Association of Fas/Apol gene promoter （-670 A/G） polymorphism in Tunisian patients with IBD

AIM： To detect a possible association between the polymorphism of the （-670 A/G） Fas/Apol gene promoter and susceptibility to Crohn＇s disease （CD） and ulcerative colitis （UC） in the Tunisian population. METHODS： The （-670 A/G） Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS： Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of （-670 A/G） Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls （P corrected = 0.004 ＂in CD patients＂ and P corrected = 0.02 ＂in UC patients＂, respectively）. Analysis also showed a statistically significant association between genotype AA of the （-670 A/G） polymorphism and the ileum localization of the lesions （P corrected = 0.048） and between genotype GG and the colon localization （P corrected = 0.009）. The analysis of IBD patients according to clinical behavior revealed no difference. CONCLUSION： Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.     

Clinical significance of serum procalcitonin in patients with ulcerative colitis

AIM:To investigate the association of procalcitonin(PCT)with ulcerative colitis(UC)activity.METHODS:Serum PCT levels,C-reactive protein(CRP)levels,the erythrocyte sedimentation rate,and the white blood cell count were analyzed in 18 patients with UC and 11 healthy volunteers.Serum PCT levels were analyzed by an electrochemiluminescence immunoassay.Severity assessments were based on Truelove and Witts’severity index.Correlation of serum PCT and CRP levels with UC activity was examined.Moreover,we assessed serum PCT and CRP levels in patients with a Mayo endoscopic subscore.RESULTS:Serum PCT levels in severe UC patients(n=7)(0.096±0.034 ng/mL)were significantly higher than in mild-to-moderate UC patients(n=11)(0.033±0.012 ng/mL)and healthy volunteers(n=11)(0.035±0.005 ng/mL)(P=0.0005 and P<0.0001,respectively).In addition,there was no difference in serum PCT levels between mild-to-moderate UC patients and healthy volunteers.Interestingly,patients with a Mayo endoscopic subscore of 3 points displayed significantly increased levels of serum PCT(0.075±0.043 ng/mL)compared with patients with a subscore of 2 points(0.03±0.011 ng/mL)(P=0.0302).Moreover,CRP levels in patients with severe UC or a Mayo endoscopic subscore of 3 points were not significantly higher than in patients with mild-to-moderate UC or a Mayo endoscopic subscore of 3 points.CONCLUSION:Serum PCT levels were significantly correlated with UC activity.     

Increased serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in patients with biopsy-proven nonalcoholic fatty liver disease

AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease(NAFLD) patients.METHODS: Fifty-three consecutive,biopsy-proven NAFLD patients(31 males and 22 females,mean age 42.5 ± 9.6 years) and 26 age- and gender-matched,healthy controls(14 males and 12 females,mean age 39 ± 10.7 years) were included.The patientswith NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy.The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses.The histological evaluation was conducted according t o t he N AF LD ac t ivi ty scoring syst em recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.The serum LOX-1 levels were measured using an ELISA kit(Life Science Inc.USCN.Wuhan,Catalog No.E1859Hu) in both patients and healthy controls.A receiver operating characteristic(ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis(NASH) and healthy controls.A P-value 0.05 was considered statistically significant.RESULTS: NAFLD and healthy control groups were similar in terms of age and sex.NAFLD patients consisted of 8 patients with simple steatosis(15%),27 with borderline NASH(51%) and 18 with definitive NASH(34%).Metabolic syndrome was found in 62.2% of the patients with NAFLD.The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/m L compared to 4.08 ± 4.32 ng/m L in healthy controls(P = 0.001).The LOX-1 levels were significantly different between controls,simple steatosis and NASH(borderline+definite) cases(4.08 ± 4.32 ng/m L,6.1 ± 6.16 ng/m L,8.92 ± 6.45 ng/m L,respectively,P = 0.004).When the cut-off value for the serum LOX-1 level was set at 5.35 ng/m L,and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%,respectively.CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls.Additionally,the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.     

溃疡性结肠炎中血浆同型半胱氨酸和褪黑素水平的关联研究

目的 探讨血浆同型半胱氨酸(HCY)和褪黑素(MLT)水平改变与溃疡性结肠炎(UC)的临床关联.方法 收集112例UC患者临床资料,以110名健康体检者为对照.采用高效液相荧光检测法(HPLC-FD)检测血浆HCY、MLT水平,酶联免疫吸附分析(ELISA)法检测血浆叶酸(FA)、维生素B12水平,并分析该四项指标与UC患者临床特征的相关性.结果 UC患者血浆HCY水平高于健康对照[(11.27±7.26)μmol/L比(8.19±4.81)μmol/L,P=0.000],血浆MLT水平低于健康对照[(49.06±31.40)pg/ml比(64.28±41.16)pg/ml,P=0.008],血浆FA水平低于健康对照[(7.64±1.95)nmol/L比(9.14±1.23)nmol/L,P=0.005]、血浆维生素B12水平低于健康对照[(108.64±32.22)pmol/L比(112.64±33.33)pmol/L,P=0.004].UC患者血浆HCY、MLT水平与UC病情分度、病变范围、病程、红细胞沉降率(ESR)、C反应蛋白(CRP)水平无关.UC患者血浆HCY与MLT水平间无明显相关性.结论 UC患者血浆HCY水平高于健康对照,MLT水平低于健康对照,但二者间无明显相关性.

Abstract：

Objective To explore the clinical correlation of the variation of plasma homocysteine (HCY), melatonin (MLT) and ulceative colitis (UC). Methods The clinical data of 112 UC patients was collected, and 110 normal healthy persons as control. The level of plasma HCY and MLT was detected by high pressure liquid chromatography-fluorescence detection (HPLC-FD) method. The level of plasma folate ( FA) and vitamin B12 was detected by enzyme-linked immunosorbent assay (ELISA) method. The correlation of these four indexes and UC was analyzed. Results The serum level of HCY in UC patients was significantly higher than that in normal healthy persons [(11. 27± 7.26) μmol/L vs (8. 19±4. 81) μmol/L, P = 0. 000]. The serum level of MLT in UC patients was significantly lower than that in normal healthy persons [(49. 06 + 31. 40) pg/ml vs (64. 28±41. 16) pg/ml,P=0. 008]. The serum level of FA in UC patients was significantly lower than that in normal healthy persons [(7. 64 + 1.95) nmol/L vs (9. 14 + 1.23) nmol/L, P = 0. 005]. The serum level of vitamin B12 in UC patients was significantly lower than that in normal healthy persons [(108. 64 ±32. 22) pmol/L vs (112. 64±33. 33) pmol/L, P = 0. 004]. There was no correlation between plasma HCY, MLT and UC disease activity degree, range, disease duration, erythrocyte sedimentation rate (ESR), or C reactive protein (CRP) in UC patients. There was no significant correlation between MLT and HCY in UC patients. Conclusions The serum level of HCY is higher in UC patients than that in normal control, and MLT is lower than that in normal control. However there is no significant correlation between them.     

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.     

Abnormal immunity and gene mutation in patients with severe hepatitis-B

AIM: To evaluate the abnormal immunity and gene mutation at precore 1896 site in patients with severe hepatitis-B.METHODS: This study included 23 patients with severe hepatitis-B, 22 patients with acute hepatitis-B and 20 controls.Mutation at precore 1896 site of HBV gene was confirmed with restriction fragment length polymorphism (RFLP) analysis.Cytokines including TNF-α, IFN-y, IL-6, and IL-8 were measured with ELISA, and T subgroups were detected with alkaline phosphatase anti alkaline phosphatase (APAAP) technique.RESULTS: In patients with severe hepatitis-B, the infective rate of HBV mutant strain was 52.5% (12/23), and only one patient with acute hepatitis-B was infected with the mutant strain. The percentage of CD8+ T lymphocyte was obviously lower (0.16±0.02%) and the ratio of CD4+/CD8+ was obviously higher (2.35±0.89) in mutant group than in wildtype group (0.28±0.05% and 1.31±0.18%, respectively,P＜0.01 or P＜0.05). The levels of cytokines in patients with severe hepatitis-B were higher (TNF-α 359.0±17.2 ng/L, IFNγ 234.7±16.5 ng/L, IL-6 347.5±31.3 ng/L, IL-8 181.1±19.6ng/L) than those in acute hepatitis-B (TNF-α 220.6±8.9ng/L, IFN-γ 174.9±12.0 ng/L, IL-6 285.8±16.5 ng/L, IL-8118.4±5.1 ng/L, P＜0.01 or 0.05). In patients with severe hepatitis-B, the levels of IFN-γ and IL-6 were higher in mutant group (273.4±26.6 ng/L, 387.7±32.5 ng/L) than in wild-type group (207.8±12.8 ng/L, 300.9±16.3 ng/L). The mortality of patients infected with HBV mutant strain was higher (100%)than that with wild-type (0.9%).CONCLUSION: In severe hepatitis-B, the infective rate of HBV mutant strain was high. The mutant strain induces more severe immune disorders in host, resulting in the activation of lymphocyte and release of cytokines. HBV DNA mutates easily in response to the altered immunity. Ultimately liver damage is more prominent.     

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (DC). METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 DC patients and 50 healthy controls. Clinical data regarding DC were gathered. RESULTS: Median serum Hcys levels in DC patients were similar to those in controls (12.26 umol/L vs 12.32 μmol/ L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028).UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125; 95%CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2=0.4;P<0.001). CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.     

Serum amyloid A levels in patients with liver diseases

BACKGROUND Serum amyloid A(SAA) is an acute phase protein mainly synthesized by the liver. SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells, the major scar forming cells in the liver. However,few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases.AIM To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B(CHB) patients.METHODS Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study. The patients included 205 with CHB, 22 with active autoimmune liver disease(AILD), 21 with nonalcoholic steatohepatitis(NASH), 14 with drug-induced liver injury(DILI), and 16 with pyogenic liver abscess. Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level. Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls. Bonferroni test was applied for post hoccomparisons to control the probability of type 1 error(alpha = 0.05/6 = 0.008).For statistical tests of other variables, P 0.05 was considered statistically significant. Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis.RESULTS All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients, with the highest SAA level found in patients with pyogenic liver abscess(398.4 ± 246.8 mg/L). Patients with active AILD(19.73 ± 24.81 mg/L) or DILI(8.036 ± 5.685 mg/L) showed higher SAA levels than those with active CHB(6.621 ± 6.776 mg/L) and NASH(6.624 ± 4.891 mg/L). Single(P 0.001) and multivariate logistic regression analyses(P = 0.039)for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L. Serum levels of SAA and CRP(C-reactive protein) were positively correlated in patients with CHB(P 0.001),pyogenic liver abscess(P = 0.045), and active AILD(P = 0.02). Serum levels of SAA(0.80-871.0 mg/L) had a broader fluctuation range than CRP(0.30-271.3 mg/L).CONCLUSION Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess. It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.     

Serum concentrations of insulin-like growth factor-binding protein 5 in Crohn’s disease

AIM:To investigate serum insulin-like growth factorbinding protein 5(IGFBP-5)levels and intestinal IGFBP-5expression in patients with Crohn’s disease(CD).METHODS:We analyzed the serum concentrations and intestinal expression of IGFBP-5 in 42 patients with CD,of whom 26 had endoscopically or radiologically proven stricture formation.Nine of the 42 patients had active disease,with a Crohn’s disease activity index>150.Serum IGFBP-5 levels were analyzed in 20 healthy controls matched by sex and age to the CD patients.Serum IGFBP-5 was measured using an enzyme-linked immunosorbent assay.Intestinal tissue was obtained from patients through endoscopic biopsies.IGFBP-5expression was detected using immunohistochemistry and was scored semiquantitatively.RESULTS:The median serum IGFBP-5 concentrations of CD patients were significantly lower compared with healthy controls[median 7.2(IQR:5.5-11.3)ng/mL vs 11.3(8.0-44.6)ng/mL,P<0.001].There was no significant difference between median serum IGFBP-5levels in CD patients with or without stricture formation[6.9(5.5-11.3)ng/mL vs 7.8(5.3-10.1)ng/mL,P=0.815].The serum IGFBP-5 levels were not significantly different between patients with active disease and inactive disease[7.2(6.5-7.6)ng/mL vs 7.2(5.5-11.3)ng/mL,P=0.890].However,a significant correlation was observed between serum IGFBP-5 levels and platelet count(PLT)(r=0.319,P=0.0395).No significant correlation was found between tissue IGFBP-5 immunohistochemical staining intensity scores and serum IGFBP-5 levels.No significant difference was found when comparing the serum IGFBP-5 levels among the patients with different tissue IGFBP-5 staining scores(absent/very weak,weak,moderate or strong).There was a significant correlation between tissue IGFBP-5staining scores and white blood cell count(r=0.391,P=0.01)and PLT(r=0.356,P=0.021).CONCLUSION:Our results indicate that serum IGFBP-5 concentrations were lower in CD patients compared to healthy controls regardless of disease activity or the presence of stricture formation.     

Serum adipokines in inflammatory bowel disease

AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.     

Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease

AIM: To investigate the probable role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the pathogenesis of inflammatory bowel disease (IBD). METHODS: Fifty-eight patients were enrolled; nineteen healthy volunteers served as controls; 8 patients were diagnosed with Crohn's disease, and 31 with ulcerative colitis. Clinical and endoscopic activity indexes of patients with Crohn's disease and ulcerative colitis respectively were estimated. Upon admission blood was sampled; sTREM-1 and TNFαwere measured by an immunoassay and malondialdehyde (MDA) by the thiobarbitourate assay, after passage through an HPLC system. RESULTS: Median±SE of TNFαof controls, patients with Crohn's disease and patients with ulcerative colitis were 6.02±3.94, 7.98±5.08 (P = NS vs controls), and 8.45±4.15 ng/L (P = 0.018 vs controls) respectively. Respective values of sTREM-1 were 53.31±32.93, 735.10±197.17 (P = 0.008 vs controls) and 435.82±279.71 ng/L (P = 0.049 vs controls). sTREM-1 was positively correlated with Crohn's disease activity index and clinical and endoscopic activity indexes of ulcerative colitis (P = 0.002, 0.001 and 0.009, respectively). sTREM-1 of patients with ulcerative colitis was positively correlated with TNFa (P = 0.001). CONCLUSION: sTREM-1 seems to behave as a novel mediator in IBD in correlation with the degree of the inflammatory reaction of the intestinal mucosa.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

非小细胞肺癌患者呼出气冷凝液中p53蛋白检测的临床意义

目的 研究非小细胞肺癌(NSCLC)患者呼出气冷凝液(EBC)中p53蛋白检测的临床意义.方法 收集98例NSCLC患者的EBC和血浆,应用双抗体夹心ABC-ELISA法检测EBC和血浆中p53蛋白表达水平,并与98名健康对照者测定值比较.用免疫组化法检测98例NSCLC患者手术切除标本癌组织中p53蛋白表达.比较肺癌组中不同分型、分期、病理类型、肿瘤大小以及有无淋巴结转移、吸烟史者EBC和血浆中p53蛋白水平和癌组织p53蛋白阳性表达率.应用 ROC曲线分析肺癌组血浆及EBC的p53蛋白诊断肺癌的特异性及敏感性.结果 ①肺癌组EBC中p53蛋白测定值高于健康对照组[(233.99±7.91)ng/L vs(130.26±4.73)ng/L,P＜0.01];肺癌组血浆p53蛋白测定值高于健康对照组[(292.58±8.79)ng/L vs(141.66±3.33)ng/L,P＜0.01].②肺癌组中央型患者EBC中p53蛋白测定值高于周围型患者[(248.22±8.58)ng/L vs(215.78±6.61)ng/L,P＜0.05].③免疫组化阳性组EBC中p53蛋白测定值高于阴性组「(249.77±8.07)ng/L vs(216.86±7.44)ng/L,P＜0.05].④肺癌组中吸烟者血浆p53蛋白测定值高于无吸烟者[(310.18±9.04)ng/L vs(254.55±6.91)ng/L,P＜0.01].⑤癌组织p53蛋白阳性表达率为47.96%(47/98).⑥血浆p53蛋白对于肺癌的诊断的敏感性为95.90%.特异性为90.04%;EBC p53蛋白埘于肺癌的诊断的敏感性为92.90%,特异性为79.59%;肺癌患者p53蛋白诊断最佳参考临界值血浆为175.68 ng/L,EBC为166.26 ng/L.结论 NSCLC患者中EBC p53蛋白的检测有助于肺癌的诊断.

Abstract：

Objective To study the clinical significance of the detection of p53 protein in exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC). Methods EBC and plasma of 98 patients with NSCLC were collected,p53 protein expression in EBC and plasma was detected by enzyme-linked immunosorbent assay,and the data were compared with those of 98 healthy controls. p53 protein expression in cancer tissue of 98 patients with NSCLC was detected by immunohistochemistry. p53 protein expression in EBC and plasma and positive expression rate of p53 protein in cancer tissue were compared among patients with different lung cancer type,stage,histologic type,tumor size,and lymph node metastasis,smoking history. The specificity and sensitivity of diagnosis of p53 protein in patients with NSCLC were analyzed by ROC curve. Results ① The level of p53 protein in EBC of patients with NSCLC was significantly higher than that in healthy control group [(233.99±7.91) ng/L vs ( 130. 26 ± 4. 73) ng/L,P ＜0. 01]. The level of p53 protein in serum of patients with NSCI.C was significantly higher than that in healthy control group [(292. 58 ± 8. 79) ng/L vs (141. 66±3. 33) ng/L,P ＜0. 01]. ② The level of p53 protein in EBC of patients with central lung cancer was higher than that in patients with peripheral lung cancer [(248. 22 ± 8. 58) ng/L vs (215. 78 ± 6.61) ng/L,P＜0. 01]. ③The level of p53 protein in EBC of patients with positive immunostaining group was higher than that in negative group [(249.77 ± 8.07) ng/L vs (216.86 ± 7.44) ng/L,P ＜ 0. 05]. ④The level of p53 protein in serum of smokers was significantly higher than that in non-smokers [(310.18 ± 9.04) ng/L vs (254. 55 ± 6. 91) ng/L,P ＜0. 01]. ⑤The positive expression rate of p53 protein in cancer tissue was 47. 96% (47/98). ⑥The sensitivity and specificity of diagnosis of p53 protein were 95. 90% and 90. 04% in plasma,and those were 92. 90% and 79. 59% in EBC. The cut off values of p53 protein were respectively 175. 68 ng/L and 166. 26 ng/L in EBC and serum. Conclusions The detection of p53 protein in EBC of patients with NSCLC is helpful for the diagnosis of lung cancer.     

Spider angiomas in Patients with liver Cirrhosis:Role of vascular endothelial growth factor and basic fibrobalast growth factor

AIM: To investigate whether vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) are associated with spider angiomas in patients with liver cirrhosis.METHODS: Eighty-six patients with liver cirrhosis were enrolled and the number and size of the spider angiomas were recorded. Fifty-three healthy subjects were selected as controls. Plasma levels of VEGF and bFGF were measured in both the cirrhotics and the controls.RESULTS: Plasma VEGF and bFGF were increased in cirrhotics compared with controls (L22±13 vs. 71±11 pg/mL, P=0.003for VEGF; 5.1±0.5 vs. 3.4-±0.5 pg/mL, P=0.022 for bFGF). In cirrhotics, plasma VEGF and bFGF were also higher in patients with spider angiomas compared with patients without spider angiomas (185±28 vs. 90±10 pg/mL, P=0.003 for VEGF;6.8±1.0 vs. 4.1±0.5 pg/mL, P=0.017 for bFGF). Multivariate logistic regression showed that young age and increased plasma levels of VEGF and bFGF were the most significant predictors for the presence of spider angiomas in cirrhotic patients (odds ratio [OR]=6.64, 95 % confidence interval [CI]=2.02-21.79, P=0.002; OR=4.35, 95 % CI=1.35-14.01,P=0.014; OR=5.66, 95 % CI=1.72-18.63, P=0.004, respectively).CONCLUSION: Plasma VEGF and bFGF are elevated in patients with liver cirrhosis. Age as well as plasma levels of VEGF and bFGF are significant predictors for spider angiomas in cirrhotic patients.     

肌抑制素与慢性阻塞性肺疾病患者的营养不良

目的 调查慢性阻塞性肺疾病(COPD)稳定期患者的营养状况,通过检测外周血清中肌抑制素的水平,探讨肌抑制素与COPD患者营养不良的关系.方法 选71例COPD稳定期患者和60例老年健康对照者,参照营养不良多参数评分(MNI)对所有受试者的营养状况进行总体评价;采用酶联免疫吸附法检测受试者血清中肌抑制素、TNFα、C反应蛋白(CRP)水平.结果 COPD患者MNI显著升高,其中MNI≥5分者55例(77%),MNI＜5分者16例.MNI≥5分者血清中肌抑制素水平为(12.18±4.76)μg/L,较MNI＜5分者[(9.73±2.85)μg/L]和健康对照者[(7.93±2.35)μg/L]显著升高(P＜0.001).COPD患者TNFα显著升高,与健康对照者比差异有统计学意义(P＜0.05).COPD患者血清肌抑制素水平与MNI、TNFα水平呈正相关(r=0.438,P=0.000;r=0.234,P=0.041).结论 COPD患者普遍存在较严重的营养不良,血清肌抑制素水平明显升高,营养不良与血清肌抑制素升高密切相关.

Abstract：

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.