Primary sclerosing cholangitis associated colitis: Characterization of clinical,histologic features,and their associations with liver transplantation

BACKGROUND Primary sclerosing cholangitis(PSC) associated inflammatory bowel disease(IBD) is a unique form of IBD(PSC-IBD) with distinct clinical and histologic features from ulcerative colitis(UC) and Crohn disease(CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n = 28), CD(n = 10), PSC and UC(PSC-UC; n = 26); PSC and CD(PSC-CD; n = 6); and PSC and no IBD(PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation(OLT) were noted.RESULTSPSC-UC patients had more isolated right-sided disease(P = 0.03), and less active inflammation in left colon, rectum(P = 0.03 and P = 0.0006), and overall(P = 0.0005) compared to UC. They required less steroids(P = 0.01) and fewer colectomies(P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC(P = 0.1). PSC-IBD(PSC-UC and PSCCD) patients with OLT had severe disease in the left colon and rectum(P = 0.04).CONCLUSION PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.     

Difference in DRB1~* gene polymorphisms between Han and Uyghur ulcerative colitis patients in China

AIM:To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS:In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People’s Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic varia-tion and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. RESULTS:There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03 , *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13 , both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequenci     

大肠肿瘤的基因表达及与细胞凋亡的抑制关系

目的探讨 bcl-2和 P53蛋白在大肠肿瘤中的表达及与细胞凋亡关系。方法用免疫组化方法观察了45例大肠腺瘤和61例大肠癌中 bcl-2和 P53蛋白的表达。结果正常大肠粘膜中 bcl-2和 p53均未见表达,而大肠腺瘤及大肠癌阳性率均较正常明显增加(P<0.01)。大肠腺瘤 p53表达随腺瘤大小增加而增加,其中≥20 mm 组阳性率(77.8%)显著高于<10 mm 组(35.0%,P<0.05)。P53蛋白阳性率也随不典型增生程度增加而增高。p53表达与大肠癌分化程度及 Duke 分期有关。大肠癌细胞凋亡指数与 bcl-2阳性表达呈负相关。大肠腺瘤中 bcl-2和 P53蛋白的表达也呈负相关。结论 bcl-2蛋白表达对大肠癌前病变.腺瘤的增殖有一定意义,p53在大肠腺瘤癌变和大肠癌进展中起重要作用,它们是参与细胞凋亡的良好指标。     

The clinical course of ulcerative colitis after orthotopic liver transplantation for primary sclerosing cholangitis: further appraisal of immunosuppression post transplantation

BACKGROUND AND AIMS: The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear. We documented the nationwide experience of the course of UC, before and after OLT for PSC. METHODS AND RESULTS: A total of 470 liver transplants were performed for 413 patients between 1992 and 2003, in the Scottish Liver Transplantation Unit, UK. Twenty-six patients had co-existing UC/PSC. Of these, data from 20 patients were studied over a median period of 11.9 years before OLT and 4.4 years after OLT; of the others, four patients required colectomy prior to OLT, one died within 7 days of transplant, and one developed UC after transplant. A significantly higher relapse rate (number of relapses/year of follow-up) was seen after OLT (median 1.0 versus 0.3; interquartile range, 0.10-1.42 and 0.01-0.40, respectively; P = 0.007). The corticosteroids requirement (number of courses/year of follow-up) after OLT was also significantly higher (0.40 versus 0.10; interquartile range, 0.51-1.13 and 0.05-0.12, respectively; P = 0.003). Twenty per cent of patients (4/20) became corticosteroid dependent after OLT. Thirty-five per cent of patients (7/20) underwent colectomy after OLT: three for severe disease and four for neoplasia/dysplasia. Five patients (19%) developed neoplasia following OLT. CONCLUSION: Despite immunosuppression, UC follows a more aggressive clinical course after OLT and is associated with a high rate of neoplasia.     

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.     

Evaluation of the IL-2/IL-2R system in patients with liver cirrhosis or carcinoma

AIM: To evaluate the interleukin-2/interleukin-2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis or carcinoma, and compare the immune function in those patients. The clinical significance of our results is also discussed. METHODS: Fifty patients with liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC), and 30 normal control subjects were studied. Cellular expression of the interleukin-2 receptor (mIL-2R) was examined by immunofluorescence, and the serum levels of IL-2 and soluble interleukin-2 receptor (sIL-2R) were measured by ELISA. RESULTS: The levels of IL-2 and mIL-2R expression in carcinoma patients were significantly lower than those in both patients with cirrhosis (P < 0.01) and control subjects (P < 0.01). The serum levels of IL-2 and the expression of mIL-2R in patients with cirrhosis were also lower than those in normal control subjects (P < 0.05). The serum levels of sIL-2R in carcinoma patients were significantly higher than those in both cirrhosis patients (P < 0.05) and control subjects (P < 0.01), and the sIL-2R levels in cirrhosis patients were higher than those in control subjects (P < 0.05). CONCLUSION: Patients with liver cirrhosis or carcinoma both have decreased immune function; however, this decrease is more pronounced in carcinoma patients. Such similarities in immune disturbances may be an important factor affecting the development of carcinoma in a cirrhotic liver.     

Increased expression of tyrosine phosphatase SHP-2 in Helicobacter pylori-infected gastric cancer

AIM:To explore the alteration of tyrosine phosphatase SHP-2 protein expression in gastric cancer and to assess its prognostic values.METHODS:Three hundred and five consecutive cases of gastric cancer were enrolled into this study.SHP-2 expression was carried out in 305 gastric cancer specimens,of which 83 were paired adjacent normal gastric mucus samples,using a tissue microarray immunohistochemical method.Correlations were analyzed between expression levels of SHP-2 protein and tumor parameters or clinical outcomes.Serum anti-Helicobacter pylori(H.pylori) immunoglobulin G was detected with enzyme-linked immunosorbent assay.Cox proportional hazards model was used to evaluate prognostic values by compassion of the expression levels of SHP-2 and disease-specific survivals in patients.RESULTS:SHP-2 staining was found diffuse mainly in the cytoplasm and the weak staining was also observed in the nucleus in gastric mucosa cells.Thirty-two point five percent of normal epithelial specimen and 62.6% of gastric cancer specimen were identified to stain with SHP-2 antibody positively(P < 0.001).Though SHP-2 staining intensities were stronger in the H.pylori(+) group than in the H.pylori(-) group,no statistically significant difference was found in the expression levels of SHP-2 between H.pylori(+) and H.pylori(-) gastric cancer(P = 0.40).The SHP-2 expression in gastric cancer was not significantly associated with cancer stages,lymph node metastases,and distant metastasis of the tumors(P = 0.34,P = 0.17,P = 0.52).Multivariate analysis demonstrated no correlation between SHP-2 expression and disease-free survival(P = 0.86).CONCLUSION:Increased expression of SHP-2 protein in gastric cancer specimen suggesting the aberrant upregulation of SHP-2 protein might play an important role in the gastric carcinogenesis.     

Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.     

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer

AIM:To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohisto-chemical staining of proliferating cell nuclear antigen (PCNA)and p53 in the detection of gastric precancerous lesions. METHODS:Ninety-five patients who were treated for abdominal discomfort,abdominal pain,bloating,and acid reflux at our hospital from January 2010 to December 2011 were included in the study.An ordinary gastroscopic procedure was initially performed to select the lesions.All subjects underwent magnifying chromo-endoscopy to observe morphological changes of gastric pits.Biopsies were then taken from each area of interest and sent for pathological examination and detection of PCNA and p53 expression by immunohistochemistry. An immunoreactivity score for each lesion was calcu-lated.Based on immunoreactivity scores,immunohisto-chemical staining was then considered. RESULTS:Compared to intestinal metaplasia,gastric pits were more diverse in size,more irregular in shape, and more disorderly in arrangement in moderate and severe dysplasia.PCNA and p53 expression was sig-nificantly higher in precancerous lesions(intestinal metaplasia and dysplasia)than in chronic gastritis. PCNA expression showed an upward trend in types A-F pits.The number of cases that showed strong PCNA positivity increased significantly with an increase in the severity of lesions.Rank sum test for independent samples showed that p53 expression was significantly higher in types E and F pits than in types A-D pits(H =33.068,P=0.000).Rank sum test for independent samples showed that PCNA expression was significantly higher in types E and F pits than in types A-D pits(H =31.791,P=0.001). CONCLUSION:The presence of types E and F pits,in which p53 and PCNA are highly expressed,is highly sug- gestive of the occurrence of early cancer,and patients developing these changes should be closely followed.     

Urotensin Ⅱ-induced insulin resistance is mediated by NADPH oxidase-derived reactive oxygen species in Hep G2 cells

AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UII for 24 h, in the presence or absence of 100 nmol/L insulin for the last 30 min. Glucose levels were detected by the glucoseoxidase method and glycogen synthesis was analyzed by glycogen colorimetric/fluorometric assay. Reactive oxygen species(ROS) levels were detected with a multimode reader using a 2′,7′-dichlorofluorescein diacetate probe. The protein expression and phosphorylation levels of c-Jun N-terminal kinase(JNK), insulin signal essential molecules such as insulin receptor substrate-1(IRS-1), protein kinase B(Akt), glycogen synthase kinase-3β(GSK-3β), and glucose transporter-2(Glut 2), and NADPH oxidase subunits such as gp91 phox, p67 phox, p47 phox, p40 phox, and p22 phox were evaluated by Western blot.RESULTS: Exposure to 100 nmol/L UII reduced the insulin-induced glucose consumption(P 0.05)and glycogen content(P 0.01) in Hep G2 cells compared with cells without UII. UII also abolished insulin-stimulated protein expression(P 0.01) and phosphorylation of IRS-1(P 0.05), associated with down-regulation of Akt(P 0.05) and GSK-3β(P 0.05) phosphorylation levels, and the expression of Glut 2(P 0.001), indicating an insulin-resistance state in Hep G2 cells. Furthermore, UII enhanced the phosphorylation of JNK(P 0.05), while the activity of JNK, insulin signaling, such as total protein of IRS-1(P 0.001), phosphorylation of IRS-1(P 0.001) and GSK-3β(P 0.05), and glycogen synthesis(P 0.001) could be reversed by pretreatment with the JNK inhibitor SP600125. Besides, UII markedly improved ROS generation(P 0.05) and NADPH oxidase subunit expression(P 0.05). However, the antioxidant/NADPH oxidase inhibitor apocynin could decrease UII-induced ROS production(P 0.05), JNK phosphorylation(P 0.05), and insulin resistance(P 0.05) in HepG 2 cells. CONCLUSION: UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG 2 cells.     

Proliferating cell nuclear antigen and P53 protein expression and prognosis in primary liver cancer

AIM: To study the individual difference and prognosis of primary liver cancer (PLC) after hepatectomy. METHODS: Two hundred specimens obtained from PLC patients were examined immunohistochemically using anti-P53 and anti-PCNA monoclonal antibodies. The mutations of p53 in exons 5-8 of the gene were examined using the polymerase chain reaction/single-stranded conformational polymorphism (PCR/SSCP) method in 60 of the 200 specimens. RESULTS: The results showed that the labeling index of proliferating cell nuclear antigen (PCNA) and expression of p53 had a parallel correlation (P < 0.001). The high labeling index of PCNA or overexpression of p53 was associated with a high risk of tumor recurrence, more aggressive growth and poor survival. CONCLUSION: Immunohistochemical assessment of PCNA and P53 can provide very useful information for the prognosis of PLC.     

miR-20a-5p调控结核分枝杆菌诱导巨噬细胞凋亡相关基因表达的研究

目的 明确小非编码RNA(microRNA,miR-20a-5p)对结核分枝杆菌(MTB)诱导人巨噬细胞凋亡相关基因表达的调控作用。方法 构建可表达或抑制miR-20a-5p、转染miR-20a-5p抑制剂(miR-20a-5p-inhibitor,简称“miR-20a-5p-inh”)、作为慢病毒载体的阴性对照(LV1-NC)的慢病毒载体,由oligo-dT引物通过固相亚磷酰胺法合成茎环寡核苷酸,并克隆到含绿色荧光蛋白(GFP)的慢病毒载体pGLV3-GFP内,将构建的miR-20a-5p、miR-20a-5p-inh、LV1-NC转染THP-1人巨噬细胞3h,培养72h后用流式细胞仪分选出GFP+THP-1细胞,并分别采用减毒MTB菌株(H37Ra)感染8h和过氧化氢(H₂O₂)处理30min 两种方法诱导。通过实时定量PCR技术测定细胞中线粒体相关抗凋亡基因Bcl-2,以及促凋亡基因Bax、Bim和Bad的转录水平。同时,用蛋白免疫印迹法检测细胞裂解物中相关蛋白的表达。结果 慢病毒转染细胞后,在无刺激的THP-1细胞中miR-20a-5p的相对荧光强度值为12.21±1.29、miR-20a-5p-inh为9.68±1.38、LV1-NC为10.64±0.96,三者的表达差异均无统计学意义(q=1.815,P=0.385;q=2.072,P=0.602);但在H37Ra和H₂O₂的刺激后,miR-20a-5p过表达时其相对荧光强度值分别为7.20±0.53、8.55±0.82,明显高于LV1-NC (4.46±0.07、5.49±0.44)(q=50.250,P=0.007;q=1.041,P<0.01),miR-20a-5p受抑制时(1.88±0.08、1.44±0.21)明显低于LV1-NC(q=3.457,P=0.031;q=4.384,P=0.001)。在感染miR-20a-5p慢病毒的THP-1细胞中,H37Ra诱导Bcl-2的表达增加(相对荧光强度值由10.67±0.89增至14.98±0.88)(q=1.064,P=0.008),而感染miR-20a-5p-inh慢病毒时Bcl-2表达减少(由10.67±0.89降至6.49±0.47)(q=3.518,P=0.003);在miR-20a-5p过表达的THP-1细胞中Bim的转录水平减少(由1.22±0.05降至0.98±0.04)(q=1.240,P=0.011),当miR-20a-5p受抑制时Bim的转录水平增加(由1.22±0.05增至1.51±0.08)(q=2.460,P=0.021)。蛋白印迹法检测凋亡相关基因Bcl-2和Bim的蛋白表达水平,结果与基因转录水平相符。 结论 miR-20a-5p的表达水平影响MTB诱导的巨噬细胞凋亡相关基因Bcl-2和Bim的表达,并且与促凋亡基因Bim的水平呈负相关,提示miR-20a-5p可能通过调控Bim的表达而影响细胞凋亡。     

Increased expression of DLX2 correlates with advanced stage of gastric adenocarcinoma

AIM:To investigate the expression of distal-less homeobox 2 (DLX2) in gastric adenocarcinoma and its clinicopathological significance. METHODS:Gastric adenocarcinoma tissues were obtained from gastrectomy specimens of 129 patients from the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University. Sixty cases of normal gastric tissues were collected from gastrectomy specimens of adjacent gastric cancer margins greater than 5 cm. Patient diagnosis was established pathologically, and no patient had received chemotherapy or radiotherapy before surgery. All tissue specimens were formalin-fixed and paraffin-embedded. Immunohistochemistry was carried out to investigate the expression of DLX2 in 129 gastric adenocarcinoma tissues and 60 adjacent normal tissues. The immunos-taining reaction was semiquantitatively evaluated based on the proportion of positive cells and the median staining intensity in normal gastric epithelial cells or tumor cells. All patients had follow-up records for more than 5 years. Correlations of DLX2 expression with clinicopathological features and prognosis of patients with gastric adenocarcinoma were analyzed. All statistical analyses were performed using the SPSS 17.0 software. RESULTS:The positive expression of DLX2 was detected in 68 (52.7%) cases of 129 gastric adenocarcinoma tissues and 14 (23.3%) cases of 60 adjacent normal tissues. The difference in DLX2 expression between gastric adenocarcinoma tissues and adjacent normal tissues was statistically significant (Ⅹ2 = 14.391, P < 0.001). Moreover, high expression of DLX2 was detected in 48 (37.2%) cases of 129 human gastric cancer tissues, but not in adjacent normal tissues. The expression of DLX2 correlated with the size of tumor (P = 0.001), depth of invasion (P = 0.008), lymph node metastasis (P = 0.023) and tumor-node-metastasis stages (P = 0.020), but was not correlated with age, gender, histological differentiation and distant metastasis. The Kaplan-Meier survival analysis revealed that s     

Human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases

AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D’Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.     

Cyclooxygenase (COX)-2 immunoreactivity and relationship to p53 and Ki-67 expression in colorectal cancer

The tumor-suppressive effects of nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to be due to a reduction in cyclooxygenase (COX)-2 activity, although the effects of COX-2 in the colonic mucosa and in colorectal cancer have not been determined. Ki-67 immunoreactivity in cancers is also attracting attention, as Ki-67 reflects cell proliferation, while p53 immunoreactivity is also of interest, as it reflects the malignancy of colorectal lesions. Accordingly, to determine these correlation, we investigated the distribution and intensity of COX-2, p53 and Ki-67 expression in both cancerous and non-cancerous tissues from patients with sporadic and ulcerative colitis (UC)-associated colorectal cancer. We selected 21 colorectal cancer specimens, obtained by surgical resection or colonoscopic biopsy, from 21 patients, including 3 with UC (13 men and 8 women; aged 42–78 years). Histological examination of hematoxylin and eosin-stained specimens revealed that 9 were well differentiated; 11, moderately differentiated; and 1 was a poorly differentiated adenocarcinoma. We used anti-COX-2, p53, and Ki-67 antisera to perform immunohistochemical staining by the labelled streptavidin biotin method and then assessed and graded the staining intensity and distribution. COX-2 staining was more intense in cancer tissue than in non-cancerous areas. Colorectal cancers associated with UC were not stained intensely. COX-2, p53, and Ki-67 positivity rates in were 38.1%, 38.1%, and 47.6%, respectively. There were no relationships among the distributions or intensities of COX-2, p53, and Ki-67 expression. Our results indicate that colorectal cancer tissues overexpress COX-2, but that there are no relationships between COX-2, p53, and Ki-67 expression, suggesting that COX-2 expression may not be related to cell proliferation or to the grade of malignancy. However, it is necessary to determine whether COX-2 in cancer tissue is involved in carcinogenesis or whether it is simply a product of cancer. (Received: July 7, 1998; accepted: Oct. 23, 1998)     

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.     

不同类型肺结核患者外周血维生素D与抗菌肽LL-37表达水平的研究

目的 评价不同类型活动性肺结核患者血清维生素D及抗菌肽LL-37表达水平的差异。 方法 搜集2017年6—12月成都市公共卫生临床医疗中心住院的178例活动性肺结核患者(包括81例单纯肺结核患者、57例肺结核并发肺外结核患者和40例结核病并发糖尿病患者,分别作为B组、C组和D组;根据病情严重程度划分,分为重症肺结核患者79例和轻症肺结核患者99例)及同期在我院进行健康体检的100名医务人员(A组)作为研究对象。采用酶联免疫吸附试验(ELISA)测定纳入人群维生素D[以25-羟基维生素D3(25-(OH)D₃)水平衡量]及LL-37的水平,分析不同类型肺结核患者与健康对照者25-(OH)D₃和LL-37水平的差异,以及肺结核严重程度与25-(OH)D₃和LL-37水平的关系。 结果 B组、C组和D组患者外周血25-(OH)D₃水平分别为(31.58±11.89)nmol/L、(25.68±13.57)nmol/L和(26.39±10.01)nmol/L,均明显低于A组的(40.57±14.32)nmol/L,差异均有统计学意义(t=4.61,P=0.000;t=6.48,P=0.000;t=5.72,P=0.000);LL-37水平分别为(26.97±10.29)μg/L、(30.75±10.16)μg/L和(31.84±11.36)μg/L,均明显高于A组的(24.38±4.57)μg/L,差异均有统计学意义(t=2.26,P=0.025;t=4.48,P=0.000;t=4.03,P=0.000)。与B组患者相比,C组和D组25-(OH)D₃水平均明显降低,LL-37水平均明显升高,差异均有统计学意义(t=2.64,P=0.008;t=2.52,P=0.011和t=2.14,P=0.032;t=2.29,P=0.022)。79例重症肺结核患者的25-(OH)D₃和LL-37水平分别为(24.59±12.36)nmol/L和(31.97±11.43)μg/L,明显低于轻症肺结核患者(99例)的25-(OH)D₃水平[(33.79±15.47)nmol/L],但高于轻症肺结核患者的LL-37水平[(27.32±10.69)μg/L],差异均有统计学意义(t=4.41,P=0.000;t=2.77,P=0.006)。 结论 活动性肺结核患者血清中维生素D水平明显低于健康人群,LL-37水平明显高于健康人群,且不同类型活动性肺结核患者血维生素D及LL-37表达水平存在差异。     

溃疡穿孔型Ⅵ型支气管结核患者经支气管镜氩气刀联合冷冻及异烟肼灌注治疗的疗效评价

目的 评估经支气管镜氩气刀联合冷冻及异烟肼灌注治疗溃疡穿孔型Ⅵ型支气管结核(endobronchial tuberculosis,EBTB)患者的临床效果。方法 搜集2013年1月至2018年8月湖南省胸科医院收治的符合纳入标准的65例溃疡穿孔型Ⅵ型EBTB患者的临床资料,将2017年1月之前收治的31例接受经支气管镜冷冻+异烟肼灌注治疗的患者作为对照组,将2017年1月至2018年8月前收治的34例接受经支气管镜氩气刀+冷冻+异烟肼灌注治疗的患者作为观察组。观察并分析两组患者瘘口愈合时间、治疗效果及并发症情况。采用SPSS 19.0软件进行数据的统计学分析,计量资料采用t检验或秩和检验,计数资料采用χ ²检验,均以P<0.05为差异有统计学意义。结果 对照组和观察组患者分别进行经支气管镜介入治疗241例次和222例次,例均治疗次数分别为(7.81±2.20)次/例和(6.53±2.05)次/例,差异有统计学意义(t=2.425,P=0.018)。对照组行冷冻+异烟肼灌注治疗次数(3.45±0.91)次/例,高于观察组行氩气刀+冷冻+异烟肼灌注治疗(2.59±0.82)次/例(t=3.987,P<0.001)。对照组瘘口愈合中位时间[12.0(10.0, 12.0) 周]长于观察组[10.0(8.0,12.0)周](Z=-2.001,P=0.045)。对照组和观察组患者治疗后痊愈和有效者分别为29例和33例、2例和1例,治疗有效率均为100.00%(χ ²=0.000,P=1.000)。两组患者在治疗过程中均未出现与治疗相关的支气管-纵隔瘘、大出血或氩气刀相关气体栓塞等严重并发症。结论 对溃疡穿孔型Ⅵ型EBTB行经支气管镜氩气刀联合冷冻及异烟肼灌注治疗,可减少治疗次数、缩短瘘口愈合时间,安全有效,值得推广。     

Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant.RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ 2 = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ2 = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05).CONCLUSION: Galectin-1 expr