Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. RESULTS: Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001). CONCLUSIONS: Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.

Association of Procalcitonin with the Patient's Infection Characteristics and Prognosis after Hematopoietic Stem Cell Transplantation.

Objective: To study whether procalcitonin (PCT) is an important indicator of infection with or without agranulocytosis and to reveal whether PCT can distinguish between infected sites and affect prognosis after hematopoietic stem cell transplantation (HSCT). Method: In the present study, 682 patients with HSCT were enrolled, and their clinical characteristics were noted. Their blood culture and inflammatory and biochemical indicators were studied. The patients were divided into respective groups according to the degree of agranulocytosis, type of bacterial infection, infected sites, and prognosis. Results: The PCT, CRP, and D-dimer levels were significantly improved in patients with positive blood culture results compared to the case for those with negative blood culture results. The PCT level was the highest in the gram-negative group. The levels of PCT and D-dimer were significantly elevated in patients with infection and agranulocytosis after HSCT compared to those in the nonagranulocytosis cohort. Interestingly, no significant difference in the PCT level was observed among any of the eight foci. Lower PCT levels were associated with higher survival in patients with infection after HSCT. Conclusion: Among patients that underwent HSCT, PCT levels were significantly elevated in those with infection and agranulocytosis, with the levels being specifically high in the gram-negative group. Moreover, lower PCT levels were associated with higher survival in patients with infection after HSCT.

Elevated lipoprotein(a) and genetic polymorphisms in the LPA gene may predict cardiovascular events.

Elevated lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD), but there are few studies on the prediction of future cardiovascular events by Lp(a) and its LPA single nucleotide polymorphisms (SNPs). The aim of this study was to investigate whether elevated Lp(a) and its SNPs can predict cardiovascular events. We evaluated whether Lp(a) and LPA SNPs rs6415084 and rs12194138 were associated with the incidence rate and severity of CHD. All participants were followed up for 5 years. Elevated Lp(a) is an independent risk factor for the risk and severity of CHD (CHD group vs. control group: OR = 1.793, 95% CI: 1.053-2.882, p = 0.043; multiple-vessel disease group vs. single-vessel disease group: OR = 1.941, 95% CI: 1.113-3.242, p = 0.027; high GS group vs. low GS group: OR = 2.641, 95% CI: 1.102-7.436, p = 0.040). Both LPA SNPs were risk factors for CHD, and were positively associated with the severity of CHD (LPA SNPs rs6415084: CHD group vs. control group: OR = 1.577, 95% CI: 1.105-1.989, p = 0.004; multiple-vessel disease group vs. single-vessel disease group: OR = 1.613, 95% CI: 1.076-2.641, p = 0.030; high GS group vs. low GS group: OR = 1.580, 95% CI: 1.088-2.429, p = 0.024; LPA SNPs rs12194138: CHD group vs. control group: OR = 1.475, 95% CI: 1.040-3.002, p = 0.035; multiple-vessel disease group vs. single-vessel disease group: OR = 2.274, 95% CI: 1.060-5.148, p = 0.038; high GS group vs. low GS group: OR = 2.067, 95% CI: 1.101-4.647, p = 0.021). After 5 years of follow-up, elevated Lp(a) and LPA SNPs rs6415084 and rs12194138 can independently predict cardiovascular events. The increase of serum Lp(a) and LPA SNPs rs6415084 and rs12194138 are associated with increased prevalence and severity of CHD, and can independently predict cardiovascular events.

Elevated Serum Small Dense Low-Density Lipoprotein Cholesterol May Increase the Risk and Severity of Coronary Heart Disease and Predict Cardiovascular Events in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Coronary heart disease (CHD) is a common and severe complication in type 2 diabetes mellitus (T2DM) patients. Increased amount of circulatory small dense low-density lipoprotein cholesterol (sdLDL-C) particles is known to be a sign of dyslipidemia and can result in atherosclerosis. However, the association between serum sdLDL-C levels and CHD in T2DM patients remains unclear. METHODS: A total of 3684 T2DM patients who received selective coronary angiography (CAG) were selected. For analyzing the association between sdLDL-C and CHD severity in T2DM, the patients with CHD were further divided into four subgroups according to the quartiles of sdLDL-C. A multivariate logistic regression was used for analyzing the risks and severity of CHD. A total of 3427 patients with continuous stable CHD were recruited and followed up for 5 years. RESULTS: Serum sdLDL-C levels in the CHD group were significantly increased compared with those in the non-CHD group [0.80 (0.49) mmol/L vs. 0.70 (0.30) mmol/L, p < 0.001]. The results from CHD subgroup analysis indicated that the sdLDL-C levels in patients with multiple-vessel disease and high Gensini score (GS) were significantly increased. By adjusting the confounding factors and analyzing with multiple logistic regression, we found that sdLDL-C independently correlated with the presence and severity of CHD (CHD: OR = 2.257; multiple-vessel disease: OR = 3.288; high GS: OR = 2.554). A total of 484 major cardiovascular events (MACEs) were documented. After Kaplan-Meier analysis and chi-squared analysis, the incidence of MACEs in the high sdLDL-C group was higher than that in the low sdLDL-C group (16.04% vs. 12.25%, p = 0.002). CONCLUSION: In T2DM patients, elevated serum sdLDL-C may increase the severity of CHD and predict cardiovascular events in the future. Therefore, serum sdLDL-C may be a potential biomarker for the surveillance of CHD in T2DM patients.

Procalcitonin and C-reactive protein predict infection in hematopoietic stem cell transplantation patients.

INTRODUCTION: Procalcitonin (PCT) and C-reactive protein (CRP) are known inflammatory markers of severe infection; however, their ability to differentiate between infections of different origins is not clear yet. In this study, we evaluated PCT and CRP as markers of infection in hematopoietic stem cell transplantation (HSCT) patients. METHODS: Blood samples were collected to determine serum concentrations of PCT, CRP, d-Dimer, and to perform blood culture analysis. Based on blood culture results, the patients were divided into two groups-positive blood culture (n = 271) patients and negative blood culture patients (n = 668); the negative blood culture group served as the control. The positive blood culture group was further divided into three groups based on the etiological agent of infection. PCT and CRP concentrations were compared, and ROC curve, sensitivity, specificity, and cutoff values were calculated. RESULTS: PCT levels in infected patients were significantly higher than those in control patients (p < 0.001); similarly, CRP and d-Dimer levels were also higher among infected patients when compared with those in the controls. A PCT level of 0.51 ng/mL was the best threshold for detecting the infection, with an AUC-ROC of 0.877, whereas the best threshold for CRP was 49.20 mg/L. PCT levels were the highest in patients with gram-negative bacteremia as compared to in those with gram-positive bacteremia and fungal infection. The optimal cutoff value of PCT for the detection of gram-negative and gram-positive infection was 1.63 ng/mL. CONCLUSION: PCT seems to be a useful marker for the diagnosis of systemic infection in HSCT patients, probably better than CRP and d-Dimer.

The detection of bacterial infections in leukemia patients using procalcitionin levels.

Bacteremic infections are the most common complications in patients with leukemia. This study aimed to assess the value of procalctionin levels in the detection of bacterial infections in leukemia patients. Blood samples of in-patients with leukemia were collected. Statistical analysis was performed to assess the correlation between the procalcitionin level on the day of the first positive blood culture and bacteremic infection. Infected patients had significantly higher procalctionin levels than uninfected patients (p < 0.001). Receiver operating characteristic curve analysis showed a high level of accuracy regarding the discrimination of bacterarmic infection (area under the curve, 0.883) and Gram-negative bateremia (area under the curve, 0.779). Procalctionin levels may help in the identification of bacterial infections in leukemia patients. Further multicentre studies are needed to verify our data regarding the use of procalctionin to distinguish between Gram-positive and Gram-negative infections.

Kaempferol Modulates Autophagy and Alleviates Silica-Induced Pulmonary Fibrosis.

Silicosis is an occupational disease characterized as inflammatory cells infiltration and severe progressive pulmonary fibrosis. Kaempferol (Kae), a flavonoid that exists in many plants and fruits, has been proved to have anti-inflammatory and antifibrosis functions. However, the effects of Kae on silicosis remain unclear. In the present study, we analyzed the therapeutic effects of Kae in 1-, 7-, and 28-day silicosis models, respectively. In the 1-day model, Kae treatment did not vary the wet-to-dry weight ratios of the lung, apoptotic rate, autophagy, or the expression of inflammatory factors. In contrast, Kae significantly inhibited pulmonary inflammation in the 7-day silicosis models and inhibited silica-induced pulmonary fibrosis in the 28-day models. Besides, we found that Kae partially restored silica-induced LC3 lipidation without increasing the p62 levels. Blocking autophagy with chloroquine antagonized the inhibitory effects of Kae on inflammation, suggesting that autophagy might be required in the therapeutic effects of Kae on silicosis. These findings indicated that Kae inhibits the progression of silica-induced pulmonary fibrosis, which may provide experimental evidences for Kae in the treatment of silicosis.

Iron chelation inhibits cancer cell growth and modulates global histone methylation status in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and new treatment strategies for CRC are required because of the existing chemotherapy resistance. Iron chelators, which have been used widely for the treatment of iron-overload disease, were reported to exert anti-proliferative effects in cancer. However, the role of iron chelation in CRC was largely unknown. In this study, we found that the iron chelator DFO inhibited CRC cell growth significantly. In addition, the gene expression profile was greatly changed by DFO treatment, and many cell growth-related genes were dysregulated. Further study showed that DFO induced a significant increase in global histone methylation in CRC cells. However, the levels of histone methyltransferases and histone demethylases did not change in response to DFO treatment, implying that the enzymatic activity of these enzymes might be regulated by iron chelation. In conclusion, this study reveals a novel role for DFO in CRC cell growth, and is the first to demonstrate that global histone methylation is modulated by iron chelation in CRC cells.