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BACKGROUND: Poor sleep quality is common among hemodialysis patients and can significantly impact their well-being. This study aimed to evaluate the effectiveness of a structured nursing intervention program in improving sleep quality in middle-aged and elderly hemodialysis patients. AIM: To evaluate the impact of nursing intervention on sleep quality in hemodialysis patients. METHODS: This cross-sectional study was conducted in a tertiary hospital, the First Affiliated Hospital of Nanchang University, in 2023. This study included 105 middle-aged and elderly hemodialysis patients aged ≥ 45 years who underwent maintenance hemodialysis for at least 3 mo, utilizing the Pittsburgh Sleep Quality Index (PSQI) to identify poor sleepers. Those identified underwent a 12-wk nursing intervention program focusing on education, relaxation techniques, and counseling. Post-intervention, sleep quality was reassessed using the PSQI. RESULTS: The study found that 68.6% of hemodialysis patients were poor sleepers. Following the 12-wk nursing intervention program, there was a significant decrease in the mean global PSQI score from 8.9 ± 3.2 to 5.1 ± 2.7 (P < 0.001), indicating improved sleep quality. This demonstrated the effectiveness of the structured nursing intervention in enhancing sleep quality for middle-aged and elderly hemodialysis patients. CONCLUSION: The structured nursing intervention program focusing on sleep hygiene education, relaxation techniques, and counseling effectively improved sleep quality among middle-aged and elderly hemodialysis patients. The significant decrease in the mean global PSQI score post-intervention indicates the positive impact of tailored nursing interventions in addressing poor sleep quality in this patient population. These findings emphasize the importance of implementing targeted nursing interventions to enhance the quality of life for hemodialysis patients by addressing the prevalent issue of poor sleep quality.
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BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Paclitaxel , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angioplastia Coronaria con Balón/métodos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Anciano , Sirolimus/uso terapéutico , Sirolimus/administración & dosificación , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , China/epidemiología , Intervención Coronaria Percutánea/métodosRESUMEN
BACKGROUND: The relationship between long-term outcomes and operator experience for left atrial appendage occlusion (LAAO) is still unknown. OBJECTIVES: This study sought to explore the association between operator LAAO experience and one-year clinical outcomes. METHODS: The RECORD study (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With AF Using the WATCHMAN Left Atrial Appendage Closure Technology; NCT03917563) was a multicenter, prospective registry that included patients with the WATCHMAN LAAO device (Boston Scientific) in China from April 1, 2019, to October 31, 2020. The current analyses included patients with solely LAAO from the registry; those who had concomitant LAAO and ablation/other procedures were excluded. The primary outcome was a composite endpoint of death, stroke, systemic embolism, and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding at 1 year. RESULTS: A total of 1,547 LAAO patients and 111 operators were included. The mean ± SD CHA2DS2-VASc and HAS-BLED scores of patients were 4.0 ± 1.8 and 2.5 ± 1.1, respectively. The mean ± SD age of operators was 47.0 ± 7.2 years, 15 (13.5%) were female, and 52 (46.8%) were electrophysiologists. Utilizing maximally selected log-rank statistics, the thresholds to categorize an experienced operator were performing ≥32 LAAOs annually or ≥134 LAAOs in total. Performing ≥32 LAAOs annually is the better criterion than ≥134 LAAOs in total (absolute net reclassification index: 25.79%; P < 0.001). Compared with the ≥32 LAAO annually group, the <32 group was associated with a 1.8-fold (HRadjusted: 1.79; 95% CI: 1.16-2.78; P = 0.009) increase in the risk of the primary endpoint, and such risk in the <32 group can be reduced by â¼12% after performing each additional 5 cases (HRadjusted per 5 cases: 0.88; 95% CI: 0.78-0.99; P = 0.033). CONCLUSIONS: Performing ≥32 LAAOs annually could be a threshold to categorize an experienced operator. Before reaching this threshold, the risk of death, stroke, systemic embolism, and BARC-defined type 3 or 5 bleeding decreased by 12% after every 5 cases performed.
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Fibronectin type III domain containing 4 (FNDC4) is highly homologous with FNDC5, which possesses various cardiometabolic protective functions. Emerging evidence suggests a noteworthy involvement of FNDC4 in fat metabolism and inflammatory processes. This study aimed to characterize the role of FNDC4 in myocardial ischemia/reperfusion (MI/R) injury and decrypt its underlying mechanisms. MI/R models of mice were established to investigate the alteration of FNDC4 in plasma and myocardium. We observed that plasma FNDC4 in MI/R-injury mice and patients experiencing acute myocardial infarction were both significantly reduced as opposed to their respective controls. Likewise, FNDC4 expression of myocardium decreased markedly in MI/R mice compared to the sham-operated group. Mice of FNDC4 knockout and myocardial overexpression were further introduced to elucidate the role of FNDC4 in MI/R injury by detecting cardiomyocyte apoptosis, myocardial infarct size, and cardiac function. Ablation of FNDC4 exacerbated cardiac dysfunction, increased myocardial infarction area and cardiomyocyte apoptosis when matched with wild-type mice post-MI/R. In contrast, FNDC4 overexpression through intramyocardial injection of rAAV9-Fndc4 significantly ameliorated cardiac function, reduced myocardial infarction area and cardiomyocyte apoptosis compared to sham group. Additionally, hypoxia-reoxygenation (H/R) was used to induce cardiomyocyte apoptosis, and to further elucidate the direct effects of FNDC4 on cardiomyocytes in vitro, and the results demonstrated that neonatal rat ventricular cardiomyocytes overexpressing FNDC4 showed less H/R-induced apoptosis, as evidenced by cleaved caspase 3 expression, TUNEL staining and flow cytometry. By performing RNA-seq analysis followed by cause-effect analysis, ERK1/2-Nrf2 pathway-mediated antioxidative effects were responsible for the protective roles of FNDC4 on cardiomyocytes. In summary, FNDC4 exerts cardioprotection against MI/R injury predominantly through mitigating oxidative stress responses and reducing cardiomyocyte apoptosis. These insights solidify the proposition of FNDC4 as a potential therapeutic aim for tackling MI/R damage.
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Accumulating evidence strongly support the key role of NLRP3-mediated pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.
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Diabetes Mellitus Experimental , Eucaliptol , Células Endoteliales de la Vena Umbilical Humana , Inflamasomas , Piroptosis , Animales , Humanos , Masculino , Ratones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/prevención & control , Angiopatías Diabéticas/patología , Eucaliptol/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/efectos de los fármacos , Sirtuina 2/metabolismo , Sirtuina 2/antagonistas & inhibidoresRESUMEN
Background: Alzheimer's disease (AD) is a leading cause of dementia, characterized by the accumulation of amyloid-beta (Aß) and hyperphosphorylated tau proteins, leading to neuroinflammation and neuronal damage. The role of the immune system in AD pathogenesis is increasingly recognized, prompting an exploration of the causal relationship between immune cells and AD by using Mendelian randomization (MR) approaches. Methods: Utilizing genome-wide association study (GWAS) data from European cohorts, we conducted an MR study to investigate the causal links between immune cell phenotypes and AD. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a genome-wide significance threshold and applied various MR methods, including MR Egger, Weighted median, and inverse variance weighted analysis, to assess the causality between 731 immune phenotypes and AD. Results: Our MR analysis identified 15 immune cell types with significant causal relationships to AD pathogenesis. Notably, the absolute count of CD28-CD4-CD8- T cells and the expression of HLA DR on B cells were linked to a protective effect against AD, while 13 other immune phenotypes were identified as contributing to the risk factors for the disease. The causal effects of AD on immunophenotypic traits are predominantly negative, implying that AD may impair the functionality of immune cells. Validation through independent datasets, such as FinnGen and GCST90027158, confirmed the causal association between six specific immune cells and AD. Conclusion: This comprehensive MR study elucidates the intricate network of causal relationships between diverse immunophenotypic traits and AD, providing novel insights into the immunopathogenesis of AD. The findings suggest potential immunological targets that could be leveraged for early diagnosis, disease monitoring, and therapeutic intervention.
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The support has been provided by clinical trials and guidelines for managing patent foramen ovale (PFO) in adults; however, the optimal approach is still unclear for treating PFO in pediatric patients. PFO and its associated clinical syndromes, imaging diagnosis, and management in pediatric patients were analyzed by a comprehensive analysis. Extensive research was performed using electronic databases, including PubMed, Cochrane, Web of Science, and EMBASE. This review includes the studies published until February 1st, 2024. A total of 583 articles were obtained, of which 54 were included in the comprehensive review. Numerous evidences have indicated that a right-to-left shunt through a PFO may be involved in cryptogenic stroke in children, although the connection between migraine and aura has not been substantiated by robust evidence. Children with sickle cell disease and a PFO were at higher risks of paradoxical embolization, rare syndromes caused by PFO could also occur in children such as platypnea-orthodeoxia syndrome, myocardial infarction, and decompression sickness. Contrast transthoracic echocardiography was deemed the most appropriate examination for children due to its favorable transthoracic windows, eliminating the need for anesthesia. This review suggested that the additional treatment was not needed as no evidence was provided for potential future complications linked to isolated PFO in children. For children facing unique circumstances related to PFO, a customized interdisciplinary consultation is essential prior to considering medical interventions.
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BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).
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Angioplastia Coronaria con Balón , Catéteres Cardíacos , Fármacos Cardiovasculares , Materiales Biocompatibles Revestidos , Enfermedad de la Arteria Coronaria , Paclitaxel , Humanos , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/mortalidad , Resultado del Tratamiento , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , China , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Factores de Tiempo , Femenino , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Stents , Anciano , Stents Liberadores de Fármacos , Estudios de Equivalencia como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: The clinical efficacy and safety of a novel left atrial appendage (LAA) occluder of the SeaLA closure system in patients with nonvalvular atrial fibrillation (NVAF) were reported. BACKGROUND: Patients with NVAF are at a higher risk of stroke compared to healthy individuals. Left atrial appendage closure (LAAC) has emerged as a prominent strategy for reducing the risk of thrombosis in individuals with NVAF. METHODS: A prospective, multicenter study was conducted in NVAF patients with a high risk of stroke. RESULTS: The LAAC was successfully performed in 163 patients. The mean age was 66.93 ± 7.92 years, with a mean preoperative CHA2DS2-VASc score of 4.17 ± 1.48. One patient with residual flow >3 mm was observed at the 6-month follow-up, confirmed by TEE. During the follow-up, 2 severe pericardiac effusions were noted, and 2 ischemic strokes were observed. Four device-related thromboses were resolved after anticoagulation treatment. There was no device embolism. CONCLUSIONS: The LAAC with the SeaLA device demonstrates encouraging feasibility, safety, and efficacy outcomes.
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AIMS: ßII spectrin is a cytoskeletal protein known to be tightly linked to heart development and cardiovascular electrophysiology. However, the roles of ßII spectrin in cardiac contractile function and pathological post-myocardial infarction remodeling remain unclear. Here, we investigated whether and how ßII spectrin, the most common isoform of non-erythrocytic spectrin in cardiomyocytes, is involved in cardiac contractile function and ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: We observed that the levels of serum ßII spectrin breakdown products (ßII SBDPs) were significantly increased in patients with acute myocardial infarction (AMI). Concordantly, ßII spectrin was degraded into ßII SBDPs by calpain in mouse hearts after I/R injury. Using tamoxifen-inducible cardiac-specific ßII spectrin knockout mice, we found that deletion of ßII spectrin in the adult heart resulted in spontaneous development of cardiac contractile dysfunction, cardiac hypertrophy and fibrosis at 5 weeks after tamoxifen treatment. Moreover, at 1 week after tamoxifen treatment, although spontaneous cardiac dysfunction in cardiac-specific ßII spectrin knockout mice had not developed, deletion of ßII spectrin in the heart exacerbated I/R-induced cardiomyocyte death and heart failure. Furthermore, restoration of ßII spectrin expression via adenoviral small activating RNA (saRNA) delivery into the heart reduced I/R injury. Immunoprecipitation coupled with mass spectrometry (IP-LC-MS/MS) analyses and functional studies revealed that ßII spectrin is indispensable for mitochondrial complex I activity and respiratory function. Mechanistically, ßII spectrin promotes translocation of NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) from the cytosol to mitochondria by crosslinking with actin filaments (F-actin) to maintain F-actin stability. CONCLUSION: ßII spectrin is an essential cytoskeletal element for preserving mitochondrial homeostasis and cardiac function. Defects in ßII spectrin exacerbate cardiac I/R injury.
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Pemetrexed is a folate analog metabolic inhibitor that is given for therapy of non-small cell lung cancer (NSCLC). Drug resistance affects the efficacy of pemetrexed in NSCLC. Lentinan is a polysaccharide extracted from Shiitake mushrooms which has antitumor roles in multiple cancers, including lung cancer. However, the effects of lentinan on pemetrexed resistance in NSCLC remain unclear. In present study, The pemetrexed-resistant NSCLC cells were established and exposed to pemetrexed and lentinan. Oxidative stress was investigated via mitochondrial membrane potential (JC-1 staining), levels of MDA and SOD.The phosphorylation and total of PI3K and Akt levels were actuated using specific activator 740Y-P and measured through western blot. We observed that Lentinan decreased IC50 of pemetrexed in resistant NSCLC cells. Lentinan aggravated pemetrexed-induced proliferation inhibition of resistant NSCLC cells via reducing PCNA levels. Lentinan exacerbated pemetrexed-triggered oxidative stress through increasing ROS and MDA levels, and reducing mitochondrial membrane potential and SOD levels. Lentinan inhibited PI3K/Akt signaling activation in pemetrexed-treated cells. Activated PI3K/Akt pathway using activator 740Y-P reversed the effects of lentinan on pemetrexed-mediated proliferation inhibition and oxidative stress. Our findings uncover that Lentinan mitigates pemetrexed resistance in NSCLC through inhibiting cell proliferation and inducing oxidative stress by suppressing PI3K/Akt signaling.
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Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Lentinano , Neoplasias Pulmonares , Estrés Oxidativo , Pemetrexed , Transducción de Señal , Humanos , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Lentinano/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Pemetrexed/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVES: To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis. METHODS: After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis. RESULTS: Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed. CONCLUSION: The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.
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Biomarcadores , Modelos Animales de Enfermedad , Infertilidad Masculina , Animales , Masculino , Ratas , Biomarcadores/metabolismo , Infertilidad Masculina/metabolismo , Infertilidad Masculina/etiología , Testículo/metabolismo , Testículo/patología , Riñón/metabolismo , Riñón/patología , Ratas Sprague-Dawley , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo , Hepatopatías/metabolismo , Hepatopatías/patología , Insuficiencia Renal/metabolismo , Insuficiencia Renal/patología , Insuficiencia Renal/etiologíaRESUMEN
The swelling behaviors and water retention of superabsorbent materials prepared from acrylic acid/acrylamide copolymer and acid-modified attapulgite under ultrasonic treatment and different pH conditions were investigated. The results demonstrated that a suitable amount of attapulgite can effectively improve the absorption capacity. The superabsorbent achieved the highest absorptions of 1257.54 g g-1 and 209.45 g g-1 in distilled water and a 0.9 wt% NaCl solution, and a higher water absorbency occurred over a wide pH range of 5-9 when the ultrasonic power was 200 W, and the attapulgite content was 10%. Addition of attapulgite could significantly increase the water absorption and retention of this kind of material, which can be applied as a sand-fixing material.
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BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.
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This study compared the therapeutic effect and safety between warfarin anticoagulation and percutaneous left atrial appendage transcatheter occlusion (PLAATO) in non-valvular atrial fibrillation (NVAF). A total of 110 patients were selected and assigned to Control group (n=55) and Observation group (n=55). The control patients were used warfarin, while the observation patients were performed PLAATO. The coagulation function, stroke and bleeding scores were compared between the two groups at different times. Left ventricular function before therapy and 1 year after therapy and adverse events during follow-up were compared between the two groups. After one month of treatment, CHA2DS2-VASC, HAS-BLED score, serum ET-1 and hs-CRP levels were lower in the PLAATO patients than in warfarin patients, but serum PDGFs levels were higher than patients in the warfarin patients (P < 0.05). One month after treatment, the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of the PLAATO patients was longer than that of the warfarin patients (P < 0.05), but the levels of fibrinogen (FIB) in the PLAATO patients were lower than that of the warfarin patients (P < 0.05). In addition, one year after therapy, the left atrial end-diastolic volume (LAEDV), left atrial end-systolic volume (LAESV) and left atrial inner diameter of the two groups were significantly reduced (P < 0.05). Left atrial appendage (LAA) occlusion can effectively improve the cardiac function and coagulation function of NVAF patients, with lower incidence of bleeding events, stroke events and higher safety.
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Anticoagulantes , Fibrilación Atrial , Coagulación Sanguínea , Cierre del Apéndice Auricular Izquierdo , Warfarina , Warfarina/efectos adversos , Warfarina/farmacología , Anticoagulantes/efectos adversos , Anticoagulantes/farmacología , Fibrilación Atrial/sangre , Fibrilación Atrial/terapia , Apéndice Atrial/fisiopatología , Accidente Cerebrovascular/etiología , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hemorragia/etiología , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Tiempo de Trombina , Coagulación Sanguínea/efectos de los fármacos , Endotelina-1/sangre , Proteína C-Reactiva/análisisRESUMEN
(1) BACKGROUND: Hashimoto's thyroiditis (HT) can cause angiogenesis in the thyroid gland. However, the molecular mechanism of endothelial cells and angiogenesis related genes (ARGs) has not been extensively studied in HT. (2) METHODS: The HRA001684, GSE29315 and GSE163203 datasets were included in this study. Using single-cell analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, machine learning algorithms and expression analysis for exploration. And receiver operator characteristic (ROC) curves was draw. Gene set enrichment analysis (GSEA) was utilized to investigate the biological function of the biomarkers. Meanwhile, we investigated into the relationship between biomarkers and different types of immune cells. Additionally, the expression of biomarkers in the TCGA-TC dataset was examined and the mRNA-drug interaction network was constructed. (3) RESULTS: We found 14 cell subtypes were obtained in HT samples after single-cell analysis. A total of 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were derived, and they had excellent diagnostic performance. Then, 27 drugs targeting biomarkers were predicted. The expression analysis showed that CD74 and HLA-B were significantly up-regulated in HT samples. (4) CONCLUSION: In this study, 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were screened and their expressions in endothelial cells was compared to offer a new reference for the recognition and management of HT.
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Células Endoteliales , Enfermedad de Hashimoto , Neovascularización Patológica , Análisis de la Célula Individual , Transcriptoma , Humanos , Enfermedad de Hashimoto/genética , Enfermedad de Hashimoto/diagnóstico , Análisis de la Célula Individual/métodos , Células Endoteliales/metabolismo , Neovascularización Patológica/genética , Biomarcadores/metabolismo , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN/métodos , AngiogénesisRESUMEN
Balloon angioplasty achieves luminal enlargement by fracturing the atherosclerotic intima at its point of least resistance, thereby creating a dissection plane and space with dehiscence of the intima from the media. This barotraumatic dissection triggers an inflammatory and proliferative reaction, resulting in a restenosis process at medium-term. In the era of plain old balloon angioplasty, quantitative angiographic studies at follow-up demonstrated that - the greater the acute luminal gain was after balloon angioplasty, the greater the late luminal loss was at follow-up. The interventional cardiologists coined the following motto "the more you gain, the more you lose". However, in the current era of drug coated balloon (DCB), it appears that this vexing conundrum could have been abrogated. A recently published DCB study in small de novo vessel has demonstrated that there was a slightly negative correlation between the volume of dissection assessed by optical coherence tomography and the angiographic late luminal loss (now gain) after Paclitaxel coated balloon treatment. In other words, the barotraumatic dissection does not necessarily herald a restenosis process in the era of DCB. This article revisits the mechanism of balloon angioplasty and explores how DCB with Paclitaxel may change the paradigm of balloon angioplasty as default treatment in CAD percutaneous treatment.
RESUMEN
Recent publications have shown the benefits of deacetylation disc-refining (DDR) as a pretreatment process to deconstruct biomass into sugars and lignin residues. Major advantages of DDR pretreatment over steam and dilute acid pretreatment are the removal of acetyl and lignin during deacetylation. DDR does not generate hydroxymethylfurfural (HMF) and furfural which are commonly produced from steam and dilute acid pretreatments. Acetate, lignin, HMF, and furfural are known inhibitors during enzymatic hydrolysis and fermentation. Another advantage of deacetylation is the production of lignin-rich black liquor, which can be upgraded to other bioproducts. Furthermore, due to the lack of sugar degradation during deacetylation, DDR has significantly less sugar loss than other pretreatment methods. Previous studies for DDR have primarily focused on corn stover, but lacked the investigative studies of other feedstocks. This study was designed to screen various DDR process conditions at pilot scale using three different feedstocks, including corn stover, poplar, and switchgrass. The impact of the pretreatment conditions was evaluated by testing hydrolysates for bioconversion to 2,3-butanediol. Pretreatment of biomass by DDR showed high-conversion-yields and 2,3-BDO fermentation production yields. Techno-economic analysis (TEA) of the pretreatment for biomass to sugar was also developed based on NREL's Aspen Model. This study shows that the cellulose and hemicellulose in poplar was more recalcitrant than herbaceous feedstocks which ultimately drove up the sugar cost. Switchgrass was also more recalcitrant than corn stover but less than poplar.
RESUMEN
BACKGROUND: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. PURPOSE: This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. METHODS: A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate mitochondrial transcription factor A (TFAM) was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. RESULTS: GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated TFAM, mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. CONCLUSION: The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.
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Alcoholes Bencílicos , Demencia Vascular , Glucósidos , Mitocondrias , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Sirtuina 3 , Sirtuinas , Animales , Glucósidos/farmacología , Demencia Vascular/tratamiento farmacológico , Sirtuina 3/metabolismo , Alcoholes Bencílicos/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Masculino , Acetilación , Fármacos Neuroprotectores/farmacología , Ratones , Factores de Transcripción/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de Unión al ADN/metabolismo , Ratas , Modelos Animales de Enfermedad , Línea Celular , Resveratrol/farmacología , Gastrodia/químicaRESUMEN
As a cost-effective photocatalyst, carbon nitride (g-C3N4) holds tremendous promise for addressing energy shortages and environmental pollution. However, its application is limited by disadvantages such as low specific surface area and easy recombination of photogenerated electron-hole pairs. This study introduces C and O co-doped g-C3N4 with a three-dimensional (3D) structure achieved through a straightforward one-step calcination process, demonstrating excellent photocatalytic activity of hydrogen production and oxytetracycline degradation, with superoxide radicals as the primary active species. We propose a plausible enhanced mechanism based on systematic characterizations and density functional theory calculations. The 3D structure confers a substantial specific surface area, enhancing both the adsorption area and active sites of catalysts while bolstering structural stability. Co-doping optimizes the band structure and electric conductivity of the catalyst, facilitating rapid migration of photogenerated charges. The synergistic effects of these enhancements significantly elevate the photocatalytic performance. This study presents a convenient and feasible method for the preparation of dual-regulated photocatalysts with outstanding performance.