[Effects of evodiamine on carbon tetrachloride-induced liver fibrosis mice based on modulating gut microbiota].

Objective: To access the effects of evodiamine on carbon tetrachloride (CCl(4)) -induced liver fibrosis mice and study the mechanism based on modulating gut microbiota. Methods: From August 2019, 30 SPF male C57BL/6 mice were randomly divided into normal, model and evodiamine groups. Mice in control group received intraperitoneal injection of olive oil (2 ml/kg, twice per week) for 6 weeks. Mice in model and evodiamine groups received intraperitoneal injection of 20% CCl(4) (2 ml/kg, twice per week) for 6 weeks to induce liver fibrosis mice. Then, mice in evodiamine group received orally of evodiamine (18 mg/kg) for 4 weeks. The levels of serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , albumin (ALB) and total protein (TP) were detected. The pathological changes of liver tissue were observed. The effects of evodiamine on the abundance and diversity of intestinal microflora in liver fibrosis mice were determined. The mRNA and protein expression levels of inflammatory factors[interleukin-6 (IL-6) , interleukin-1ß (IL-1ß) , and tumor necrosis factor α (TNF-α) ] in liver tissue were measured. Results: Compared with the normal group, the body weight, serum ALB and TP levels of the model group were decreased, the liver index, ALT and AST levels were increased, and the intestinal flora Shannon and Simpson indexes were decreased (P<0.01) . Compared with the normal group, the abundance of Lactobacillus, Akkermansia and Bacteroides in the feces of the model group decreased, while the abundance of Enterococcus and Lachnoclostridium increased (P<0.01) . Compared with the normal group, the mRNA and protein expressions levels of IL-6, IL-1ß, and TNF-α in the liver tissue of the model group were significantly increased (P<0.01) . Compared with the model group, evodiamine could reduce liver index and serum ALT and AST levels, increase ALB and TP levels (P<0.05) , improve inflammatory cell infiltration and fibrosis degree in liver tissue, and up regulate intestinal flora Shannon and Simpson indexes in liver fibrosis mice (P<0.05) . Compared with the model group, evodiamine could increase the abundance of Lactobacillus, Akkermansia, Bacteroides, and reduce the abundance of Enterococcus and Lachnoclostridiun (P<0.05) . Compared with the model group, evodiamine could reduce the mRNA and protein levels of IL-6, IL-1ß and TNF-α in liver tissue of liver fibrosis mice (P<0.05) . Conclusion: Evodiamine can ameliorate CCl(4)-induced liver fibrosis through modulating gut microbiota and inhibiting the inflammatory response in liver.

[Study on the effect of integrated traditional Chinese and western medicine in the treatment of brucellosis].

Objective: To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes. Methods: In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed. Results: The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant (P>0.05) . The difference was not statistically significant (P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment (P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group (P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment (P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment (P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group (P<0.05) . Conclusion: The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

[Analysis of clinical characteristics and prognosis of 235 pancreatic neuroendocrine tumors underwent Sunitinib treatment].

Objective: To investigate the clinical characteristics, treatment, and prognostic factors of pancreatic neuroendocrine tumors (pNETs) patients treated with Sunitinib. Methods: The clinical data of pNETs patients from Pfizer Drug Assistance Program of Cancer Foundation of China from April 2013 to November 2017 were retrospectively analyzed. Follow-up and statistical analysis were performed. Results: A total of 235 patients were enrolled, the patients' overall survival time was between 4 and 252 months, the 3-years and 5-years survival rates were 73.8% and 60.8%, respectively. Univariate analysis showed that factors such as age, Ki-67 index and surgery were associated with the 3-years survival rates of pNETs patients (P<0.05). Multivariate analysis demonstrated that the age, Ki-67 index and surgery were independent prognostic factors for pNETs patients (P<0.05). For patients with liver metastases, univariate analysis revealed that surgery was associated with prognosis (P<0.05). The 5-years survival rate of 124 patients with extending usage of Sunitinib was 53.3%. Conclusion: PNETs are rare tumors with atypical clinical symptoms and the patients often have metastasis at the initiate diagnosis. The age, Ki-67 index and surgery are associated with the prognosis of pNETs patients.

[Prognostic analysis of colon and rectal neuroendocrine neoplasm in different stages].

Objective: To explore the survival difference of patients with colon and rectal neuroendocrine neoplasm (NEN) at different stages. Methods: We identified 8 679 patients with colorectal NEN diagnosed between 1988 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) registry, including 5 437 rectal NEN and 3 242 colon NEN ( 1 681 cecum NEN ). Survival curve was drawn by Kaplan-Meier method. Prognostic factors were analyzed by univariate analysis and multivariate Cox regression model. Results: The ratio of male patients with colon and rectal NEN was similar to female (P=0.095). Rectal NEN patients were younger (P<0.001), more highly differentiated (P<0.001), and with earlier stage (P<0.001). Survival analysis showed that the survival of rectal NEN was superior to that of colon NEN, with 10-year tumor-specific survival rates of 86.8% and 44.8% respectively (P<0.001). Multivariate Cox analysis showed that age, gender, marital status, primary tumor site, grade, stage and surgery were independent prognostic factors of colorectal NEN (all P<0.01). The most important factor was stage (HR=3.531), followed by differentiation grade (HR=1.856). Stratified analysis displayed that the survival of rectal NEN in stage Ⅰ, Ⅱ and Ⅳ were better than those of corresponding stage of colon NEN (all P<0.05), but worse in stage Ⅲ (P=0.012). While the survival of rectal NEN were significantly better than those of colon NEN within all stages after excluding 1681 cases of cecal NEN (all P<0.05). Among the patients with well-differentiated NEN, the survival of rectal NEN in stage Ⅰ, Ⅲ and Ⅳ were better than those of corresponding stage of colon NEN (all P<0.05) while there was no significant difference in stage Ⅱ(P=0.169). For poor-differentiated NEN, only the survival of rectal NEN patients in stage Ⅳ (P=0.001) was significant longer than those of colon NEN, while there was no significant difference in stage Ⅰ, Ⅱ and Ⅲ (stage Ⅰ: P=0.760; stage Ⅱ: P=0.181; stage Ⅲ: P=0.313). Conclusions: The survival of NEN patients in colon and rectum is different. Cecum NEN should be considered as a separated tumor for prognostic analysis due to its special clinicopathologic characteristics.