Clinical features of primary sclerosing cholangitis and inflammatory bowel disease / 中华内科杂志

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing / 中华医学杂志(英文版)

BACKGROUND@#Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis.@*METHODS@#C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups.@*RESULTS@#After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315).@*CONCLUSIONS@#Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing / 中华医学杂志(英文版)

Background@#Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis.@*Methods@#C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups.@*Results@#After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315).@*Conclusions@#Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada / 中华医学杂志(英文版)

Background@#Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD). This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada.@*Methods@#Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics.@*Results@#Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ± 12.8 years vs. 61.6 ± 14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002).@*Conclusions@#As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Amoxicillin-Clarithromycin-Containing Bismuth Quadruple Therapy for Primary Eradication of Helicobacter pylori / 中国医学科学院学报

Objective To evaluate the efficacy and safety of amoxicillin-clarithromycin-containing bismuth quadruple regimen as a primary therapy for Helicobacter pylori (Hp) eradication.Methods A total of 102 Hp-infected outpatients diagnosed by C-or C-urea breath test from December 2015 to June 2017 were enrolled and received 14-day bismuth quadruple therapy (esomeprazole 20 mg bid,bismuth potassium citrate 220 mg bid,amoxicillin 1000 mg bid,and clarithromycin 500 mg bid for 14 days). Hp status was assessed by C-or C-urea breath test 4 weeks,8 weeks,6 months,and 12 months after the treatment. The primary outcome was Hp eradication rate,which was analyzed by intention-to-treat (ITT) and per-protocol (PP) analyses. The second outcomes were Hp infection recurrence,symptomatic benefit from Hp eradication,and safety. Results A total of 101 patients,of which 65 patients had dyspeptic symptoms before eradication,completed the study. Hp eradication rates by ITT analysis and by PP analysis were 88.2% and 89.1%,respectively. Only in two of 84 patients,who were followed for 8 weeks after eradication,Hp became positive. No Hp recurrence happened at the 6-month and 12-month follow-up and the annual recurrence rate was 2.4%. The symptomatic relief rates at the 4-week,8-week,6-month and 12-month follow-up were 81.5%,75.4%,71.2%,and 70.2% respectively. Eleven of 101 patients had mild and similar side-effects,which were well tolerated.Conclusion Amoxicillin-clarithromycin-containing bismuth quadruple regimen can be used as the standard therapy for Hp eradication.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada / 中华医学杂志(英文版)

BACKGROUND@#Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to explore the clinical-pathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada.@*METHODS@#Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics.@*RESULTS@#Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ± 12.8 years vs. 61.6 ± 14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002).@*CONCLUSIONS@#As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease / 中国医学科学院学报

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×10/L. CD4+T cells in two patients were less than 200×10/L. Four patients had elevated serum cytomegalovirus DNA. The level of β-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

Signal Transducer and Activator of Transcription 3 for the Differentiation of Hepatocellular Carcinoma from Cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overexpression and constitutive activation of signal transducer and activator of transcription (STAT) 3 have been suggested in the tumorigenesis of many human cancers, including multiple carcinomas, melanoma, and lymphoma. The diagnosis of hepatocellular carcinoma (HCC) in lobectomy specimens is usually straightforward, but distinguishing cirrhosis from well-differentiated HCC can be challenging in core biopsies. Our aims were to investigate the expression level of STAT3 and phosphorylated STAT3 (pSTAT3) in HCC and cirrhosis, and the application of STAT3 in the differential diagnosis of HCC and cirrhosis.</p><p><b>METHODS</b>Sixty cases were divided into three groups: patients with HCC only (Group 1), HCC and cirrhosis (Group 2), and cirrhosis only (Group 3). Formalin-fixed and paraffin-embedded tissue sections were stained immunohistochemically for STAT3, pSTAT3, and CD163. The values obtained from the tissue sections of each group were compared in statistical analysis.</p><p><b>RESULTS</b>STAT3 showed a high level in HCC and was a significant marker for differentiating HCC from cirrhosis (P < 0.0001). The odds ratio between HCC and cirrhosis increased 34.4 times when the intensity of STAT3 increased by 1 level. Spearman's correlation and Chi-square tests also demonstrated that expression level of STAT3 did not correlate with age, gender, or the presence of a cirrhotic background.</p><p><b>CONCLUSIONS</b>STAT3 staining differs significantly in HCC and cirrhosis. The findings reinforce the role of STAT3 in the tumorigenesis of HCC and provide a useful marker to differentiate HCC from cirrhosis in challenging liver biopsies.</p>

Preoperative Corticosteroid Usage and Hypoalbuminemia Increase Occurrence of Short-term Postoperative Complications in Chinese Patients with Ulcerative Colitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Clarifying the risk factors for postoperative complications and taking measures to minimize these complications will improve the outcomes in patients with ulcerative colitis (UC). This study aimed to systemically explore the risk factors for short-term postoperative complications in Chinese UC patients undergoing ileocolorectal surgery.</p><p><b>METHODS</b>Forty-nine UC patients undergoing proctocolectomy or ileostomy were retrospectively enrolled. Univariate and multivariate logistic regression analyses were conducted to reveal the risk factors among the clinical, laboratory, and surgical variables as well as preoperative medications.</p><p><b>RESULTS</b>Twenty-two (44.9%) patients who suffered from at least one short-term postoperative event had more severe hypoalbuminemia (P = 0.007) and an increased prevalence of preoperative corticosteroid usage (prednisone more than 20 mg daily or equivalent) for more than 6 weeks (59.1% vs. 25.9%, P = 0.023) compared with patients without short-term postoperative complications. Based on the multivariate logistic regression analysis, the odds ratio (95% confidence interval) values of these two risk factors were 1.756 (0.889-3.470, P = 0.105) and 3.233 (0.916-11.406, P = 0.068), respectively. In 32 severe UC patients, prolonged preoperative hospital stay worsened the short-term postoperative outcomes.</p><p><b>CONCLUSIONS</b>Preoperative corticosteroids usage and hypoalbuminemia worsened the short-term outcomes following ileocolorectal surgery in Chinese UC patients.</p>

Inhibitory effect of a Ras homologue member I on pancreatic cancer and its modulation on epithelium growth factor receptor-Ras-Raf-mitogen-activated protein kinase/extracellular regulated protein kinase/1/2 pathway / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the regulation of epithelium growth factor receptor (EGFR), pan-Ras, and extracellular regulated protein kinase (ERK) with both a ras homologue member I (ARHI) suppression and epithelium growth factor (EGF) stimulation.</p><p><b>METHODS</b>After identification and implication, the constructed plasmid pIRES2-EGFP-ARHI was transfected into Panc-1. The untransfected cell was also explored as controls. The growth curve was drawn to indicate the proliferation effect of ARHI. EGFR-ELISA was performed to investigate the expression of EGFR. Western blot analysis was used to investigate the expression of protein MAPK/ERK1/2, pan-Ras in Panc-1.</p><p><b>RESULTS</b>The proliferation rate of Panc-1 was inhibited by ARHI compared with both empty plasmid and untransfected cell. The amount of EGFR was parallel in both transfected and untransfected cell but affected by EGF stimulation. The amount of pan-Ras was decreased after ARHI transfection. The optimum concentration of EGF effect on P-ERK was 50 ng/ml.</p><p><b>CONCLUSION</b>Both ARHI and EGF play roles in the EGF-EGFR-Ras-Raf-MAPK/ERK1/2 pathway.</p>

Trends in etiologies of chronic pancreatitis within 20 years: analysis of 636 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of chronic pancreatitis has increased during recent years in Asia-Pacific areas as well as in China. The etiologies vary in different regions and periods. This study aimed to investigate the changing etiologies of chronic pancreatitis within 20 years at Peking Union Medical College Hospital in China.</p><p><b>METHODS</b>Retrospective analysis of the etiologies of 636 cases of chronic pancreatitis at Peking Union Medical College Hospital from 1990 to 2010 was performed. Patients were divided into two groups according to two time periods (1990 - 2000 and 2001 - 2010). Statistical analysis was performed using the chi-square test.</p><p><b>RESULTS</b>The morbidity rate of chronic pancreatitis in China has recently increased. The main etiology changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%). The main etiology of biliary diseases is stones in the cholecyst or bile duct, and the percentage of cholecystitis cases has increased. Autoimmune disease, including autoimmune pancreatitis, has increased quickly and currently accounts for 7.3% of cases because a greater number of autoimmune pancreatitis cases are being diagnosed. Approximately 9.5% of chronic pancreatitis cases are caused by multiple factors such as alcohol abuse and bile duct stones. Other factors include cholecystectomy and acute pancreatitis.</p><p><b>CONCLUSIONS</b>The main etiology of chronic pancreatitis has changed from biliary disease to alcohol abuse in recent years. Autoimmune factors have also obviously increased.</p>

Effects of K-ras gene mutation on colon cancer cell line Caco-2 metastasis by regulating E-cadherin/beta-catenin/p120 protein complex formation and RhoA protein activity / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of K-ras gene mutation on colon cancer cell line Caco-2 metastasis by regulating E-cadherin/beta-catenin/p120 protein complex formation and RhoA protein activity.</p><p><b>METHODS</b>K-ras wild-type colon cancer cell line Caco-2 was transiently transfected by phr-GFP vector (control group), transfected by mutant K-ras gene phr-K-ras (Val12) vector (transfection group), transfected by mutant K-ras gene phr-K-ras (Val12) vector and treated by specific MAPK pathway inhibitor PD98059 (MAPK inhibition group), or transfected by mutant K-ras gene phr-K-ras (Val12) vector and treated by specific PI-3K pathway inhibitor LY294002 (PI-3K inhibition group), respectively. Cell migration was tested by Transwell experiment. E-cadherin and beta-catenin protein expression and intracellular location were detected by cell immunofluorescence method. Intracellular p120 protein expression was detected by Western blot. beta-catenin protein level which combined with E-cadherin was detected by immunoprecipitation. RhoA activity was analyzed by Pull-down assay.</p><p><b>RESULTS</b>The Caco-2 cell migration rate was (19.8 +/- 5.6) % in transfection group, which was significantly higher than that in control group [(14.0 +/- 4.2) %] (P = 0.001) and in MAPK inhibition group [(15.8 +/- 1.2) %] (P = 0.044), but was not significantly different from that in PI-3K inhibition group [(17.5 +/- 2.8) %] (P = 0.095). Immunofluorescence method showed that the E-cadherin and beta-catenin stain located in the cell membrane decreased in transfection group. Western blot showed that the total intracellular p120 protein decreased in transfection group and PI-3K inhibition group. Immunoprecipitation data showed that beta-catenin protein level combined with E-cadherin decreased in transfection group and PI-3K group. Pull-down test showed that RhoA protein activity was up-regulated in transfection group.</p><p><b>CONCLUSION</b>K-ras gene mutation stimulates the migration of colon cancer cell Caco-2, which may be achieved by decreasing the E-cadherin/beta-catenin/p120 protein complex formation via MAPK pathway and increasing the RhoA protein activity.</p>