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[ ABSTRACT] AIM: To explore the role of chemokine receptor CXCR 4 in the pathogenesis of protein C system (PCS) in ulcerative colitis (UC).METHODS:In vivo, the mice were divided into control group and UC group .The mac-roscopic score, microscopic score and ulcer index were assessed .The mRNA levels and activity of myeloperoxidase ( MPO) , cyclooxygenase-2 ( COX-2 ) , stromal cell-derived factor-1α( SDF-1α) and monocyte chemotactic protein 1 (MCP-1) both in colonic tissue and plasma were determined .The expression and location of CXCR4,β-arrestin, p-JNK, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) were detected.The activity of protein C (PC) and protein S ( PS) was measured in each group .In vitro, mouse colonic microvascular endothelial cells were isolated , cultured and identified.Both CXCR4-overexpressing and CXCR4-silencing colonic mucosa microvascular endothelial cells were con-structed.The effects of SDF-1αon the protein levels of EPCR , TM,β-arrestin and p-JNK, and on the activity of PC , PS and activated protein C ( APC) were observed .RESULTS:Compared with control group , UC mice showed increased gross score, histopathological score and ulcer index (P<0.05).The mRNA levels and activity of MPO, COX-2, SDF-1αand MCP-1 in colon and plasma were increased (P<0.01).The protein levels of CXCR4,β-arrestin and p-JNK were up-regu-lated, EPCR expression was down-regulated in colon, and the activity of PC and PS in plasma was decreased (P<0.05 or P<0.01).CXCR4 overexpression further aggravated SDF-1α-induced PCS inhibition in colonic mucosa microvascular en-dothelial cells, and further up-regulated the protein levels of β-arrestin and p-JNK (P<0.05).CONCLUSION:PCS is inhibited in UC.CXCR4 is involved in the regulation of PCS inhibition by mediating chemokines and acting on colonic mu -cosa microvascular endothelial cells through β-arrestin-JNK pathway .
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AIM: To explore the role of purinergic signaling mediated by ATP in the Alzheimer ’ s disease (AD)-related colon motility disorder and its related molecular mechanisms .METHODS:(1)Clinical trials:AD patients in our hospital were collected and studied .Radioimmunoassay was used for the determination of plasma motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and nitric oxide (NO), and high-performance liquid chroma-tography ( HPLC) was applied to test the level of adenosine triphosphate ( ATP) .The patients were assessed by neuropsy-chology and scored accordingly .( 2 ) In animal experiments , AD mice received Morris water maze test , and the spatial learning and memory function were evaluated .The plasma levels of MTL , CCK, VIP and NO were examined by radioimmu-noassay , and the level of ATP was measured by HPLC .Choline acetyltransferase ( ChAT ) , VIP, nitric oxide synthase ( NOS) and ATP synthase were detected by immunohistochemistry .Western blot and immunohistochemistry were used to detect the expression of P2Y receptor.(3) In vitro, organ bath was applied to observe the effect of α,β-methylene ATP (α,β-MeATP), an agonist of P2Y receptor, on both spontaneous and electrically evoked contraction of colonic smooth muscle strip, and the technique of intracellular microelectrode was applied to observe the effect of α,β-MeATP on the membrane potential of colonic smooth muscle cells .RESULTS:Compared with control group , the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed.Mini-Mental State Examination (MMSE) score was decreased (P<0.05), Alzheimer’s Disease Assess-ment Scale-Cognitive Subscale (ADAS-Cog) score, Neuropsychiatric Inventory (NPI) score and Alzheimer’s Disease Co-operative Study-Activities of Daily Living Scale ( ADCS-ADL ) were all increased as compared with control group ( P <0.01).The 4~6 d escape latency of APP/PS1 AD mice was significantly prolonged (P<0.05), and the space explora-tion ability distinctly reduced (P<0.05).In AD mice, the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed .The protein expres-sion of colonic ATP synthase was significantly increased (P<0.05), but the expression of ChAT, VIP and NOS was not changed.The expression of P2Y receptor was increased (P<0.01).The results of in vitro experiment displayed that α,β-MeATP, from 20 μmol/L to 100 μmol/L, inhibited the spontaneous contraction of colonic smooth muscle strip in the nor-mal mice and AD mice ( P<0.05 or P<0.01 ) , and this inhibition was reversed by Na +channel inhibitor tetrodotoxin (TTX) (P<0.05 or P<0.01).In addition, the effect of α,β-MeATP at 100μmol/L on the AD mice was more obvious than that on the normal mice (P<0.05), and this inhibition was also antagonized by TTX (P<0.05 or P<0.01), pro-minent in AD group as compared with control group (P<0.05).In 10 Hz electrically evoked contraction of colonic smooth muscle strip,α,β-MeATP inhibited both the normal and AD mice (P<0.05 or P<0.01), while the inhibition was more obvious in the AD mice at the concentration of 40μmol/L or 100μmol/L (P<0.05 or P<0.01).CONCLUSION:AD patients and AD mice are accompanied by decreased MTL and CCK levels , and enhanced NO level , thus inducing colonic motor dysfunction along with AD .Meanwhile, ATP in plasma, purinergic neurons , and P2Y receptor expression are in-creased in the AD mice .Purinergic signaling mediated by ATP inhibits colonic smooth muscle strip contraction and further paralyzes the colonic movement function in AD .
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<p><b>OBJECTIVE</b>To compare the postoperative recovery among patients undergoing orthotopic bladder substitution with sigmoid or ileal grafts.</p><p><b>METHODS</b>The clinical data and postoperative recovery (postoperative complications, continence recovery time and postoperative hospital stay) of 84 patients receiving orthotopic bladder substitution with sigmoid or ileal grafts after radical cystectomy for bladder cancer were analyzed.</p><p><b>RESULTS</b>Of the 84 cases, 70 had continent urinary reservoirs constructed, among whom 58 (aged 48-89 years) received an ileal neobladder (IN) and 12 (aged 28-80 years) received a sigmoid neobladder (SN). The postoperative complications rate, continence recovery time and postoperative hospital stay in IN group was 29.3% (17/58), 91.4%, and 23.5 days, as compared to 58.3%(7/12) (P=0.04), 66.7% (P=0.03), and 25 days (P=0.04) in patients in SN group, respectively.</p><p><b>CONCLUSION</b>A neobladder constructed from ileal grafts achieves better postoperative recovery results compared to a neobladder constructed from sigmoid grafts.</p>