Objective To evaluate the changes in 5'-adenosine monophosphate-activated protein kinase (AMPK) signal transduction pathway in hippocampal neurons of aged rats during transient global cerebral ischemia/reperfusion (I/R).Methods Ninety-six aged male Sprague-Dawley rats aged 18-22 months,weighing 450-600 g,were randomly allocated to one of two groups (n=48 each):sham operation group (group OS) and transient global cerebral I/R group (group OTIR).Ninety-six yong male Sprague-Dawley rats aged 3 months,weighing 200-250 g,were randomly divided into 2 groups (n=48 each):sham operation group (group AS) and transient global cerebral I/R group (group ATIR).The global cerebral I/R was produced by 3 min four-vessel occlusion followed by reperfusion according to Pulsinelli.On 3,5 and 7 days of reperfusion,12 rats in each group were chosen and sacrificed.Their brains were removed and hippocampal CA1 region was dissected for detection of neuronal apoptosis (by TUNEL) and expression of phosphorylated AMPKα (p-AMPKα) (by Western blot).The apoptotic rate (AR) was calculated.Results Compared with OS group,the AR was significantly increased and the expression of p-AMPKα was up-regulated at each time point in OTIR group,and the AR was significantly decreased and the expression of p-AMPKα was down-regulated at each time point in AS group (P ＜ 0.05).Compared with AS groupthe AR was significantly increased at each time point and the expression of p-AMPKα was up-regulated on day 3 and 5 of reperfusion in ATIR group (P ＜ 0.05).The AR was significantly lower at each time point and the expression of p-AMPKα was down-regulated on day 5 and 7 of reperfusion in ATIR group than in OTIR group (P ＜ 0.05).Conclusion Transient global cerebral I/R can activate AMPK signal transduction pathway in hippocampus of aged rats.The activation of AMPK signal transduction pathway is stronger and the cerebral I/R injury is more severe in aged rats than in young rats.

OBJECTIVETo further understand the anatomical basis of pelvic autonomic nerve preservation.

METHODSAutopsy of five adult male donated cadavers was performed. Meanwhile, ten videos of laparoscopic total mesorectal excision for male mid-low rectal cancer admitted from January to June 2012 were observed and studied. Anatomical features of pelvic autonomic nerve were compared between autopsy and laparoscopic appearance.

RESULTSAutopsy observations indicated that:the abdominal aortic plexus was situated upon the sides and front of the aorta, between the origins of the superior and inferior mesenteric arteries. The superior hypogastric plexus was a plexus of nerves situated on the the bifurcation of the abdominal aorta to sacrum; after incision of sacrum fascia was done cling to the sacrum; the pelvic splanchnic nerves and sacral splanchnic nerves were demonstrated; pelvic splanchnic nerves were splanchnic nerves that arised from ventral rami of the second, third, and often the fourth sacral nerves to provide preganglionic parasympathetic innervation to the hindgut;sacral splanchnic nerves providing postganglionic fibers, emerged from the sympathetic trunk, were then joined by the pelvic splanchnic nerves to form the inferior hypogastric plexuses which were placed lateral to the rectum.Laparoscopic observations showed that:abdominal aortic plexus and superior hypogastric plexus were unclear; at the level of sacroiliac joint, the hypogastric nerve began where the superior hypogastric plexus split into a right and left plexus, situated under the loose connective tissue, and continued inferiorly on its corresponding side of the body at the level of the 3rd sacral vertebra;left hypogastric nerve was closed to posterior of mesorectum;denonvilliers fascia was thin, reflective fascial structure, and easily removed together with mesorectum excision because of anterior loose structure.

CONCLUSIONSLigation of the inferior mesenteric artery at its origin is safe.Excessive dissection of the connective tissue covering the surface of the aorta should be avoided to protect the abdominal aortic plexus.Sharp dissection performed by pursuing the outer surface of the mesorectum maintaining the integrity of mesorectum, could avoid the superior hypogastric plexus and hypogastric nerves injury posteriorly, and protect the inferior hypogastric plexues while cutting lateral ligament laterally. The integrity of Denonvilliers fascia during anterior resection of rectum should be confirmed to avoid urogenitalis aparatus branches damage.

Adult ; Autonomic Nervous System ; anatomy & histology ; Autopsy ; Humans ; Laparoscopy ; Male ; Pelvis ; innervation ; Rectal Neoplasms ; surgery

Humans ; Femoral Artery/surgery* ; Hip Dislocation, Congenital ; Hip Joint ; Treatment Outcome

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.

OBJECTIVE: To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology. METHODS: TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice. RESULTS: Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05). CONCLUSION LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.
Mice ; Animals ; Toll-Like Receptor 4 ; Colitis-Associated Neoplasms ; Network Pharmacology ; Mice, Inbred C57BL ; Colonic Neoplasms/pathology*

Objective : To investigate the effects of linoleic acid ( LA) on the diversity and structure of intestinal flora in mice． Methods : Twelve SPF grade male C57BL /6J mice at 7 weeks were randomly divided into control group ( CTRL group) and linoleic acid group (LA group) ．One day before the linoleic acid diet was supplemented， the normal food was removed from the LA group and the mice in the LA group were fasted for one night，so that the LA diet was more acceptable to the mice in the LA group，and LA was given on the day of the experiment recording， and the feed was updated at any time to ensure that the mice could eat freely until the end of modeling．After 12 weeks of modeling，mouse feces were collected，and mixed samples were collected for every two mice feces，and then 16sRNA high-throughput sequencing was performed to analyze intestinal flora structure，Alpha and Beta diversity. Results : 16sRNA high-throughput sequencing showed that LA intervention damaged the richness and diversity of intestinal flora．The results of principal component analysis showed that the composition of flora in CTRL group was different from that in LA group．At gate level，the relative abundance of Actinobacteria in LA group increased (P < 0. 01) ．At the genus level，the relative abundance of L．Duchennei in the LA group decreased (P＜0. 05) ，but the relative abundance of Bifidobacterium，Faecalibaculum and Erysipelotrichaceae in the LA group increased ( all P < 0. 01) ． Conclusion LA intervention could reduce the richness and diversity of intestinal flora in mice，and adjust the structure of intestinal flora．There were significant differences between beneficial bacteria and pathogenic bacte- ria in intestinal flora after LA intervention，which provided certain basis for the treatment of bioactive compounds of linoleic acid and the therapeutic adjustment of intestinal microorganisms as targets.