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Background and aims: Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. Methods: We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Results: Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (ß = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; ß = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; ß = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (ß = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (ß = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Conclusion: Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.
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Background & Objective: Anemia in patients with heart failure (HF) is a growing concern. However, there has no bibliometric analysis in this area up to now. The aim of this study is to explore the status and trends in the field of anemia in HF through the bibliometric analysis, and to provide an outlook on future research. Methods: We retrieved publications from the Web of Science Core Collection database, and the following data analysis and visualization tools were utilized to perform data processing, statistical computing and graphics generation: VOSviewer (v.1.6.18), CiteSpace (v.6.2 R5), Scimago Graphica (v.1.0.36), Biblimatrix and Microsoft Excel. Results: We identified a total of 3490 publications from 2004 to 2023. The publications in the field of anemia in HF are growing steadily. The United States, the United Kingdom, and Italy were the leading countries in this area. Stefan D Anker, as the most influential author, held the most total citations and publications. Harvard University was the most productive institution in this area. The European Journal of Heart Failure had published the most papers. Through the analysis of co-citations, 14 major clusters based on cluster labels were identified. Keyword analysis showed that mortality, outcome, prevalence, and risk were the most frequent keywords, and the potential research hotspots in the future will be intravenous iron and iron deficiency. Conclusion: This study provides a comprehensive analysis of countries, authors, institutions, journals, co-cited references, and keywords in the field of anemia in HF through bibliometric analysis and data visualization. The status, hotspots and future trends in this field offer a reference for in-depth research. Further studies are necessary in the future to broaden the spectrum of research in this field, to evaluate comprehensive approaches to treating anemia in patients with HF, and to find rational targets for the management of anemia.
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Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.
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Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.
Subject(s)
Dimethylamines , Environmental Pollutants , Glucuronosyltransferase , Humans , Fluorescent Dyes , Uridine , Molecular Docking SimulationABSTRACT
BACKGROUND AND OBJECTIVE: Cardiac rehabilitation (CR) has been demonstrated to improve outcomes in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, the optimal CR initiation time and duration remain to be determined. This study aimed to explore the impact of the time factors on the CR outcomes in AMI patients who received PCI by the method of meta-regression analysis. METHODS: We searched five databases (PubMed, Embase, Cochrane Library, Web of Science and Google scholar) up to October 31, 2023. Meta-regression analysis was utilized to explore the impact of the time factors on the effect sizes. Subgroups with more than 3 studies were used for meta-regression analysis. RESULTS: Our analysis included 16 studies and a total of 1810 patients. The meta-regression analysis revealed that the initiation time and duration of CR had no significant impact on the occurrence of arrhythmia, coronary artery restenosis and angina pectoris. The initiation time and duration of CR also had no significant impact on the changes in left ventricular ejection fraction (LVEF, starting time: estimate = 0.160, p = 0.130; intervention time: estimate = 0.017, p = 0.149), left ventricular end-diastolic volume (LVEDV, starting time: estimate = - 0.191, p = 0.732; intervention time: estimate = - 0.033, p = 0.160), left ventricular end-systolic volume (LVESV, starting time: estimate = - 0.301, p = 0.464; intervention time: estimate = 0.015, p = 0.368) and 6-minute walk test (6MWT, starting time: estimate = - 0.108, p = 0.467; intervention time: estimate = 0.019, p = 0.116). CONCLUSION: Implementation of CR following PCI in patients with AMI is beneficial. However, in AMI patients, there is no significant difference in the improvement of CR outcomes based on different CR starting times within 1 month after PCI or different durations of the CR programs. It indicates that it is feasible for patients with AMI to commence CR within 1 month after PCI and continue long-term CR, but the time factors which impact CR are intricate and further clinical research is still needed to determine the optimal initiation time and duration of CR.
Subject(s)
Cardiac Rehabilitation , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Stroke Volume , Time Factors , Ventricular Function, LeftABSTRACT
BACKGROUND: Guanxinning tablet (GXNT), a Chinese patent medicine, is composed of salvia miltiorrhiza bunge and ligusticum striatum DC, which may play the role of endothelial protection through many pathways. We aimed to explore the molecular mechanisms of GXNT against atherosclerosis (AS) through network pharmacology and molecular docking verification. METHODS: The active ingredients and their potential targets of GXNT were obtained in traditional Chinese medicine systems pharmacology database and analysis platform and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. DrugBank, TTD, DisGeNET, OMIM, and GeneCards databases were used to screen the targets of AS. The intersection targets gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were performed in DAVID database. GXNT-AS protein-protein interaction network, ingredient-target network and herb-target-pathway network were constructed by Cytoscape. Finally, we used AutoDock for molecular docking. RESULTS: We screened 65 active ingredients of GXNT and 70 GXNT-AS intersection targets. The key targets of protein-protein interaction network were AKT1, JUN, STAT3, TNF, TP53, IL6, EGFR, MAPK14, RELA, and CASP3. The Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling pathway were the main pathways. The ingredient-target network showed that the key ingredients were luteolin, tanshinone IIA, myricanone, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone. The results of molecular docking showed that tanshinone IIA, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone all had good binding interactions with AKT1, EGFR and MAPK14. CONCLUSION: The results of network pharmacology and molecular docking showed that the multiple ingredients within GXNT may confer protective effects on the vascular endothelium against AS through multitarget and multichannel mechanisms. AKT1, EGFR and MAPK14 were the core potential targets of GXNT against AS.
Subject(s)
Atherosclerosis , Drugs, Chinese Herbal , Mitogen-Activated Protein Kinase 14 , Humans , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Atherosclerosis/drug therapy , ErbB Receptors , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
All-solid-state lithium-sulfur batteries (ASSLSBs) would be a promising candidate for the next-generation batteries due to the utilization of energy-dense electrodes and the non-flammable oxide solid-state electrolytes (SSEs), but still face great challenges such as low ionic conductivity of SSEs, poor interfacial contact and lithium (Li) dendrite propagation. Herein, we regulated the crystallinity degrees of the large-scale-fabricated Li1.5Al0.5Ge1.5(PO4)3 (LAGP) SSEs and explored the critical role of crystallinity optimization in reinforcing the basic properties of LAGP, developing a fundamental explanation for the inherent relation between the crystallinity and the performance of ASSLSBs. Benefiting from the optimized crystallinity (â¼99.9 %), the large-scale-fabricated LAGP not only realizes the low surface roughness and high ionic conductivity (2.11 × 10-4 S cm-1) to improve interfacial contact and reduce resistance in ASSLSBs, but also possesses the dense internal structure with low porosity (1.49 %) to physically resist dendritic propagation and penetration. Consequently, the ASSLSB with the optimized LAGP delivers a high reversible capacity of 647.9 mAh/g even after 150 cycles at 0.1 C. This work confirms the significance of crystallinity in understanding the working mechanisms of oxide SSEs and developing future high-performance ASSLSBs.
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Background: There is growing emphasis on the cardiotoxicity research over the past 12 years. To look for the hotspots evolution and to explore the emerging trends in the field of cardiotoxicity, publications related to cardiotoxicity were acquired from the Web of Science Core Collection on August 2, 2022. Methods: We used the CiteSpace 5.8 R3 and VOSviewer 1.6.18 to perform bibliometric and knowledge-map analysis. Results: A total of 8,074 studies by 39,071 authors from 6,530 institutions in 124 countries or regions were published in different academic journals. The most productive country was absolutely the United States, and the University of Texas MD Anderson Cancer Center was the institution with the largest output. Zhang, Yun published the most articles, and the author who had the most frequent co-citations was Moslehi, Javid. New England Journal of Medicine was the most frequently cited journals in this field. Mechanisms of cardiotoxicity have received the most attention and was the main research directions in the field. The disease of cardiotoxicity together with the related risk factors are potential research hotspots. Immune checkpoint inhibitor and myocarditis are two recently discussed and rapidly expanding research topic in the areas of cardiotoxicity. Conclusions: This bibliometric analysis provided a thorough analysis of the cardiotoxicity, which would provide crucial sources of information and concepts for academics studying this area. As a rapidly expanding field in cardiology, the related field of cardiotoxicity will continue to be a focus of research.
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Objective: To compare the efficacy and safety of bioresorbable scaffolds (BRS) with drug-eluting stents (DES) in patients with myocardial infarction undergoing percutaneous coronary interventions (PCI). Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing BRS with DES on clinical outcomes with at least 12 months follow-up. Electronic databases of PubMed, CENTRAL, EMBASE, and Web of Science from inception to 1 March 2022 were systematically searched to identify relevant studies. The primary outcome of this study was the device-oriented composite endpoint (DOCE) consisting of cardiac death, target-vessel myocardial infarction, and target lesion revascularization. Secondary outcomes were a composite of major adverse cardiac events (MACE, all-cause death, target-vessel myocardial infarction, or target vessel revascularization) and the patient-oriented composite endpoint (POCE, defined as a composite of all-cause death, myocardial infarction, or revascularization). The safety outcomes were definite/probable device thrombosis and adverse events. Results: Four randomized clinical trials including 803 participants with a mean age of 60.5 ± 10.8 years were included in this analysis. Patients treated with BRS had a higher risk of the DOCE (RR 1.62, 95% CI: 1.02-2.57, P = 0.04) and MACE (RR 1.77, 95% CI: 1.02-3.08, P = 0.04) compared with patients treated with DES. No significant difference on the POCE (RR 1.33, 95% CI: 0.89-1.98, P = 0.16) and the definite/probable device thrombosis (RR 1.31, 95% CI: 0.46-3.77, P = 0.61) were observed between BRS and DES. No treatment-related serious adverse events were reported. Conclusion: BRS was associated with a higher risk of DOCE and MACE compared with DES in patients undergoing PCI for myocardial infarction. Although this seems less effective in preventing DOCE, BRS appears as safe as DES. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=321501], identifier [CRD 42022321501].
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Resistive gas sensors are considered promising candidates for gas detection, benefiting from their small size, ease of fabrication and operation convenience. The development history, performance index, device type and common host materials (metal oxide semiconductors, conductive polymers, carbon-based materials and transition metal dichalcogenides) of resistive gas sensors are firstly reviewed. This review systematically summarizes the functions, functional mechanisms, features and applications of seven kinds of guest materials (noble metals, metal heteroatoms, metal oxides, metal-organic frameworks, transition metal dichalcogenides, polymers, and multiple guest materials) used for the modification and optimization of the host materials. The introduction of guest materials enables synergistic effects and complementary advantages, introduces catalytic sites, constructs heterojunctions, promotes charge transfer, improves carrier transport, or introduces protective/sieving/enrichment layers, thereby effectively improving the sensitivity, selectivity and stability of the gas sensors. The perspectives and challenges regarding the host-guest hybrid materials-based gas sensors are also discussed.
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PURPOSE: To establish and verify a novel radiation resistance related index for predicting biochemical recurrence and tumor immune environment in prostate cancer (PCa) patients. MATERIALS AND METHODS: The transcriptome information of PCa were obtained from GEO and TCGA portal. We identified radiation resistance related genes (RRGs) between radioresistant and radiosensitive PCa cells. We conducted multivariate Cox analysis to construct a novel radiation resistance related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Internal and external validations were conducted. Preliminary experimental verifications were performed. RESULTS: We identified 194 differentially expressed RRGs and three radiation resistance related molecular clusters for PCa. Moreover, we established a novel radiation resistance related index and succeeded in conducting internal and external validations. High-risk populations meant significantly worse BCRFS in training, testing and validating cohort. The area under receiver operating characteristic curve were 0.809, 0.698, and 0.712 in training, testing, and validating cohort. The immune microenvironment was significantly different between high and low-risk score patients. Preliminary experiment identified and validated three potential biomarkers related to radiation resistance (ZNF695, TM4SF19, CCDC3) of PCa. CONCLUSIONS: This study successfully established and verified a novel radiation resistance related index, which had an excellent performance in predicting BCR and tumor immune microenvironment in patients with PCa.
Subject(s)
Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/radiotherapy , ROC Curve , Risk Factors , Tumor Microenvironment/geneticsABSTRACT
A family of half-titanocene complexes bearing π,π-stacked aryloxide ligands and their catalytic performances towards ethylene homo-/co- polymerizations were disclosed herein. All the complexes were well characterized, and the intermolecular π,π-stacking interactions could be clearly identified from single crystal X-ray analysis, in which a stronger interaction could be reflected for aryloxides bearing bigger π-systems, e.g., pyrenoxide. Due to the formation of such interactions, these complexes were able to highly catalyze the ethylene homopolymerizations and copolymerization with 1-hexene comonomer, even without any additiveson the aryloxide group, which showed striking contrast to other half-titanocene analogues, implying the positive influence of π,π-stacking interaction in enhancing the catalytic performances of the corresponding catalysts. Moreover, it was found that addition of external pyrene molecules was capable of boosting the catalytic efficiency significantly, due to the formation of a stronger π,π-stacking interaction between the complexes and pyrene molecules.
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BACKGROUND Obstructive sleep apnea (OSA) is a common disease that can lead to intermittent hypoxia, increased sympathetic overdrive, and excessive oxidative stress, and eventually lead to cardiovascular/cerebrovascular diseases and metabolic disorders. The prevalence of OSA is reported to be higher in people with certain cardiovascular diseases (CVD). Therefore, the relationship between OSA and CVD has been gradually favored by researchers. MATERIAL AND METHODS Data were downloaded from the Web of Science Core Collection database. Citespace was used to remove duplicated data and construct knowledge visual maps. RESULTS A total of 7047 publications were obtained. The USA was the largest contributor as well as an important player in the cooperation network between nations. The leading institution was the Mayo Clinic. Our study ultimately identified the top 5 hotspots and 4 research frontiers in this field. Top 5 hotspots were: the specific types of obstructive sleep apnea-related cardiovascular and metabolic co-morbidities, the curative effects of CPAP on these co-morbidities, the specific mechanisms of co-morbidities, the importance of polysomnography on OSA and its co-morbidities with CVD, and the prevalence of OSA and its co-morbidities with CVD in particular populations. The top 4 frontiers were: the relationship between OSA and resistant hypertension, the molecular mechanisms of OSA and its co-morbidities with CVD, specific medications and treatment guidelines for the co-morbidities, and the mainstream research methods in this field. CONCLUSIONS This study provides insight and valuable information for researchers and helps to identify new perspectives concerning potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.
Subject(s)
Cardiovascular Diseases , Research , Sleep Apnea, Obstructive , Bibliometrics , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/therapy , Comorbidity , Continuous Positive Airway Pressure/methods , Disease Management , Humans , International Cooperation , Metabolic Networks and Pathways , Polysomnography/methods , Prevalence , Research/organization & administration , Research/statistics & numerical data , Risk Factors , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/metabolism , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapyABSTRACT
OBJECTIVE: To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG). METHODS: This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial. RESULTS: At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group. CONCLUSION: In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].
Subject(s)
Heart Failure , Quality of Life , Adult , Aged , Aged, 80 and over , Chronic Disease , Double-Blind Method , Heart Failure/drug therapy , Humans , Middle Aged , Natriuretic Peptide, Brain , Peptide Fragments , Prospective Studies , Stroke Volume , Ventricular Function, LeftABSTRACT
Several effectors from phytopathogens usually target various cell organelles to interfere with plant defenses, and they generally contain sequences that direct their translocation into organelles, such as chloroplasts. In this study, we characterized a different mechanism for effectors to attack chloroplasts in wheat (Triticum aestivum). Two effectors from Puccinia striiformis f. sp. tritici (Pst), Pst_4, and Pst_5, inhibit Bax-mediated cell death and plant immune responses, such as callose deposition and reactive oxygen species (ROS) accumulation. Gene silencing of the two effectors induced significant resistance to Pst, demonstrating that both effectors function as virulence factors of Pst. Although these two effectors have low sequence similarities and lack chloroplast transit peptides, they both interact with TaISP (wheat cytochrome b6-f complex iron-sulfur subunit, a chloroplast protein encoded by nuclear gene) in the cytoplasm. Silencing of TaISP impaired wheat resistance to avirulent Pst and resulted in less accumulation of ROS. Heterogeneous expression of TaISP enhanced chloroplast-derived ROS accumulation in Nicotiana benthamiana. Co-localization in N. benthamiana and western blot assay of TaISP content in wheat chloroplasts show that both effectors suppressed TaISP from entering chloroplasts. We conclude that these biotrophic fungal effectors suppress plant defenses by disrupting the sorting of chloroplast protein, thereby limiting host ROS accumulation and promoting fungal pathogenicity.
Subject(s)
Basidiomycota/physiology , Chloroplasts/metabolism , Plant Diseases/microbiology , Plant Immunity , Plant Proteins/metabolism , Triticum/immunology , Biological Transport , Disease Resistance , Triticum/microbiologyABSTRACT
IMPORTANCE: Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials. OBJECTIVE: To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period. DESIGN: We performed post hoc descriptive analyses of data from five trials conducted under EFIC. SETTING: Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada. PARTICIPANTS: Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury. EXPOSURES: Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study's enrollment period. OUTCOMES: TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification. RESULTS: Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew. CONCLUSIONS AND RELEVANCE: There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research.
Subject(s)
Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Emergencies , Humans , Informed Consent , Out-of-Hospital Cardiac Arrest/epidemiology , Out-of-Hospital Cardiac Arrest/therapy , Resuscitation , United States/epidemiologyABSTRACT
BACKGROUND: Percutaneous coronary intervention (PCI) is an effective revascularization strategy in patients with coronary heart disease (CHD). However, recent studies had indicated that postPCI patients usually suffer from a low-quality life. Cardiac rehabilitation (CR) has been recommended by numerous guidelines in the clinic for these patients. And Baduanjin exercise can significantly benefit patients with CHD. Regrettably, the effect of Baduanjin exercise on postPCI patients is still not clear. Therefore, this systematic review and meta-analysis protocol is planned to explore the effect of Baduanjin exercise in patients with CHD who have undergone PCI. METHODS: PubMed, Excerpta Medica Database, Cochrane Library, Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Database, and China National Knowledge Infrastructure will be searched for appropriate articles from respective inceptions until December 1th, 2020. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Disagreements will be resolved first by discussion and then by consulting a third author for arbitration. The primary outcome will include left ventricular ejection fraction. And the change in the scores on the Seattle Angina Questionnaire, SF-36 health survey scale, Zung Self-rating Anxiety scale and self-rating depression scale will be used as the secondary outcomes. RevMan 5.3 will be used for meta-analysis. RESULTS: This systematic review and meta-analysis will explore whether Baduanjin exercise is an effective intervention in postPCI patients. CONCLUSION: This systematic review and meta-analysis will provide convincing evidence of Baduanjin exercise that specifically focuses on CR of Baduanjin exercise on CHD after PCI. REGISTRATION NUMBER: INPLASY202130065.
Subject(s)
Cardiac Rehabilitation/methods , Coronary Disease/rehabilitation , Exercise Movement Techniques/methods , Medicine, Chinese Traditional/methods , Percutaneous Coronary Intervention/rehabilitation , Adolescent , Adult , Female , Humans , Male , Meditation/methods , Meta-Analysis as Topic , Randomized Controlled Trials as Topic , Research Design , Systematic Reviews as Topic , Treatment Outcome , Young AdultABSTRACT
Calcium phosphate cement (CPC) is promising for bone and dentin repair and regeneration. However, there has been no report of biphasic CPC for inducing dentin regeneration. The aim of this study was to develop a novel biphasic CPC containing ß-tricalcium phosphate (ß-TCP), and investigate its effects on odontogenic differentiation of human dental pulp stem cells (hDPSCs) and macrophage polarization. New biphasic CPC was formulated with different ratios of ß-TCP to an equimolar mixture of tetracalcium phosphate and dicalcium phosphate anhydrous. Mechanical properties, biocompatibility, and odontogenic differentiation induction ability of the cements and the inflammatory reaction to the cements were examined. A series of CPC containing ß-TCP were developed. CPC with 20% ß-TCP exhibited homogeneity and injectability, an acceptable setting time, and a twofold increase in compressive strength. Significant increases in hDPSCs' alkaline phosphatase activity, mineral deposit, DMP1 and DSPP gene, and protein expressions were obtained for 20% TCP-CPC, compared with traditional CPC (p < 0.01). The addition of ß-TCP did not promote macrophage polarization to the proinflammation phenotype. The addition of 10% and 20% ß-TCP promoted macrophage polarization to the anti-inflammatory phenotype. In conclusion, a biphasic ß-TCP-modified CPC was developed for the first time, demonstrating substantially increased dentin regeneration capability, while promoting macrophages to an anti-inflammation phenotype. The novel biphasic CPC is promising for tooth tissue engineering and dentin regeneration applications. Impact statement Dental pulp exposure from dental caries, wounds, or deep cavity preparation can cause pain and infection, which may lead to root canal treatment or tooth extraction. Maintaining pulp vitality is a major challenge in stomatology. We developed a new injectable ß-tricalcium phosphate (ß-TCP)-calcium phosphate cement (CPC) for the regeneration of dentin. Compared with traditional CPC, the new CPC +20%TCP possessed good cytocompatibility, acceptable injection force, higher compressive strength (increased by 63%), and greater odontogenic expression and mineral deposits (increased by more than twofolds), while avoiding any proinflammatory drawback. This new biphasic CPC is promising for dental pulp-capping, base, and liner applications to promote dentin regeneration, as well as potentially for bone tissue engineering applications, which warrant further studies.
Subject(s)
Dental Caries , Calcium Phosphates/pharmacology , Cell Differentiation , Dental Pulp , Dentin , Humans , Hydroxyapatites , Macrophages , Phenotype , Stem CellsABSTRACT
Mild hypothermia is a well-established technique for alleviating neurological injuries in clinical surgery. RNA-binding protein motif 3 (RBM3) has been identified as a crucial factor in mediating hypothermic neuroprotection, providing its induction as a promising strategy for mimicking therapeutic hypothermia. However, little is known about molecular control of RBM3 and signaling pathways affected by hypothermia. In the present study, human SH-SY5Y neuroblastoma cells were used as a neural cell model. Screening of signaling pathways showed that cold exposure led to inactivation of ERK and AMPK pathways, and activation of FAK and PLCγ pathways, with activities of p38, JNK and AKT pathways moderately changed. Next, various small molecule inhibitors specific to these signaling pathways were applied. Interestingly, only FAK-specific inhibitor exhibited a significant inhibitory effect on hypothermia-induced RBM3 gene transcription and protein expression. Likewise, FAK silencing using siRNA technique significantly abrogated the induction of RBM3 by hypothermia. Moreover, FAK inhibition accounted for an inactivation of Src, a known kinase downstream of FAK. Next, either the silencing of Src by siRNA or its inactivation by a chemical inhibitor, strongly blocked the induction of RBM3 by cooling. Notably, in HEK293 and PC12 cells, FAK/Src activation was also shown to be indispensable for hypothermia-stimulated RBM3 expression. Lastly, the CCK8 and Western blot assays showed that both FAK/Src inacitivation and their knockdown substantially abrogate the neuroprotective effects of mild hypothermia against rotenone in SH-SY5Y cells. These data suggest that FAK/Src signaling axis regulates the transcription of Rbm3 gene and mediates neuroprotective effects of mild hypothermia.