy. Miss rates were calculated according to patient-based methods. Chi-square test was used to analyze the relative factors influencing the adenoma miss rate of per-patient. Then the meaningful factors were chosen into the logistic regression model for multiple factors analysis. Results Of 432 patients,116(26. 9%)had missed adenomas on first colonoscopy. Single factor analysis found that the size of adenoma( χ2 = 89. 686,P = 0. 000),the shape of adenoma( χ2 = 68. 488,P = 0. 000),the location of adenoma(χ2 = 77. 055,P = 0. 000)and adenoma tissue types(χ2 = 417. 000,P = 0. 000)were the risk factors for miss rates of colorectal adenomas. Number of polyps(χ2 = 8. 450,P= 0. 038),the organi-zation type of polyp(χ2 = 10. 718,P= 0. 013)and proficiency of colonoscopists(χ2 = 56. 069,P= 0. 000), the quality of bowel preparation(χ2 = 39. 195,P = 0. 000),insertion time(χ2 = 13. 133,P = 0. 001)were also the risk factors for miss rates of colorectal adenomas. Logistic regression analysis showed that the bigger the adenoma size,the less missed adenomas(OR= 0. 341,95%CI:0. 173-0. 671). Also,the longer insertion time took,the lower the adenoma miss rate(OR = 0. 987,95% CI:0. 981-0. 994). Per-patient miss rates were lower for high-risk adenomas compared with low-risk adenomas(OR = 0. 324,95%CI:0. 154-0. 680). Adenomas happening in multiple parts of bowel easily leads to missing(OR= 3. 791,95%CI:1. 505-9. 546). Conclusion The missed diagnosis of adenomas is not only significantly associated with features of missed adenomas,but also with skills of colonoscopists,insertion time,and bowel preparation. The key is high-quality index colonoscopy to avoid adenomas missing.

Objective To evaluate the efficacy of L?Arabinose for bowel preparation before colonos?copy. Methods A total of 170 patients who underwent colonoscopy were randomized into 2 groups. The ex?perimental group (n=85) used L?Arabinose for bowel preparation, while the control group (n=85) used polyethylene glycol electrolyte solution ( PEG?ELS ) . The degree of comfort, adverse effects, and the visibility during colonoscopy were observed. Results Premedication of L?Arabinose for bowel preparation yielded to more comfort ( U=-4?349,P=0?000) , less adverse effects (χ2=29?27,P=0?000) , and similar visibility during colonoscopy ( U=-0?875,P=0?381) compared with PEG?ELS. Conclusion L?Arabinose is safe, comfortable, and effective for bowel preparation before colonoscopy.

Objective To evaluate the efficacy of premedication of pronase and simethicone before upper gastrointestinal endoscopy. Methods A total of 4 690 patients undergoing upper gastrointestinal en?doscopy from January 2014 to November 2014 were recruited at gastrointestinal endoscopy center in Beijing Military General Hospital. All patients were randomized into 3 groups. The pronase plus simethicone group( n=1 602) took 40 ml mixed solution of pronase, sodium bicarbonate and simethicone orally 20 minutes before endoscopy. The simethicone group( n=1 548) took 40 ml simethicone orally 20 minutes before endoscopy. And the control group( n=1 540) took 10 ml lidocaine hydrochloride mucilage orally 5 minutes before endos?copy. The visibility during gastroscopy was observed. Results Each patient underwent gastroscopy, and no severe adverse event occurred during the procedure. The visibility of 82?3%( n=1 318) of the pronase plus simethicone group, 67?7%( n=1 048) of the simethicone group and 28?1% patients( n=432) of the control group respectively reached grade A or B. The visibility during gastroscopy in the pronase plus simethicone group was higher than that in the simethicone group(χ2=89?42, P=0?000) , while that in the simethicone group was higher than that of the control group(χ2=486?30, P=0?000). Conclusion Premedication of pronase and simethicone can improve the visibility during gastroscopy.

Objective To investigate the endoscopic findings and treatment of gastrointestinal neu-roendocrine neoplasms.Methods Endoscopic manifestation and treatment were analyzed retrospectively in 72 patients who were diagnosed as having gastrointestinal neuroendocrine neoplasms by endoscopy and pathol-ogy from May 2011 to December 2014.Results In 72 patients of gastrointestinal NEN,rectum was most commonly involved (48 patients,66.7%),followed by the stomach (16 patients,22.2%),duodenum, esophagus and the ileocecal valve.There were certain features in rectal neuroendocrine neoplasms under endoscopy,mostly manifested by submucosal tumors.But gastric,esophageal,and small intestine NEN man-ifestations showed various forms,without specific typical features,and easy to be misdiagnosed.Some patients diagnosed as having NEN G1 or G2 underwent EMR,ESD or laparoscopy combined with endoscopy resection.Patients diagnosed as having NEN G2 or neuroendocrine carcinoma by pathology received surgical resection,chemotherapy or palliative treatment.All 50 patients underwent endoscopic treatment successful-ly.Perforation occurred in one duodenal bulbar G1 patient during ESD.No bleeding occurred during and after the operation.All patients after treatment were followed up for 15.6 +13.2 months on average with no recurrence or metastasis.Conclusion Manifestations of gastrointestinal neuroendocrine neoplasms vary under endoscopy.Some tumors that locate in mucosa or submucosa with diameter less than 1cm can be resec-ted through EMR or ESD.

Objective:To detect the expression of microRNA-218 (miR-218) in human acute lymphocyte leukemia (ALL) T lymphocytes ( CCRF-CEM) ,explore its effects on the biological features of CCRF-CEM cells and the expression of its target gene c-kit, so as to provide new insights for leukemia treatment.Methods: Using the quantitative real-time polymerase chain reaction ( qRT-PCR) ,we detected the expression of miR-218 in the normal peripheral blood T lymphocytes and CCRF-CEM cells.Forty-eight hours after the miR-218 mimic was transfected into the CCRF-CEM cells,the expression of miR-218 in the CCRF-CEM cells was detected by qRT-PCR.The effect of miR-218 on the CCRF-CEM cell viability was detected using MTT.The effect of miR-218 on the proliferation and apoptosis of CCRF-CEM cell was analyzed using flow cytometry.c-kit gene was identified to be a target gene of miR-218 by luciferase reporter enzyme system,and the effect of miR-218 on the expression of KIT protein in cells were determined using Western blot.Results:As shown by qRT-PCR,compared with that in the normal peripheral blood T lymphocytes,the expressions of miR-218 in ALL T lymphocytes cell lines were significantly decreased ( P<0.01 ) .Compared with the control group, the expression of miR-218 increase significantly in CCRF-CEM cells transfected with miR-218 mimic for 48 hours ( P<0.01).MTT showed that the cell viability decreased significantly after the over-expression of miR-218 in the CCRF-CEM cells ( P<0.05 ) .Flow cytometry showed that the S-phase fraction significantly declined after the over-expression of miR-218 ( P<0.01 ) , and meanwhile the apoptosis of cells also significantly increased (P<0.01).Luciferase reporter gene assay showed that,compared with the control group,the relative luciferase activity significantly declined in the miR-218 mimic transfection group (P<0.01).Compared with the control group,the expression of KIT protein in the CCRF-CEM cells transfected with miR-218 mimic for 48 hours significantly decreased ( P<0.01).Conclusion:The expression of miR-218 decreases in ALL T lymphocytes cell lines.MiR-218 can negatively regulate the expression of KIT protein,inhibit the proliferation and increase the apoptosis of CCRF-CEM cells.Treatment based on the enhanced expression of miR-218 may be a promising strategy for leukemia.

Objective To observe the effects of MSH2 gene re expression on estrogen-induced apoptosis of colon cancer cells LOVO,and to explore its mechanisms.Methods According to different plasmid and whether with estradiol intervention,colon cancer LOVO cells were divided into empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,estrogen receptor (ER) β with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group,and received corresponding treatment.The expression of MSH2,ERβ protein and apoptosis related caspase 3 protein were detected by Western blotting.Cell viability was measured by cell counting kit-8.Cell DNA fragments of each group were isolated with apoptosis DNA fragments isolation kit.And the DNA ladder was observed.The rate of apoptosis was detected by flow cytometer.Single factor variance analysis was performed for comparison among multiple groups,and t test was used for comparison between the two groups.Results After transfection,the expression of the MSH2 and ERβ at protein level in LOVO cells significantly increased and neither of their expression was effected by estradiol.The expression levels of caspase 3 cleavaged active fragments of ERβ with estradiol group and ERβ with MSH2 and ethanol group were higher than other groups,and there was no significant difference between these two groups.The LOVO cell viability of empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,ERβ with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group was 1.72 ±0.25,1.74 ± 0.31,1.77 ± 0.35,1.74±0.33,1.70±0.34,1.02±0.48,1.71±0.31 and 1.07±0.18,respectively,and the differences between the groups were statistically significant (F=3.791,P＜0.05).Among them,the LOVO cell viability of ERβ with estradiol group was lower than that of ERβ with ethanol group,accordingly,that of ERβ with MSH2 and estradiol group was lower than that of ERβ with MSH2 and ethanol group,that of ERβ with estradiol group was lower than that of empty plasmid with estradiol group,that of ERβ with MSH2 and estradiol group was lower than that of MSH2 with estradiol group,and the differences were statistically significant (t=3.158,3.075,3.648,3.253,all P＜0.05).DNA ladder formed from DNA fragments of apoptosis cells was seen in ERβ with estradiol group and ERβ with MSH2 and estradiol group.The apoptosis rate of empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,ERβ with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group was 7.86±0.19,7.87±0.39,8.39±1.02,9.05±1.54,7.54±0.99,19.77±2.35,7.76±1.32 and 19.30±1.75,respectively,and the differences between groups were statistically significant (F=45.436,P＜0.05).Among them,the apoptosis rate of ERβ with ethanol group was lower than that of ERβ with estradiol group,that of ERβ with MSH2 and ethanol group was lower than that of ERβ with MSH2 and estradiol group,that of empty plasmid with estradiol group was lower than that of ERβ with estradiol group,that of ERβ with MSH2 and estradiol group was lower than that of MSH2 with estradiol group,and the differences were statistically significant (t =8.260,9.133,8.596,7.617,all P＜ 0.05).Conclusions Estrogen may promote colon cancer cell apoptosis through ERβ pathway.The process of apoptosis maybe related with caspase protein,MSH2 may not be involved in the regulation of this signal pathway.

10.3969/j.issn.1007-3969.2013.05.002

Objective To evaluate the efficacy and safety of submucosal injection using endoscopic water-jet in peroral endoscopic myotomy (POEM) for treatment of patients with achalasia of cardia (AC). Methods A retrospective analysis was performed on the data of 126 AC patients undergoing POEM in PLA General Hospital from March 2013 to February 2016. All the 126 patients were divided into two groups, 73 in the water-jet group and 53 in the needle injection group. The time to creating a submucosal tunnel, entire operation time, and incidence of complications were compared between the two groups. Results The time to creating a submucosal tunnel and the entire operation time of the water-jet group were both significantly less than those of the needle injection group (6. 38±0. 94 min VS 13. 81±1. 13 min, P<0. 05;27. 81±5. 76 min VS 70. 25±22. 67 min, P<0. 05). The hospital stay of patients after operation was less in the water-jet group than that in the needle injection group (4. 38±1. 87 days VS 5. 64±1. 83 days, P<0. 05). The incidence of bleeding [5. 5％ (4/73) VS 17. 0％ (9/53), P<0. 05] and fever [12. 3％ (9/73) VS 26. 4％ (14/53), P<0. 05] were lower in the water-jet group than those in the needle injection group. The incidences of perforation and pectoralgia were not significantly different between the two groups ( both P>0. 05 ) . Conclusion Endoscopic water-jet injection is safe and effective in POEM, which effectively shortens the time to creat a submucosal tunnel and the operation time, and reduces the incidences of complications including bleeding and fever.

Objective:To investigate the early recognition of coronary artery lesions(CAL)in Kawasaki disease(KD)and its relationship with monocyte/high-density lipoprotein cholesterol(HDL-C)ratio(MHR).Methods:A total of 216 children with KD who were hospitalized in Affiliated Hospital of Nantong University from June 2019 to June 2022 were selected as the research subjects,and divided into training set(162 cases)and test set(54 cases).The clinical data of the children were collected,and the children in the training set were divided into the CAL group(45 cases)and the NCAL group(117 cases)according to the diagnostic results of echo-cardiography,and the differences in clinical data and laboratory test results were compared between the two groups;Logistic regres-sion analysis was used to analyze the risk factors of CAL in children with KD;Pearson was used to analyze the correlation between MHR and CAL in children with KD.According to the MHR quantile,the children in the CAL group were divided into low MHR group(≤0.28),medium MHR group(0.29～0.42)and high MHR group(≥0.43),and they were analyzed and compared.Cox regression model was used to analyze the relationship between MHR and CAL risk in children with KD,and a predictive model was constructed based on the independent risk factors of CAL in children with KD.Results:There were 162 KD children with fever,and summer was a high incidence period;compared with the NCAL group,the CAL group had statistically significant differences in age,gender,fever time,KD type,MHR,WBC,PLT,NLR,and CRP(all P<0.05);Pearson correlation analysis showed that MHR was positively cor-related with the degree of coronary artery dilatation in children with CAL(r=0.743,P=0.001).and the risk of CAL in the KD children in the high MHR group was significantly higher than that in the low MHR group(HR=2.857,95%CI:1.329～6.431,P=0.003);Logis-tic regression analysis showed that gender,fever time,MHR,WBC,NLR and CRP were independent risk factors for CAL in children with KD.A prediction model was constructed based on the independent risk factors of CAL:Logit(P)=1.342+0.359×gender+0.181×ever time+1.064×MHR+0.459×WBC+0.146×NLR+0.211×CRP,P=e logit(P)/1+e logit(P),the AUC of this model was 0.874(95%CI:0.799～0.892),compared with the test set(AUC was 0.881,95%CI:0.785～0.913),the difference was not statistically sig-nificant(P>0.05);the AUC of MHR for predicting CAL in children with KD was 0.796,the sensitivity was 0.896,and the specificity was 0.824,which could be used as an early predictor of CAL in children with KD.Conclusion:MHR has a certain predictive value in the diagnosis of CAL in children with KD,and can reflect the degree of CAL in children with KD to a certain extent.Therefore,it is necessary to pay attention to the changes of MHR in children with KD in clinical practice.