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BACKGROUND: Histamine is a regulator of gastric acid secretion, which is involved in the development of duodenal ulcer (DU). Histamine is metabolized by both histamine N-methyltransferase (HNMT) and diamine oxidase, and its local action is terminated primarily by methylation which is catalyzed by HNMT. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay was used to identify the polymorphism of the point mutation C314T of HNMT gene of 498 Chinese patients with DU and 151 healthy individuals. RESULTS: In normal controls, the allele frequency of HNMT T314 was 3.3%, which was significantly lower than American Caucasians. The HNMT T314 allele was detected in 3.5% of the DU patients. In cases and controls, the frequency of C/C genotypes were 93.0% and 93.4%, respectively. The HNMT T/T genotype was not found in this population. No significant differences were seen in both genotype frequencies and allele frequencies between DU groups and controls. After stratified by H. pylori infection, they also could not reach significant differences in our current study. CONCLUSION: The HNMT T314 allele frequency is lower in Chinese population than in American Caucasians. No association can be found in the involvement of HNMT C314T polymorphism in the susceptibility to duodenal ulcer.
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Duodenal Ulcer/genetics , Genetic Predisposition to Disease , Histamine N-Methyltransferase/genetics , Polymorphism, Genetic , Base Sequence , Case-Control Studies , China , DNA Primers , Humans , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
Objective:To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO).Method:The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH 4 (methane) and H 2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman′s Rank correlation analysis,and the Z test were used for statistical analysis. Results:Based on the international recommended diagnostic criteria for SIBO,which are fasting CH 4 ≥10 ppm (parts per million) or H 2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH 4 and H 2 were higher in the case group than in the control group [CH 4: 3(2,7) vs. 3(1,3) ppm, H 2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH 4 levels was statistically significant ( Z=6.22, P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH 4 alone,0.531 for H 2 alone, and 0.620 for CH 4 combined with H 2. The cut-off values were fasting CH 4≥4 ppm,fasting H 2≥13 ppm,and fasting CH 4 ≥5 ppm (or CH 4≥4 ppm and H 2≥24 ppm),respectively. Measuring CH 4 alone and CH 4 combined with H 2 was effective for determining the presence of gastrointestinal symptoms ( P<0.05). When CH 4 alone or CH 4 combined with H 2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria ( P>0.05). The specificity of CH 4 alone was 79.9%,and the accuracy of CH 4 alone was 68.8%. The specificity of CH 4 combined with H 2 was 85.0%,and the accuracy of CH 4 combined with H 2 was 71.7%. Conclusion:Rapid one-time determination of CH 4 and H 2 in exhaled breath may a viable diagnostic method for SIBO, and using CH 4 combined with H 2 ( i.e.,fasting CH 4≥5 ppm, or CH 4 ≥4 ppm and H 2 ≥24 ppm) as cutoff values may be feasible.
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Objective:To introduce a new method of root reconstruction for proximal repair of acute type A aortic dissection, and to retrospectively analyze its short-term efficacy.Methods:From January 2018 to October 2019, a total of 455 patients with acute Stanford type A aortic dissection received surgical treatment. Among them, 343 patients underwent double-jacket-wrapping(DJW) root reinforcement(11 patients underwent leaflet suspension), 81 patients underwent Bentall surgery, 15 Wheat operations, 12 untreated roots, and 4 David operations. Compared 343 patients who underwent double-jacket-wrapping root reconstruction and 81 patients who underwent Bentall surgery. The perioperative indicators and short-term survival of the two groups were compared.Results:No patients died intraoperatively. The 30-day mortality rate in the DJW group and the Bentall group were 10.5% and 7.4%, respectively( P=0.403); cardiopulmonary bypass time were(218.8±68.4) min and(240.2 ± 59.8), P=0.011; aortic clamp time were(150.6 ± 47.9) min and(181.3 ±45.6)min, P=0.000. There was no difference between the operation time and the deep hypothermia circulatory time between the two groups. The mean follow-up was(11.7±6.4) months. Seven and two follow-up deaths occurred in the DJW group and the Bentall group, respectively, and the cause of death was not related to the aortic root. The degree of aortic regurgitation after DJW was 0.7±0.5, which was significantly lower than that before surgery( P=0.000). Conclusion:Compared with Bentall surgery, DJW method is a safe and effective method for the repair of acute type A aortic dissection roots, which can obtain good perioperative and early curative effects.
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Objective To investigate the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on intestinal barrier and intestinal development in offspring mice and its possible mechanism.Methods Six C57BL/6 pregnant mice with the same conception time of 6 weeks were selected and randomly divided into experiment group given 108 cfu/ml LGG live bacteria and control group given LGG inactivated bacteria by gavage from the 18th day of pregnancy until natural birth.The progeny mice in the two groups were continued to be gavaged with 107 cfu/ml of LGG live bacteria or LGG inactivated bacteria on days 1-5 of birth.The body weight changes of 3 week'progeny mice were recorded.The colonization of LGG bacteria in offspring mice was detected at 2nd and 3rd weeks.The mRNA of intestinal proinflammatory cytokines and tight junction molecules were evaluated by real-time PCR method.HE,immunohistochemistry,immunofluorescence staining and enzyme-linked immunosorbent assay were used to evaluate the intestinal barrier of 3-week old off spring mice.Results Compared with the control group,the progeny mice of the experiment group showed no significant difference in body weight at the first week,and the body weight increased at the second week and the third week [2ndweek:(3.790±0.240) g vs.(4.326±0.140) g,t=3.707,P=0.006;3rd week:(7.295±0.326) g vs.(8.040±0.370) g,t=3.130,P=0.011].LGG colonization can be detected only in the feces of progeny mice in the experiment group.Intestinal colonization can promote the growth of small intestine villi and colon crypt depth [jejunum:(320.000±22.514) μm vs.(265.100±15.611) μm,t=8.258,P＜0.001;ileum:(150.500±13.099) μm vs.(111.000±11.308) μm,t=9.958,P＜0.001;colon:(295.000±15.209) μm vs.(233.100±6.678) μm,t=9.129,P＜0.001].Compared with the control group,the number of goblet cells in the colonic crypt of the experiment group increased (11.62 ± 0.780 vs.35.24 ±1.370,t=15.000,P＜0.001),and the relative mRNA expression levels of pro-inflammatory factors as IFN-γ (1.280±0.232 vs.0.512±0.206,t=4.970,P=0.001),IL-6 (1.364±0.271 vs.0.941±0.215,t=2.452,P=0.040),IL-10 (1.341±0.320vs.0.744±0.294,t=2.762,P=0.025)andTNF-α (3.702±0.150 vs.2.581±0.500,t=2.553,P=0.034) in the experiment group decreased;the expression levels of the intimate tight junction molecules (Claudin3) (1.283±0.152 vs.1.881±0.172,t=4.932,P=0.001) and the atresia protein molecule (Occludin) (1.164±0.342 vs.0.812±0.224,t=3.67,P=0.016) significantly increased.Conclusion Early life LGG colonization protects the intestinal barrier by inhibiting lowgrade intestinal inflammation.This study will lay the experimental foundation for the supplementation of probiotics in early life so as to prevent intestinal diseases.
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Objective To observe the effects of maternal high fat diet (MHFD) during pregnancy and lactation on intestinal barrier function in offspring mice.Methods C57BL/6 pregnant mice were divided into high fat diet (MHFD) group and normal diet group (MND) randomly and were given high fat diet and normal diet during pregnancy (3 weeks) and lactation (3 weeks) respectively.Both groups of offspring mice were naturally given and bodyweight of pups was monitored at birth and weekly.After weaning,the intestinal permeability of offspring mice was detected by fluorescein isothiocyanate conjugated-dextran method (FITC-D).Immunofluorescence was used to detect the expression of ZO-1 in intestinal tissues.HE staining was used to assess the villus length and crypt depth.The intestinal cell proliferation (expression of Ki-67) and Mucin 2 (MUC2) were assessed by immunohistochemistry.PAS staining was used to evaluate the goblet cells.The expression of inflammatory cytokines including IL-1β,IL-6,and TNF-α in intestinal tissue were measured by real-time PCR.Results At the age of 2 and 3 weeks,the offspring in MHFD group were significantly heavier than those in MND group.HE staining showed no obvious microscopic inflammation in both groups of 3 weeks old offspring mice,however,the relative expression levels of IL-1β (1.95±0.53 vs.1.13±0.15;t =3.65,P=0.005),IL-6 (1.40±0.71 vs.0.73±0.17;t=2.72,P=0.04),and TNF-α (1.63±0.53 vs.1.04±0.12;t=2.64,P=0.02) mRNA were significantly higher in the MHFD group.Compared with the 3 weeks old offspring mice in MND group,MHFD significantly increased the permeability of intestine and decreased the expression of ZO-1 in membrane.The number of Ki-67 positive cells (18.00±4.74 vs.24.60±4.17;t =3.31,P=0.004) in each villus,goblet cells (14.70±2.91 vs.28.10±4.95;t =7.38,P＜0.001) and MUC2 positive cells (20.60± 3.13 vs.30.00±3.33;t=6.50,P＜0.001) in each crypt were significantly lower than those in MND group.Conclusion Maternal high fat diet in early life of offspring mice can induce intestinal low grade inflammation and lead to the disruption of intestinal mucosal barrier in offspring mice,which may be involved in the progeny diseases.
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Objective To analyze the clinical and pathological features of upper gastrointestinal serrated lesions.Methods A total of 21 patients with upper gastrointestinal serrated lesions in Tianjin Medical University General Hospital between January 2011 and December 2015 were retrospective analyzed.Data of the patients including demographics, clinical and pathological features were collected.Among the 21 patients, 18 patients, who underwent colonoscopy simultaneously or within six months, were selected as the study group, each patient was compared to 4 randomly selected controls without serrated lesions, who also underwent colonoscopy within the same time period.Differences of colorectal neoplasia detection were analyzed between the cases and controls.Results The mean age of 21 patients was 55.3±17.2 years, and 11 cases were male.Involving the locations of serrated lesions, 17 cases were found in the stomach (including 3 in the cardia, 9 in the corpus, and 5 in the antrum), and followed by 3 in the duodenum and 1 in lower esophagus.The mucosa pathological morphology showed that 6 cases were serrated hyperplasia, 8 cases were hyperplastic polyps, 6 cases were serrated adenomas with low grade dysplasia and 1 case was in the duodenum intramucosal carcinoma.Seven (38.9%) colorectal adenomas were found in the study group, including 3 (16.7%) non-advanced colorectal adenomas and 4 (22.2%) advanced colorectal adenomas.Eight (11.1%) colorectal adenomas were found in the control group, including 5 (6.9%) non-advanced colorectal adenomas and 3 (4.2%) advanced colorectal adenomas.The rate of colorectal adenoma detection in the study group was significantly higher than that in the control group (38.9% VS 11.1%, P=0.010, OR=5.091, 95%CI:1.534-16.890).Conclusion Upper gastrointestinal serrated lesions can be found in various mucosal lesions with different pathological morphologies.Moreover colonoscopy is likely to be recommended to detect concurrent colorectal adenoma for these patients.
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Objective@#To discuss the perioperative and follow-up results of different surgical methods for acute Stanford type A aortic dissection patients and analyzed the results.@*Methods@#The clinic data of 351 acute Stanford type A aortic dissection patients received surgical therapy at Department of Thoracic and Cardiovascular Surgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital from January 2008 to December 2015 were analyzed retrospectively. There were 272 male and 79 female patients, aging from 22 to 83 years with a mean age of (52±13) years. According to root size, aortic valve structure and the status of dissection involvement, these patients were devided into three major groups: 218 cases with root reconstruction using Dacron felts, 34 cases with root reconstruction concomitant with aortic valve resuspension repair and 99 cases in with Bentall procedure. Proper shape based on the status of dissection involvement of Dacron patch was cut and put between the middle and outerlayer of aorta, then inside the inner layerone band Dacron felt was sutured with the aorta and the new middle layer with Dacron patch as mentioned above. In some cases the prolapsed aortic valve was re-suspended to the aortic cusp. Clinical outcomes among the 3 procedures were compared by χ2 test, Fisher′s exact test, t test and analysis of variance.@*Results@#Cardiopulmonary bypass, cross-clamp, and circulatory arrest times of all the patients were (250±78), (171±70) and (31±10) minutes, respectively. The 30-day mortality was 9.2%(33/351), while no difference among the 3 procedures (9.6%, 8.8% and 9.1%). In the average follow-up time of (26.0±23.0) months (range from 0.5 to 90.0 months), survival rates were similar among the 3 procedures (77.7%, 77.4% and 77.8%). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (diameter of 50 mm).@*Conclusions@#The indication of root management of acute Stanford type A aortic dissection is based on the diameter of aortic root, structure of aortic leaflets, and the dissection involvement. For most acute Stanford type A aortic dissection patients, aortic root reconstruction is a feasible and safe method.
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Objective To investigate the effects of intestinal microbiota of patients with chronic constipation on the expression of serotonin transporter (SERT) and the bowel movement in mice.Methods Fecal samples of patients with slow transit constipation met Rome Ⅲ criteria and healthy normal controls were collected and made into fecal microbiota solution.Twenty specfic pathogen free (SPF) mice were divided into experiment group and control group.The mice of two groups were both pre-treated with streptomycin to establish the germ-free mice model.The mice of control group were gavaged with mixed fecal microbiota solution of healthy normal controls and the mice of experiment group were gavaged with mixed fecal microbiota solution of patients with chronic constipation.Mice were sacrificed after fed for 15 days.Defecation parameters and ink discharge time of mice were detected.The expressions of SERT mRNA and SERT protein in mice intestinal tissues were detected with real time-polymerase chain reaction and Western blotting.The 5-hydroxytryptamine (5-HT) levels of mice intestinal tissues were evaluated by enzyme-linked immunosorbent assay (ELISA) and double immunofluorescent staining.The methods of t test and Chi-square test were performed for statistical analysis.Results On the 15th day,the total number of the feces within 2 h of the experiment group and control group was 8.55±1.83 and 12.14±2.90,respectively,and the difference was statistically significant (t=3.33,P＜0.05).The weight of feces were (151.90 ± 32.42) mg and (246.72 ± 64.01) mg,respectively,and the difference was statistically significant (t=4.18,P＜0.01).The dry weight of feces were (65.52±11.76) mg and (92.93±23.07) mg,respectively,and the difference was statistically significant (t=3.37,P＜0.05).The water content of feces were (56.63 ± 3.01) ％ and (61.95 ± 3.70) ％,respectively,and the difference was statistically significant (t=3.57,P＜0.05).The defecating time of first black feces of the experiment group and control group were (83.24±11.31) min and (69.06±2.72) min,respectively,and the difference was statistically significant (t=-2.74,P＜0.05).The expressions of SERT mRNA and SERT protein levels in mice intestine tissues of the experiment group were significantly higher than those of the control group (t =2.61,-6.89;both P＜0.05).5-HT level of mice intestinal tissues of the experimental group and control group were (151.69± 10.18) ng/mL and (198.77 ± 25.99) ng/mL,respectively,and the difference was statistically significant (t=-4.13,P＜0.01).Conclusion Intestinal microbiota of patients with chronic constipation may influence the expression of SERT in the mice intestinal tissues,and then decrease the level of 5-HT,slowing the bowel movement in mice.
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Objective To evaluate necessity of colonoscopy in symptomatic subjects with colorectal neoplasia screening score.Methods Data of consecutive patients who underwent routine colonoscopy between October 2015 and December 2015 were prospectively collected.APCS score and HKCS score were used to evaluate the detection rate of colorectal tumors in groups of different risks and to predict the necessity of colonoscopy in symptomatic subjects.Results There were 815 subjects with mean age of 51.2± 14.8 years.Colorectal neoplasia and advanced neoplasia were identified in 170 (20.9％) and 43 (5.3％) cases.APCS score was classified as average risk (AR),moderate risk (MR) and high risk (HR),which included 234,400 and 161 cases,respectively.The detection rates of colorectal neoplasia in AR,MR and HR groups were 9.5％,20.0％ and 41.0％,respectively,and those of advanced neoplasia were 0％,5.5％ and 13.0％,respectively.Detection rate of colorectal neoplasia in the HR group showed 6.7 times of that in the AR group (95％CI:3.9-11.2).HKCS score was classified as AR and HR,which included 633 and 182 cases in the present study.The detection rates of colorectal neoplasia in these groups were 16.3％ and 36.8％,and those of advanced neoplasia were 3.2％ and 12.6％.Detection rate of colorectal neoplasia in HR group was 3.0 times of that in AR group (95％CI:2.1-4.3).Conclusion APCS score and HKCS score are both suitable for evaluating the necessity of colonoscopy in symptomatic subjects.It is necessary for HR patients to undergo colonoscopy to detect colorectal neoplasia,however,AR patients evaluated by APCS score can delay colonoscopy to economize medical resources and avoid unnecessary complications.
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Objective To analyze the clinical and pathological features of advanced colorectal serrated adenoma(ACSA). Methods The endoscopic and pathological features of 156 cases of ACSA and 121 cases of non-ACSA diagnosed in General Hospital, Tianjin Medical University from January 2010 to March 2016 were retrospectively analyzed and compared.Results ACSA and non-ACSA cases accounted for 56.3%(156/277)and 43.7%(121/277)of all patients with colorectal serrated lesions,respectively. The mean age of ACSA patients was 57.79±13.65 years and 89(57.1%)of these patients were male. There was no significant difference in age and gender between ACSA and non-ACSA patients. A total of 161 ACSA lesions were diagnosed,including 71 sessile serrated adenoma/polyps and 90 traditional serrated adenomas. Among the 161 ACSA lesions,there were 29(18.0%)lesions whose diameter≥10 mm, and 84(52.2%) lesions located in the proximal colon, which were more than non-ACSA(84/161 VS 49/134,P=0.007). ACSA was classified under endoscopy into pedunculated type(20/161),sub-pedunculated type(35/161), sessile type(24/161),flat type(79/161)and laterally spreading tumor(3/161), and the distribution of lesion type was significantly different from non-ACSA(P<0.001). One hundred and sixty(99.4%)ACSA lesions were diagnosed as dysplasia, including 158 low degree dysplasia and 2 high degree dysplasia.Moreover,16 ACSA patients were accompanied with synchronous advanced colorectal neoplasia(sACN), and large serrated polyps(diameter≥10 mm)might have a strong association with sACN(OR=4.35, 95%CI:1.467-12.894, P<0.05). Conclusion ACSA is more common in proximal colon and sub-pedunculated type,sessile type and flat type. ACSA diameter≥10 mm is significantly associated with sACN.
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Objective To assess the results of colonoscopy surveillance in 5 years after polypectomy of non-advanced colorectal adenoma and to identify its risk factors. Methods Patients undergoing colonosco-py and followed up with colonoscopy within 5 years between January 2003 and December 2013 were retro-spectively analyzed.No substance or only small quantity of clear water left in the intestinal tract and colono-scopes accessing ileocecus were regarded as complete examination. The initial colonoscopy was regarded as the baseline colonoscopy. Patients with non-advanced adenomas were assigned to the case group and those without were to the control group. Data of clinical characteristics and colorectal findings were estimated and risk factors were identified. Results A total of 828 patients were included,374 patients in the case group and 454 in the control group on baseline colonoscopy.The case group had a low incidence of advanced adeno-mas at a 1 to 5 years interval when compared with the control group,both with adequate baseline examination [1. 5%(5/ 326)VS 2. 2%(9/ 408),P = 0. 51]. The detection rates of advanced adenomas on follow-up colonoscopy at 1 to 3 years and 3 to 5 years in case group were 1. 7%(3/ 178)and 1. 4%(2/ 148),respec-tively(P>0. 05).Regression analysis showed age≥50 years old and being male were the independent risk factors for advanced adenomas recurrence within 5 years follow-up. No colon cancer was found in 828 patients during the follow-up. Conclusion Surveillance colonoscopy intervals within 5 years is of little benefit to pa-tients who had adequate polypectomy. Too early reexaminations due to concerns about advanced adenomas recurrence can be avoided.
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Objective To initially explore the feasibility and quality control of producing fecal-derived microbiota enteric capsules.Methods Fecal-derived microbiota was put into double layered enteric capsules.The bacteria colony numbers of fresh prepared glycerol containing fecal-derived microbiota liquid,glycerol containing and glycerol free fecal-derived microbiota after stored at -80 ℃ for 72 h were counted with standard plate count methods in order to investigate the stability after frozen.Methylene blue was taken as the standard,resistance to acid and release rate of capsules was evaluated.The t test was performed for statistical analysis.Results The preparation process of double layered microbiota capsules was simple and practicable.The data of 12 plates of each microbiota were acquired.The number of bacteria colony of fresh prepared glycerol containing fecal-derived microbiota ((5.08 ±1.37)×107 colony-forming units (cfu)/mL)was significantly more than that of the group without glycerin ((1.73±0.64)×107 cfu/mL)at -80 ℃for 72 h (t = 7.621 ,P <0.01).There was no significant difference in the number of bacteria colony between glycerin containing frozen fecal-derived microbiota ((4.67±1 .56)×10 7 cfu/mL)and fresh fecal-derived microbiota (t = 0.694,P = 0.495).Regression equations were achieved with fecal-derived microbiota containing methylene blue,and there was a good linear relation between 0.5 μg/mL and 8.0 μg/mL.Three fecal-derived microbiota enteric capsules containing methylene blue were prepared.Their resistance to acid was 96.0%,99.1 %,and 95 .5 %,while the release rate was 88.6%,95 .1 % and 86.5 %, respectively.All met the requirement of Chinese Pharmacopoeia to enteric capsules.Conclusion The preparation of double layered fecal-derived microbiota enteric capsules had feasible technology and stable quality,which could provide reference in prevention and treatment of diseases related with colonic microbiota imbalance.
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Objective To explore the necessity of colonoscopy in young patients with chronic constipation.Methods Data of patients aged 18-50 underwent colonoscopy at Tianjin Medical University General Hospital with chronic constipation as the sole indication between April 2003 and May 2014 were analyzed.Endoscopic and pathologic reports were analyzed.Results During the study period,a total of 563 patients were included,who were aged 18-50 with chronic constipation as the sole indication,of which 260 patients were aged 18-35,and 303 patients were aged 36-50.No lesion was found during colonoscopy in 167 (29.7％) patients,whereas in other 396 (70.3 ％) patients positive findings were reported,including polyps in 45 patients (of which 13 were with multiple polyps),adenomas in 20(17 in distal colon,3 in proximal colon).In patients aged 18-35,3 cases of adenomas(3/260,1.2％) were found,of which 1 patient (1/260,0.4％)had advanced adenoma.In patients aged 36-50,17 cases of adenomas(17/303,5.6％) were found,of which 4 (4/303,1.3％) were advanced ones.Colorectal cancers were found in 2 patients (0.7％,2/303),both in patients aged 36-50.The detection rate for colorectal neoplasms (including adenoma and cancer) in patients with chronic constipation aged 18-35 was significantly lower than that in patients aged 36-50[1.2％(3/260) VS 6.3％(19/303),P=0.002,95％CI:0.05-0.60].Conclusion The detection rate for colorectal neoplasms in patients aged 18-35 years with chronic constipation is relatively low,and colonoscopy is not recommended for them.
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<p><b>OBJECTIVE</b>To investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.</p><p><b>METHODS</b>Mice with EGFR gene defects in macrophages (Egfr(fl/fl) LysM-Cre) and with EGFR gene expression in macrophages (LysM-Cre) (control group) were treated with azoxymethane (AOM) to establish colorectal tumor models. These models were treated with or without berberine (BER) intervention. The number of colorectal tumors and the gut length in the two groups were measured. The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling. Western blot was used to detect the expression of cleaved-caspase-3 protein.</p><p><b>RESULTS</b>After treated with AOM, the colorectal tumor number was 10.26 ± 1.43 in the LysM-Cre group and 7.62 ± 1.05 in the Egfr(fl/fl) LysM-Cre group, showing a significant difference (P = 0.021). The gut length was (6.04 ± 1.06) cm in the LysM-Cre group and (6.39 ± 0.92) cm in the gfrfl/flLysM-Cre group, with a non-significant difference between the two groups (P = 0.075). After treated with AOM plus BER intervention, the colorectal tumor number of the LysM-Cre group was 8.35 ± 1.22 and that in the Egfr(fl/fl) LysM-Cre group was 2.66 ± 0.38, showing a very significant difference between the two groups (P = 0.006). The gut length of the LysM-Cre group was (7.34 ± 1.16) cm and that of the Egfr(fl/fl) LysM-Cre group was (10.01 ± 1.72) cm (P = 0.028). After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31 ± 3.43)% and that in the Egfr(fl/fl) LysM-Cre group was (75.85 ± 2.92)% (P = 0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43 ± 3.09)% and that in the Egfr(fl/fl) LysM-Cre group was significantly lower (29.65 ± 2.47)% (P = 0.018). The ratio of annexin V-positive tumor cells was (0.95 ± 0.13)% in the LysM-Cre group, not significantly different from (1.13 ± 0.16)% in the Egfr(fl/fl) LysM-Cre group (P = 0.175). After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10 ± 1.97)%, significantly lower than the (47.08 ± 2.83)% in the Egfr(fl/fl) LysM-Cre group (P = 0.010). The level of cleaved-caspase-3 protein expression was 235.92 ± 19.73 in the Egfr(fl/fl) LysM-Cre group, significantly higher than the 119.71 ± 12.87 in the LysM-Cre group (P = 0.012).</p><p><b>CONCLUSIONS</b>The growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages. The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.</p>
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Animals , Mice , Antineoplastic Agents , Pharmacology , Therapeutic Uses , Apoptosis , Berberine , Pharmacology , Therapeutic Uses , Caspase 3 , Colorectal Neoplasms , Drug Therapy , Genes, erbB-1 , Physiology , Immunohistochemistry , Macrophages , MetabolismABSTRACT
Objective To investigate secondary bile acid induced canceration process of intestinal adenoma and effects on intestinal microflora in Apcmin/+ mice.Methods Forty four-week-old mice (20 Apcmin/+mice and 20 wild-type C57BL/6J mice) were divided into four groups:wild-type control group (regular drinking water),wild-type deoxycholic acid (DOC) group (with 0.2 ％ DOC in drinking water),Apcmin/+ control group and Apcmin/+ DOC group.Fecal pellets of Apcmin/+ mice were collected at 0 week and 12 week after administration.The changes of intestinal microflora were analyzed by pyrosequencing.All mice were sacrificed after 12 weeks.The number,size and location of intestinal adenoma were observed.The pathological type of adenoma was evaluated after hematcxylin-eosin (HE) staining.Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry.Cell apoptosis was determined by in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling technique (TUNEL).Independent t test was used for the quantitative data comparison between two groups.Results No intestinal tumors were found in the wild-type mice.The total number of intestinal adenoma of Apcmin/+ DOC group significantly increased,compared with that of Apcmin/+ control group (57.00 ± 3.07 vs 21.50± 4.69,t=20.03,P＜0.01),the increase of the adenoma with maximum diameter between 1 to 2 mm was most significant (30.62± 7.73 vs 7.75 ± 4.59,t =8.04,P＜ 0.05),the rate of adenoma canceration also significantly increased compared with that of Apcmin/+ control group.The percentage of PCNA positive cells significantly increased compared with that of Apcmin/+ control group ((90.17 ± 2.14) ％ vs (41.97 ± 4.26) ％,t=31.97,P＜0.01).The percentage of cell apoptosis significantly declined ((1.40± 1.12) ％ vs (7.50 ± 0.65)％,t =14.90,P＜ 0.01).The diversity of intestinal flora of Apcmin/+ DOC group significantly decreased.The ratio of Firmicutes and Bacteroidetes significantly increased compared with control group (0.586 7±0.148 4 vs 0.387 3±0.013 6,t=2.36,P＜0.05).The number of pathogenic bacteria increased in Apcmin/+ DOC group and probiotics significantly decreased.Conclusion DOC can induce intestinal flora imbalance in Apcmin/+ mice and promote intestinal adenoma into adenocarcinoma through increasing tumor cell proliferation and inhibiting cell apoptosis.
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Objective To evaluate the association of gastric hyperplastic polyps with colorectal neo-plasia.Methods Data of consecutive patients who underwent esophagogastroduodenoscopy (EGD)and colonoscopy between January 2011 and December 2013 were reviewed retrospectively.They were compared with patients without gastric polyps who also underwent EGD in the same period.The relationship between gastric polyps and colorectal neoplasia was analyzed.Results The incidence of colorectal neoplasia in gas-tric hyperplastic polyps group was higher than that of the control group [24.0% (46 /192)VS 10.4%(40 /384),P =0.000].An increased incidence of colorectal adenomas in gastric hyperplastic polyps group was found,but there was no difference in the incidence of colorectal cancer in gastric hyperplastic polyps group and control group[2.1%(4 /192)VS 2.3%(9 /384),P =1.000].Stratification analysis suggested that the incidence of colorectal neoplasia in gastric hyperplastic polyps group who aged over 50 was signifi-cantly higher than that in the control group[28.5%(43 /151)VS 10.6%(29 /274),P =0.017],regard-less of different genders and the number of gastric hyperplastic polyps.Conclusion The incidence of color-ectal neoplasia in gastric hyperplastic polyps has significantly increased,especially in those aged over 50 years,regardless of different genders and the number of gastric hyperplastic polyps.Such patients should undergo colonoscopy to detect colorectal neoplasia.
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Objective The purpose of this study was to explore the risk factors of recurrence of atrial fibrillation (AF) after surgical radiofrequency ablation in patients undergoing cardiac valve surgery.Metbods Retrospective analysis was made in 255 cardiac valve patients undergoing concomitant radiofrequency modified Maze operation from April 2010 to December 2012 in Nanjing Drum Tower Hospital.Multivariate logistic regression analysis was used to screen independent risk factors for predicting recurrence of AF.Results Excluding 8 patients died after surgery,11 cases who were junctional rhythm after ablation or received pacemaker implantation and 60 lost case,176 patients were finished follow-up.107 cases maintained stable sinus rhythm (SR),whereas other 69 cases developed AF recurrence.Multivariate logistic regression analysis found larger left atrial size,higher B-type natriuretic peptide,lower preoperative heart rate and postoperative AF rhythm before discharge were independent risk factors for predicting AF recurrence.Conclusion Larger left atrial size,higher B-type natriuretic peptide and lower preoperative heart rate before surgery can impact outcome of surgical radiofrequency ablation in patients undergoing cardiac valve surgery after following 12(4-38)months.They can be used in clinical practice to choose more suitable cardiac valve patients with AF for surgical ablation.Postoperative appearance of AF rhythm before discharge indicated a poor prognosis,which should be interfered with drugs or electrical cardioversion.
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<p><b>BACKGROUND</b>Sporadic fundic gland polyps (FGPs) are common gastric polyps. Some studies reported that FGPs dramatically increased due to proton pump inhibitors (PPIs) use and a decreased prevalence of Helicobacter pylori (H. pylori) infection in Western countries. However, data are still controversial. This study aimed to identify the relationships between these two factors and FGPs in China.</p><p><b>METHODS</b>Consecutive patients with FGPs detected were retrospectively analyzed. Data including patients' age, sex, symptoms, H. pylori infection, history of PPIs use, and the polyps were documented. Each patient was compared with two randomly selected age- and sex-matched controls with similar symptoms in the same period.</p><p><b>RESULTS</b>During the period from March 2011 to March 2012, a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls. The mean age was (55.12±12.61) years, and 75.91% were women. The prevalence of H. pylori in patients with FGPs was significantly lower than in those without FGPs (22.30% (64/287) vs. 42.26% (224/530), P < 0.001, OR 0.392, 95% CI 0.283-0.544). Overall, a total of 54 patients with FGPs (54/328, 16.46%) and 136 patients without FGPs (136/656, 20.73%) received PPIs therapy (P = 0.110). According to the different duration of PPIs use, no significant differences of PPIs use were found between the cases and controls among all subgroups. Moreover, the PPIs use was also similar, regardless of age, sex, H. pylori infection, and the number of polyps.</p><p><b>CONCLUSION</b>Sporadic FGPs may not be induced by PPIs therapy but negatively correlate with H. pylori infection in China, which is not the same with the data in Western countries.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenomatous Polyps , Epidemiology , China , Epidemiology , Endoscopy, Digestive System , Gastric Fundus , Pathology , Helicobacter Infections , Epidemiology , Proton Pump Inhibitors , Retrospective Studies , Stomach Neoplasms , EpidemiologyABSTRACT
Objective To investigate the effects of berberine on tumor-associated macrophages (TAM)and the expression of cyclooxygenase-2 (COX-2)of intestinal polyps in Apc(Min/+) mice.Methods A total of 20 Apc(Min/+) mice,four weeks old,were equally divided into the control group and the berberine group,10 in each group.The mice of the control group drank plain water,while the mice of berberine group drank water with 0.1 % berberine.After 12 weeks,all the mice were sacrificed.The intestine and colon were isolated,and the numbers of polyps were counted.The expression of F4/80,inducible nitric oxide synthase-2 (iNOS),macrophage mannose receptor (MR)and COX-2 was detected by immunohisto-chemistry method.The relative expression of COX-2 at protein level was measured by Western blotting. The t test was performed for comparison between two independent groups.Results The total number of intestinal polyps,the number of small intestinal polyps and the number of colon polyps of the berberine group (11 .50±2.05 ,10.50±1 .77 and 1 .00±0.46,respectively)were all less than those of the control group (30.63±1 .69,28.00±2.00 and 2.63±0.74,respectively),and the differences were statistically significant (t=16.727,16.952 and 3.162,P =0.001 ,0.001 and 0.010,respectively).The percentage of F4/80 positive cells in the stroma of polyps of the berberine group ((17.40 ±4.23 )%)was less than that of the control group ((31 .24±6.34)%),and the difference was statistically significant (t =5 .327, P =0.043).The percentage of iNOS positive cells in the stroma of polyps of the berberine group ((7.43± 1 .78 )%) was higher than that of the control group ((2.72±0.68)%), and the difference was statistically significant (t=7.335 ,P =0.004).The percentage of MR positive cells in stroma of polyps of the berberine group ((19.52±1 .54)%)was less than that of the control group ((12.63±0.68)%),and the difference was statistically significant (t=5 .634,P =0.016).The percentage of COX-2 positive cells in stroma of polyps of berberine group ((3.38 ± 0.51 )%)was less than that of the control group ((7.60±0.57 )%),and the difference was statistically significant (t = 7.234,P = 0.001 ).The relative expression of COX-2 at protein level of polyps of the berberine group was lower than that of the control group. Conclusion Berberine may take the role in inhibiting the growth of intestinal polyps in Apc(Min/+) mice through interfering the differentiation of TAM in polyps and suppression the expression of COX-2.
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ObjectiveTo evaluate the risk of colorectal neoplasia among patients with gastric or duodenal adenoma.MethodsWe retrospectively reviewed 39 patients with gastric or duodenal adenomas between 2007 and 2011 as the study group.A total of 78 patients without upper gastrointestinal adenomas who underwent colonoscopy were included as a control group.Colonoscopic findings were compared between the two groups.ResultsPositive finding rate of colorectal neoplasia in study group was 51.3％ (20/39),with adenomas in 38.5％ (15/39) and cancer in 12.8％ (5/39),which were all significantly higher than those of the control group,14.1％ (11/78) ( P ＜ 0.001 ),12.8％ ( 10/78 ) ( P ＜ 0.05 ) and 1.3％ ( 1/78 ) ( P ＜ 0.05),respectively.The results were similar when upper digestive tract was further divided into stomach and duodenum(50.0％ vs.12.5％ and 52.2％ vs.15.2％ ).ConclusionPatients with gastric or duodenal adenomas are at a significantly higher risk for colorectal neoplasia.Colonoscopy should be recommended for these patients.