Objective To determine the effect of prokinetic agents such as domperidone, mo-sapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats, and also to explore the mechanism. Methods The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the inter-digestive phase. The effect of the prokinetic agents on the amplitude and freqency of gastric and duo-denal electromyologram in the SD rats was compared. The antagonists such as atropine, phento-lamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. Results All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats (P<0.05). The effect of itopride was the most obvious among the 3 groups (P<0.05), and clarithromycin had the weakest effect (P<0.05). The amplitude and frequency of gastric and duodenal fast waves in the SD rats in the groups of clarithromycin, domperidone, mosa-pride, itopride, and physiological saline were inhibited by atropine (P<0.05) , but not by phento-lamine and propranolol. Conclusion Itopride, mosapride, domperidone, and clarithromycin can in-crease the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

Objective: To investigate the clinicopathologic and prognostic features of Claudin-low breast cancers (CLBC). Methods: Tissue microarray sections were scored semiquantitatively for the immunohistochemical expression of claudin-1, -3, -4, -7 and -8 in 233 cases of invasive breast cancers collected from Qingdao Central Hospital from January 2010 to December 2011. Results: The expression rate of Claudin-3 (72/212, 33.9%) and -4 (56/212, 45.2%) was most similar, and Claudin-4 showed the highest expression. Twenty one cases (21/212, 9.0%) were diagnosed as CLBC, with triple-negative breast cancer (TNBC) accounted for the highest proportion (11/21, 52.4%). Among the CLBC cases, the invasive carcinoma no special type (66.7%, 14/21) and metaplastic carcinoma (14.3%, 3/21) were mostly seen, while metaplastic squamous carcinoma did not show Claudin-low pattern. Compared to the non CLBC in this cohort, CLBC had higher proportion of histologic grade 3 and tumors larger than 2 cm, and the proportions were slightly lower than TNBC. Patients with CLBC had lower 5 year disease-free(P>0.05) and overall survival rates(P=0.018). Conclusion CLBC shows distinct clinicopathologic and prognostic features comparing to other subtypes, and is associated with poor prognosis.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment