Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.@*METHODS@#This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.@*RESULTS@#A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).@*CONCLUSIONS@#The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Influence of Helicobacter pylori infection on anxiety and depression in patients with chronic gastritis / 中华消化杂志

Objective:To evaluate the influence of Helicobacter pylori ( H. pylori) infection on anxiety and depression in patients with chronic gastritis. Methods:From December 1 2020 to June 30 2021, 387 patients with chronic gastritis who visited the outpatient Department of Gastroenterology, the First Hospital Affiliated to Air Force Medical University were continuously recruited. According to the status of current H. pylori infection, the patients were divided into H. pylori uninfected group and H. pylori infected group. The general demographic information of patients was collected. Hamilton anxiety scale, Hamilton depression rating scale-24, Pittsburgh sleep quality index (PSQI) and gastrointestinal symptom rating scale (GSRS) were filled in. The detection rates of anxiety and depression were compared between the H. pylori uninfected group and the H. pylori infected group according to demographic characteristics. Chi-square test and multiple logistic regression analysis were used for statistical analysis. Results:Finally, 360 patients with chronic gastritis were enrolled, including 200 patients in H. pylori uninfected group and 160 patients in H. pylori infected group. The detection rates of anxiety and depression of the H. pylori infected group were both higher than those of the H. pylori uninfected group (48.1%, 77/160 vs. 30.0%, 60/200; 25.0%, 40/160 vs. 12.5%, 25/200), and the differences were statistically significant ( χ2=12.39 and 9.39, P<0.001 and=0.002). The detection rate of anxiety of male patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (45.1%, 32/71 vs. 24.5%, 27/110); the detection rate of depression of female patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (30.3%, 27/89 vs. 11.1%, 10/90), and the differences were statistically significant ( χ2=8.27 and 10.09, P=0.004 and 0.001). The detection rates of anxiety and depression of patients less than 48 years old in the H. pylori infected group were both higher than those in the H. pylori uninfected group (46.2%, 37/80 vs. 21.9%, 21/96; 20.0%, 16/80 vs. 7.3%, 7/96), and the differences were statistically significant ( χ2=11.73 and 6.20, P=0.001 and 0.013). The detection rates of anxiety and depression of the patients with high school education and below in the H. pylori infected group were higher than those in the H. pylori uninfected group (56.5%, 48/85 vs. 31.7%, 38/120; 32.9%, 28/85 vs. 14.2%, 17/120), and the differences were statistically significant ( χ2=12.57 and 10.24, P<0.001 and =0.001). The results of multivariate analysis showed that H. pylori infection, history of hypertension, PSQI score ≥8, GSRS score ≥7, chronic superficial gastritis and chronic atrophic gastritis were independent risk factors of anxiety in patients with chronic gastritis( P<0.001, =0.013, =0.001, <0.001, =0.036, =0.021), and the risk of anxiety of patients with H. pylori infection was 2.509 times as much as that in uninfected patients (95% confidence interval 1.512 to 4.163). H. pylori infection, PSQI score ≥8, GSRS score≥7, and having overnight dish ≥3 times per week all were independent risk factors of depression in patients with chronic gastritis( P=0.004, =0.002, <0.001, =0.001). The risk of depression in patients with H. pylori infection was 2.563 times as much as that in uninfected patients (95% confidence interval 1.356 to 4.846). Conclusion:H. pylori infection is correlated to anxiety and depression in patients with chronic gastritis, and it is an independent risk factor of anxiety and depression in patients with chronic gastritis.

Analysis of clinical features of 43 cases of inflammatory bowel disease complicated with intra- and extra-intestinal tumors / 中华消化杂志

Objective:To analyze the clinical characteristics of patients with inflammatory bowel disease (IBD) complicated with intra- and extra-intestinal tumors, and so as to provide reference for clinical practice.Methods:From October 2008 to March 2022, the clinical data of 2 360 IBD patients diagnosed at the First Affiliated Hospital of Air Force Military Medical University were collected, and the IBD patients complicated with intra- and extra-intestinal tumors were screened out. IBD with colorectal cancer, small intestine cancer and intestinal lymphoma were enrolled into intra-intestinal tumor group, IBD complicated with other tumors except intra-intestinal tumors were enrolled into extra-intestinal tumor group. The clinical characteristics of the 2 groups were retrospectively compared, and the risk factors affecting survival of IBD complicated intra- and extra-intestinal tumor were analyzed. Kaplan-Meier method was used to draw the survival curve, Cox regression model was performed to analyze the prognostic risk factors, and independent sample t test, Fisher′s exact test and log-rank test were used for statistical analysis. Results:A total of 43 IBD patients with intra- and extra-intestinal tumor were screened out, and the overall tumor incidence rate was 1.82% (43/2 360). The rate of IBD complicated with intra-intestinal tumor accounted for 1.27% (30/2 360). Among them, the rate of ulcerative colitis (UC) complicated with intra-intestinal tumor was 1.48% (25/1 685), and the rate of Crohn′s disease (CD) complicated with intra-intestinal tumor was 0.74% (5/675). The rate of IBD with extra-intestinal tumor accounted for 0.55% (13/2 360). Among them, the rate of UC complicated with extra-intestinal tumor was 0.71% (12/1 685), and the rate of CD complicated with extra-intestinal tumor was 0.15% (1/675). There were no significant differences in the rate of intra- and extra-intestinal tumors between UC and CD patients (both P>0.05). In the intra-intestinal tumor group, the age when diagnosed with IBD and the age when tumor diagnosed were (37.0±13.8) years old and (47.7±13.5) years old, which were both lower than those of the extra-intestinal tumor group ((51.8±6.2) years old and (60.7±7.8) years old), and the differences were statistically significant ( t=-3.69 and -3.24, P=0.001 and 0.002). The lesion location when tumor diagnosed of UC patients with intra-intestinal tumor mainly was extensive colonic type(64.0%, 16/25), followed by left part colonic type and rectal type in turn (28.0%, 7/25 and 8.0%, 2/25). In UC patients with extra-intestinal tumor, mainly was rectal type (8/12), followed by left part colonic type (3/12) and extensive colonic type (1/12) in turn. There was statistically significant difference bwtween the UC patients with intra- and extra-intestinal tumor in the extent of lesions when tumor diaghosed (Fisher′s exact test, P<0.001). The activity of IBD of intra-intestinal tumor group when tumor diagnosed mainly was severe activity phase (46.7%, 14/30), followed by moderate activity phase, mild activity phase and remission phase in turn (33.3%, 10/30; 20.0%, 6/30 and 0). The activity of IBD of extra-intestinal tumor group when tumor diagnosed mainly was remission phase (7/13), followed by moderate activity phase, mild activity phase and severe activity phase in turn (3/13, 2/13 and 1/13). There were statistically significant differences between the 2 groups in the composition of IBD activity when tumor diagnosed (Fisher′s exact test, P<0.001). The survival analysis indicated the median survival time of IBD complicated with intra-intestinal tumor group was 145.9 months, and that of the extra-intestinal tumor group was 29.9 months. The results of multivariate Cox analysis showed that the occurrence of extra-intestinal tumor was an independent risk factor of patient survival rate( HR=5.119, 95% confidence interval 1.485 to 17.643, P=0.010). Conclusions:IBD patients had a high risk of developing intra- and extra-intestinal tumors. The intra-intestinal tumor group mainly is extensive colonic type and severe active period, while the extra-intestinal tumor group mainly is rectal type and remission period. Compared with that of the extra-intestinal tumor group, the age at time of IBD onset and tumor diagnosed of intestinal tumor are younger, and the survival time is longer.

The specialist instruction for diagnosis and treatment of chronic atrophic gastritis and clinical application of Lamb′s tripe extract and vitamin B12 capsule / 中华消化杂志

Chronic atrophic gastritis (CAG) and gastric intestinal metaplasia (GIM) significantly increase the risk of gastric cancer. Blocking the development of CAG and GIM would help to decrease the incidence of gastric cancer. It was revealed that eradication of Helicobacter pylori could reverse gastric mucosa atrophy. Recent studies reported that GIM could be reversed to a certain extent. Clinical studies demonstrated that Lamb′s tripe extract and vitamin B12 capsule exhibited significant reversal effects on GIM. The present study systemically reviewed the diagnosis and treatment of CAG and clinical application of Lamb′s tripe extract and vitamin B12 capsule, and established the specialist instruction that would guide the reversal treatment of CAG and GIM.

Analysis of the anxiety and depression in patients with gallbladder polyps, gallbladder stones and post-cholecystectomy / 中华消化杂志

Objective:To investigate the anxiety and depression in patients with gallbladder polyps, gallbladder stones and post-cholecystectomy.Methods:From December 2020 to August 2021, consecutive patients who visited the Department of Gastroenterology, First Affiliated Hospital of Air Force Medical University, were enrolled and divided into normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group, with 100 patients in each group. Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to evaluate patients′ anxiety or depression. Quality of life, sleep quality and severity of gastrointestinal symptom were assessed by short form 36 (SF-36), Pittsburgh sleep quality index (PSQI) scale and gastrointestinal symptom rating scale (GSRS) respectively. The incidence of anxiety or depression of patients in the 4 groups were compared, and the related risk factors of anxiety and depression were analyzed. Chi-square test and multiple logistic regression were used for statistical analysis.Results:Among 400 patients, 89 patients (22.2%) suffered from anxiety; and the incidences of anxiety of normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were 9.0% (9/100), 19.0% (19/100), 25.0% (25/100) and 36.0% (36/100) respectively. There was statistically significant difference in the incidence of anxiety among the 4 groups ( χ2=22.12, P<0.001). The incidence rates of anxiety of the gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were all higher than that of the normal gallbladder group, and the differences were all statistically significant ( χ2=4.15, 9.07 and 20.90, P=0.042, 0.003 and <0.001). The incidence of anxiety of post-cholecystectomy group was higher than that of gallbladder polyp group, and the difference was statistically significant ( χ2=7.25, P=0.007). Among the 400 patients, 70 patients (17.5%) suffered from depression. The incidence rates of depression of the normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were 5.0% (5/100), 10.0% (10/100), 24.0% (24/100) and 31.0% (31/100) respectively. There was statistically significant difference in the incidence of depression among the 4 groups ( χ2=30.27, P<0.001). The incidences of depression of the gallbladder stone group and post-cholecystectomy group were both higher than that of the normal gallbladder group and gallbladder polyp group, and the differences were statistically significant ( χ2=14.56, 22.90, 6.94 and 13.53, P<0.001, <0.001, =0.008 and <0.001). The results of multivariate analysis showed that history of cholecystectomy, history of coronary heart disease, consumption of overnight food ≥3 times per week, PSQI score ≥ 8 and GSRS score ≥9 were independent risk factors for anxiety ( OR, 95%confidence interval: 4.02, 1.60 to 10.13; 10.01, 2.15 to 46.68; 4.15, 1.87 to 9.19; 4.69, 2.58 to 8.52; 3.02, 1.64 to 5.58; P=0.003, 0.003, <0.001, <0.001, and <0.001). Gallbladder stones history of cholecystectomy, consumption of overnight food ≥3 times per week, consumption of fresh fruit < 200 g/d, PSQI score ≥8 and GSRS score ≥9 were independent risk factors for depression ( OR, 95%confidence interval: 4.40, 1.38 to 14.06; 4.97, 1.54 to 16.12; 4.23, 1.61 to 11.08; 3.78, 1.32 to 10.85; 5.59, 2.78 to 11.27, 4.19, 1.94 to 9.04; P=0.012, 0.007, 0.003, 0.014, <0.001 and <0.001). Conclusions:The incidences of anxiety and depression in patients with gallbladder stones or post-cholecystectomy are higher than that of people with normal gallbladder. A history of cholecystectomy is the independent risk factor for anxiety and depression. Gallbladder stones is the independent risk factor of depression. Clinical attention should be paid to the mental state of patients with gallbladder polyps, gallbladder stones, especially post-cholecystectomy.

The relationships between functional gastrointestinal diseases and psychological factors, diet and lifestyles: a network analysis / 中华内科杂志

Objective:To investigate the relationship between common functional gastrointestinal diseases symptoms with psychological factors, diet and lifestyles by using the network analysis method which has achieved great success in the field of psychology in recent years.Method:A questionnaire survey was conducted in two military units using the cluster sampling method during July 2020, and a total of 1 805 subjects were included. Functional gastrointestinal disease symptoms were evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). The state, trait anxiety scale and stress response scale were used to evaluate the mental and psychological state by self-evaluation. R was used to build the network and calculate statistical parameters.Results:1 486 of the 1 805 subjects (82.3%) had experienced functional gastrointestinal diseases symptoms within 2 weeks, but most of them were mild. Network analysis shows that there was a strong interaction between digestive system symptoms with different clinical manifestations (Spearman coefficient ranges 0.31-0.56). There was a clear relationship between functional gastrointestinal symptoms and mental and psychological factors (Spearman coefficient ranges 0.16-0.27), but there was no clear interaction with diet, age, education level, body mass index, etc. Functional gastrointestinal diseases symptoms were connected with mental and psychological factors through two nodes: stress and indigestion. The stability coefficient of node strength correlation was 0.75, indicating that the network was stable.Conclusions:The current study revealed the network structure and features of functional gastrointestinal diseases symptoms with mental and psychological factors. The key linking nodes provided potential interfering target for controlling functional gastrointestinal symptoms related to mental and psychological factors.

Analysis of the efficacy of lamb′s tripe extract and vitamin B12 capsule in the treatment of 240 cases of chronic atrophic gastritis / 中华消化杂志

Objective:To investigate the efficacy and related factors of lamb′s tripe extract and vitamin B12 capsule (LTEVB12) in the treatment of chronic atrophic gastritis.Methods:From October 1st 2016 to April 30th 2021, 240 patients with chronic atrophic gastritis visited the Department of Gastroenterology at Xijing Hospital, Air Force Medical University were retrospectively analyzed. All patients regularly took LTEVB12 (110 U/day, 3 times/day) for six months. At the end of treatment, endoscopy and gastric mucosal biopsy were conducted. The therapeutic effects were evaluated by comparing the changes of operative link on gastritis assessment (OLGA) and operative link on gastritis assessment based on intestinal metaplasia (OLGIM) staging before and after treatment. The related factors affecting the efficacy of the drug were analyzed. Multivariate logistic regression analysis was used for statistical analysis.Results:After half a year of treatment, the reversal efficiency of atrophy and intestinal metaplasia was 45.4% (109/240) and 37.9% (91/240), respectively, and the total efficiency was 62.9% (151/240). The reversal efficiency of OLGA and OLGIM staging reversed from high stage (stage Ⅲ to Ⅳ) to low stage (stage 0 to Ⅱ) was 53.4% (63/118) and 54.5% (36/66), respectively. The results of multivariate analysis showed that female, vitamin supplementation (≥3 times/week), negative or successful eradication of Helicobacter pylori and mild inflammatory status (inflammation score: 1 to 2) were associated with improving the efficacy of LTEVB12 (odds ratio=1.798, 3.730, 2.817 and 4.631, 95% confidence interval 1.055 to 3.064, 1.197 to 11.627, 1.171 to 6.779, 1.480 to 14.493; all P<0.05). High consumption of pickled food (≥3 times/week) was associated with reducing efficacy of LTEVB12 (odds ratio=0.384, 95%confidence interval 0.200 to 0.740). Conclusion:LTEVB12 has better reversal therapeutic effect on atrophy and intestinal metaplasia, and may reduce the risk of gastric cancer in patients with chronic atrophic gastritis.

Analysis of the trend of medication use in patients with ulcerative colitis in a single center from 2010 to 2019 / 中华消化杂志

Objective:To analyze the trend of medication use in patients with ulcerative colitis (UC) in recent ten years in at Xijing Hospital, Air Force Military Medical University.Methods:From 2010 to 2019, the clinical data of 1 425 patients diagnosed with UC in the Department of Gastroenterology at Xijing Hospital, Air Force Medical University, were retrospectively collected. According to the period of medication, the UC patients were divided into year 2010 to 2014 group and year 2015 to 2019 group. The general information and the medication trend of year 2010 to 2014 group and year 2015 to 2019 group were analyzed. And then according to gender and age (<40 years old and ≥40 years old), patients were divided into subgroups and analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The number of UC patients of year 2010 to 2014 group and year 2015 to 2019 group was 369 and 1 056, respectively. The percentages of patients in remission of the two groups were 9.5% (35/369) and 12.0% (127/1 056), respectively; the percentages of mild patients were 40.4% (149/369) and 41.6% (439/1 056), respectively; the percentages of moderate patients were 37.4% (138/369) and 28.9% (305/1 056), respectively; the percentages of severe patients were 12.7% (47/369) and 17.5% (185/1 056), respectively. There was no significant difference in the proportion of UC patients with different degrees between year 2010 to 2014 group and year 2015 to 2019 group ( P>0.05). There were no significant differences in the age and proportion of female between the year 2010 to 2014 group and year 2015 to 2019 group ((46.2±15.3) years old vs. (44.6±30.6) years old; 45.8%, 169/369 vs. 44.8%, 473/1 056; both P>0.05). The utilization rates of 5-aminosalicylic acid (5-ASA), glucocorticoid, immunosuppressants, and biological agents of the year 2015 to 2019 group were all higher than those of the year 2010 to 2014 group (96.8%, 1 022/1 056 vs. 90.0%, 332/369; 29.9%, 316/1 056 vs. 14.6%, 54/369; 8.4%, 89/1 056 vs. 2.4%, 9/369; 4.8%, 51/1 056 vs. 0.5%, 2/369, respectively), and the differences were all statistically significant ( χ2=26.766, 33.256, 15.315 and 14.038, all P<0.01). Within each of the year 2010 to 2014 group and the year 2015 to 2019 group, there were no significant differences between the female and male in the age, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents ((47.2±13.6) years old vs. (45.3±16.5) years old, (43.1±12.9) years old vs. (45.8±39.5) years old, 88.8%, 150/169 vs. 91.0%, 182/200; 96.8%, 458/473 vs. 96.7%, 564/583; 13.6%, 23/169 vs. 15.5%, 31/200; 28.3%, 134/473 vs. 31.2%, 182/583; 2.4%, 4/169 vs. 2.5%, 5/200; 7.0%, 33/473 vs. 9.6%, 56/583; 0 vs. 1.0%, 2/200; 5.3%, 25/473 vs. 4.5%, 26/583; all P>0.05). In the patients aged≥40 years old of the year 2010 to 2014 group, the proportion of females was higher than that of the patients aged <40 years old (50.2%, 121/241 vs. 37.5%, 48/128), and the utilization rate of 5-ASA in patients aged ≥40 years old was lower than that of patients aged <40 years old (85.9%, 207/241 vs. 97.7%, 125/128), and the differences were statistically significant ( χ2=5.438 and 12.824, P=0.020 and P<0.01). In the year 2010 to 2014 group, there were no statistically significant differences in the utilization rates of glucocorticoid, immunosuppressants and biological agents between patients aged ≥40 years old and patients aged <40 years old (13.7%, 33/241 vs. 16.4%, 21/128; 2.1%, 5/241 vs. 3.1%, 4/128; 0 vs. 1.6%, 2/128; all P>0.05). In the year 2015 to 2019 group, the utilization rate of biological agents in patients aged≥40 years old was lower than that in patients aged<40 years old (3.7%, 23/630 vs. 46.5%, 198/426), and the difference was statistically significant ( χ2=4.721, P=0.030). In the year 2015 to 2019 group, there were no statistically significant differences in female proportion, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents between patients aged≥40 years old and patients aged <40 years old (43.7%, 275/630 vs. 46.5%, 198/426; 96.0%, 605/630 vs. 97.9%, 417/426; 29.7%, 187/630 vs. 30.3%, 129/426; 8.6%, 54/630 vs. 8.2%, 35/426; all P>0.05). Conclusions:Compared with year 2010 to 2014, the number of UC patients remarkably increased in the year 2015 to 2019 in the Department of Gastroenterology, Xijing Hospiatal, Air Force Medical University. The utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents all increased in UC patients. The medication trends of UC patients with different gender were almost the same. The medication trends of UC patients with different age were different.

Efficacy and safety of Changsulin ? compared with Lantus ? in type 2 diabetes: a phase Ⅲ multicenter, randomized, open-label, parallel, controlled clinical trial / 中华内科杂志

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Psychoanalysis of 300 patients with chronic gastritis / 中华消化杂志

Objective:To analyze the difference of psychosocial characteristics in patients with chronic gastritis.Methods:From June to December 2018, a total of 300 patients with chronic gastritis visited Xijing Hospital were consecutively enrolled. The patients were divided into chronic non-atrophic gastritis (CNAG) group, chronic atrophic gastritis (CAG) group and CAG with intestinal metaplasia group, with 100 cases in each group. Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), living events scale (LES) and Eysenck personality questionnaire (EPQ) were used for evaluation and analysis. Chi square test, analysis of variance, nonparametric rank sum test and Kruskal Wallis H test were used for statistical analysis. Results:The incidences of anxiety of the CAG group and the CAG with intestinal metaplasia group were both significantly higher than that of the CNAG group (64.0%, 64/100; 53.0%, 53/100; and 34.0%, 34/100; respectively), and the differences were statistically significant ( χ2=0.007 and 0.001, both P<0.05). The incidence of depression of the CAG with intestinal metaplasia group was significantly higher than those of CNAG group and the CAG group (24.0%, 24/100; 15.0%, 15/100 and 13.0%, 13/100; respectively), and the differences were statistically significant ( χ2=0.108 and 0.045, both P<0.05). The negative event score of LES of CAG with intestinal metaplasia group was higher than those of CNAG group and CAG group (0 (0, 6.75), 0 (0, 1.00), 0 (0, 0.75) respectively), and the differences were statistically significant ( Z=-2.619 and -3.022, both P<0.05). The proportion of patients with LES score ≥20 points (high mental stress) of CNAG group, CAG group and CAG with intestinal metaplasia group gradually increased (8.0%, 8/100; 9.0%, 9/100 and 18.0%, 18/100; respectively), and the difference was statistically significant ( χ2=0.036, P<0.05). In male patients and patients under 50 years old, the incidence of depression and the proportions of patients with LES score ≥20 points of CAG with intestinal metaplasia group were higher than those of CNAG group (22.5%, 9/40 vs. 9.6%, 5/52; 47.5%, 19/40 vs. 16.2%, 11/68; 22.5%, 9/40 vs. 7.7%, 4/52; and 20.0%, 8/40 vs. 4.4%, 3/68), and the differences were statistically significant ( χ2=0.015, 0.001, 0.043 and 0.013, all P<0.05). The results of EPQ showed that the psychoticism, extraversion or introversion, stability and concealment of CNAG group and CAG with intestinal metaplasia group, were mostly normal (43.3 to 56.7), accounting for 62.0% (62/100) and 45.0% (45/100), 56.0% (56/100) and 44.0% (44/100), 54.0% (54/100) and 44.0% (44/100), 59.0% (59/100) and 45.0% (45/100), respectively. The percentage of patients with high score (>56.7) of etraversion or introversion and concealment in CAG group and the CAG with intestinal metaplasia group were higher than those in the CNAG group (48.0%, 48/100; 23.0%, 23/100; 4.0%, 4/100 and 46.0%, 46/100; 21.0%, 21/100 and 7.0%, 7/100, respectively), and the differences were statistically significant ( χ2=0.001, 0.001, 0.001 and 0.004, all P<0.01). Conclusions:Anxiety is associated with CAG and intestinal metaplasia, while depression is associated with intestinal metaplasia. In male patients and patients under 50 years old, depression, negative event and high psychiatric stress are more significantly related to intestinal metaplasia. The mental characteristics of extroversion, emotional instability, psychoticism and concealment are closely associated with CAG.

Role and mechanisms of hepatocyte nuclear factor 4α in bile acid induced gastric intestinal metaplasia / 中华消化杂志

Objective To investigate the roles and mechanisms of hepatocyte nuclear factor 4α (HNF4α) in chenodeoxycholic acid (CDCA) induced gastric intestinal metaplasia (IM).Methods After the immortalized gastric mucosal epithelial cells GES-1 were stimulated with CDCA at different concentration,the changes of HNF4α,caudal-related homeobox 2 (CDX2) and trefoil factor family 3 (TFF3) expressions at mRNA and protein levels in GES-1 cells and gastric cancer cell lines (AGS,SGC7901 and BGC823) were detected by real time-polymerase chain reaction (RT-PCR) and Western blotting.After GES-1 were transfected with HNF4α short hairpin RNA (shRNA) or control shRNA,and followed by CDCA stimulation,the expressions of HNF4α,CDX2 and TFF3 at protein level were determined by Western blotting.HNF4α was overexpressed in GES-1 cells and SGC7901 cells,and HNF4α was silenced in BGC823 cell line and AGS by lentiviral vector system.The expressions of HNF4α,CDX2 and TFF3 at mRNA and protein levels were tested by RT-PCR and Western blotting.Luciferase reporter assay was used to analyze the regulation role of HNF4α on CDX2.T test was performed for statistical analysis.Results The expressions of HNF4α in GES-1,SGC7901,BGC823 and AGS cells at mRNA level were 1.00 ± 0.12,263.01±10.23,848.01±18.13 and 3 049.86±91.75,respectively.The mRNAlevels of HNF4α in AGS,BGC823 and SGC7901 cells were all higher than that of GES-1 cells,and the differences were statistically significant (t=33.23,46.72 and 25.62,all P＜0.01).The expressions of HNF4α in GES-1,SGC7901,BGC823 and AGS at protein level were consistent with mRNA level.The expressions of CDX2 and TFF3 at protein level of HNF4α shRNA transfected group were lower than those of non-HNF4α shRNA transfected group.In GES-1 cells,the expressions of HNF4α,CDX2 and TFF3 of HNF4α overexpressed group at mRNA level were 16 281.839 ± 1 843.017,6.275 ± 0.137 and 17.310± 1.533,respectively;which were all higher than those of overexpressed control group (1.000 ± 0.048,1.000 ± 0.012 and 1.000±0.108,respectively),and the differences were statistically significant (t =8.83,38.29 and 10.61,all P＜0.01).In AGS cells,the expressions of HNF4α,CDX2 and TFF3 of HNF4α silenced group at mRNA level were 0.021 ± 0.001,0.088 ± 0.007 and 0.074 ± 0.002,respectively,which were lower than those of silenced control group (1.000 ± 0.108,1.000 ± 0.131 and 1.000 ± 0.122),and the differences were statistically significant (t=9.09,6.93 and 7.57,all P＜0.01).In GES-1 overexpressed cells and AGS silenced cells,the expressions of HNF4α,CDX2,TFF3 at protein level were consistent with mRNA level.In double reporter plasmid containing the CDX2 promoter CDX2 1 (-2 000～-1 bp) and CDX2-2 (-1 510～1 bp),after transfected with HNF4α shRNA,the activities were 0.387 ± 0.013 and 0.533 ± 0.040,respectively,which were lower than those of HNF4α shRNA transfected control group (0.605 ± 0.012 and 0.882 ± 0.019),and the differences were statistically significant (t =21.49 and 13.53,both P＜0.01).Conclusion HNF4α may be involved in bile acid induced intestinal metaplasia by upregulating the expression of CDX2.

Comparison of acarbose and metformin as add-on therapy to insulin in uncontrolled patients with type 2 diabetes mellitus: A randomized, open-labeled, and parallel group study / 中华内分泌代谢杂志

Objective To evaluate efficacy and safety of acarbose compared with metformin as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled with insulin. Methods This was a randomized, open-labeled, and parallel group study. Ninety-one type 2 diabetic patients ( HbA1C7.5%-11.0%) who were suboptimally controlled despite receiving twice daily injection of insulin (30-60 U/d for at least 8 weeks) were enrolled. They were randomly assigned 1 ∶ 1 ∶ 1 to continuation of insulin, insulin with acarbose (Ins+Aca), and insulin with metformin (Ins+Met) groups to insulin treatment. The levels of HbA1C, oral glucose tolerance test, blood lipids etc were measured at baseline and 12 weeks, and adverse events were recorded. Results The mean HbA1C levelsdecreasedfrom(7.9±0.4)%atbaselineto(7.0±0.3)%atweek12(P＜0.01)intheIns+Acagroupand(7.8 ±0.2)%to(7.0±0.3)%in the Ins+Met group(P＜0.01), while no significant change in HbA1Cin the insulin alone group. Adding acarbose to insulin resulted in similar reductions in HbA1Crelative to metformin (P＝0.431). The achievement rate of HbA1Cbelow 7.0%at week 12 was the same(both 70%) between the Ins+Aca group and the Ins+Met group. Insulin combined with acarbose in improving blood glucose fluctuation effect was more significant than that incombinationwithmetformin(P＜0.01),withstandarddeviation(SD)ofbloodglucose[(1.1±0.5vs2.7±0.6) mmol/L, P＜0.01], postprandial blood glucose fluctuations [(0.5 ± 0.7 vs 2.8 ± 0.4) mmol/L, P＜0.01], the maximumbloodglucosefluctuations[(2.8±0.7vs4.6±0.6)mmol/L,P＜0.01].Theweightlossoccurredinboththe Ins+AcaandtheIns+Metgroups[-(0.5±0.8vs1.0±0.4)kg].Therewasnosignificantchangesinbloodpressure and lipid profile. Hypoglycemic episodes were comparable in all groups. No serious adverse event was noted in any group. Conclusions Adding acarbose or metformin to insulin therapy could achieve improvements in glycemic control with similar reductions in HbA1Clevels and weight, when comparing with insulin treatment alone. Add-on acarbose to insulin therapy may exist more effectively on glucose fluctuation than that of add-on metformin, which may have important clinical implications in those patients with postprandial hyperglycemia, large blood glucose fluctuation, and intolerance to metformin.

Effects of migration on glucose metabolism of the population / 中华内分泌代谢杂志

Most migrations occur movement from less developed regions to developed areas ( most of which involve people migrating from South Asia to Europe) . Migrants had a higher risk of diabetes in the migratory population than that in the locals, earlier of illness, more severe insulin resistance, and more likely failure of pancreaticβcell function, which lead to increased complications such as macrovasular and microvascular diseases. These differences may be related to the genetic, epigenetic, lifestyle, as well as the social security of the migrant population.

Effects of DPP-4 inhibitors on cardiovascular risk in type 2 diabetic patients / 中华内分泌代谢杂志

As diabetes is a major independent risk factor for the development of cardiovascular disease (CVD), cardiovascular safety should be taken into account when it refers to the treatment of type 2 diabetes (T2DM). Relevant evidence has suggested that dipeptidyl peptidase 4 (DPP-4) inhibitors could regulate cardiovascular system function by multiple various mechanisms,with inconsistent results among clinical trials. Meta-analysis showed that DPP-4 inhibitors could significantly reduce the CVD risk factors. However,the results from three large scale cardiovascular safety studies were of non-inferiority results. The baseline elder age of participants with longer duration of diabetes and more risk factors of CVD could contribute to the non-inferiority cardiovascular outcomes of DPP-4 inhibitors. Recent clinical trials further indicated that alogliptin and sitagliptin could attenuate atherosclerosis progression of patients with T2DM,which would bring new implications for the clinical use of DPP-4 inhibitors. More research should be designed to further explore the specific mechanism.

Clinical study on berberine, amoxicillin, lansoprazole, bismuth quadruple therapy for Helicobacter pylori eradication in 283 patients / 中华消化杂志

Objective To assess the efficacy and safety of berberine, amoxicillin, lansoprazole, bismuth quadruple therapy for Helicobacter pylori (H.pylori)eradication.Methods From December 2015 to April 2016,566 patients with initial treatment of H.pylori infection were prospectively enrolled.Patients were divided into observation group (berberine, amoxicillin, lansoprazole, bismuth) and control group (clarithromycin, amoxicillin, lansoprazole, bismuth), 283 cases in each group, and the treatment courses in two groups were both 14 days.Four weeks after completion of the treatment, the eradication rate of H.pylori and adverse effect rate of the two groups were compared.Student t test and Chi square test were performed for comparison between the two groups.Results There was no statistically significant difference in the baseline demographic data including gender,age, body mass index (BMI), symptom score between patients of the two groups (all P>0.05).Four weeks after completion of the treatment, the eradication rates of observation group and control group were 87.5%(244/279) and 87.1%(242/278) according to per-protocol analysis, and which were 86.2%(244/283) and 85.5 %(242/283) according to intention-to-treat analysis.There was no statistically significant difference between the two groups (x2=0.021,0.058;both P>0.05).The adverse effect rates of the two groups were 12.5%(35/279) and 16.5%(46/278), and there was no statistically significant difference (x2=1.795,P=0.180).Conclusions Both the new quadruple regimen containing berberine, amoxicillin and bismuth, and the standard quadruple regimen containing clarithromycin, amoxicillin and bismuth both can effectively eradicate H.pylori infection.The new regimen might be recommended as first-line eradication regimen in Xi′an district or area with high clarithromycin resistance.

Progress in Diagnosis and Treatment of Hereditary Diffuse Gastric Cancer / 胃肠病学

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited disease,and may be related to the mutation of CDH1 or CTNNA1 genes.Microscopically,signet-ring cell carcinoma is suggested frequently in endoscopic biopsy or gastrectomy specimens.Some patients may have concomitant extra-stomach tumor (frequently breast cancer in females).Detection of CDH1 gene mutation should be performed in high-risk individuals,and diagnosis and treatment should be carried out by a multidisciplinary team.Prophylactic gastrectomy is recommended for those with pathogenic CDH1 mutation.Endoscopic surveillance is an option for those with CDH1 mutation of undetermined significance and those without germline CDH1 mutation.This review discussed the concept,genetic characteristics,clinicopathological features and genetic screening of HDGC for providing a reference for clinicians.

Application and discussion of teaching model of Team-based learning teaching integrated with evi-dence-based medicine introduced clinical case in Type 2 diabetes mellitus clinical training / 中华医学教育探索杂志

The knowledge of endocrine metabolic diseases represented by type 2 diabetes mellitus is highly specialized, complicated, and has many clinical guidelines. In this context, team based learning teaching combined with case teaching based on evidence-based medicine was applied in the actual class teaching. The class was divided into several groups and the students were encouraged to discuss and study from each other with the guidance of teachers. Consequently, students' learning interests and spirit of team-work were greatly enhanced, the way of thinking using evidence-based medicine and their ability to solve the practical clinical problems were also improved.

What the results of Acarbose Cardiovascular Evaluation(ACE) Study will be? / 中华内分泌代谢杂志

The prevalence of prediabetes is increasing rapidly in China, and with higher prevalence in coronary heart disease and hypertension patients. Diabetes can be controlled and prevented, previous studies have confirmed that lifestyle interventions and drug interventions can delay the progression of prediabetes to diabetes, and acarbose can be used for the primary prevention of cardiovascular events in impaired glucose tolerance(IGT) and diabetic patients, but benefits of drug intervention for secondary prevention of cardiovascular disease in IGT population are uncertain. The Acarbose Cardiovascular Evaluation(ACE) Study is a multicentre, randomized, placebo-controlled, double-blind study, with the aim of assessing the use of acarbose to reduce the risk of cardiovascular events and the onset of diabetes in IGT patients with cardiovascular disease in China , the results will be very meaningful and valuable for the prevention and treatment of diabetes. We will predict the results of ACE Study based on previous evidences.

Lineage conversion of mouse fibroblasts to pancreatic α-cells

α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation. The cell functions in vivo and in vitro were evaluated. Lineage-specific and functional-related gene expression was tested by realtime PCR, insulin tolerance test (ITT), glucose tolerance test (GTT), Ki67 and glucagon immunohistochemistry analysis were done in iAlpha cells transplanted nude mice. iAlpha cells possess α-cell function in vitro and alter blood glucose levels in vivo. Transplantation of iAlpha cells into nude mice resulted in insulin resistance and increased β-cell proliferation. Taken together, we present a novel strategy to generate functional α-like cells for the purposes of disease modeling and regenerative medicine.

Role of reproductive factors in female patients with primary biliary cholangitis / 临床肝胆病杂志

ObjectiveTo investigate the role of productive factors in the development of primary biliary cholangitis (PBC). MethodsA total of 273 female patients with a definite diagnosis of PBC who visited Xijing Hospital from October 2013 to August 2015 were enrolled. The patients with autoimmune hepatitis, primary sclerosing cholangitis overlap syndrome, and hepatic encephalopathy and those with incomplete data after telephone follow-up were excluded, and 54 female PBC patients who had female relatives were finally enrolled (PBC group). The female relatives who were less than 10 years older or younger than the patients were collected, and those with severe systemic diseases and incomplete data after telephone follow-up were excluded; finally 88 relatives were enrolled (relative group). The questionnaire for female reproductive factors in PBC was used to survey all these enrolled patients and collect data. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and a multivariate logistic regression analysis was used for the analysis of dose-response relationship. ResultsThe PBC group had a significantly higher number of births than the relative group (2.55±1.84 vs 1.84±0.95, t=2.708, P=0.009). Furthermore, there was a significant dose-response pattern between the number of births and the development of PBC (P=0.002). ConclusionThe number of births may be associated with the development of PBC in a dose-response manner. As for the female population susceptible to PBC, a reduction in the number of births may reduce the possibility of PBC.