Obesity Paradox in Patients with Acute Coronary Syndrome: Is Malnutrition the Answer?

BACKGROUND: Obesity paradox has been reported in patients with cardiovascular disease, showing an inverse association between obesity as defined by BMI (in kg/m2) and prognosis. Nutritional status is associated with systemic inflammatory response and affects cardiovascular disease outcomes. OBJECTIVES: This study sought to examine the influence of obesity and malnutrition on the prognosis of patients with acute coronary syndrome (ACS). METHODS: This study included consecutive patients diagnosed with ACS and underwent coronary angiogram between January 2009 and February 2023. At baseline, patients were categorized according to their BMI as follows: underweight (<18), normal weight (18-24.9), overweight (25.0-29.9), and obese (>30.0). We assessed the nutritional status by Prognostic Nutritional Index (PNI). Malnutrition was defined as a PNI value of <38. RESULTS: Of the 21,651 patients with ACS, 582 (2.7%) deaths from any cause were observed over 28.7 months. Compared with the patient's state of normal weight, overweight, and obesity were associated with decreased risk of all-cause mortality. Malnutrition was independently associated with poor survival (hazards ratio: 2.64; 95% CI: 2.24, 3.12; P < 0.001). In malnourished patients, overweight and obesity showed a 39% and 72% reduction in the incidence of all-cause mortality, respectively. However, in nourished patients, no significant reduction in the incidence of all-cause mortality was observed (all P > 0.05). CONCLUSIONS: Obesity paradox appears to occur in patients with ACS. Malnutrition may be a significant independent risk factor for prognosis in patients with ACS. The obesity paradox is influenced by the status of malnutrition.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Melatonin Induces Anti-Inflammatory Effects to Play a Protective Role via Endoplasmic Reticulum Stress in Acute Pancreatitis.

BACKGROUND/AIMS: Melatonin, which is mainly secreted by the pineal gland and released into blood, has anti-inflammatory properties in acute pancreatitis. Many studies show that melatonin can relieve inflammation in taurocholate-induced acute pancreatitis. However, the mechanisms of its anti-inflammatory effects are still undefined, especially the relationship between melatonin and endoplasmic reticulum stress. We explored the anti-inflammatory activity of melatonin in AR42J and rat models. METHODS: The CCK-8 assay was used to assess effects of melatonin on AR42J cell viability. Inflammatory degree and the expressions of endoplasmic reticulum stress related molecules were examined by quantitative RT-PCR and western blotting. The degree of inflammation in the tissue was also accessed by pathological grading. Finally, we used the western blotting method to verify apoptosis and autophagy. RESULTS: Endoplasmic reticulum stress was obviously activated in early stage inflammation in AR42J and rat models. Melatonin could induce anti-inflammatory effects via endoplasmic reticulum stress. Melatonin significantly inhibited inflammatory cytokines and the expression of ERS-related molecules. Finally, it played a protective role by promoting apoptosis and autophagy of the cells, which were damaged in the process of inflammatory reaction. CONCLUSION: Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in acute pancreatitis to play a protective role.

Clinical characteristics and prognostic importance of anticoagulant use in ischemic left ventricular aneurysm: a retrospective cohort study.

There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.

Clinical Characteristics and Outcomes in Patients With Apical and Nonapical Hypertrophic Cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy, with distinct clinical characteristics and outcomes. We aimed to clarify the natural history of patients with ApHCM and identify the risk of end-stage heart failure incidence. METHODS AND RESULTS: This retrospective study was conducted on patients with hypertrophic cardiomyopathy in China between January 2009 and February 2024. Patients were stratified into ApHCM and non-ApHCM groups. The primary outcome was a composite of major adverse cardiovascular events, including all-cause deaths, heart failure hospitalization, sudden cardiac death, and ventricular tachycardia. The secondary outcome was the incidence of end-stage heart failure, defined as left ventricular ejection fraction <50%. Kaplan-Meier and univariable and multivariable Cox proportional analyses were applied. Adjustment variables were included for important baseline characteristics, comorbidities, and medication use. Of 5653 patients enrolled with hypertrophic cardiomyopathy, 584 (10.3%) had ApHCM and 5069 (89.7%) had non-ApHCM. During the median follow-up period of 4.6 years (1.6-8.0 years), major adverse cardiovascular events occurred in 32.2% (n=1808), with a lower incidence in patients with ApHCM than non-ApHCM (20.4% versus 33.3%, P<0.001). Non-ApHCM was an independent predictor of major adverse cardiovascular events (hazard ratio [HR], 1.65 [95% CI, 1.36-1.99]; P<0.001). In the serial cohort, patients with ApHCM exhibited a lower incidence of end-stage heart failure than those with non-ApHCM (12.4% versus 2.7%, P<0.001). Non-ApHCM was associated with a higher risk of end-stage heart failure development (HR, 2.31 [95% CI, 1.28-4.15]; P<0.001). In subgroup and sensitivity analysis, the results were consistent for our main and secondary outcomes. CONCLUSIONS: ApHCM is relatively common in hypertrophic cardiomyopathy and shows lower rates of all-cause mortality and heart failure hospitalizations than non-ApHCM.

Clinical characteristics and prognosis of patients with hypertrophic cardiomyopathy and heart failure with preserved ejection fraction.

BACKGROUND: Whether heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of developing systolic dysfunction and a poor prognosis in hypertrophic cardiomyopathy (HCM) patients is unknown. OBJECTIVE: We aimed to assess risk factors for the development of end-stage (ES) heart failure (HF) (ejection fraction < 50%) and compare the prognosis of different HF phenotypes. METHODS: This retrospective study was conducted on patients with HCM in China between January 2009 and February 2023. Patients were stratified into three different groups: HCM-non-HF, HCM-HFpEF and HCM-heart failure with reduced ejection fraction (HCM-HFrEF). The primary outcome was a composite of major adverse cardiac events (MACEs), including all-cause deaths, HF hospitalization, sudden cardiac death and ventricular tachycardia. RESULTS: Of 3,620 HCM patients enrolled, 1,553 (42.9%) had non-HF, 1,666 (46.0%) had HFpEF, and 579 patients (11.1%) had HFrEF at baseline. During the median follow-up period of 4.0 years (IQR 1.4-9.4 years), patients with HCM-HFpEF exhibited a higher incidence of ES-HF than those with HCM-non-HF (12.4% vs. 2.7%, P < 0.001). HFpEF was an independent risk factor for ES-HF development (HR 3.84, 2.54-5.80, P < 0.001). MACEs occurred in 26.9% with a higher incidence in HCM-HFpEF than HCM-non-HF (36.6% vs 12.2%, P < 0.001). HFpEF was an independent predictor of MACEs (HR 2.13, 1.75-2.59, P < 0.001). CONCLUSIONS: HFpEF is common in HCM. Compared to non-HF, it increases the risk of LVEF decline and poor prognosis. It may aid in risk stratification and need close echocardiography follow-up.

High-Sensitivity C-Reactive Protein Is Associated With Heart Failure Hospitalization in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease and Normal Left Ventricular Ejection Fraction Undergoing Coronary Angiography.

BACKGROUND: Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction. METHODS AND RESULTS: The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25]). CONCLUSIONS: There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

Reduced- or Half-Dose Rivaroxaban Following Left Atrial Appendage Closure: A Feasible Antithrombotic Therapy in Patients at High Risk of Bleeding?

The optimal antithrombotic strategy after percutaneous left atrial appendage closure (LAAC) has not yet been established. The advisability of administering low-dose direct oral anticoagulation after LAAC to patients at high risk of bleeding is uncertain. Thus, in the present study, we evaluated the safety and effectiveness of reduced-(15 mg) or half-dose rivaroxaban (10 mg) versus warfarin regarding real-world risks of thromboembolism, bleeding, and device-related thrombosis (DRT) after LAAC. Patients with non-valvular atrial fibrillation and HASBLED ≥ 3 who had undergone successful LAAC device implantation from October 2014 to April 2020 were screened and those who had received 10 mg or 15 mg rivaroxaban or warfarin therapy were enrolled. The patients were followed up 45 days and 6 months after LAAC to evaluate outcomes, including death, thromboembolism, major bleeding, and DRT. Of 457 patients with HASBLED ≥ 3 who had undergone LAAC, 115 had received warfarin and 342 rivaroxaban (15 mg: N = 164; 10 mg: N = 178). There were no significant differences in the incidence of thromboembolism or DRT between the warfarin and both doses of rivaroxaban groups (all p > 0.05). The incidence of major bleeding was significantly higher in the warfarin group than in either the reduced- or half-dose rivaroxaban groups (warfarin vs. rivaroxaban 15 mg: 2.6% vs. 0%, p = 0.030; warfarin vs. rivaroxaban 10 mg: 2.6% vs. 0%, p = 0.038). Either reduced- or half-dose rivaroxaban may be an effective and safe alternative to warfarin therapy in patients with LAAC and who are at high risk of bleeding, the risk of thromboembolism being similar and of major bleeding lower for both doses of rivaroxaban.

Clinical Outcome After Left Ventricular Thrombus Resolution: Who Needs Long-Term or Lifetime Use of Anticoagulants?

Background Patients with left ventricular thrombus (LVT) resolution can have LVT recurrence and risk for thromboembolism. However, these outcomes after LVT resolution are not well known. We aimed to assess the prevalence, risk factors, and clinical outcomes for LVT recurrence in patients with LVT resolution to inform follow-up and treatment. Methods and Results Patients with LVT resolution were identified retrospectively from a large echocardiography database between January 2009 and May 2022. Participants had echocardiograms at 3 time points, including baseline at LVT diagnosis, at LVT resolution, and a follow-up for identification of LVT recurrence. The cumulative LVT recurrence rate was estimated by the Kaplan-Meier method, and predictors of LVT recurrence were evaluated using Cox regression analysis. Among 115 patients with LVT resolution, 28 (24.3%) had LVT recurrence at a median follow-up of 1.2 (0.5-2.8) years. LV aneurysm (hazard ratio [HR], 2.59 [95% CI, 1.20-5.58], P=0.015) and anticoagulant use (HR, 0.12 [95% CI, 0.04-0.41], P=0.001) were predictors of LVT recurrence on multivariable analysis. Patients with an LV aneurysm who did not receive any anticoagulation demonstrated an LVT recurrence rate of 69.5%, whereas those without an LV aneurysm who received anticoagulation had a recurrence rate of 0%. Patients with LVT recurrence had a higher incidence of an embolic event (10.7% versus 1.1%, P=0.016). Conclusions LVT recurrence after LVT resolution is common, especially in those with an LV aneurysm, and is associated with a higher embolic risk. Continued anticoagulation is protective against LVT recurrence, although bleeding risk needs to be considered. These findings can inform follow-up and treatment of patients with documented LVT resolution.

The association between hyperuricemia and left atrial enlargement in healthy adults.

BACKGROUND: Although hyperuricemia (HU) has been reported to be related to atrial fibrillation (AF), the relationship between HU and left atrial (LA) enlargement is unclear. The aim of this study was to investigate the interaction between HU and LA enlargement in healthy adults in China. METHODS: This study retrospectively surveyed 5,392 people (3,336 males and 2,056 females) who underwent health checks. Basic data were obtained from all participants, including baseline characteristics and general health status through laboratory tests, echocardiography, and interviews. Multinomial logistic regression was used to analyze the experimental data and determine the association between HU and LA enlargement. In addition, the relationship between HU and LA enlargement in different gender groups was analyzed. RESULTS: The prevalence of HU in this study was 20.3%. Compared with the normal LA group, the prevalence of HU in the LA enlargement group was significantly higher [31.5% vs. 18.1%; P<0.001; odds ratio (OR) =2.09, 95% confidence interval (CI): 1.78-2.45]. After adjustment for confounding variables, the interrelation of HU on LA enlargement was found to be independent in the total participants (OR =1.25, 95% CI: 1.04-1.51; P=0.017), especially in women (OR =1.73; 95% CI: 1.10-2.74; P=0.019) but not in men (P=0.195). CONCLUSIONS: HU is independently associated with LA enlargement in healthy adults, especially in women.

Sex-influenced association of metabolic syndrome with lower extremity arterial disease in type 2 diabetes.

AIM: The present study is undertaken to investigate the relationship between metabolic syndrome (MS) and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM) patients. METHODS: A multi-center cross-sectional study was conducted on 8374 T2DM patients (4521 males and 3853 females) from 30 hospitals across China from June 2016 to January 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were presented to show the association between MS and LEAD. The univariate and multiple logistic analyses were performed to examine the association between MS and the prevalence of LEAD. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on the number and individual of MS components. RESULTS: Finally, 1809(21.60%) T2DM patients meet the diagnostic criteria of LEAD. Of the 3853 female subjects, 841(21.83%) patients were in the LEAD group and of the 4521 male subjects, 968(21.41%) patients were in the LEAD group. When adjusting for confounding variables, MS was significantly associated with the prevalence of LEAD in all enrolled T2DM patients (OR = 1.22, 95%CI: 1.09-1.37, P = 0.001). However, upon analyzing LEAD in different sex groups, the significant association remained in females (OR = 1.33, 95%CI: 1.12-1.58, P < 0.001), but not in males (OR = 1.11, 95%CI: 0.95-1.29, P = 0.202). CONCLUSIONS: Our results suggest that MS is specifically associated with an increased risk of LEAD in female T2DM patients. However, MS may not be a significant factor in the prevalence of LEAD in male T2DM patients.

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Importance: It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective: To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants: This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions: Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures: The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results: Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance: Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration: ClinicalTrials.gov Identifier: NCT02631668.

Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas.

BACKGROUND: The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM: To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS: This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS: Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION: H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

Association between Hemoglobin Glycation Index and NAFLD in Chinese Nondiabetic Individuals.

Purpose: Limited studies have preliminarily identified a positive association between nonalcoholic fatty liver disease (NAFLD) and hemoglobin glycation index (HGI). However, this association has not been fully established. We aim to investigate the association between NAFLD and HGI in Chinese nondiabetic individuals and to construct a risk score based on HGI to predict a person's risk of NAFLD. Methods: After strict exclusion criteria, 5,903 individuals were included in this retrospective cross-sectional study. We randomly selected 1,967 subjects in the enrollment to obtain an equation of linear regression, which was used to calculate predicted HbA1c and drive HGI. The other subjects were classified into four categories according to HGI level (≤-0.22, -0.21∼0.02, 0.03∼0.28, and ≥0.29). All subjects retrospectively reviewed the baseline characteristics, laboratory examinations, and abdominal ultrasonography. Results: The prevalence of NAFLD in this population was 20.7%, which increases along with the growth of HGI levels (P < 0.001). Adjusted to multiple factors, this trend still remained significant (OR: 1.172 (95% CI, 1.074-1.279)). The combined NAFLD risk score based on HGI resulted in an area under the receiver operator characteristic curve (AUROC) of 0.85 provided sensitivity, specificity, positive predictive value, and a negative predictive value for NAFLD of 84.4%, 71.3%, 65.0%, and 88.0%, respectively. Conclusions: NAFLD is independently associated with HGI levels in Chinese nondiabetic individuals. And, NAFLD risk score may be used as one of the risk predictors of NAFLD in nondiabetic population.

A development of LC-MS method combining ultrafiltration and lyophilization for determination of r-RGD-Hirudin in human serum.

A reliable and validated LC-MS method was established for determination of r-RGD-Hirudin in human serum. Ultrafiltration was used instead of liquid-liquid extraction or solid phase extraction for water solubility drug r-RGD-Hirudin extraction. Freeze drying was used for concentration. The experiment conditions, including pre-processing procedure and LC-MS, have been investigated and optimized. Comparing with reported assays, the current method showed significant improvement in specificity, linearity, precision and sensitivity. This method has been successfully applied in clinical research of r-RGD-Hirudin.

Peripheral Arterial Disease in Type 2 Diabetes Is Associated with an Increase in Fibrinogen Levels.

BACKGROUND: The present study is undertaken to investigate the fibrinogen levels in type 2 diabetes mellitus (T2DM) and its relation to peripheral artery disease (PAD) based on a more accurate and applied noninvasive measurements of duplex ultrasonography. METHODS: We performed a cross-sectional study including 1096 T2DM patients (474 males and 622 females). The odds ratios (ORs) and 95% confidence intervals (CIs) were presented to show the association between PAD and fibrinogen in the subjects divided by fibrinogen levels quarterly. Furthermore, the univariate and multiple logistic analyses were performed to explore the correlation between PAD and fibrinogen levels, individual components in the cross-sectional study. RESULTS: Finally, 887 (80.9%) T2DM patients meet the diagnostic criteria of PAD and these patients had considerably higher serum fibrinogen concentration than non-PAD group (P < 0.001). Multiple logistic analyses revealed that higher fibrinogen quartiles were positively related with the development of PAD in the adjusted model. After adjusting for known confounding parameters, the ORs for PAD were 1.993 (95% CI: 1.322-3.005, P < 0.001), 2.469 (95% CI: 1.591-3.831, P < 0.001), and 2.942 (95% CI, 1.838-4.711, P < 0.001) for Q2, Q3, and Q4, respectively (all P values <0.05). CONCLUSIONS: Our results suggest that serum fibrinogen concentration can be considered as an independent risk factor for PAD in T2DM patients.

Melatonin attenuated inflammatory reaction by inhibiting the activation of p38 and NF­κB in taurocholate­induced acute pancreatitis.

The aim of the present study was to investigate the protective mechanism underlying of melatonin in severe acute pancreatitis (SAP). A total of 64 male Sprague­Dawley rats were randomly divided into four groups: The sham operation (SO) group, SAP group, melatonin treatment (MLT) group and p38 inhibitor (SB203580) treatment (SB) group. Acute pancreatitis was induced by 5% taurocholate through retrograde infusion into the biliopancreatic ducts. The melatonin and SB203580 treatment groups were administered with MLT and SB 30 min before operation the induction of SAP. Rats in each group were euthanized at 6 and 12 h following SAP induction. Blood and pancreatic tissues were removed for inflammatory examination. Peripheral blood mononuclear cells (PBMCs) were isolated following sacrifice to measure the phosphorylation of p38 and nuclear factor­κB (NF­κB was measured as p65 and phosphorylation of p65). The pretreatment of melatonin significantly attenuated the severity of pancreatitis. In addition, melatonin also reduced serum amylase and proinflammatory cytokine levels, including tumor necrosis factor­α, interleukin (IL)­1 and IL­6. The mean pathological scores for pancreatic tissues in the MLT group were higher than those for samples in the SO group, but were lower than those for samples in the SAP group at each time-point. Phosphorylation of p38 and p65 levels in the melatonin treatment group were lower than that in the SAP group, and higher in the SAP group than in the SO group, and the SB203580 treatment group. Furthermore, melatonin significantly inhibited the activation of p38 and NF­κB in PBMCs. The authors revealed that melatonin may attenuate inflammatory reactions by inhibiting the activation of p38 MAPK and NF­κB in both acute pancreatitis rats and PBMCs. SAP is a severe disease with a high risk of morbidity and mortality. It is important to attenuated inflammatory reaction in acute pancreatitis. Thus, the authors studied melatonin, which is synthesized by the pineal gland and released into the blood. Previous studies have shown that melatonin serves a protective role in the early course of human acute pancreatitis, and melatonin concentration variations are closely related to the severity of acute pancreatitis. It may be concluded that melatonin may attenuates inflammatory reactions by inhibiting the activation of p38 MAPK and NF­κB in both acute pancreatitis rats and PBMCs.

Melatonin Attenuates Endoplasmic Reticulum Stress in Acute Pancreatitis.

OBJECTIVES: The objective of this study is to explore the effect of melatonin on endoplasmic reticulum stress in acute pancreatitis (AP) and the molecular mechanism. METHODS: Acute pancreatitis was induced in vivo in Sprague-Dawley rats by the retrograde injection of 5% taurocholate into the biliopancreatic duct and in vitro by treating AR42J cells with cerulein (10 nmol/L) plus lipopolysaccharide (LPS) (10 mg/L). The rats and cells were treated with melatonin (50 mg/kg in rats and 0.5, 1, and 2 mmol/L in AR42J cells) 30 minutes before AP was induced. After 9 hours, the cells and rat pancreas tissue were collected for Western blot, reverse transcription polymerase chain reaction, histological examination, immunohistochemistry, and immunofluorescence analysis. RESULTS: Inositol-requiring 1α (IRE1α)-mediated Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) pathway were activated early in AR42J cells and rat AP models. Melatonin significantly inhibited the expression of proinflammatory cytokines. Western blot and immunohistochemical results all indicated that melatonin regulated apoptosis-related protein expression. In addition, melatonin treatment resulted in significantly reduced pancreatic tissue injury, as revealed by histological changes and pathological scores. Furthermore, melatonin treatment significantly reduced the activation of IRE1α-mediated JNK/NF-κB pathway-related proteins. CONCLUSIONS: These findings suggest that melatonin protects AR42J cells and Sprague-Dawley rats against AP-associated injury, probably through downregulation of IRE1α-mediated JNK/NF-κB pathways.