Clinical characteristics and the risk factors for the exacerbation of symptoms in patients with inflammatory bowel disease during the COVID-19 pandemic.

Background: In 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant caused a large-scale outbreak of coronavirus disease 2019 (COVID-19) in China. It is not clear the risk factors that lead to the exacerbation of symptoms in patients with inflammatory bowel disease (IBD) after COVID-19 infection. Our study aims to find out the risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection and to provide guidance for the clinical management of IBD. Methods: This is a retrospective, observational study. The online questionnaire was distributed to conduct a survey to collect demographic, clinical, and IBD related characteristics in IBD patients. Univariate and multivariate regression analyses were conducted to assess the independent effects. Results: In total, 534 cases of IBD patients were analyzed in our study. Among them, 466 (87.3%) cases diagnosed with COVID-19, 160 (34.3%) cases experienced exacerbation of IBD symptoms, and 84 (18.0%) patients opted for medication discontinuation. Male sex (OR 2.04, 95% CI 1.34-3.49, p = 0.001), and the decrease in body mass index (BMI) (OR 0.93, 95% CI 0.87-1.00, p = 0.035) were positively correlated with the exacerbation of IBD symptoms. Furthermore, the medication discontinuation (OR 2.60, 95% CI 1.58-4.30, p < 0.001) was strongly positively correlated with the exacerbation of IBD symptoms. No significant association was seen between age, comorbidities, smoking, disease activity, vaccination, therapy for COVID-19 and the worsening of IBD symptoms. Conclusion: This study confirms that the infection rate of COVID-19 in China IBD patients was comparable to the general population. Male sex, the decrease in BMI and medication discontinuation are significant risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection.

Use of double-balloon endoscopy and an endoscopic scoring system to assess endoscopic remission in isolated small bowel Crohn's disease after treatment with infliximab.

Background: It is unclear how clinical and endoscopic factors affect the attainment of endoscopic remission (ER) in patients with small bowel Crohn's disease (SB-CD) who are infliximab-naïve. Objectives: We aimed to identify the effect of different factors on attaining ER using double-balloon endoscopy (DBE) evaluation. Design: A single-center retrospective observational study was conducted from 1 January 2018 to 30 November 2022. Among 262 patients who were screened for isolated SB-CD by baseline DBE, 108 patients were assessed for effectiveness during maintenance infliximab therapy by a second DBE evaluation. Methods: DBE findings before and after infliximab therapy were compared. ER was defined as a simple endoscopic score for CD (SES-CD) below 3, and segmental ER as SES-CD activity of 0. Multivariate regression with calculations of odds ratios (OR) was used to determine the impact of different factors on attaining ER. Results: In all, 41 patients (38.0%) achieved ER. An elevated C-reactive protein at week 6 was independently associated with a decreased probability of ER [OR: 0.86, 95% confidence interval (CI) = 0.75-0.98, p = 0.03]. Segmental ER of the terminal ileum, rather than the proximal ileum, was associated with a higher rate of ER (60.9% versus 38.2%, p = 0.01). High baseline SES-CD (⩾16) was unrelated to overall ER. For patients with disease in the terminal ileum, those with moderate/severe disease were less likely to attain segmental ER than those with mild disease [adjusted odds ratios (aOR): 0.27, 95% CI: 0.09-0.83, p = 0.02]. A large ulcer in the terminal ileum was associated with a lower rate of segmental ER (aOR: 0.18, 95% CI: 0.06-0.56, p = 0.01). Conclusion: For infliximab-naïve patients with SB-CD, the overall severity of the endoscopic score was unrelated to attainment of ER. Patients were less likely to attain segmental ER if they had greater endoscopic inflammation or larger ulcers in the terminal ileum.

Geographical heterogeneity in the disease characteristics and management of patients with inflammatory bowel disease, the preliminary results of a Chinese database for IBD (CHASE-IBD).

Background: The incidence of inflammatory bowel disease (IBD) is rapidly increasing in China, a vast country with significant geographical differences. The socioeconomic status of Eastern China is significantly higher than that of Western China. Objectives: This study aimed to describe the geographical heterogeneity in the characteristics and management of patients with IBD in both Eastern and Western China. Design: This was a multicenter, cross-sectional study. Methods: Patients with IBD with ages ⩾18 years up to 18 January 2023 were included in the analysis from the Chinese database for IBD. Logistic regression was used to identify risk factors associated with surgeries among patients with IBD. Results: Among 8305 patients with IBD, the ratio of ulcerative colitis (UC) to Crohn's disease (CD) was 4.13 and 0.33 in Western and Eastern China, respectively. The median age at diagnosis of UC and CD was 40.69 and 28.58 years, respectively. There was a male predominance among patients with UC (54.3%) and CD (68.0%). The two regions exhibited a similar distribution of disease locations in UC. However, Western China had a higher proportion of L2 involvement (30.0% versus 19.1%) and more advanced disease behavior (B2 and B3) (48.8% versus 39.8%) than Eastern China. Patients with IBD in Western China received more 5-aminosalicylic acid and corticosteroids and fewer immunomodulators and biologicals. In terms of surgical risk, Eastern China [versus Western China, odds ratios (OR): 5.36, 95% confidence intervals (CI): 2.96-9.68] was associated with a higher risk of surgery in UC, while Western China (versus Eastern China, OR: 3.39, 95% CI: 2.37-4.86) was associated with a higher risk of surgery in CD. Conclusion: Geographical heterogeneity exists in the disease characteristics and management of IBD in Eastern and Western China. These findings have the potential to guide the formulation of location-specific strategies aimed at enhancing the long-term outcomes of patients with IBD.

Evaluation of symptomatic small bowel stricture in Crohn's disease by double-balloon endoscopy.

PURPOSE: To assess the efficacy of double-balloon endoscopy (DBE) for the detection of small-bowel strictures in Crohn's disease (CD). METHODS: This tertiary-referral hospital cohort study was conducted between January 2018 and May 2022. CD patients with symptoms of small-bowel stricture were enrolled sequentially. All of the patients were subjected to both computed tomography enterography (CTE) and DBE, and their symptoms of stricture were assessed using the Crohn's Disease Obstructive Score (CDOS). The diagnostic yield of DBE was compared to that of CTE, and the relationship between the DBE findings and CDOS was investigated. The factors influencing the DBE diagnosis were examined using Cox regression analysis. RESULTS: This study included 165 CD patients. The CDOS scores were higher in 95 patients and lower in 70 patients. DBE detected 92.7% (153/165) and CTE detected 85.5% (141/165) of the strictures. The DBE diagnostic yields were 94.7% (90/95) in the high CDOS patients and 91.4% (64/70) in the low CDOS patients (P = 0.13). Patients with a history of abdominal surgery and abscess had a lower diagnosis rate in the multivariate analysis. CONCLUSION: DBE has been demonstrated to be an efficient diagnostic method for detecting small bowel strictures in CD patients. Additionally, there was no difference in the diagnostic yields between patients with low and high obstructive scores.

Fecal calprotectin predicts endoscopic activity and mucosal healing of small bowel Crohn's disease evaluated by double-balloon endoscopy.

PURPOSE: Fecal calprotectin (FC) levels can reflect the level of intestinal inflammation. Crohn's disease (CD), which affects the small bowel, has not been linked to FC levels. We determined if FC levels and endoscopic activity were related by performing double-balloon endoscopy (DBE). METHODS: Herein, patients with small bowel CD diagnosed by DBE between January 2020 and January 2022 were prospectively observed. Feces and blood samples of patients were collected before performing DBE and checked for the levels of FC and serological biomarkers. The endoscopic activity and mucosal healing (MH) were evaluated using the partial simple endoscopic score (pSES-CD). RESULTS: In all 254 CD patients, FC levels were correlated with pSES-CD (r = 0.775, P < 0.001). Even in patients with isolated small bowel CD, FC levels were strongly correlated with pSES-CD (r = 0.753, P < 0.001). In all patients, FC as an endoscopic remission indicator was found to have an area under the curve (AUC) of 0.872, with a cut-off value of 156.09 µg/g. In patients with isolated small bowel CD, FC yielded a high AUC of 0.865 for predicting endoscopic remission, with a cut-off value of 211.48 µg/g, sensitivity of 73.95%, and specificity of 91.30%. FC was optimally cut-off at 76.99 µg/g to predict MH in accordance with the AUC of 0.877. CONCLUSIONS: Using DBE findings, FC was found to be significantly correlated with pSES-CD. Even in isolated small bowel CD, FC may be a more reliable marker of accurately predicting endoscopic remission and MH.

Differential Diagnosis of Crohn's Disease and Ulcerative Primary Intestinal Lymphoma: A Scoring Model Based on a Multicenter Study.

Background: Differential diagnosis of Crohn's disease (CD) and ulcerative primary intestinal lymphoma (UPIL) is a tough problem in clinical practice. Aims: Our study identified key differences between CD and UPIL patients and aimed to further establish a scoring model for differential diagnosis. Methods: A total of 91 CD and 50 UPIL patients from 9 tertiary inflammatory bowel disease centers were included. Univariate and multivariate analyses were used to determine significant markers for differentiating CD and UPIL. A differential scoring model was established by logistic regression analysis. Results: The differential model was based on clinical symptoms, endoscopic and imaging features that were assigned different scores: intestinal bleeding (-2 points), extraintestinal manifestation (2 points), segmental lesions (1 point), cobblestone sign (2 points), homogeneous enhancement (-1 point), mild enhancement (-1 point), engorged vasa recta (1 point). A total score of ≥1 point indicates CD, otherwise UPIL was indicated. This model produced an accuracy of 83.66% and an area under the ROC curve of 0.947. The area under the ROC curve for validation using the 10-fold validation method was 0.901. Conclusion: This study provided a convenient and useful model to differentiate CD from UPIL.

Real-world Short-term Effectiveness of Ustekinumab in Crohn's Disease: Results from a Multicenter, Prospective Study in China.

Ustekinumab effectively induced a clinical response and clinical remission, with remission rates superior to those in the UNITI-1 study. Ustekinumab is more effective in biologic-naive patients with Crohn's disease than those who were not responsive to anti­tumor necrosis factor treatment.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis.

BACKGROUND: Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS: A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS: A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS: High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Antiviral therapy effectively improves liver hemodynamics as evidenced by serum biomarker and contrast-enhanced ultrasound examinations in patients with hepatitis B cirrhosis.

BACKGROUND AND AIMS: To prospectively evaluate the effects of antiviral therapy on liver hemodynamics in patients with hepatitis B cirrhosis. METHODS: Seventy consecutive eligible HBV-related cirrhotic inpatients were enrolled in the prospective study. Fifty-two received different nucleoside analogs monotherapy and 18 denied antiviral therapy. Their liver biochemistry profiles and HBV-DNA were measured at the baseline and every 3 months. Peripheral blood vWF and sCD163, as well as liver ultrasound Doppler parameters including portal vein diameter (PVD), portal vein velocity (PVV), portal vein congestion index (PV-CI), hepatic vein damping index (HV-DI), hepatic arterial arrival time (HAAT), hepatic vein arrival time (HVAT) and intrahepatic cycle time (HV-HA), were measured at the baseline and the follow-up periods. RESULTS: In the antiviral group, all patients achieved complete virologic and liver biochemical responses after 3-month antiviral treatment. Furthermore, the response states were maintained till the follow-up endpoint. However, in the non-antiviral group, HBV DNA replication resulted in higher levels of ALT and AST compared to the baseline values (P < 0.05). In the antiviral group, PVD, PV-CI, HV-DI, vWF-Ag and sCD163 were all significantly reduced than the baseline values (P < 0.05), and PVV was significantly increased than the baseline value (P < 0.05). CONCLUSIONS: Antiviral therapy could effectively suppress hepatocyte inflammation and alleviate the dysfunction of intrahepatic vascular endothelial and hepatic macrophages, which might improve hepatic hemodynamic function in HBV-related cirrhosis.

Measurement of red blood cell 6-thioguanine nucleotide is beneficial in azathioprine maintenance therapy of Chinese Crohn's disease patients.

OBJECTIVE: It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine (AZA) therapy. This study is designed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn's disease (CD). MATERIAL AND METHOD: We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014. Demographic material, CD activity index, 6-TGN concentration, and laboratory tests were recorded at baseline and at each visit. In addition, 6-TGN was measured when drug adverse effects occurred. All patients achieved maintenance stage were administered a stable AZA dose at least 3 months before enrollment and were followed up at least 12 months. Thiopurine S-methyltransferase (TPMT) genotype was measured before AZA treatment. RESULTS: Sixty-nine patients receiving maintenance therapy were analyzed. A positive correlation was found between 6-TGN levels and AZA dose (r = 0.258, p = 0.032). The mean 6-TGN concentration was 302.06 ± 115.84 in the remission group vs. 264.94 ± 164.53 pmol/8 × 10(8) RBC in those with active disease (t = 0.847, p = 0.40), and 197.74 ± 66.54 pmol/8 × 10(8) RBC in patients who relapsed vs. 310.26 ± 122.38 pmol/8 × 10(8) RBC for those in sustained remission (t= -2.541, p = 0.013). In the leukopenia group, the 6-TGN concentration was 469.11 ± 115.53 pmol/8 × 10(8) RBC vs. 257.31 ± 83.74 pmol/8 × 10(8) RBC in the non-leukopenia group (t = 7.622, p < 0.001). There was a significant negative correlation between leukocyte count and 6-TGN concentration (r= -0.326, p = 0.006). CONCLUSIONS: 6-TGN measurement is a helpful method of preventing disease relapse and avoiding leukopenia in individual azathioprine maintenance therapy.

Association of MYO9B gene polymorphisms with inflammatory bowel disease in Chinese Han population.

AIM: To explore the association of MYO9B gene polymorphisms with clinical phenotypes and intestinal permeability of individuals with inflammatory bowel disease (IBD) in China. METHODS: A total of 442 IBD patients and 402 healthy volunteers were genotyped for two single nucleotides (rs962917 and rs1545620) using the ligase detection reaction and polymerase chain reaction. Allelic and genotype frequency analyses were performed for the two groups. Intestinal permeability was evaluated using lactulose (L) and mannitol (M) excretion. The association of MYO9B gene polymorphisms with intestinal permeability between the normal and high intestinal permeability groups was analyzed. RESULTS: Overall, there was no significant difference in the genotypic and allelic frequencies of MYO9B between IBD patients and controls. Although no association was found with ulcerative colitis in the comparison between the subgroups, the frequencies of rs962917 and rs1545620 were different in the Crohn's disease (CD) subgroup with ileocolitis (CC vs CT and TT, P = 0.014; and AA vs AC and CC, P = 0.022, respectively). rs1545620 variants appear to be the genetic susceptibility factor for perianal disease in CD patients (AA vs AC CC, P = 0.029). In addition, the L/M ratio was significantly higher in IBD patients than in controls (0.065 ± 0.013 vs 0.020 ± 0.002, P = 0.02), but no association was found between the MYO9B gene and the L/M ratio in IBD patients. CONCLUSION: MYO9B gene polymorphisms may influence the sub-phenotypic expression of CD in China. No association between these MYO9B polymorphisms and intestinal permeability in IBD patients was found.

Early predictors of responses and clinical outcomes of corticosteroid treatment for severe ulcerative colitis.

BACKGROUND: Patients with severe ulcerative colitis (SUC) have a high risk of requiring colectomy or resorting to a second-line treatment. However, neither clinical outcomes nor factors predictive of poor response have been clearly established in the treatment of SUC. OBJECTIVE: To assess prospectively the effects and predictors of corticosteroids (CS) use in clinical outcomes of SUC during 1 year of follow-up. MATERIAL AND METHODS: Consecutive inpatients with SUC, who had been treated with intravenous CS, were enrolled. Patients were monitored by clinical, laboratory, and endoscopic examinations, and the data were recorded for 1 year. Univariate and multivariate analyses were performed at 1 week. RESULTS: There were 22.6% (14/62) nonresponders at 7 days. Several predictors were associated with nonresponse to CS. These included Mayo Score at baseline (p = 0.007), partial Mayo Score, number of bowel movements, blood presence in stool, abdominal pain, and levels of C-reactive protein (CRP), hemoglobin (Hgb), platelet count (PLT), and erythrocyte sedimentation rate (ESR) on day 3 (p < 0.05). Multiple logistic regression analysis identified the Partial Mayo Score at day 3 as an independent predictor of outcome (p = 0.012). A total of 12 patients underwent colectomy within 1 year. The short-term response rates to intravenous cyclosporin (CsA) and infliximab (IFX) in SUC were 71.4% (5/7) and 77.8% (7/9), respectively. CONCLUSIONS: Many patients with SUC eventually became refractory to or dependent on CS. The Mayo score and laboratory characteristics were factors useful in predicting short-term outcome of CS treatment. Secondary medical therapy can help avoid emergency surgery.

[Jinghuaweikang capsules combined with triple therapy in the treatment of Helicobacter pylori associated gastritis and duodenal ulcer and analysis of antibiotic resistance: a multicenter, randomized, controlled, clinical study].

OBJECTIVE: To explore the efficacy of Jinghuaweikang capsules plus triple therapy (LACJ) in treatment of Helicobacter pylori (H. pylori) associated gastritis or duodenal ulcer, compare it with bismuth-containing quadruple therapy (LACB) and standard triple therapy (LAC) and analyze the antibiotic sensitivity of gastric mucosal H. pylori strains from the failed patients. METHODS: A total of 565 patients with H. pylori infection were recruited from 11 hospitals from January 2010 to June 2011. There were 336 males and 229 females. They underwent gastroendoscopy examination due to upper gastrointestinal symptoms and had never received H. pylori eradication therapies. Duodenal ulcer patients were divided randomly into LACJ therapy group, LACB therapy group and LAC therapy group while gastritis patients LACJ therapy group and LACB therapy group. Group LAC received lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg, twice a day, for 7 d (d1-7). Group LACJ: LAC therapy plus Jinghuaweikang, 3 capsules, twice a day, for 7 d (d1-7) then Jinghuaweikang, 3 capsules, twice a day, for 14 d (d8-21). Group LACB: LAC plus bismuth potassium citrate 220 mg, twice a day, for 7 d (d1-7) and then bismuth potassium citrate 220 mg, twice a day, for 14 d (d8-21). All duodenal ulcer patients received lansoprazole (30 mg, once a day) for 14 days after the first 7-day of treatment (d 8-21). At least 28 days after the end of treatment, all patients underwent (13)C urea breath test. Gastric mucosa was collected under endoscopy from the failed patients. The detection technique of gene chip was employed to detect antibiotics resistant gene from mucosa. RESULTS: The eradication rates of duodenal ulcer patients in groups LACJ, LACB and LAC were as follows: per-protocol (PP), 80.2% (77/96), 89.9% (89/99) and 72.2% (70/97) (P = 0.007), intention-to-treat (ITT), 78.6% (77/98), 88.1% (89/101) and 70.0% (70/100) (P = 0.007). No statistical differences existed between groups LACJ and LACB or LAC (all P > 0.05). But there were statistical differences between groups LACB and LAC (both P = 0.002). The eradication rates of PP and ITT of chronic gastritis patients in groups LACJ and LACB were as follows: 75.8% (97/128), 74.6% (97/130) vs 83.8% (109/130), 80.1% (109/136) (both P > 0.05). The symptomatic improvements of abdominal pain, burning and acid reflux of duodenal ulcer patients in group LACJ were higher than those in groups LACB and LAC. There were statistical differences between groups LACJ and LAC (all P < 0.05). The symptomatic improvements of bloating and belching for chronic gastritis patients in group LACJ were higher than those of group LACB. But no significant difference existed between two groups (all P > 0.05). Sixty samples of gastric mucosa were collected from the failed patients. The detection rates of antibiotic-resistant gene to clarithromycin and amoxicillin were 60.0% (36/36) and 18.3% (11/60) respectively. CONCLUSIONS: The efficacy of LACJ for the treatment of H. pylori infection patients is similar to LACB and superior to LAC. And the symptomatic improvement of patients is better than the other two regimens. The main cause of treatment failure is antibiotic resistance of H. pylori strains.

[Significance of plasmic homocysteine, folate and Vitamin B(12) in ulcerative colitis].

OBJECTIVE: To investigate the clinical significance of plasmic homocysteine (Hcy), folate (FA) and Vitamin B(12) (VitB(12)) in patients with ulcerative colitis (UC). METHODS: Plasmic Hcy in 112 cases of UC patients and 110 controls were detected by HPLC-FD method. Plasmic FA, VitB(12) in 76 cases of UC patients and 12 controls were detected by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The level of plasmic Hcy in UC patients was(11.27±7.26) µmol/L, significantly higher than that in controls[(8.19±4.81) µmol/L, P<0.05], and was not significantly correlated with disease index, extent and duration of UC(P>0.05). The level of FA and VitB(12) in UC patients were (7.64±1.95) nmol/L and (108.64±32.22) pmol/L respectively, lower than those in controls[(9.14±1.23) nmol/L and (112.64±33.33) pmol/L, P<0.05]. The level of plasmic Hcy was negatively correlated with the level of FA and VitB(12) in UC patients(P<0.05). The level of plasmic FA decreased to some extent with UC disease duration. CONCLUSION: Plasmic Hcy is elevated in UC patients, which may be related to the decrease of FA and VitB(12).

Significance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion.

BACKGROUND AND AIMS: Collagen type IV and hyaluronic acid (HA) are the major components of basement membrane and extracellular matrix, respectively. Cathepsin D is an aspartyl lysosomal protease involved in the degradation of the basement membrane and extracellular matrix. The aim of this study is to investigate the clinical significance of collagen type IV and hyaluronic acid in gastric juice and serum in diagnosis of gastric cancer and the degrading effect of cathepsin D on collagen type IV and HA. METHODS: Fifty gastric cancer patients were enrolled in our study compared with 41 patients with precancerous lesion and 30 control subjects. Collagen type IV and HA in gastric juice and serum were analyzed by radioimmunoassay. Expression of cathepsin D and collagen type IV in tissue were analyzed by immunohistochemical staining with monoclonal antibodies. RESULTS: The contents of collagen type IV and HA in gastric juice and HA in serum were significantly higher in patients with gastric cancer than those in patients with precancerous lesion and control group (p < 0.05, p < 0.0001). Gastric cancer patients with lymph node metastasis had a higher level of collagen type IV and HA in gastric juice than those in patients without metastasis (p = 0.049, p = 0.043). The expression of cathepsin D had significantly increased in patients with gastric cancer compared to the control group (p < 0.0001). The continuous expression of collagen type IV in basement membrane in gastric cancer group was lower than that in the precancerous lesion group and control group (p < 0.0001). CONCLUSIONS: The analysis of collagen type IV and HA in gastric juice and serum may provide a simple aid in diagnosing gastric cancer and evaluating whether metastasis is occurring or not.

Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans.

AIM: To observe the pharmacokinetics and pharmaco-dynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.

[A randomized controlled Multi-center clinical trial on mosapride in the treatment of functional dyspepsia].

OBJECTIVE: To evaluate the effectiveness and safety of mosapride on treatment of functional dyspepsia. METHODS: Randomized controlled clinical trial was conducted and patients suffered from functional dyspepsia were included. 5 mg mosapride was given three times daily for 4 weeks in the treatment group. 10 mg domperidone was given three times daily for 4 weeks as control. Changes on symptom score, gastric empty or new occurring events were included as outcomes. RESULTS: 231 patients suffered from functional dyspepsia were selected by inclusion and exclusion criteria from August 15 to Oct 22, 1999. Of these, 108 (46.8%) were males, versus 123 (53.2%) females and 118 (51.2%) in the treatment group and 113 (48.9%) as controls. 222 (96.1%) patients were followed up. Results showed that the total efficacy rates in early satiety and abdominal distension were 84.5% and 90.1% in mosapride after the 2 weeks of treatment. Mosapride seemed to be more effective in improving symptoms of belching and heartburn than that in controls (P < 0.05). In 4 weeks, the total efficacy in improving symptoms of abdominal distention and belching showed more effective in mosapride than that in controls (P < 0.05). Decrease of symptoms score was more in mosapride than that in controls (P < 0.05). Mosapride was less effective in controls in improving the gastric empty in terms of proportion (46.2% vs. 25.9%, P = 0.020) and range (46.2% vs. 24.0%, P = 0.003). Side effects would include diarrhea, constipation, headache, dizziness, insomnia, skin scare and the like. There was no significant difference between the two groups (9.6% in mosapride vs. 14.0% in controls). CONCLUSION: Mosapride was safe and effective in improving the symptoms and gastric empty of functional dyspepsia.

Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma.

AIM: To investigate the role of cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) in the development of gastric carcinoma and correlation between expression of COX-2 and VEGF and clinicopathologic features in tissues from patients with gastric carcinoma. METHODS: 281 patients with gastric carcinoma who underwent surgical resection between 1990 and 1999 at the First Affiliated Hospital, Anhui Medical University, PRC, were followed up. Expression of COX-2 and VEGF was investigated retrospectively in 232 gastric carcinoma tissues and 60 noncancerous specimens by using immunohistochemistry. RESULTS: The 5-year survival rates of early gastric carcinoma (EGC) and advanced gastric carcinoma (AGC) were 93.4 % and 59.0 %, respectively. Survival time was highly correlated with lymph node metastasis, vascular invasion, depth of invasion and treatment with chemotherapy. Compared with paired noncancerous tissues, expression of COX-2 and VEGF and microvessel density (MVD) value in carcinoma tissue were significantly higher. The MVD value was much higher in COX-2-positive group and VEGF-positive group than that in COX-2-negative group and VEGF-negative group. Expression of COX-2 and VEGF, as well as MVD value were highly correlated with lymph node metastasis and vascular invasion. The 5-year survival rate of patients with expression of COX-2 or VEGF was significantly lower than that of patients without COX-2 or VEGF expression. Multivariate analysis revealed that VEGF overexpression, lymph node metastasis, COX-2 overexpression, depth of invasion and vascular invasion were all independent prognostic factors of gastric carcinoma. CONCLUSION: Overexpression of COX-2 and VEGF in patients with gastric carcinoma can enhance the possibility of invasion and metastasis, implicating a poor prognosis. They may serve as the fairly good prognostic factors to indicate biologic behaviors of gastric carcinoma.