Background:Tryptophan(TRP)is an essential amino acid,and can produce 5-hydroxytryptamine(5-HT)via 5-HT signal pathway and kynurenine( KYN)metabolic pathway under the catalysis of enzyme,thereby participating in the pathogenesis of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome(IBS-D). Aims:To investigate the relationship between visceral sensitivity and TRP metabolic pathway in patients with IBS-D. Methods:Thirty patients with IBS-D and 30 healthy controls from June 2012 to January 2014 at Guangdong Provincial TCM Hospital were enrolled. Score of gastrointestinal symptom rating scale( GSRS)was evaluated. Visceral sensitivity was measured by anorectal manometry. RT-PCR and Western blotting were used to detect mRNA and protein expressions of colon mucosal IDo, respectively. Serum 5-HT,5-HIAA,TRP,IDo,KYN,KYNA concentrations and IDo activity,KAT activity were determined by high performance liquid chromatography assay. Results:Compared with control group,GSRS score was significantly increased(P < 0. 05),initial perception threshold,defecation threshold,pain threshold were significantly decreased(P < 0. 05),anorectal constriction pressure was significantly increased( P < 0. 05),serum 5-HT,5-HIAA concentrations were significantly increased(P < 0. 05),mRNA and protein expressions of IDo were significantly increased (P < 0. 05),serum KYN was significantly increased(P < 0. 05),KYNA was significantly decreased(P < 0. 01),IDo activity was significantly incseased(P < 0. 01),and KAT activity was significantly decreased in IBS-D group(P < 0. 01). Correlation analysis showed that initial perception threshold,defecation threshold,pain threshold and anorectal constriction pressure were correlated with 5-HT,5-HIAA,TRP,KYN,KYNA,IDo activity and KAT activity in patients with IBS-D (P < 0. 05). Conclusions:TRP metabolic pathway is correlated with visceral hypersensitivity in patients with IBS-D.

This study was aimed to investigate the effect of baicalin on the proportion of Th22 cells and the concentration of IL-22 bothin vivo andin vitro, in order to explore the immune mechanism of baicalin on inflammatory bowel disease mice model. The 3.5% dextran sodium sulfate (DSS) was used on C57BL/6 mice for the establishment of colitis mice model. Mice were randomly divided into the blank control group, model group, and baicalin group. Flow cytometry and ELISA were used in the detection of the proportion of Th22 cells and concentration of IL-22 in peripheral blood serum, respectively. The spleen lymphocytes of mice were isolated and cultured by baicalin medium (0, 10, 20, 40μM) for 48 h. Flow cytometry was used in the detection of the proportion of Th22 cells. The results showed that baicalin reduced the proportion of Th22 cells and the expression of IL-22 bothin vivo andin vitro experiments. It was concluded that baicalin can inhibit Th22 cell differentiation and expression of IL-22in vitro and DSS-induced colitis mice. It indicated that baicalin had a good treatment potential in Th22 cell-mediated inflammatory diseases.

Objective To investigate the cytokines levels in peripheral blood of ulcerative colitis (UC) patients at active stage, and to observe the effect of baicalin at various concentrations on the cytokines. Methods Quantitative polymerase chain reaction (Q-PCR) assay was used for the detection of interleukin 4 receptor (IL4R), IL6R, IL23R and RAR-related orphan receptor C (RORC) expression in single peripheral mononuclear cell of UC patients. Enzyme-linked immunosorbent assay (ELISA) was used to examine the serum levels of interferon gamma (IFN-γ), IL-4, IL-5, IL-6, IL-10, and transforming growth factor beta (TGF-β) levels in UC patients, and was applied for in-vitro detection of these indicators after baicalin intervention. Results Q-PCR results showed that IL4R, IL6R, IL23R, RORC gene expression levels in UC patients were increased to various degrees as compared to diarrhea-predominant irritable bowel syndrome (IBS-D) patients and the healthy volunteers, and then the levels were decreased to various degrees after intervention by baicalin at different concentrations, in particular at 20 and 40μmol/L. The results of ELISA showed that serum levels of cytokines of IFN-γ, IL-5, IL-6 in UC patients were increased to various degrees while IL-4, IL-10 and TGF-β1 was decreased as compared to IBS-D patients and the healthy volunteers. Baicalin at the concentrations of 20 and 40 μmol/L had an effect on decreasing IFN-γ, IL-5, IL-6 and on increasing IL-4 and IL-10. Conclusion Higher concentrations of baicalin show obvious effect on inhibiting RORC and IL23R expression, on decreasing IFN-γ, IL-5, IL-6 levels, and on increasing IL-4, IL-10 and TGF-β1 levels, which indicated that the therapeutic mechanism of baicalin in relieving ulcerative colonic inflammation is related with the regulation of immune function.

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.

This study was aimed to examine the effect of Shaoyao Tang (SYT) on the treatment of dextran sulfate sodium (DSS)-induced experimental colitis in mice via targeting the Notch signaling pathway.The mice were equally and randomly divided into the normal control group (control),model group (DSS),DSS + SYT group (17.8 g· kg-1),n=10.Mice were administered with 3.5％ DSS for 7 days for the model establishment.And then,SYT was given to the model group on the second day after the induction of colitis with DSS for 7 days.The effects were studied by the disease activity index (DAI),histological analysis by HE staining,myeloperoxidase (MPO) activity.ELISA was used to measure secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the colon tissues.The expression of mRNA and protein of Notch-1,Hes-1,Math-1 and Mucin-2 (Muc-2) were detected using real-time PCR and immunohistochemistry.The results showed that compared with the model group,SYT attenuated symptoms of colitis by decreasing DAI score,histopathologic score and MPO activity,as well as increasing the colon length.SYT treatment also inhibited the production of IL-6 and TNF-a in colon tissues of mice.Furthermore,SYT significantly blocked the expression of mRNA and protein of Notch-1 and Hes-1,but increased the expression of Math-1 and Muc-2.It was concluded that SYT exerted the anti-inflammatory activity in mice model of DSS-induced colitis by inhibiting the Notch signaling pathway.

Objective To investigate the prognostic value of serum neutrophil gelatinase-associated lipid transport protein (NGAL) and renal injury molecule 1 (KIM-1) in assessing neonatal sepsis with a-cute renal injury. Methods A total of 63 cases of renal injury with neonatal sepsis was collected from De-partment of Pediatrics, Affiliated Children's Hospital of Capital Institute of Pediatrics. The general condition of the patients, and neonatal critical case score ( NCIS) were recorded. The expressions of NGAL and KIM-1 in serum of all children were measured by venous blood and urine. Each case was followed up for 28 days to track the death of newborns. Pearson correlation analysis was used to test the correlation among NGAL, KIM-1, and NCIS;Multivariate regression analysis was used for NGAL, KIM-1, and other risk factors asso-ciated with neonatal sepsis kidney injury 28 days mortality. Receiver operating characteristic ( ROC) curve was used to compare the value of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury. The val-ues of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury were analyzed by ROC curve. Re-sults ⑴ After 28 days of follow-up, 63 cases of neonatal sepsis, and 22 died were found, which was ac-counted for 34. 92 percent of the total. ⑵ Compared to the survival group, the expressions of NGAL and KIM-1 in the death group were increased ( P<0. 01 ) . ⑶ Pearson correlation analysis showed that NGAL and KIM-1 expressions in peripheral blood were negatively correlated with NCIS. ⑷Multivariate regression analysis showed that NGAL and KIM-1 were independent risk factors for neonatal sepsis kidney injury ( P<0. 01). ⑸ ROC curve analysis showed that the area under the curve of NGAL and KIM-1 was 0. 79 (95％CI:0. 75-0. 93), and 0. 84 (95％ CI:0. 71-0. 90), NGAL and KIM-1 were better than single detection with NGAL, or KIM-1, area under curve (AUC) was 0. 89 (95％ CI:0. 78-0. 94) (P<0. 01). Sensitiv-ity of KIM-1 was superior to that of NGAL, and specificity of NGAL was superior to KIM-1. The sensitivity and specificity of both were better than single detection with NGAL and KIM-1. Conclusions NGAL and KIM-1 have good predictive value in assessing neonatal sepsis kidney injury mortality.