HSPD1 Supports Osteosarcoma Progression through Stabilizing ATP5A1 and thus Activation of AKT/mTOR Signaling.

Malignant transformation is concomitant with excessive activation of stress response pathways. Heat shock proteins (HSPs) are stress-inducible proteins that play a role in folding and processing proteins, contributing to the non-oncogene addiction of stressed tumor cells. However, the detailed role of the HSP family in osteosarcoma has not been investigated. Bulk and single-cell transcriptomic data from the GEO and TARGET databases were used to identify HSPs associated with prognosis in osteosarcoma patients. The expression level of HSPD1 was markedly increased in osteosarcoma, correlating with a negative prognosis. Through in vitro and in vivo experiments, we systematically identified HSPD1 as an important contributor to the regulation of proliferation, metastasis, and apoptosis in osteosarcoma by promoting the epithelial-mesenchymal transition (EMT) and activating AKT/mTOR signaling. Subsequently, ATP5A1 was determined as a potential target of HSPD1 using immunoprecipitation followed by mass spectrometry. Mechanistically, HSPD1 may interact with ATP5A1 to reduce the K48-linked ubiquitination and degradation of ATP5A1, which ultimately activates the AKT/mTOR pathway to ensure osteosarcoma progression and EMT process. These findings expand the potential mechanisms by which HSPD1 exerts biological effects and provide strong evidence for its inclusion as a potential therapeutic target in osteosarcoma.

Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.

This study integrates pharmacology databases with bulk RNA-seq and scRNA-seq to reveal the latent anti-PDAC capacities of BBR. Target genes of BBR were sifted through TargetNet, CTD, SwissTargetPrediction, and Binding Database. Based on the GSE183795 dataset, DEG analysis, GSEA, and WGCNA were sequentially run to build a disease network. Through sub-network filtration acquired PDAC-related hub genes. A PPI network was established using the shared genes. Degree algorithm from cytoHubba screened the key cluster in the network. Analysis of differential mRNA expression and ROC curves gauged the diagnostic performance of clustered genes. CYBERSORT uncovered the potential role of the key cluster on PDAC immunomodulation. ScRNA-seq analysis evaluated the distribution and expression profile of the key cluster at the single-cell level, assessing enrichment within annotated cell subpopulations to delineate the target distribution of BBR in PDAC. We identified 425 drug target genes and 771 disease target genes, using 57 intersecting genes to construct the PPI network. CytoHubba anchored the top 10 highest contributing genes to be the key cluster. mRNA expression levels and ROC curves confirmed that these genes showed good robustness for PDAC. CYBERSORT revealed that the key cluster influenced immune pathways predominantly associated with Macrophages M0, CD8 T cells, and naïve B cells. ScRNA-seq analysis clarified that BBR mainly acted on epithelial cells and macrophages in PDAC tissues. BBR potentially targets CDK1, CCNB1, CTNNB1, CDK2, TOP2A, MCM2, RUNX2, MYC, PLK1, and AURKA to exert therapeutic effects on PDAC. The mechanisms of action appear to significantly involve macrophage polarization-related immunological responses.

Identification of UNC5B as a novel aggressive biomarker for osteosarcoma based on basement membrane genes.

BACKGROUND: The prognosis of patients with metastatic osteosarcoma is poor, and the variation of basement membrane genes (BMGs) is associated with cancer metastasis. However, the role of BMGs in osteosarcoma has been poorly studied. METHODS: BMGs were collected and differentially expressed BMGs (DE-BMGs) were found through difference analysis. DE-BMGs were further screened by univariate Cox regression and Lasso regression analyses, and six key BMGs were identified and defined as basement membrane genes signatures (BMGS). Then, BMGS was used to construct the osteosarcoma BMGS risk score system, and the osteosarcoma patients were divided into high- and low-risk groups based on the median risk score. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE scores were used to investigate the differences in immune infiltration between the two scoring groups. Additionally, we investigated whether UNC5B affects various features in tumors by bioinformatic analysis and whether UNC5B was involved in multiple biological functions of osteosarcoma cells by wound healing assay, transwell assay, and western blot. RESULTS: The osteosarcoma BMGS risk score reliably predicts the risk of metastasis, patient prognosis, and immunity. UNC5B expression was elevated in osteosarcoma, and correlated with various characteristics such as immune infiltration, prognosis, and drug sensitivity. In vitro assays showed that UNC5B knockdown reduced osteosarcoma cells' capacity for migration and invasion, and EMT process. CONCLUSION: A novel BMGS risk score system that can effectively predict the prognosis of osteosarcoma was developed and validated. The UNC5B gene in this system is one of the key aggressive biomarkers of osteosarcoma.

Multi-physical field simulation calculation and analysis of simulated high-level waste liquid spray calcination.

Aiming at the independent research and development of a simulated high-level waste liquid spray calcination transformation treatment test device, a three-dimensional multi-physical field model of spray calcination was established by means of finite element analysis method. In this paper, the simulated high-level waste liquid is a mixed solution of nitrate solution and sucrose. The main chemical components of nitrate dissolution are HNO3 and NaNO3. The process of evaporation and calcination of high-level waste liquid to form oxides is also called the pretreatment of high-level waste liquid or the conversion of high-level waste liquid. In this experiment, the atomized droplets sprayed at high speed are evaporated, dried and calcined in turn in the calciner to obtain the calcined product. The distribution law of temperature flow field and chemical reaction state and results inside the test device were revealed by simulation calculation. The results show that under the condition of multi-physical field coupling, the chemical reaction temperature has an effect on the yield of the product. The temperature is positively correlated with the product concentration, and the effect of temperature on the yield of NO2 is greater than that of Na2O. At the same time, in this chemical reaction, the concentration of reactants (NaNO3 and HNO3) had a positive correlation with the concentration of main products (NO2 and Na2O). However, the rate of increase in the concentration of the main products (NO2 and Na2O) decreased with the increase of the concentration of the reactants (NaNO3 and HNO3).

An electrochemical H2S sensor based on the screen printing Fe@Pt/C/PTFE sensing electrode.

A novel electrochemical gas sensor for sensitive detection of H2S at room temperature is constructed based on the Fe@Pt/C composite material. The core-shell structured Fe@Pt catalyst was synthesized by a two-step reduction method and physically dispersed in Vulcan XC-72 carbon powders. The core-shell structure increases the effective catalytic surface area of Pt while significantly reducing the usage of the noble metal Pt, leading to improved catalytic performance and decreased production costs. Additionally, the mature screen-printing process is used to coat the catalyst film. A waterproof and breathable PTFE film was used as the substrate and the parameters in the screen printing process were also optimized to achieve the best gas sensing performance of the electrode film. Through the detection of hydrogen sulfide (H2S) with different concentrations, it is found that the sensor strictly shows linear correlation in the range of 1-20 ppm, R2 = 0.99974. Notably, the sensor exhibits high sensitivity (658.45 nA ppm-1) and a low detection limit of 0.33 ppm. Moreover, the consistency and stability of the sensor are satisfactory. The constructed gas sensor is expected to be well applied to industrial H2S detection.

A novel "on-off-on" electrochemiluminescence strategy based on RNA cleavage propelled signal amplification and resonance energy transfer for Pb2+ detection.

BACKGROUND: Lead (Pb) is one of the most toxic heavy-metal pollutants. Additionally, lead ions (Pb2+) can accumulate in the human body through the food chain, causing irreversible damage through organ damage and system disorders. In the past few years, the detection of Pb2+ has mainly relied on instrumental methods such as atomic absorption spectroscopy (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). Nonetheless, these techniques are complicated in terms of equipment and procedures, along with being time-intensive and expensive in terms of detection. These drawbacks have limited their wide application. Hence, there is a pressing need to develop detection techniques for Pb2+ that are not only cost-efficient but also highly sensitive and specific. RESULTS: A novel "on-off-on" electrochemiluminescence (ECL) sensor for detecting Pb2+ was developed based on the resonance energy transfer (RET) effect between AuNPs and boron nitride quantum dots (BN QDs) and the recognition of Pb2+ by DNAzyme along with the cleavage reaction of the substrate chain. Poly(6-carboxyindole)/stannic sulfide (P6ICA/SnS2) nanocomposite was employed as a co-reaction accelerator to consequently facilitate the production of intermediate SO4•-. This effective enhancement of the reaction led to an improved ECL intensity of BN QDs and enabled the sensor platform to exhibit a higher original ECL response. Benefiting from the combination of the DNAzyme signal amplification strategy with the "on-off-on" design, the ECL sensor showed satisfactory selectivity, good stability, and high sensitivity. This ECL sensor exhibited a linear detection range (LDR) of 10-12-10-5 M and a limit of detection (LOD) of 2.6 × 10-13 M. SIGNIFICANCE: In the present work, an "on-off-on" ECL sensor is constructed based on RET effect for ultrasensitive detection of Pb2+. P6ICA/SnS2 was investigated as the co-reaction accelerator in this sensor. Moreover, this ECL sensor exhibited excellent analytical capability for detecting Pb2+ in actual water samples, providing a method for detecting other heavy metal ions as well.

Transcriptome Analysis Reveals the Immune Infiltration Profiles in Cervical Cancer and Identifies KRT23 as an Immunotherapeutic Target.

Cervical cancer (CC) is one of the most common malignancies in women worldwide. Dismal prognosis rates have been associated with conventional therapeutic approaches, emphasizing the need for new strategies. Recently, immunotherapy has been used to treat various types of solid tumors, and different subtypes of the tumor microenvironment (TME) are associated with diverse responses to immunotherapy. Accordingly, understanding the complexity of the TME is pivotal for immunotherapy. Herein, we used two methods, "ssGSEA" and "xCell," to identify the immune profiles in CC and comprehensively assess the relationship between immune cell infiltration and genomic alterations. We found that more adaptive immune cells were found infiltrated in tumor tissues than in normal tissues, whereas the opposite was true for innate cells. Consensus clustering of CC samples based on the number of immune cells identified four clusters with different survival and immune statuses. Then, we subdivided the above four clusters into "hot" and "cold" tumors, where hot tumors exhibited higher immune infiltration and longer survival time. Enrichment analyses of differentially expressed genes (DEGs) revealed that the number of activated immune signaling pathways was higher in hot tumors than that in cold tumors. Keratin, type I cytoskeletal 23 (KRT23), was upregulated in cold tumors and negatively correlated with immune cell infiltration. In vitro experiments, real-time reverse transcription-quantitative polymerase chain reaction, cytometric bead arrays, and ELISA revealed that knockdown of KRT23 expression could promote the secretion of C-C motif chemokine ligand-5 and promote the recruitment of CD8+ T cells. We also constructed a model based on DEGs that exhibited a high predictive power for the survival of CC patients. Overall, our study provides deep insights into the immune cell infiltration patterns of CC. Moreover, KRT23 has huge prospects for application as an immunotherapeutic target. Finally, our model demonstrated a good predictive power for the prognosis of CC patients and may guide clinicians during immunotherapy.

Mid-Term Outcome after Tricuspid Valve Replacement.

OBJECTIVE: To evaluate the mid-term survival rate after tricuspid valve replacement (TVR). METHODS: We retrospectively studied 110 consecutive patients who underwent TVR from January 2007 to November 2017. A survival analysis was performed with the Kaplan-Meier method and the log-rank test. RESULTS: The median survival was 65.81 months. Mean age was 50 (range 39 to 59) years. Forty-eight patients (43.6%) were male, and 62 patients (56.4%) were female. Most of the patients (78.5%) were categorized into the New York Heart Association (NYHA) functional classes III/IV. Seventy-two patients (65.5%) had isolated TVR. Six-three patients (57.3%) had previously undergone heart surgery. The Kaplan-Meier survival rates at one year, three years, and five years were 59.0%±5%, 52.0%±6%, and 48.0%±6%, respectively. A Cox regression analysis demonstrated that the risk factors for mid-term mortality were advanced NYHA class (hazard ratio [HR] 2.430, 95% confidence interval [CI] 1.099-5.375, P=0.028), need for continuous renal replacement therapy (CRRT) treatment (HR 3.121, 95% CI 1.610-6.050, P=0.001), and need for intra-aortic balloon pump (IABP) treatment (HR 3.356, 95% CI 1.072-10.504, P=0.038). CONCLUSION: In TVR, impaired cardiac function before the operation and a need for CRRT or IABP treatment after the operation is independently associated with increased mid-term mortality.

Mid-term outcome after tricuspid valve replacement

Abstract Objective: To evaluate the mid-term survival rate after tricuspid valve replacement (TVR). Methods: We retrospectively studied 110 consecutive patients who underwent TVR from January 2007 to November 2017. A survival analysis was performed with the Kaplan-Meier method and the log-rank test. Results: The median survival was 65.81 months. Mean age was 50 (range 39 to 59) years. Forty-eight patients (43.6%) were male, and 62 patients (56.4%) were female. Most of the patients (78.5%) were categorized into the New York Heart Association (NYHA) functional classes III/IV. Seventy-two patients (65.5%) had isolated TVR. Six-three patients (57.3%) had previously undergone heart surgery. The Kaplan-Meier survival rates at one year, three years, and five years were 59.0%±5%, 52.0%±6%, and 48.0%±6%, respectively. A Cox regression analysis demonstrated that the risk factors for mid-term mortality were advanced NYHA class (hazard ratio [HR] 2.430, 95% confidence interval [CI] 1.099-5.375, P=0.028), need for continuous renal replacement therapy (CRRT) treatment (HR 3.121, 95% CI 1.610-6.050, P=0.001), and need for intra-aortic balloon pump (IABP) treatment (HR 3.356, 95% CI 1.072-10.504, P=0.038). Conclusion: In TVR, impaired cardiac function before the operation and a need for CRRT or IABP treatment after the operation is independently associated with increased mid-term mortality.

N-Terminal Pro-B-Type Natriuretic Peptide in Tricuspid Valve Replacement.

The aim of the present study was to retrospectively investigate the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in tricuspid valve replacement (TVR). A total of 73 TVR patients who had NT-proBNP measured on the first postoperative morning during a period of 10 years from February 2008 to December 2018 were included in the study. The endpoint was postsurgery all-cause in-hospital mortality. The outcome-based cut-point optimization was performed using X-tile software. NT-proBNP with the maximum χ2 score and the minimum P value will be used as the optimal cut-point. Kaplan-Meier analysis and log-rank test were adopted to calculate and compare survival rates stratified by tertiles and the cut-point. Predictive capabilities of NT-proBNP were tested using univariable and multivariable Cox regression. Overall, 20 (27.3%) in-hospital deaths occurred. Postsurgery hospital stay was 21 days (interquartile range, 16-32 day). NT-proBNP were divided into low (<1262 pg/mL), medium (1262-4003 pg/mL), and high (≥4003 pg/mL) tertiles. The optimal cut-off point determined using X-tile was 3639 pg/mL. Kaplan-Meier analysis revealed a strong association between worse survival and elevated NT-proBNP expressed as tertiles (log-rank P = 0.002) and stratified by optimal cut point (log-rank P < 0.001). Multivariable Cox survival analysis demonstrated that NT-proBNP was a strong predictor of mortality (logNT-proBNP hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.33-3.37; P = 0.002). In NT-proBNP tertiles model, multivariable Cox survival analysis showed that patients in the medium and high NT-proBNP tertiles had 6.32-fold (adjusted HR, 7.32; 95% CI, 0.76-70.69; P = 0.085) and 16.11-fold (adjusted HR, 17.11; 95% CI, 1.92-152.68, P = 0.011) increased risk for mortality, respectively, compared with patients in the low tertile. Elevated postoperative NT-proBNP level is a potential independent and strong in-hospital postsurgery mortality risk factor in TVR, thus may serve as a useful surrogate marker for risk-stratification.

In Vivo Generation of Gut-Homing Regulatory T Cells for the Suppression of Colitis.

Current therapies for gut inflammation have not reached the desired specificity and are attended by unintended immune suppression. This study aimed to provide evidence for supporting a hypothesis that direct in vivo augmentation of the induction of gut-homing regulatory T (Treg) cells is a strategy of expected specificity for the treatment of chronic intestinal inflammation (e.g., inflammatory bowel disease). We showed that dendritic cells (DCs), engineered to de novo produce high concentrations of both 1,25-dihydroxyvitamin D, the active vitamin D metabolite, and retinoic acid, an active vitamin A metabolite, augmented the induction of T cells that express both the regulatory molecule Foxp3 and the gut-homing receptor CCR9 in vitro and in vivo. In vivo, the newly generated Ag-specific Foxp3+ T cells homed to intestines. Additionally, transfer of such engineered DCs robustly suppressed ongoing experimental colitis. Moreover, CD4+ T cells from spleens of the mice transferred with the engineered DCs suppressed experimental colitis in syngeneic hosts. The data suggest that the engineered DCs enhance regulatory function in CD4+ T cell population in peripheral lymphoid tissues. Finally, we showed that colitis suppression following in vivo transfer of the engineered DCs was significantly reduced when Foxp3+ Treg cells were depleted. The data indicate that maximal colitis suppression mediated by the engineered DCs requires Treg cells. Collectively, our data support that DCs de novo overproducing both 1,25-dihydroxyvitamin D and retinoic acid are a promising novel therapy for chronic intestinal inflammation.

Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis.

Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (Treg) cells. Tolerogenic dendritic cells (TolDCs) are one such therapy. However, ex vivo generated TolDCs may be converted into immunogenic DCs in a proinflammatory environment. In this study, we identified a potential novel myelin-specific therapy that works with immunogenic DCs, hence without the in vivo conversion concern. We showed that immunization with DCs, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase for de novo synthesis of a focally high 1,25-dihydroxyvitamin D concentration in the peripheral lymphoid tissues, induced Treg cells. In addition, such engineered DCs, when pulsed with a myelin antigen, led to myelin-specific suppression of ongoing experimental allergic encephalomyelitis (an MS animal model), and the disease suppression depended on forkhead-box-protein-P3(foxp3)+ Treg cells. Our data support a novel concept that immunogenic DCs can be engineered for myelin-specific therapy for MS.-Li, C.-H., Zhang, J., Baylink, D. J., Wang, X., Goparaju, N. B., Xu, Y., Wasnik, S., Cheng, Y., Berumen, E. C., Qin, X., Lau, K.-H. W., Tang, X. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis.

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta-Analysis.

Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38-3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03-1.07, p < 0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.

Serum C-reactive protein level but not its gene polymorphism is associated with Takayasu arteritis.

Takayasu arteritis (TA) patients with active disease often have elevated serum C-reactive protein (CRP) levels, which usually decline with the disease remission. The serum CRP concentration has been showed to be related to CRP gene polymorphisms in previous studies. The present study aims to investigate the associations of serum level of CRP and CRP polymorphisms with TA. A total of 178 unrelated Chinese Han TA patients and 229 unrelated Chinese Han individuals without documented disease were enrolled in our studies. After a systemic search in the HapMap database, four single-nucleotide polymorphisms (SNPs) were selected, namely, rs1800947, rs3093077, rs1205, and rs2808630. The ligase detection reaction (LDR) was used in genotyping. CRP concentrations were determined using turbidimetric immunoassay. Genotype frequencies and allele frequencies of CRP variations were similar between TA patients and controls. CRP haplotype frequencies in patients were not significantly different from those of controls. No significant association between serum CRP concentrations and genotypes was found. Moreover, no association was found in CRP concentration between patients with types I, II, and III TA or between patients with or without pulmonary involvement. By contrast, serum CRP concentration was directly correlated with disease severity. In conclusion, CRP polymorphisms were not associated with TA susceptibility or serum CRP levels in the Chinese Han population. However, higher CRP level was correlated with a more serious disease status, which implies that CRP possibly contributes to the progression of TA.

Airway hyperresponsiveness induced by repeated esophageal infusion of HCl in guinea pigs.

Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.

The role of cardiac pacing in carotid sinus syndrome: a meta-analysis.

PURPOSE: Cardiac pacing can be used to treat carotid sinus syndrome (CSS), but clinical studies have shown conflicting results. We conducted a systematic review and meta-analysis to evaluate the role of pacing for CSS. METHODS: A systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. Prospective randomized studies that compared cardiac pacing with standard therapy or pacing with different algorithms were included if the recurrence of syncope or the number of falls was observed. RESULTS: Eight studies enrolling 540 patients were identified. In open-label studies, the recurrence of syncope was reduced significantly by cardiac pacing compared with standard therapy. The recurrence of syncope was not different between single- and dual-chamber pacing, but a lower rate of patients with pre-syncope was observed in the group with dual-chamber pacing. Double-blind clinical studies failed to observe the role of cardiac pacing for preventing falls in patients with CSS. CONCLUSION: The results of meta-analysis supported the use of cardiac pacing for patients with dominant cardioinhibitory CSS.

Relationships between use of statins and arterial stiffness in normotensive and hypertensive patients with coronary artery disease.

BACKGROUND: Statins improve arterial stiffness in patients with coronary artery disease (CAD). Hypertension is a predominant contributor of arterial stiffening. However, the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated. Therefore, in this study, we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients. METHODS: Brachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients, including 220 hypertensive CAD patients (121 used statins, 99 did not) and 217 normotensive CAD patients (105 used statins, 112 did not). The normotensive and hypertensive CAD patients were matched according to age, sex, and body mass index (BMI). RESULTS: In the normotensive and hypertensive CAD patients, lipid profiles were significantly improved in the statin group compared with the non-statin group. No significant differences in the administered statins (i.e., atorvastatin, simvastatin, rosuvastatin, and pravastatin) and statin therapy duration were found between normotensive and hypertensive CAD patients (all P > 0.05). No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients, normotensive CAD patients, or hypertensive CAD patients (all P > 0.05). ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients ((1331.68 ± 167.52) cm/s vs. (1468.61 ± 244.54) cm/s, P = 0.002) but not in hypertensive CAD patients (P > 0.05). In multiple linear regression analyses, statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P = 0.018) but not in hypertensive CAD patients (P > 0.05). CONCLUSIONS: Statins may significantly improve arterial stiffness in CAD patients, and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population. Further studies are required to investigate the effect of statins on arterial stiffness in normotensive and hypertensive CAD patients.

Associations between oxidized-lipoprotein receptor 1 G501C and 3'-UTR-C188T polymorphisms and coronary artery disease: a meta-analysis.

OBJECTIVE: Previous case-control studies have suggested that the variations of the oxidized-lipoprotein receptor 1 (OLR1) gene (G501C, 3'-UTR-C188T) are associated with coronary artery disease (CAD). However, other studies have not confirmed this relationship. The objective of this study was to assess the relationship between OLR1 variations and CAD. METHODS: We conducted a meta-analysis. Databases, including PubMed, EMbase, Chinese Biological Medical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched to obtain genetic association studies. Data were extracted by two authors, and pooled odds ratios (OR) with 95% CI were calculated. RESULTS: The meta-analysis included 8 studies with 4,963 cases and 14,864 controls for 3'-UTR-C188T and 9 studies with 5,660 cases and 15,405 controls for G501C. The pooled OR for 3'-UTR-188T was 1.29 (95% CI 1.05-1.58, p = 0.02) compared to the C allele in the dominant model, and it was 1.38 (95% CI 1.09-1.74, p = 0.007) in the recessive model. The pooled OR for 501C was 0.79 (95% CI 0.57-1.10, p = 0.16) compared to the G allele in the dominant model, and it was 0.86 (95% CI 0.71-1.04, p = 0.12) in the recessive model. No publication bias was found in the present meta-analysis. CONCLUSION: The synthesis of available evidence supports that OLR1 3'-UTR-188T increases the susceptibility to CAD. However, G501C is not associated with CAD.

Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population.

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.