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PURPOSE: This study systematically reviewed our team's research on the mechanism and assessment of liver fibrosis in BA, summarized our experience, and discussed the future development direction. METHODS: In this study, Pubmed and Wanfang databases were searched to collect the literature published by our team on the mechanisms of liver fibrosis in BA and the assessment of liver fibrosis in BA, and the above research results were systematically reviewed. RESULTS: A total of 58 articles were retrieved. Among the included articles, 25 articles related to the mechanism of liver fibrosis in BA, and five articles evaluated liver fibrosis in BA. This article introduces the key pathways and molecules of liver fibrosis in BA and proposes a new grading system for liver fibrosis in BA. CONCLUSIONS: The new BA liver fibrosis grading method is expected to assess children's conditions, guide treatment, and improve prognosis more accurately. In addition, we believe that the TGF-ß1 signaling pathway is the most important in the study of liver fibrosis in BA, and at the same time, the study of EMT occurrence in BA should also be deepened to resolve the controversy on this issue.
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Atresia Biliar , Cirrosis Hepática , Humanos , Atresia Biliar/complicaciones , Cirrosis Hepática/diagnóstico , Factor de Crecimiento Transformador beta1/metabolismo , PronósticoRESUMEN
In this comprehensive review, we examine the intricate interplay between inflammation, ferroptosis, and atrial fibrillation (AF), highlighting their significant roles in AF pathophysiology and pathogenesis. Augmented inflammatory responses are pivotal to AF, potentially leading to atrial remodeling and reentry phenomena by impacting calcium channels and atrial tissue fibrosis. A strong correlation exists between inflammatory cytokines and AF, underscoring the importance of inflammatory signaling pathways, such as NOD-like receptor thermal protien domain associated protein 3 (NLRP3) inflammasome, Nuclear Factor kappa B (NF- κ B) signaling, and Tumor necrosis factor- α (TNF- α ) signaling in AF development. Ferroptosis, a non-apoptotic regulated mode of cell death, has been widely studied in relation to cardiovascular diseases including heart failure, myocardial infarction, cardiomyopathy, and reperfusion injury. The interaction between ferroptosis and inflammation is complex and mutually influential. While significant progress has been made in understanding the inflammation-AF relationship, the role of inflammation as a conduit linking ferroptosis and AF remains underexplored. The specific pathogenesis and key molecules of atrial fibrosis caused by ferroptosis are still not fully understood. Here we review the role of inflammatory signaling in ferroptosis and AF. We elucidated the association between ferroptosis and AF, aiming to unveil mechanisms for targeted inhibition of atrial cell fibrosis and to propose novel therapeutic strategies for AF. This exploration is vital for advancing our knowledge and developing more effective interventions for AF, a condition deeply intertwined with inflammatory processes and ferroptotic pathways.
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Objective: The goal of the research is to investigate the link between serum potassium levels and death after 28 days in sepsis patients, utilizing an extensive sample of patients from the multi-center Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Current research on serum potassium levels and 28-day mortality in sepsis patients is questionable. This study adds to the growing body of evidence linking serum potassium levels to the 28-day possibility of death in patients with sepsis. Methods: We collected 349,08 patients with sepsis from the retrospective cohort MIMIC-IV database, using serum potassium level on the first day of admission to the intensive care unit as the exposure variable and mortality at 28 days as the outcome variable. And controlled for confounding characteristics including gender, age, ethnicity, and vital signs during admission. Results: Serum potassium has a U-shaped connection with 28-day mortality in patients suffering from sepsis. The turning point was 4.10 mmol/L (95 % confidence interval: 4.03 to 4.22). Serum potassium and 28-day mortality were negatively linked on the inflection point's left side (OR: 0.72; 95 % CI: 0.63 to 0.83, P < 0.0001); on the opposing side of the point of inflexion, serum potassium was enthusiastically attached to 28-day mortality. (OR: 1.13; 95 % CI: 1.06 to 1.21, P < 0.0001). Conclusion: The research conducted found that too high or too low potassium levels were linked to a 28-day risk of mortality in humans with sepsis.
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AIMS: Pulsed field ablation (PFA) is an emerging non-thermal ablative modality demonstrating considerable promise for catheter ablation of atrial fibrillation (AF). However, these PFA trials have almost universally included only Caucasian populations, with little data on its effect on other races/ethnicities. The PLEASE-AF trial sought to study the 12-month efficacy and the safety of a multi-electrode hexaspline PFA catheter in treating a predominantly Asian/Chinese population of patients with drug-refractory paroxysmal AF. METHODS AND RESULTS: Patients underwent pulmonary vein (PV) isolation (PVI) by delivering different pulse intensities at the PV ostium (1800 V) and atrium (2000 V). Acute success was defined as no PV potentials and entrance/exit conduction block of all PVs after a 20-min waiting period. Follow-up at 3, 6, and 12 months included 12-lead electrocardiogram and 24-h Holter examinations. The primary efficacy endpoint was 12-month freedom from any atrial arrhythmias lasting at least 30 s. The cohort included 143 patients from 12 hospitals treated by 28 operators: age 60.2 ± 10.0 years, 65.7% male, Asian/Chinese 100%, and left atrial diameter 36.6 ± 4.9 mm. All PVs (565/565, 100%) were successfully isolated. The total procedure, catheter dwell, total PFA application, and total fluoroscopy times were 123.5 ± 38.8 min, 63.0 ± 30.7 min, 169.7 ± 34.6 s, and 27.3 ± 10.1 min, respectively. The primary endpoint was observed in 124 of 143 patients (86.7%). One patient (0.7%) developed a small pericardial effusion 1-month post-procedure, not requiring intervention. CONCLUSION: The novel hexaspline PFA catheter demonstrated universal acute PVI with an excellent safety profile and promising 12-month freedom from recurrent atrial arrhythmias in an Asian/Chinese population with paroxysmal AF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05114954.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Ablación por Catéter/métodos , Ablación por Catéter/efectos adversos , Venas Pulmonares/cirugía , Venas Pulmonares/fisiopatología , Anciano , Resultado del Tratamiento , Pueblo Asiatico , China , Catéteres Cardíacos , Recurrencia , Electrocardiografía Ambulatoria , Factores de Tiempo , Diseño de Equipo , Frecuencia Cardíaca , Potenciales de AcciónRESUMEN
Biochar is widely accepted as a green and effective amendment for remediating heavy metals (HMs) contaminated soil, but its long-term efficiency and safety changes with biochar aging in fields. Currently, some reviews have qualitatively summarized biochar aging methods and mechanisms, aging-induced changes in biochar properties, and often ignored the potential eco-environmental risk during biochar aging process. Therefore, this review systematically summarizes the study methods of biochar aging, quantitatively compares the effects of different biochar aging process on its properties, and discusses the potential eco-environmental risk due to biochar aging in HMs contaminated soil. At present, various artificial aging methods (physical aging, chemical aging and biological aging) rather than natural field aging have been applied to study the changes of biochar's properties. Generally, biochar aging increases specific surface area (SSA), pore volume (PV), surface oxygen-containing functional group (OFGs) and O content, while decreases pH, ash, H, C and N content. Chemical aging method has a greater effect on the properties of biochar than other aging methods. In addition, biochar aging may lead to HMs remobilization and produce new types of pollutants, such as polycyclic aromatic hydrocarbons (PAHs), environmentally persistent free radicals (EPFRs) and colloidal/nano biochar particles, which consequently bring secondary eco-environmental risk. Finally, future research directions are suggested to establish a more accurate assessment method and model on biochar aging behavior and evaluate the environmental safety of aged biochar, in order to promote its wider application for remediating HMs contaminated soil.
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Carbón Orgánico , Metales Pesados , Contaminantes del Suelo , Carbón Orgánico/química , Contaminantes del Suelo/análisis , Contaminantes del Suelo/química , Metales Pesados/análisis , Restauración y Remediación Ambiental , Suelo/química , Medición de RiesgoRESUMEN
Background: In recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA). Methods: Genome-wide association studies (GWAS) data of 41 inflammatory cytokines, 731 immune cell traits, and 1400 metabolites were obtained from public databases as exposure factors. The outcome information was obtained from a GWAS meta-analysis of 499 children with BA and 1928 normal controls. Inverse variance weighting was the primary causality analysis. Cochran Q-test, MR-Egger intercept, MR pleiotropy residual sum and outlier, and 'leave-one-out' analyses were used for sensitivity analysis. Reverse MR, MR-Steiger, and Linkage Disequilibrium Score were used to exclude the effects of reverse causality, genetic association, and linkage disequilibrium. Results: MR results showed that a total of seven traits had potential causal relationships with BA, including three inflammatory cytokines: eotaxin (odds ratio (OR)=1.45, 95% confidence interval (CI): 1.08 to 1.95, p FDR=0.18), G-CSF (OR=4.21, 95% CI: 1.75 to 10.13, p FDR=0.05) and MCP-1/MCAF (OR=1.53, 95% CI: 1.12 to 2.10, p FDR=0.14); three immune cell traits: CD8dim NKT/T cells ratio (OR=0.59, 95% CI: 0.45 to 0.77, p FDR=0.06), CD8dim NKT counts (OR=0.58, 95% CI: 0.43 to 0.78, p FDR=0.06), CD8dim NKT/lymphocyte ratio (OR=0.63, 95% CI: 0.49 to 0.81, p FDR=0.06); one metabolite: X-12261 levels (OR=2.86, 95% CI: 1.73 to 4.74, p FDR=0.06). Conclusions: In this study, eotaxin, G-CSF, MCP-1/MCAF, and X-12261 levels were shown to be risk factors for BA. However, CD8dim NKT/T cells ratio, CD8dim NKT counts, and CD8dim NKT/lymphocyte ratio were protective factors for BA. These findings provided a promising genetic basis for the etiology, diagnosis, and treatment of BA.
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly impacting patients' quality of life and increasing the risk of death, stroke, heart failure, and dementia. Over the past two decades, there have been significant breakthroughs in AF risk prediction and screening, stroke prevention, rhythm control, catheter ablation, and integrated management. During this period, the scale, quality, and experience of AF management in China have greatly improved, providing a solid foundation for the development of guidelines for the diagnosis and management of AF. To further promote standardized AF management, and apply new technologies and concepts to clinical practice in a timely and comprehensive manner, the Chinese Society of Cardiology of the Chinese Medical Association and the Heart Rhythm Committee of the Chinese Society of Biomedical Engineering have jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation. The guidelines have comprehensively elaborated on various aspects of AF management and proposed the CHA2DS2-VASc-60 stroke risk score based on the characteristics of AF in the Asian population. The guidelines have also reevaluated the clinical application of AF screening, emphasized the significance of early rhythm control, and highlighted the central role of catheter ablation in rhythm control.
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Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFß and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFß-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin-proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFß. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.
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Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Complejo de la Endopetidasa Proteasomal , Infarto del Miocardio/genética , Factor de Crecimiento Transformador beta , UbiquitinasRESUMEN
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly impacting patients' quality of life and increasing the risk of death, stroke, heart failure, and dementia. Over the past two decades, there have been significant breakthroughs in AF risk prediction and screening, stroke prevention, rhythm control, catheter ablation, and integrated management. During this period, the scale, quality, and experience of AF management in China have greatly improved, providing a solid foundation for the development of the guidelines for the diagnosis and management of AF. To further promote standardized AF management, and apply new technologies and concepts to clinical practice timely and fully, the Chinese Society of Cardiology of Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation. The guidelines comprehensively elaborated on various aspects of AF management and proposed the CHA2DS2VASc60 stroke risk score based on the characteristics of the Asian AF population. The guidelines also reevaluated the clinical application of AF screening, emphasized the significance of early rhythm control, and highlighted the central role of catheter ablation in rhythm control.
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Fibrilación Atrial , Ablación por Catéter , Guías de Práctica Clínica como Asunto , Fibrilación Atrial/terapia , Fibrilación Atrial/diagnóstico , Humanos , ChinaRESUMEN
The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.
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OBJECTIVE: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.
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Fibrilación Atrial , Compuestos de Bencidrilo , Glucósidos , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Fibrilación VentricularRESUMEN
Background: Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA. Methods: Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed. Results: A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I2=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I2=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I2=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I2=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I2=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I2=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I2=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I2=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I2=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I2=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I2=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups. Conclusions: For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.
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A 60-year-old male patient suffered from frequent episodes of atrial tachycardia (AT), after the index procedure of catheter ablation for paroxysmal atrial fibrillation. During the repeat procedure, the activation map showed that the earliest activation site was located at the roof of left atrium. Multiple ablations at the earliest activation site on the roof failed to terminate the AT; however, ablation within the pulmonary artery at an adjacent anatomical site successfully eliminated the AT, even without recording distinct near-field potential.
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BACKGROUND: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. HYPOTHESIS: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. STUDY DESIGN: Controlled laboratory study. METHODS: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. RESULTS: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P = .015) and migration (P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P = .005) and interleukin-1α (P = .042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P = .019) and fiber alignment (P < .001) of the repaired tendons. CONCLUSION: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. CLINICAL RELEVANCE: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries.
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Tendón Calcáneo , Traumatismos de los Tendones , Animales , Conejos , Tendón Calcáneo/patología , Tenocitos , Tejido Adiposo/patología , Traumatismos de los Tendones/cirugía , Macrófagos/patología , Células Madre/fisiología , Proliferación CelularRESUMEN
Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods.
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Conductos Biliares Extrahepáticos , Atresia Biliar , Humanos , Atresia Biliar/diagnóstico , Atresia Biliar/cirugía , HígadoRESUMEN
Optimal dosing of direct oral anticoagulants (DOACs) for stroke prevention in "gray area" patients with atrial fibrillation (AF) remains a challenge for clinicians. In Asia, this is concerning in patients who are very elderly, have low body weight, and are at a high risk of bleeding. This review aims to summarize the dose reduction criteria for DOACs, discuss the evidence on dosing of DOACs across Asian regions, and collate opinions from authors across Asia. Nonrecommended dosing of DOACs is common in Asia, primarily due to the fear of bleeding, with the total clinical benefit of higher dosing being overlooked. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care-Atrial Fibrillation Patients) trial and real-world case studies provide some evidence on the use of low-dose DOACs in gray area patients. Opinions on dose adjustment guidance, concomitant medication adjustments, and therapeutic drug monitoring were collated. Research is needed to fill the evidence gaps on optimal DOAC doses for gray area patients.
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PURPOSE: To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora. METHODS: A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography. RESULTS: Taxonomic analysis revealed significant differences in the composition of the intestinal microbiota between BA patients and controls, with a reduction in diversity and a higher abundance of Proteobacteria, Streptococcus and Lactobacillus in the BA group. Database and clinical data analyses concluded that Streptococcus/Bacteroides (AUC = 0.9035, 95% CI 0.8347-0.9722, P < 0.0001) or Streptococcus/Eggerthella (AUC = 0.8333, 95% CI 0.6340-1.000, P = 0.027) was the best microbiota to differentiate between BA and DC. Serum butyrate levels were low in the BA and DC groups and differed from the HC group (P = 0.01, P = 0.04). Butyrate levels in BA were negatively correlated with jaundice clearance and cholangitis, but not statistically significant. CONCLUSIONS: Our study reveals changes in the composition of the gut microbiota in BA, especially the butyrate-producing microbiota, and suggests the potential for using gut microbiota as a noninvasive diagnostic benefit for BA. Low levels of serum butyrate in BA may indicate a poor prognosis.
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Atresia Biliar , Microbioma Gastrointestinal , Niño , Humanos , Microbioma Gastrointestinal/genética , Butiratos , Pronóstico , ARN Ribosómico 16SRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a prevalent and chronic cardiovascular disorder associated with various pathophysiological alterations, including atrial electrical and structural remodeling, disrupted calcium handling, autonomic nervous system dysfunction, aberrant energy metabolism, and immune dysregulation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in the pathogenesis of AF. OBJECTIVE: This discussion aims to elucidate the involvement of AF-related lncRNAs, with a specific focus on their role as miRNA sponges that modulate crucial signaling pathways, contributing to the progression of AF. We also address current limitations in AF-related lncRNA research and explore potential future directions in this field. Additionally, we summarize feasible strategies and promising delivery systems for targeting lncRNAs in AF therapy. CONCLUSION: In conclusion, targeting AF-related lncRNAs holds substantial promise for future investigations and represents a potential therapeutic avenue for managing AF.
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BACKGROUND: Atrial fibrillation (AF) has been accepted as an inflammatory atrial myopathy. Interleukin 6 (IL-6)-dependent inflammatory signaling pathways take context-dependent effects on cardiovascular diseases. IL-6 trans-signaling is predominantly pro-inflammatory. However, its effect on AF is unclear. OBJECTIVE: The purpose of this study was to investigate the role of IL-6 trans-signaling in AF. METHODS: Circulating levels of IL-6, soluble IL-6 receptor, and soluble glycoprotein 130 (sgp130) in patients with AF and controls were measured to estimate the activation of IL-6 trans-signaling. A mouse model of AF was established by transverse aortic constriction surgery. Sgp130Fc administration was used for the selective blockade of IL-6 trans-signaling. Studies were conducted to evaluate the effects and underlying mechanisms of sgp130Fc on AF inducibility and atrial conduction abnormalities and structural remodeling. RESULTS: In patients, the elevation of IL-6 trans-signaling level was positively associated with AF occurrence. IL-6 trans-signaling activation was recapitulated in the mouse model of AF. In transverse aortic constriction-challenged mice, the selective blockade of IL-6 trans-signaling with sgp130Fc attenuated AF inducibility, which was attributable to the amelioration of slow conduction and conduction heterogeneity induced by atrial dilation, fibrosis, and reduction in connexin 40 and redistribution of connexin 43. Sgp130Fc administration also reduced immune cell infiltration and oxidative stress in the mouse atrium and abrogated IL-6 trans-signaling activation-mediated connexin dysregulation and reactive oxygen species production in atrial myocytes. CONCLUSION: IL-6 trans-signaling activation contributes to AF development, and its selective blockade may promise a novel therapeutic strategy.