Assessment of platelet activation and phagocytic activity in gastric cancer patients

AIM: To assess the activation of platelets and their phagocytic activity in the course of gastric cancer. METHODS: Forty-three gastric cancer patients were recruited to the study. The patients were divided into 3 groups depending on tumor stage. Group E included 6 patients with early gastric cancer; group A included 18 patients with locally advanced cancer; and group M included 19 patients with metastatic cancer. The investigations were performed twice, prior to surgery and 12-14 d afterwards. RESULTS: The platelet count and the level of sP-selectin were found to increase with the disease progression. The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients. Irrespective of tumor stage, a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects. Despite increased platelet count and stimulation of thrombocytopoiesis, the phagocytic functions of blood platelets were markedly impaired. Tumor development seems to impair metabolic processes. CONCLUSION: A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.     

Age-dependent slowing of enteric axonal transport in insulin-resistant mice

AIM:To investigate retrograde tracer transport by gastric enteric neurons in insulin resistant mice with low or high glycosylated hemoglobin(Hb).METHODS:Under anesthesia,the retrograde tracer fluorogold was superficially injected into the fundus or antrum using a microsyringe in KK Cg-Ay/J mice prior to onset of type 2 diabetes mellitus(T2DM;4 wk of age),at onset of T2DM(8 wk of age),and after 8,16,or 24 wk of untreated T2DM and in age-matched KK/HIJ mice.Six days later,mice were sacrificed by CO 2 narcosis followed by pneumothorax.Stomachs were removed and fixed.Sections from fundus,corpus and antrum were excised and mounted on a glass slide.Tracer-labeled neurons were viewed using a microscope and manually counted.Data were expressed as the number of neurons in short and long descending and ascending pathways and in local fundus and antrum pathways,and the number of neurons in all regions labeled after injection of tracer into either the fundus or the antrum.RESULTS:By 8 wk of age,body weights of KKAy mice(n=12,34±1 g) were heavier than KK mice(n=17,29±1 g;F(4,120)=4.414,P=0.002] and glycosylated Hb was higher [KK:(n=7),4.97%±0.04%;KKAy:(n=6),6.57%±0.47%;F(1,26)=24.748,P<0.001].The number of tracer labeled enteric neurons was similar in KK and KKAy mice of all ages in the short descending pathway [F(1,57)=2.374,P=0.129],long descending pathway [F(1,57)=0.922,P=0.341],local fundus pathway [F(1,53)=2.464,P=0.122],local antrum pathway [F(1,57)=0.728,P=0.397],and short ascending pathway [F(1,53)=2.940,P=0.092].In the long ascending pathway,fewer tracer-labeled neurons were present in KKAy as compared to KK mice [KK:(n=34),302±17;KKAy:(n=29),230±15;F(1,53)=8.136,P=0.006].The number of tracer-labeled neurons was decreased in all mice by 16 wk as compared to 8 wk of age in the short descending pathway [8 wk:(n=15),305±26;16 wk:(n=13),210±30;F(4,57)=9.336,P<0.001],local antrum pathway [8 wk:(n=15),349±20;16 wk:(n=13),220±33;F(4,57)=8.920,P<0.001],short ascending pathway [8 wk:(n=14),392±15;16 wk:(n     

Antifibrotic effects of ambrisentan,an endothelin-A receptor antagonist,in a non-alcoholic steatohepatitis mouse model

AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model.METHODS: Fatty liver shionogi(FLS) FLS-ob/ob mice(male, 12 wk old) received ambrisentan(2.5 mg/kg orally per day; n = 8) or water as a control(n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver.RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group(18.0 μg/g ± 6.1 μg/g vs 33.9 μg/g ± 13.5 μg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group(0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1(TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related m RNA expression in the liver were not significantly different between the groups.CONCLUSION: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.     

Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C

BACKGROUND & AIMS: Interferon-induced depression is a major complication in antiviral therapy of chronic hepatitis C. Little is known about underlying mechanisms and reliable predictive factors associated with cytokine-induced depressive symptoms. METHODS: In a cohort of 139 hepatitis C-infected outpatients treated with interferon alfa-2b, we investigated the impact of functional gene variants of the cerebral serotonin (5-HT) signalling pathway previously implicated in depression risk. Depression was monitored using the Hospital Anxiety and Depression Scale (HADS). All patients were genotyped for functional variations in the 5-HT(1A) receptor (HTR1A), 5-HT transporter (SLC6A4, 5-HTT), and tryptophan hydoxylase-2 (TPH2). RESULTS: Homozygosity for the HTR1A-1019G variant significantly increased both incidence and severity of interferon-induced depression. Maximum increases in HADS depression scores during antiviral therapy correlated with HTR1A variation (P = .011). Clinically relevant depression was significantly associated with the HTR1A-1019G genotype (P = .017; OR, 2.95). 5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%). CONCLUSIONS: Our findings suggest an impact of allelic variation in 5-HT(1A) receptor expression on the development of interferon alfa-induced depression during antiviral treatment of chronic hepatitis C. Prediction models of interferon-induced depressive symptoms based on HTR1A variation offer a perspective for an antidepressant selective serotonin reuptake inhibitor prophylaxis in patients genetically at risk for interferon-induced depression.     

Increased duodenal expression of miR-146a and -155 in pediatric Crohn&rsquo;s disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs.     

胃癌患者血清肿瘤标志CA50和CEA的意义

目的比较胃恶性和良性病变血清人类结肠癌抗原 CA50和 CEA 的变化。方法用放射免疫法测定33例健康对照和86例胃部疾病(胃癌34例,胃溃疡27例和慢性萎缩性胃炎25例)患者血清 CA50和 CEA 含量,胃癌包括窦部27例,体部3例和底部9例,组织学类型包括腺癌21例,上皮癌4例和未分类9例;胃溃疡包括窦部18例,体部3例和底部9例;萎缩性胃炎均伴有肠上皮化生。结果与正常人比较,胃癌血清 CA50(112.67±38.36 kU/L vs 16.26±6.14 kU/L,P<0.01)和 CEA(10.28±3.76μg/L vs 3.12±1.03 μg/L,P<0.01)明显升高;CA50(>22 kU/L)阳性率在胃癌是53.0%(18/34),CEA(>5 μg/L)阳性率是55.8%(19/34);CA50和 CEA 升高呈正相关(r=0.648,P<0.01)。胃癌手术后(n=21),血清 CA50(46.4±25.9 kU/L,P<0.01)和 CEA(6.85±2.43μg/L,P<0.01)有明显下降。胃溃疡和萎缩性胃炎血清 CAS0(P<0.05)轻度升高,而 CEA 无明显变化(P>0.05)。结论血清 CAS0和 CEA 升高可作为诊断晚期胃癌的指标,胃癌手术后血清 CA50和 CEA 明显降低,提示联合测定血清CA50和 CEA 对晚期胃癌的诊治有一定临床意义。     

Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain

AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose amitriptyline(10 mg at bedtime)to a conventional dose of rabeprazole(20 mg/d)(group A,n = 20)vs a double-dose of rabeprazole(20 mg twice daily)(group B,n = 20)for patients with FCP whose symptoms were refractory to PPI.The primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom score.RESULTS:The between-group difference in global symptom scores was statistically significant during the last week of treatment(overall mean difference;3.75 ± 0.31 vs 4.35 ± 0.29,the between-group difference;P < 0.001).Furthermore,70.6% of patients in group A had their symptoms improve by > 50%,whereas only 26.3% of patients in group B had a similar treatment response(70.6% vs 26.3%,P = 0.008).Specifically,patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B(52.37 ± 17.00 vs 41.32 ± 12.34,P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84,P = 0.01,respectively).CONCLUSION:Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.     

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.     

Studies on surgical operations and prognosis of extrahepatic bile duct cancer

AIM: To perform a clinical evaluation of the surgical procedures of extrahepatic bile duct cancer and their influence on prognosis. METHODS: A total of 55 patients with pathologically and clinically verified extrahepatic bile duct cancer treated in our department between January 1984 and December 1993 were analyzed retrospectively. Clinical courses, with respect to the surgical procedures, investigated by follow-up and the survival period was assessed. RESULTS: Among the 55 patients, 24 received surgery that involved the upper third of extrahepatic biliary tract, 12 involving the middle third, and 19 involving the lower third. The diagnosis of bile duct cancer was confirmed histopathologically in 42 of the patients, with a clear predominance of adenocarcinoma (97.6%). Eleven (26.2%) of the patients received curative resection, 30 received palliative procedures (i.e. biliary-enteric bypass (n = 14) and external drainage (n = 16)), 6 received permanent percutaneous transhepatic cholangio-drainage (PTCD) alone, and 8 received exploratory laparotomy only or conservative treatment. Forty-eight patients (87.3%) were followed-up. The overall mean survival period was 10.8 ± 9.7 mo (¯x ± s); patients with curative resection had the longest survival period (21.4 ± 16.7 mo, P < 0.01) and highest survival rate (P < 0.05). A significant survival difference was observed for patients with biliary-enteric anastomosis as compared with those who had external drainage, etc. (P < 0.05), but there was no significant difference in survival period between patients who had preoperative PTCD (n = 23) and those who did not (n = 26) (P < 0.05). CONCLUSION: Curative resection is the treatment of choice for suitable patients with extrahepatic bile duct cancer; biliary-enteric anastomosis is preferable for those with unresectable tumor in order to improve prognosis and quality of life.     

Neurotensin receptor 1 overexpression in inflammatory bowel diseases and colitis-associated neoplasia

AIM: To explore the association of neurotensin receptor 1 (NTSR1) with inflammatory bowel diseases (IBD) and colitis-associated neoplasia. METHODS: NTSR1 was detected by immunohistochemistry in clinical samples of colonic mucosa with IBD colitis, colitis-associated raised low-grade dysplasia (LGD) including dysplasia-associated lesions or masses (DALMs, n = 18) and adenoma-like dysplastic polyps (ALDPs, n = 4), colitis-associated high-grade dysplasia (HGD, n = 11) and colitis-associated colorectal carcinoma (CACRC, n = 13), sporadic colorectal adenomatous polyp (SAP, n = 17), and sporadic colorectal carcinoma (SCRC, n = 12). The immunoreactivity of NTSR1 was semiquantitated (as negative, 1+, 2+, and 3+) and compared among different conditions.RESULTS: NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with significantly more cases showing > 2+ intensity (68.75% in LGD vs 32.26% in nondysplastic mucosa, P = 0.001). However, no significant difference existed between DALMs and ALDPs. CACRC and HGD showed a further stronger expression, with significantly more cases showing 3+ intensity than that in LGD (61.54% vs 12.50% for CACRC vs LGD, P = 0.022; 58.33% vs 12.50% for CACRC/HGD vs LGD, P = 0.015). No significant difference existed between colitis-associated and non-colitic sporadic neoplasia. CONCLUSION: NTSR1 in colonic epithelial cells is overexpressed in IBD, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma.     

Changes in patients&rsquo; symptoms and gastric emptying after Helicobacter pylori treatment

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.     

High-frequency electrical stimulation of cervical vagi reduces airway response to methacholine

AIM: To test whether high-frequency electrical stimulation (HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine (MCh). METHODS: Guinea pigs were pretreated with saline (Sal, n = 9) or ovalbumin (Ova, n = 10) aerosol for two weeks (5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance (R_L) and dynamic pulmonary compliance (C_dyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation (LES, monophasic, 50 Hz) and HES (monophasic and biphasic, 1 and 2.5 kHz) for about 10 s or 2 min on the responses of R_L and C_dyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the R_L responses to MCh was assessed. RESULTS: Before MCh challenge, LES, but not HES, significantly increased R_L by about 30% (P < 0.01) and decreased C_dyn by about 20% (P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated R_L and diminished C_dyn more in Ova- than Sal-treated animals (R_L: 313% ± 52% vs 113% ± 17%, P < 0.01; C_dyn: -56% ± 7% vs -21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased R_L and this decrease was greater in Ova- (about 45%) than Sal-treated animals (about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased C_dyn more in Ova- (about 20%) than Sal-treated animals (about 13%, P < 0.01). In addition, bivagotomy almost eliminated the R_L and C_dyn responses to MCh. CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.     

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

AIM:To identify factors that influence long-term liver function following radiofrequency ablation(RFA)in patients with viral hepatitis-related hepatocellular carcinoma.METHODS:A total of 123 patients with hepatitis B virus-or hepatitis C virus-related hepatocellular carcinoma(HCC)(n=12 and n=111,respectively)were enrolled.Cumulative rates of worsening Child-Pugh(CP)scores(defined as a 2-point increase)were examined.RESULTS:CP score worsening was confirmed in 22patients over a mean follow-up period of 43.8±26.3mo.Multivariate analysis identified CP class,platelet count,and aspartate aminotransferase levels as significant predictors of a worsening CP score(P=0.000,P=0.011 and P=0.024,respectively).In contrast,repeated RFA was not identified as a risk factor for liver function deterioration.CONCLUSION:Long-term liver function following RFA was dependent on liver functional reserve,the degreeof fibrosis present,and the activity of the hepatitis condition for this cohort.Therefore,in order to maintain liver function for an extended period following RFA,suppression of viral hepatitis activity is important even after the treatment of HCC.     

Association of arterial stiffness with coronary flow reserve in revascularized coronary artery disease patients

AIM: To investigate the association of arterial wave reflection with coronary flow reserve(CFR) in coronary artery disease(CAD) patients after successful revascularization.METHODS: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured(1) reactive hyperemia index(RHI) using fingertip peripheral arterial tonometry(RH-PAT Endo-PAT);(2) carotid to femoral pulse wave velocity(PWVc-Complior);(3) augmentation index(AIx), the diastolic area(DAI%) and diastolic reflection area(DRA) of the central aortic pulse wave(Arteriograph);(4) CFR using Doppler echocardiography; and(5) blood levels of lipoprotein-phospholipase A2(LpPLA2).RESULTS: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx(b =-0.38, r = 0.009), DAI(b = 0.36, P = 0.014), DRA(b = 0.39, P = 0.005) and RT(b =-0.29,P = 0.026). Additionally, patients with CFR 2.5 had higher PWVc(11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc(139.1 ± 17.8 vs 125.2 ± 19.1 mm Hg, P = 0.026), AIx(38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI(1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI(44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA(42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and Lp PLA2(268.1 ± 91.9 vs 199.5 ± 78.4 ng/m L, P = 0.002) compared with those with CFR ≥ 2.5. Elevated Lp PLA2 was related with reduced CFR(r =-0.33, P = 0.001), RHI(r =-0.37, P 0.001) and DRA(r =-0.35, P = 0.001) as well as increased PWVc(r = 0.34, P = 0.012) and AIx(r = 0.34, P = 0.001). CONCLUSION: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.     

Altered tryptophan hydroxylase 2 expression in enteric serotonergic nerves in Hirschsprung&rsquo;s-associated enterocolitis

AIM: To determine if expression of colonic tryptophan hydroxylase-2 (TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung’s-associated enterocolitis. METHODS: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung’s disease (HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung’s-associated enterocolitis (HAEC). Controls were collected at colostomy closure in children with anorectal malformation (n = 10). The distribution of expression of TPH2 was evaluated using immunofluorescence and confocal microscopy. Protein expression of TPH2 was quantified using western blot analysis in the deep smooth muscle layers. RESULTS: TPH2 was co-expressed in nitrergic and cholinergic ganglia in the myenteric and submucosal plexuses in ganglionic colon in HSCR and healthy controls. Co-expression was also seen in submucosal interstitial cells of Cajal and PDGFRα⁺ cells. The density of TPH2 immuno-positive fibers decreased incrementally from ganglionic bowel to transition zone bowel to aganglionic bowel in the myenteric plexus. Expression of TPH2 was reduced in ganglionic bowel in those affected by pre-operative HAEC compared to those without HAEC and healthy controls. However, expression of TPH2 was similar or high compared to controls in the colons of children who had undergone diverting colostomy for medically refractory HAEC. CONCLUSION: Altered TPH2 expression in colonic serotonergic nerves of patients with HSCR complicated by HAEC may contribute to intestinal secretory and motor disturbances, including recurrent HAEC.     

Differences in HER2 over-expression between proximal and distal gastric cancers in the Chinese population

AIM: To investigate HER2 expression and its correlation with clinicopathological variables between proximal and distal gastric cancers (GC) in the Chinese population. METHODS: Immunostaining of HER2 was performed and scored on a scale of 0-3 in 957 consecutive GC cases, according to the revised scoring criteria of HercepTest TM as used in the ToGA trial. Correlations between HER2 expression and clinicopathologic variables of proximal (n = 513) and distal (n = 444) GC were investigated. RESULTS: Our results showed that HER2 expression was significantly higher in the proximal than in distal GC (P < 0.05). Overall, HER2 expression was significantly higher in male patients (P < 0.01), the Lauren intestinal type (P < 0.001), low-grade (P < 0.001) and pM1 (P < 0.01) diseases, respectively. There was a significant difference in HER2 expression among some pTNM stages (P < 0.05). In contrast, HER2 expression in the distal GC was significantly higher in male patients (P < 0.001), low-grade histology (P < 0.001), the Lauren intestinal type(P < 0.001), and pM1 (P < 0.001). In the proximal GC, however, higher HER2 expression scores were observed only in tumors with low-grade histology (P < 0.001) and the Lauren intestinal type (P < 0.001). CONCLUSION: HER2 over-expression in GC of Chinese patients was significantly more common in proximal than in distal GC, and significantly correlated with the Lauren intestinal type and low-grade histology in both proximal and distal GC, and with pM1 disease and male gender in distal GC.     

Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.     

Elevated serum levels of human relaxin-2 in patients with esophageal squamous cell carcinoma

AIM: To assess the prognostic value of serum human relaxin 2 (H2 RLN) level in patients with esophageal squamous cell carcinoma (ESCC). METHODS: From October 1998 to September 2009, 146 patients with histopathologically confirmed ESCC were enrolled in this study. One hundred patients underwent en bloc esophagectomy, and 46 patients with unresectable tumors underwent palliative surgery. Five of the 146 patients died of surgical complications. Serum levels of H2 RLN were measured by enzyme linked immunosorbent assay. The relationship between serum H2 RLN level and each of the clinicopathological parameters was analyzed using the χ2 test. Patients were classified into two groups according to their H2 RLN level (< 0.462 ng/mL vs ≥ 0.462 ng/mL). When any analysis cell had fewer than five cases, the Fisher’s exact test was used. The statistical difference between groups A and B in each clinicopathological category was determined by the Student’s t test (two-tailed) or analysis of variance. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: ESCC patients tended to have significantly higher serum H2 RLN concentrations (0.48 ± 0.17 ng/ mL, n=141) compared with the healthy control group (0.342 ± 0.12 ng/mL, n=112). There was a significant difference between patients with lymph node involvement (0.74 ± 0.15 ng/mL, n=90), distant metastasis (0.90 ± 0.19 ng/mL, n=32) and those without lymph node involvement (0.45 ± 0.12 ng/mL, n=51), and distant metastasis (0.43 ± 0.14 ng/mL, n=109), respectively (P < 0.01). Patients with high H2 RLN levels (≥ 0.462 ng/mL) had a poorer prognosis than patients with low serum H2 RLN levels (< 0.462 ng/mL; P=0.0056). The H2 RLN level was also correlated with survival and