AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and...AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.展开更多
BACKGROUND Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease(IBD).The prevalence rate of IBD in China is the highest in Asia,but there is little research on fatigue ...BACKGROUND Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease(IBD).The prevalence rate of IBD in China is the highest in Asia,but there is little research on fatigue in patients with IBD.Neither the relationship between fatigue and quality of life(QoL)nor the relationship between fatigue and work productivity(WP)in Chinese IBD patients has been reported.AIM To investigate the prevalence of fatigue related to IBD in Eastern China,to identify the risk factors associated with fatigue,to assess the impact of fatigue on QoL,and to evaluate the relationship between fatigue and WP.METHODS A cross-sectional study was conducted in a Regional Tertiary IBD Diagnostic and Treatment Center in Eastern China.Clinical data of patients were collected,and disease activity was evaluated.Blood samples were analyzed to assess anemia,albumin,and inflammation.Fatigue was assessed using the multidimensional fatigue inventory.QoL and WP were measured using the short inflammatory bowel disease questionnaire and the work productivity and activity impairment general health questionnaire,respectively.The patients also completed assessments of depression(Patient Health Questionnaire-9)and anxiety(Generalized Anxiety Disorder 7-item Scale).RESULTS A total of 311 IBD patients,comprising 168 Crohn's disease patients and 143 ulcerative colitis patients,were enrolled.The prevalence of fatigue in patients with IBD was 60.77%.In a univariate logistic regression analysis,factors such as disease activity,depression,anxiety,anemia,and IBD-related surgery were individually related to a significantly increased risk of fatigue in IBD patients.Multivariate logistic regression analysis indicated that depression[odds ratio(OR)=8.078,95%confidence interval(CI):4.113-15.865],anxiety(OR=2.373,95%CI:1.100-5.119),anemia(OR=2.498,95%CI:1.290-4.834),and IBD-related surgery(OR=2.035,95%CI:1.084-3.819)were related to fatigue in IBD patients.There was a negative correlation between fatigue and QoL(r=-0.831;P<0.0001)but a positive correlation between fatigue and WP loss.CONCLUSION The prevalence of fatigue in IBD patients in Eastern China is remarkably high even in clinical remission.Factors such as depression,anxiety,anemia,and IBDrelated surgery are major risk factors for fatigue in IBD patients.In addition,fatigue has a negative impact on QoL and is positively correlated with WP loss.展开更多
BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease(IBD) commonly display a significantly increased rate of morbidity and mortality.With increasing use of immunosuppressive agents ...BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease(IBD) commonly display a significantly increased rate of morbidity and mortality.With increasing use of immunosuppressive agents and biological agents,opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.AIM To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.METHODS A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios(OR) and 95% confidence intervals(CIs).RESULTS Seventy(28.11%) out of 249 IBD patients developed opportunistic infections.Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247(95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457(95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab(IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity(OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.CONCLUSION Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.展开更多
A microwave-assisted general method for the synthesis of 2-aminovinyl benzimidazoles has been developed.Treatment of the 1,2-phenylenediamines and N-arylated/N,N-dialkylated 3-aminoacroleins with bis（cyclopentadienyl...A microwave-assisted general method for the synthesis of 2-aminovinyl benzimidazoles has been developed.Treatment of the 1,2-phenylenediamines and N-arylated/N,N-dialkylated 3-aminoacroleins with bis（cyclopentadienyl）zirconium（IV） dichloride（Cp2Zr Cl2） as the catalyst under microwave irradiation for 3–5 min followed by in situ Mn O2 oxidation afforded thirteen 2-aminovinyl benzimidazoles in good yields.展开更多
The triphosphates and homodinucleotides of AZT and d4T have been efficiently synthesized from the corresponding nucleoside 5-H-phosphonate monoesters via the reactive pyridinium phosphoramidate intermediates.
A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole ...A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole （DCI） activator. Further coupling of the nucleoside 5＇-tetraphosphates with nucleoside 5＇-phosphoropiperidates via the P（V）-N activation strategy provided a reliable synthetic method for both symmetrical and asymmetrical dinucleoside pentaphosphates.展开更多
基金Supported by National Natural Science Foundation of China,No.81473506Natural Science Foundation of Zhejiang Province,No.LY13H030011 and No.LY17H290009+2 种基金State Administration of Traditional Chinese Medicine of Zhejiang Province,No.2013ZB050Department of Zhejiang Province to Build Funded Project,No.WKJ-ZJ-1531Zhejiang TCM Science and Technology Project,No.2016ZB047,No.2017ZA056 and No.2018ZB046
文摘AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.
基金The National Natural Science Foundation of China,No.81473506 and No.81470814Zhejiang TCM Science and Technology Project,No.2021ZA057,No.2019ZA056,and No.2018ZB046.
文摘BACKGROUND Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease(IBD).The prevalence rate of IBD in China is the highest in Asia,but there is little research on fatigue in patients with IBD.Neither the relationship between fatigue and quality of life(QoL)nor the relationship between fatigue and work productivity(WP)in Chinese IBD patients has been reported.AIM To investigate the prevalence of fatigue related to IBD in Eastern China,to identify the risk factors associated with fatigue,to assess the impact of fatigue on QoL,and to evaluate the relationship between fatigue and WP.METHODS A cross-sectional study was conducted in a Regional Tertiary IBD Diagnostic and Treatment Center in Eastern China.Clinical data of patients were collected,and disease activity was evaluated.Blood samples were analyzed to assess anemia,albumin,and inflammation.Fatigue was assessed using the multidimensional fatigue inventory.QoL and WP were measured using the short inflammatory bowel disease questionnaire and the work productivity and activity impairment general health questionnaire,respectively.The patients also completed assessments of depression(Patient Health Questionnaire-9)and anxiety(Generalized Anxiety Disorder 7-item Scale).RESULTS A total of 311 IBD patients,comprising 168 Crohn's disease patients and 143 ulcerative colitis patients,were enrolled.The prevalence of fatigue in patients with IBD was 60.77%.In a univariate logistic regression analysis,factors such as disease activity,depression,anxiety,anemia,and IBD-related surgery were individually related to a significantly increased risk of fatigue in IBD patients.Multivariate logistic regression analysis indicated that depression[odds ratio(OR)=8.078,95%confidence interval(CI):4.113-15.865],anxiety(OR=2.373,95%CI:1.100-5.119),anemia(OR=2.498,95%CI:1.290-4.834),and IBD-related surgery(OR=2.035,95%CI:1.084-3.819)were related to fatigue in IBD patients.There was a negative correlation between fatigue and QoL(r=-0.831;P<0.0001)but a positive correlation between fatigue and WP loss.CONCLUSION The prevalence of fatigue in IBD patients in Eastern China is remarkably high even in clinical remission.Factors such as depression,anxiety,anemia,and IBDrelated surgery are major risk factors for fatigue in IBD patients.In addition,fatigue has a negative impact on QoL and is positively correlated with WP loss.
基金National Natural Science Foundation of China,No.81473506Natural Science Foundation of Zhejiang Province,No.LY16H290001 and No.LY17H290009+1 种基金Project of Department of Construction of Zhejiang Province,No.WKJ-ZJ-1531Zhejiang TCM Science and Technology Project,No.2016ZB047 and No.2017ZA056
文摘BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease(IBD) commonly display a significantly increased rate of morbidity and mortality.With increasing use of immunosuppressive agents and biological agents,opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.AIM To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.METHODS A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios(OR) and 95% confidence intervals(CIs).RESULTS Seventy(28.11%) out of 249 IBD patients developed opportunistic infections.Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247(95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457(95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab(IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity(OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.CONCLUSION Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.
基金supported by the National Natural Science Foundation of China(No.51801170)the National Postdoctoral Program for Innovative Talents,China(No.BX20180265)+2 种基金the Natural Science Foundation of Hunan Province,China(No.2019JJ50570)the China Postdoctoral Science Foundation(No.2019M652786)the Research Initiation Project of Xiangtan University,China(No.18QDZ24)。
基金the National Natural Science Foundation of China (Nos.21262014 to Q.Sun and 21003018 to H.-B.Sun)Key Project of Chinese Ministry of Education (No.212092)Research Funds (Nos.ky2012zy08 and 2013QNBJRC001) from JXSTNU for financial support
文摘A microwave-assisted general method for the synthesis of 2-aminovinyl benzimidazoles has been developed.Treatment of the 1,2-phenylenediamines and N-arylated/N,N-dialkylated 3-aminoacroleins with bis（cyclopentadienyl）zirconium（IV） dichloride（Cp2Zr Cl2） as the catalyst under microwave irradiation for 3–5 min followed by in situ Mn O2 oxidation afforded thirteen 2-aminovinyl benzimidazoles in good yields.
基金National Natural Science Foundation of China (Nos. 21002041 and 21262014)Natural Science Foundation of Jiangxi Province (No. 20114BAB203008)+2 种基金Project of the Science Funds of Jiangxi Education Office (No. GJJ12589)Key Project of Chinese Ministry of Education (No. 212092)Scientific Research Foundation of Chinese Ministry of Human Resources and Social Security for Returned Chinese Scholars for financial support
文摘The triphosphates and homodinucleotides of AZT and d4T have been efficiently synthesized from the corresponding nucleoside 5-H-phosphonate monoesters via the reactive pyridinium phosphoramidate intermediates.
基金the National Natural Science Foundation of China(Nos.21002041 and 21262014)Key Project of Chinese Ministry of Education(No.212092)+1 种基金Scientific Research Foundation of Chinese Ministry of Human Resources and Social Security for Returned Chinese Scholars(2011),and Research Funds(Nos.ky2012zy08 and 2013QNBJRC001)Startup Funds for PhDs(2010)from JXSTNU for financial support
文摘A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole （DCI） activator. Further coupling of the nucleoside 5＇-tetraphosphates with nucleoside 5＇-phosphoropiperidates via the P（V）-N activation strategy provided a reliable synthetic method for both symmetrical and asymmetrical dinucleoside pentaphosphates.
