Significant association of insulin and proinsulin with clustering of cardiovascular risk factors

AIM: To investigate the association between true insulin and proinsulin and clustering of cardiovascular risk factors. METHODS: Based on the random stratified sampling principles, 1196 Chinese people (533 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Biotin-avidin based double monoclonal antibody ELISA method was used to detect the true insulin and proinsulin, and a risk factor score was set to evaluate individuals according to the number of risk factors. RESULTS: The median (quartile range) of true insulin and proinsulin was 4.91 mIu/L (3.01-7.09 mIu/L) and 3.49 pmol/L (2.14-5.68 pmol/L) respectively, and the true insulin level of female subjects was significantly higher than that of male subjects (P=0.000), but the level of proinsulin displayed no significant difference between males and females (P = 0.566). The results of covariate ANOVA after age and sex were controlled showed that subjects with any of the risk factors had a significantly higher true insulin level (P=0.002 for hypercholesterolemia, P=0.021 for high low-density lipoprotein cholesterol, P= 0.003 for low high-density lipoprotein cholesterol, and P=0.000 for other risk factors) and proinsulin level (P=0.001 for low high-density lipoprotein cholesterol, and P=0.000 for other risk factors) than those with no risk factors. Furthermore, subjects with higher risk factor scores had a higher true insulin and proinsulin level than those with lower risk factor scores (P=0.000). The multiple linear regression models showed that true insulin and proinsulin were significantly related to cardiovascular risk factor scores respectively (P=0.000). CONCLUSION: True insulin and proinsulin are significantly associated with the clustering of cardiovascular risk factors.     

Role of the postoperative cholesterol in early al-lograft dysfunction and survival after living do-nor liver transplantation

BACKGROUND:Many studies have confirmed that serum total cholesterol(sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver.However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed.METHODS:Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group(sTC 1.42 mmol/L, 57 recipients) and high sTC group(sTC ≥1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short-and long-term outcomes were compared between the two groups.RESULTS:Recipients with sTC 1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction(38.6% vs 10.3%, P0.001), 90-day mortality(28.1% vs 10.9%, P=0.002)and severe complications(29.8% vs 17.2%, P=0.041) compared to recipients with sTC ≥1.42 mmol/L. The multivariate analysis demonstrated that sT C 1.42 mmol/L had a 4.08-fold(95% CI:1.83-9.11, P=0.001) and 2.72-fold(95% CI:1.23-6.00,P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC 1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC ≥1.42 mmol/L(67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%,68% and 66%, P=0.026, respectively). Cox multivariate anal-ysis showed that sTC 1.42 mmol/L was an independent predicting factor for total recipient survival(HR=2.043; 95% CI:1.173-3.560; P=0.012) and graft survival(HR=1.905; 95% CI:1.115-3.255; P=0.018).CONCLUSIONS:sTC 1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short-and long-term outcomes.     

Polymorphisms at cholesterol 7α-hydroxylase,apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease

AIM: To investigate the relationship between gallbladderstone disease (GSD) and single nucleotide polymorphismsof cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (APO) B gene exon 26,APOEgene exon 4 ormicrosatellite polymorphism of low density lipoproteinreceptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A,APOB,APOE and LDLRgenes were determined in 105 patients with GSD diagnosedby B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaicbiochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher inpatients with GSD (24.47±3.09) than in controls (23.50±2.16).Plasma total cholesterol was lower in patients with GSD(4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L),P<0.01 after adjusted for age,sex and BMI.The significantlyhigher frequency of A allele of CYP7A gene polymorphismand X allele of APOBgene polymorphism was seen in GSDpatients.Percentages of A allele in patients and controlswere 62.86% and 54.38% (P<0.05) and those of X allele8.57% and 4.01% (P<0.01).Subjects with A allele hadsignificantly lower plasma total cholesterol and LDLcholesterol than subjects with CC homozygote.In a multiplevariable logistic regression model,the BMI (OR=1.13,95%CI: 1.05-1.22),A allele (OR=1.48,95% CI: 1.05-2.09) andX allele (OR=2.28,95% CI: 1.14-4.59) were positivelyassociated with GSD (P<0.05).Plasma total cholesterol(OR=0.69,95% CI: 0.64-0.74) was negatively related toGSD (P<0.05).CONCLUSION: With an association analysis,it was determinedthat A allele of CYP7A gene and X allele of APOB genemight be considered as risk genes for GSD.These allelesare related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showedthat besides BMI,GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSDrequires further investigations.     

Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P 0.001),waist circumference(r =0.356,P 0.001),percent body fat(r = 0.296,P 0.001),systolic blood pressure(r = 0.202,P 0.001),total cholesterol(r = 0.134,P 0.001),triglycerides(r = 0.292,P 0.001),cystatin C(r = 0.069,P 0.001) and uric acid(r = 0.142,P 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P 0.001),waist circumference(r = 0-0.243,P 0.001),percent body fat(r =-0.217,P 0.001),systolic blood pressure(r =-0.132,P 0.001),total cholesterol(r =-0.106,P 0.001),triglycerides(r =-0.205,P 0.001),cystatin C(r =-0.044,P 0.001) and uric acid(r =-0.096,P 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.     

Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats

AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS ＋ Lianshu group, LPS ＋ berberine group （n = 10 in each group）. Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^＋, K^＋, Cl and hematocrit, plasma nitrogen monoxide （NO）, diamine oxidase （DAO）, and D （-）-lactate were measured. The number of IgA＋ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer＇s yeast-induced pyrexia （10 mL/kg of 20% aqueous suspension）. Acetaminophen （250 mg/kg, intragastric administration, bid） was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer＇s yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin （2 mg/kg）. Atropine （10 g/kg） was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS： The frequency of diarrhea was higher in LPS group than in LPS ＋ Lianshu group and LPS ＋ berberine group （36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01）, and lower in LP5 ＋ Lianshu group than in LPS ＋ berberine group （P = 0.03）. The levels of Na＋, glucose, Cl, K^＋ were significantly lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05）. The level of hematocrit was lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05）. The plasma levels of NO, DAO and D （-）-lactate were higher in LPS group than in normal group （79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01）, and lower in LPS ＋ Lianshu group than in LP5 ＋ berberine group （48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05）. The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS ＋ Lianshu group than in LPS group. The number of IgA＋ plasma cells and amount of SIgA were higher in LPS ＋ Lianshu group than in LPS group （1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000）. Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION： Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.     

Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice

AIM:To investigate the effects of Lactobacillus plantarum(L.plantarum) CAI6 and L.plantarum SC4 on hyperlipidemic mice.METHODS:Male Kunming mice were fed a highcholesterol diet for 28 d to construct hyperlipidemic models.Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L.plantarum CAI6,L.plantarum SC4,and physiological saline through oral gavage for 28 d.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C) levels were measured by commercially available enzyme kits.FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2(Nrf2) expression.The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation.RESULTS:Compared with normal mice,hyperlipidemic mice possessed significantly higher TC(3.50 ± 0.43 vs 2.89 ± 0.36,P < 0.01),TG(1.76 ± 0.07 vs 1.10 ± 0.16,P < 0.01),and LDL-C(1.72 ± 0.20 vs 0.82 ± 0.10,P < 0.01) levels,resulting in an increase of atherogenic index(AI)(2.34 ± 1.60 vs 0.93 ± 0.55,P < 0.05) and LDL-C/HDL-C ratio(1.43 ± 0.12 vs 0.51 ± 0.16,P < 0.05).After treatment with L.plantarum CAI6/L.plantarum SC4,TG(1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07,P < 0.01/P < 0.05) and LDL-C(1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20,P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased.In addition,TC,HDL-C,AI,and LDL-C/HDL-C ratio were all positively changed.Meanwhile,the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression(73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84,P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice.CONCLUSION:L.plantarum CAI6 and L.plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice.     

Polymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease

AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (APO) B gene exon 26, APOEgene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaic biochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47&#177;3.09) than in controls (23.50&#177;2.16).Plasma total cholesterol was lower in patients with GSD (4.66&#177;0.92 mmol/L) than in controls (4.91&#177;0.96 mmol/L),P&lt;0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7A gene polymorphism and X+ allele of APOBgene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P &lt;0.05) and those of X+ allele 8.57% and 4.01% (P&lt;0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P &lt;0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to GSD (P&lt;0.05).CONCLUSION: With an association analysis, it was determined that A allele of CYP7A gene and X+ allele of APOB gene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSD requires further investigations.     

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.     

Relationship between diastolic blood pressure and adverse outcomes in ST-elevation myocardial infarction undergoing percutaneous coronary intervention

Background Low diastolic blood pressure(DBP)was reported to be associated with reduced coronary blood flow,subclinical myocardial damage,and cardiovascular events. The aim of this study was to explore the impact of low DBP on clinical outcomes in patients with ST-elevation myocardial infarction(STEMI)undergoing percutaneous coronary intervention(PCI). Methods A total of 1232 patients with STEMI were retrospectively enrolled and divided into two groups according to admission DBP level:≥70 mm Hg(n=817)and < 70 mm Hg(n=415). The relationship between DBP and in-hospital and 1-year adverse events was evaluated.Results In-hospital death occurred in 2.4% of patients. The in-hospital mortality(5.3% vs. 1.0%,P<0.001)and major adverse clinical events(11.1% vs. 7.5%,P=0.033)were significantly higher in patients with a low DBP.DBP <70 mm Hg was associated with in-hospital death(adjusted odds rate=3.31,95%CI:1.36-8.07,P=0.009).Additional significant indicators included eGFR < 60 mL/min/1.73 m^2 and intra aorta balloon pump(IABP)treatment. Seventy-seven(6.3%)patients died in the one-year follow-up. DBP < 70 mm Hg was associated with increased risk of 1-year death(8.9% vs. 4.8%,Log-rank=9.9,P=0.002). Conclusion Low DBP was associated with increased risk of in-hospital and 1-year adverse prognosis in patients with STEMI undergoing PCI,which could be a tool for risk assessment.     

Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer

AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups(r s = 0.494, P = 0.0001 and r s= 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls(controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.     

Stroke and myocardial infarction in Chinese patients: comparison of risk factors and in-hospital outcomes

Although coronary heart disease (CHD) and stroke share important risk factors,some associations differ between these two components of cardiovascular diseases.The objective of this study was to compare vascular risk factor profiles and in-hospital outcomes in acute stroke (AS) and acute myocardial infarction (AMI) patients.Methods We evaluated 383 consecutive patients who were admitted to the 94th Hospital of Chinese PLA and the Third Hospital of Nanchang with diagnoses of AS (ischemic stroke or intracerebral hemorrhage;n = 310) or AMI (n = 73) during a 2-year period.The frequency of risk factors and inhospital mortality rates were assessed in both groups.Results AS patients were significantly older than AMI patients ( 68.9 ± 9.1 years vs.62.8 ±11.7 years;P ＜ 0.01).AMI was significantly more common than AS in patients younger than 65 years;51% of this group had AMI and 26% had AS (P ＜ 0.001).Hypertension was more common in AS patients than in AMI patients (69% vs.58%;P = 0.042).Patients who died did not differ significantly in age between the groups.In-hospital mortality rates were significantly higher in AS than AMI cases (31% vs.12%,P ＜ 0.001 for all patients;37% vs.5%,P ＜ 0.001 for men).Women hospitalized for AMI were more likely to die in hospital than men (28% vs.5%;P = 0.002).Conclusions Patients with stroke and with AMI differ in their risk factor profile.Age at the time of presentation was a significant differentiating factor between patients with AS and AMI.We observed significantly higher in-hospital mortality for patients with AS (when adjusted for age) than for patients with AMI.(J Geriatr Cardiol 2008;5:223-226)     

Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease

AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.     

Prognosticvalueofincreasedcarbohydrateantigeninpatientswithheart failure

AIM:To study the prognostic value of carbohydrateantigen 125(CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide(NT-proBNP) in stable heart failure(HF) patients.METHODS:The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011.Patients were included in the study if they had a previous documented episode of HF and received HF treatment.CA125 and NT-proBNP concentrations were measured.The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis,and their combined predictive ability was tested by the integrated discrimination improvement(IDI) index.RESULTS:The mean age of the 156 patients was 72 ± 12 years.During follow-up(17 ± 8 mo),27 patients died,1 received an urgent heart transplantation and 106 required hospitalization for HF.Higher CA125 values were correlated with outcomes:58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not(P 0.05),and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors(P 0.01).After adjusting for propensity scores,the highest risk was observed when both biomarkers were elevated vs not elevated(HR = 8.95,95%CI:3.11-25.73; P 0.001) and intermediate when only NT-proBNP was elevated vs not elevated(HR = 4.15,95%CI:1.41-12.24; P 0.01).Moreover,when CA125 was added to the clinical model with NT-proBNP,a 4%(P 0.05) improvement in the IDI was found.CONCLUSION:CA125 60 KU/L identified patients in stable HF with poor survival.Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.     

Biochemical characteristics of neonatal cholestasis induced by citrin deficiency

AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose [3.2 (2.0-4.4) mmol/L in NICCD vs 4.1 (3.4-5.1) mmol/L in BA and 4.0 (3.4-4.6) mmol/L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol/L in N ICCD vs 4.57 (3.81-5.26) mmol/L in BA and 4.00 (3.24-4.74) mmol/L in INC, P = 0.0155] levels. The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range):0.54 (0.40-0.74)] than that in BA patients [0.77 (0.72-0.81), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045]. A much higher AST/ALT ratio was found in NICCD patients [2.46 (1.95-3.63)] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA/D-Bil ratio [3.36 (1.98-4.43) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA/TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) in BA patients and 24.2 (21.4-26.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION:NICCD has significantly different bio- chemical indices from BA or INC. TBA excretion in NICCD appeared to be more severely disturbed than that of bilirubin and cholesterol.     

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced- stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were signifi cantly different. These were lower in the steroid-withdrawal group than in the steroid- maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection didnot increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased signifi cantly. This may have led to an increase in long-term survival rate.     

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding

AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the differencewas compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups(70.8 ± 11.4 vs 62.4 ± 12.0, P 0.001; 8(8.2%) vs 15(21.7%), P 0.05; 65(66.3%) vs 13(18.8%), P 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant(P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group(log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio(HR) for recurrent bleeding was 2.986(95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216(95%CI: 1.035-26.278, P = 0.028).CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.     

Markers of inflammation and cardiovascular disease in recently diagnosed celiac disease patients

AIM To evaluate novel risk factors and biomarkers of car-diovascular disease in celiac disease(CD) patients compared with healthy controls. METHODS Twenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo. Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile andthe activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina.RESULTS Regarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2(5.0-11.3) m U/L vs 4.6(2.6-6.7) m U/L, P 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45(1.04-2.24) vs 1.00(0.51-1.45), P 0.05] and lower Quantitative Sensitive Check index [0.33(0.28-0.40) vs 0.42(0.34-0.65), P 0.05] indexes. Folic acid concentration [5.4(4.4-7.9) ng/m L vs 12.2(8.0-14.2) ng/m L, P 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher(4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoprotein-cholesterol(HDL-C)(45 ± 15 mg/d L vs 57 ± 17 mg/d L, P 0.05) and apo A-I(130 ± 31 mg/d L vs 155 ± 29 mg/d L, P 0.05) levels, as well as higher total cholesterol/HDL-C [4.19(3.11-5.00) vs 3.52(2.84-4.08), P 0.05] and apo B/apo A-I(0.75 ± 0.25 vs 0.55 ± 0.16, P 0.05) ratios in comparison with control subjects. No statistically significant differences were detected in lipoprotein-associated lipid transfer protein and enzymes.CONCLUSION The presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.     

The relationship of body mass index and hyperuricemia in hypertensive adults over 80 years

Background Hyperuricemia (HUA) and hypertension are associated with the increasing risk and mortality of cardiovascular disease (CVD) . However,the relationship between body mass index (BMI) and HUA in hypertensive adults over 80 years remains uncertain. Methods Observational trial was designed and 308 patients who were newly diagnosed as essential hypertension without anti-hypertensive therapy were enrolled into our study. According to the cut-off value of serum UA,participants were stratified into normal (420 μmol/L for men and 360 μmol/L for women) and increased UA groups (≥420 μmol/L for men and ≥360 μmol/L for women) . Serum UA level,blood pressure and other baseline characteristics were compared,logistic regression analysis and receiver operating characteristic curve (ROC) were performed. Results The mean (SD) serum uric level was 382.2 (108.7) μmol/L and the prevalence of hyperuricemia was 45% among men and 50% among women.BMI was significantly higher (22.6 vs. 24.0 kg/m~2,P=0.003) and FBG was lower (5.13 vs. 4.98 mmol/L,P=0.025) in increased UA group among aged women,and BMI and FBG were found the independent determinants for UA increase in female subjects according to logistic regression analysis,and the odd ratio were 1.154 (95% interval confidence 1.058-1.259,P=0.001) and 0.646 (95% interval confidence 0.44-0.949,P=0.026),respectively.Moreover,evaluation of receiver operating characteristic curve (ROC) showed that area under the curve for BMI to predict UA increase was 0.627+0.039,P=0.001 in women. However,the results mentioned above were only found in elderly women,not in men. Conclusions Our study indicates that aged women have higher prevalence of HUA than men,and that BMI is independently associated with serum uric acid level for hypertensive women but not for men over 80 years old. Therefore,BMI is a useful predictor of serum uric acid level in elderly women with hypertension.     

Serum insulin, insulin resistance, p-cell dysfunction, and gallstone disease among type 2 diabetics in Chinese population: A community-based study in Kinmen, Taiwan

AIM: To explore the association of serum insulin, insulin resistance, and β-cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We used a community-based study conducted between 1991 and 1993 in Kinmen, Taiwan to identify type 2 diabetics. A screening program for GSD was performed in 2001 by a panel of specialists who employed real-time ultrasound sonography to examine the abdominal region after the patient had fasted for at least 8 h. Screening was conducted in 2001 on 848 patients diagnosed with type 2 diabetes. The HOMA method was used to compare the profile differences for insulin resistance (HOMA IR) and β-cell dysfunction (HOMA β-cell). RESULTS: We studied 440 type 2 diabetics who attended sonography check-ups. After excluding eight insulin-treated diabetics, the prevalence of GSD among the remaining 432 was 13.9% (26/187) among males and 14.7% (36/245) among females. After adjustment for other GSD-associated risk factors in addition to age and obesity, GSD risk increased among females with levels of serum insulin [4th vs 1st quartile odds ratios (OR) = 4.46 (95%CI: 1.71-11.66)] and HOMA IR [4th vs 1st quartile OR = 4.46 (95%CI: 1.71-11.66)]. Better HOMA β-cell function was significantly related to decreased risk of GSD [4th vs 1st quartile OR = 0.16 (95%CI: 0.03-1.70)]. Among males, age and central obesity were the most significant risk factors for GSD. No association of GSD with serum insulin, HOMA IR, and HOMA β-cell was observed among males. CONCLUSION: Serum insulin, insulin resistance, and β-cell dysfunction are risk factors for GSD in females, but not males with type 2 diabetes.