Diverse Concepts in Definitions of Dilated Cardiomyopathy: Theory and Practice.

Our understanding of dilated cardiomyopathy (DCM) is evolving as new insights into the underlying pathophysiology become available. Professional organizations and clinical experts are improving definitions of DCM, allowing for more accurate treatment recommendations. This review summarized key published literature describing definitions and/or diagnostic criteria for DCM. Embase was searched from database inception to September 19, 2022 for 1) publications reporting definitions of DCM by major professional organizations and related opinion papers, and 2) clinical studies in DCM and heart failure with reduced ejection fraction. Sixty-eight records were included in this review. Definitions of DCM provided by two major professional organizations (American Heart Association (AHA) and European Society of Cardiology (ESC)) agreed on the clinical presentation of DCM; however, they differed in the classification of DCM within the larger context of cardiomyopathy taxonomies. Both organizations agreed that DCM could be clinically defined by the presence of left ventricular dilation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease. AHA guidelines divided cardiomyopathies into two major groups (primary and secondary) based on predominant organ involvement. DCM was classified as primary cardiomyopathy with mixed (genetic and/or acquired) etiology. Conversely, ESC published a clinically oriented taxonomy in which cardiomyopathies were grouped into specific morphological and functional phenotypes; each was subclassified into familial or non-familial forms. Opinion papers further elaborated on the complex interplay between genetics and environment in the etiology of DCM. Several articles summarized the importance of the new and updated diagnostic tools, such as cardiac magnetic resonance imaging, electrocardiogram, and other biomarkers, in correctly identifying the etiology of DCM. Within clinical studies, most inclusion criteria used standard definitions proposed by leading professional associations (AHA and ESC). Clinical study investigators sometimes used a narrower definition of DCM using additional criteria for the left ventricular ejection fraction threshold value and left ventricular dilatation. Current efforts in cardiology research are focused on a more granular understanding of DCM etiology and the natural history of the disease. Definitions of DCM found in clinical studies mainly rely on published guidelines, with some studies adding idiosyncratic inclusion criteria refining the broad definitions of DCM.

Roles of Nitric Oxide and Brassinosteroid in Improving Fruit Quality during Postharvest: Potential Regulators?

Most postharvest fruits are highly perishable, which directly impairs fruit taste and causes an economic loss of fresh products. Thus, it is necessary to find effective techniques to alleviate this issue. Recently, nitric oxide (NO) and brassinosteroid (BR) have been developed as postharvest alternatives to improve fruit quality. This work mainly reviews the recent processes of NO and BR in improving fruit quality during postharvest. Exogenous NO or BR treatments delayed fruit senescence, enhanced disease resistance, and alleviated chilling injury in postharvest fruit, and potential physiological and biochemical mechanisms mainly include (1) enhancing antioxidant and defense ability, (2) affecting ethylene biosynthesis, (3) regulating sugar and energy metabolism, (4) mediating plant hormone signaling, and (5) regulating protein S-nitrosylation and DNA methylation. This review concludes the functions and mechanisms of NO and BR in improving postharvest fruit quality. Additionally, a specific finding is the possible crosstalk of applications of NO and BR during postharvest fruit storage, which provides new insights into the applicability of NO and BR for delaying fruit senescence, enhancing disease resistances of fruit, and alleviating chilling injury in postharvest fruit.

Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence is highly correlated with increased mortality. Microvascular invasion (MVI) is indicative of aggressive tumor biology in HCC. AIM: To construct an artificial neural network (ANN) capable of accurately predicting MVI presence in HCC using magnetic resonance imaging. METHODS: This study included 255 patients with HCC with tumors < 3 cm. Radiologists annotated the tumors on the T1-weighted plain MR images. Subsequently, a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC. Postoperative pathological examination is considered the gold standard for determining MVI. Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm. RESULTS: Using the bagging strategy to vote for 50 classifier classification results, a prediction model yielded an area under the curve (AUC) of 0.79. Moreover, correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI, whereas tumor sphericity was significantly correlated with MVI (P < 0.01). CONCLUSION: Analysis of variable correlations regarding MVI in tumors with diameters < 3 cm should prioritize tumor sphericity. The ANN model demonstrated strong predictive MVI for patients with HCC (AUC = 0.79).

Structure and luminescence characteristics of self-activated vanadate garnet phosphors.

Vanadate phosphors include [VO4] tetrahedra with Td symmetry. Due to the charge transfer (CT) between V5+-O2-, the phosphor with [VO4] tetrahedra exhibits strong emission in the visible region and can effectively absorb ultraviolet (UV) light. Garnet structured vanadate phosphors have attracted much attention due to their easily controllable composition. In this paper, we successfully prepared phosphors with high quantum efficiency. The lattice structure and luminescent properties of the samples were studied in detail. Vanadate garnet phosphors have the same structure. The phosphors exhibit broadband emission peaks under 266 nm and 355 nm near-ultraviolet (UV) excitation, emitting bright greenish-white and yellowish-white light. The emission wavelength of the phosphor is red-shifted. The phosphors exhibit high internal quantum efficiency (IQE) for the NaSr2Mg2V3O12 and KCa2Mg2V3O12 samples. In this paper, the structure and luminescence characteristics of greenish-white-emitting and yellowish-white-emitting vanadate phosphors with high quantum efficiency are investigated.

The Kansas City Cardiomyopathy Questionnaire in Relation to New York Heart Association Class.

BACKGROUND: In order to identify candidacy and treatment response for patients with obstructive hypertrophic cardiomyopathy (oHCM), clinicians need an accurate means of assessing symptoms, function, and quality of life. While the New York Heart Association (NYHA) Classification is most often used, the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) is more accurate and sensitive to change, although less familiar to practicing clinicians. To support interpreting the KCCQ, we describe cross-sectional and changes in KCCQ scores in the context of the NYHA. METHODS: Participants from the EXPLORER-HCM trial (NCT03470545) completed the KCCQ-23 and clinicians assigned NYHA classes at study visits. Participants were included if they had baseline and week 30 data for cross-sectional and longitudinal changes. Median KCCQ-23 scores were compared by NYHA class at baseline and week 30 and by change in NYHA class from baseline to week 30. RESULTS: Cross-sectionally, the KCCQ-23 Overall Summary Scores (KCCQ-23 OSS) and Clinical Summary Scores (KCCQ-23 CSS) had an inverse relationship with NYHA at baseline and 30 weeks, with marked variations in KCCQ-23 scores among patients assigned to the same NYHA class. When improving from NYHA class II to I, the median changes in KCCQ-23 OSS and KCCQ-23 CSS were 10 (IQR 4, 22) and 8 (IQR 2, 20), respectively. The changes were larger when improving from NYHA class III to II and from NYHA class III to I. CONCLUSION: KCCQ-23 scores are inversely related to NYHA classes, with significant variability within classes. Changes in scores are not linear, suggest greater differences when patients move between NYHA Class II and III than Class I and II. These insights may help clinicians better understand cross-sectional and changes in KCCQ scores.

The Psychometric Performance of the Kansas City Cardiomyopathy Questionnaire-12 in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: A primary goal of treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function, and quality of life. While the psychometric properties of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) have been described in oHCM, they have not been assessed for the shorter 12-item version (KCCQ-12), which is increasingly used in clinical practice. METHODS AND RESULTS: Using data from the EXPLORER-HCM trial, the psychometric properties of the KCCQ-12 were evaluated. The KCCQ-12 domain and summary scores had moderate correlations with the most relevant clinical (New York Heart Association class, exercise duration, peak oxygen consumption) and patient-reported measures (EQ-5D-5L visual analog scale, Work Productivity and Activity Impairment [WPAI] questionnaire, and Hypertrophic Cardiomyopathy Symptom Questionnaire [HCMSQ]). KCCQ-12 domain scores had strong internal consistency and test-retest reliability, demonstrated significant and proportional changes with different magnitudes of clinical change (assessed with the patient global impression of change and patient impression of severity), and demonstrated close equivalence to the KCCQ-23 scores. CONCLUSIONS: The KCCQ-12 demonstrated good psychometric performance for patients with oHCM, comparable to that of the KCCQ-23, supporting its use in clinical practice to care for patients with oHCM.

The First-In-Class Deubiquitinase-Targeting Chimera Stabilizes and Activates cGAS.

Deubiquitinase-targeting chimera (DUBTAC) is a promising technology for inducing targeted protein stabilization (TPS). Despite its therapeutic potential, very few proteins have been stabilized by DUBTACs to date. The limited applicability of this technology is likely due to the modest DUBTAC-induced protein stabilization effect, and the scarcity of effective deubiquitinase ligands that can be harnessed for DUBTAC development. Here, we report the discovery of MS7829 and MS8588, the first-in-class DUBTACs of cGAS, a key component of the cGAS-STING pathway. While these DUBTACs are based on a cGAS inhibitor, they effectively stabilized cGAS and activated the cGAS/STING/IRF3 signaling. To develop these cGAS DUBTACs, we optimized EN523, an OTUB1 covalent ligand, into an improved ligand, MS5105. We validated MS5105 by generating a MS5105-based CFTR DUBTAC, which was approximately 10-fold more effective in stabilizing the ΔF508-CFTR mutant protein than the previously reported EN523-based CFTR DUBTAC. Overall, this work advances the DUBTAC technology for TPS.

Prevalence of Genetically Associated Dilated Cardiomyopathy: A Systematic Literature Review and Meta-Analysis.

Background: Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation globally. Disease-associated genetic variants play a significant role in the development of DCM. Accurately determining the prevalence of genetically associated DCM (genetic DCM) is important for developing targeted prevention strategies. This review synthesized published literature on the global prevalence of genetic DCM across various populations, focusing on two of the most common variants: titin (TTN) and myosin heavy chain 7 (MYH7). Methods: MEDLINE® and Embase were searched from database inception to September 19, 2022 for English-language studies reporting the prevalence of genetic DCM within any population. Studies using family history as a proxy for genetic DCM were excluded. Results: Of 2,736 abstracts, 57 studies were included. Among the global adult or mixed (mostly adults with few pediatric patients) DCM population, median prevalence was 20.2% (interquartile range (IQR): 16.3-36.0%) for overall genetic DCM, 11.4% (IQR: 8.2-17.8%) for TTN-associated DCM, and 3.2% (IQR: 1.8-5.2%) for MYH7-associated DCM. Global prevalence of overall pediatric genetic DCM within the DCM population was similar (weighted mean: 21.3%). Few studies reported data on the prevalence of genetic DCM within the general population. Conclusions: Our study identified variable prevalence estimates of genetic DCM across different populations and geographic locations. The current evidence may underestimate the genetic contributions due to limited screening and detection of potential DCM patients. Epidemiological studies using long-read whole genome sequencing to identify structural variants or non-coding variants are needed, as well as large cohort datasets with genotype-phenotype correlation analyses.

Structural characterization of Li2(MgxZn1-x)2W2O9 for bluish-white luminescence in rare earth-free tungstate phosphors.

Self-activated phosphors have attracted considerable attention due to their low synthesis temperature, high excitation threshold, and broad emission spectrum. And self-activated tungstate phosphors are distinguished by their low cost and stable chemical properties. Generally, it is difficult to observe luminescence from tungstate phosphors at room temperature. Furthermore, blue-emitting tungstate phosphors with high quantum efficiency are rarely reported. In this study, we succeeded in discovering high quantum-efficiency bluish-white-emitting Li2(MgxZn1-x)2W2O9 phosphors and investigating their detailed crystal structures. Upon near-ultraviolet excitation at 266 nm, these phosphors exhibit a broadband emission peak. The red shift of emission is slight with increasing Zn content in Li2(MgxZn1-x)2W2O9. A highly compact octahedral [WO6] unit is observed in the Li2(MgxZn1-x)2W2O9 phosphors. The phosphors exhibit high internal quantum efficiencies (IQEs) of 68.70% (M = Mg), 43.90% (M = Mg0.5Zn0.5), and 22.90% (M = Zn), respectively. This study provides a bluish-white-emitting tungstate phosphor with high quantum efficiency.

Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer's disease by enhancing microglial function.

[Effects of laser combined with periodontal basic treatment on periodontal indices, subgingival microflora, adiponectin, MMP-13 and IL-1ß in gingival crevicular fluid in patients with periodontitis].

PURPOSE: To investigate the effects of laser combined with periodontal basic treatment on periodontal indices, subgingival flora, adiponectin, matrix metalloproteinase-13 (MMP-13) and interleukin-1ß (IL-1ß) in patients with periodontitis. METHODS: A retrospective analysis was performed on 100 patients with periodontitis diagnosed and treated in Hengshui People's Hospital from December 2022 to July 2023. According to treatment methods, the patients were divided into control group (n=51) and experimental group (n=49). The control group received periodontal basic treatment, and the experimental group received laser treatment on the basis of the control group. The periodontal indexes, subgingival microflora, adiponectin, MMP-13, IL-1ß and bone metabolic factors of gingival crevicular fluid before and after treatment were compared between the two groups, as well as the clinical therapeutic effect. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: After treatment, probing depth(PD), bleeding on probing(BOP), gingival index(GI) and plaque index (PLI) in the experimental group were lower than before treatment (P＜0.05), PD, BOP and PLI in the control group were lower than before treatment (P＜0.05), and PD, BOP, GI and PLI in the experimental group were significantly lower than those in control group (P＜0.05). After treatment, Lactobacillus, Clostridium and Bacteroides in both groups were significantly lower than before treatment (P＜0.05), and the experimental group was significantly lower than the control group(P＜0.05). After treatment, adiponectin in gingival crevicular fluid increased in both groups compared with before treatment(P＜0.05), and MMP-13 and IL-1ß in gingival crevicular fluid decreased in both groups compared with before treatment (P＜0.05), and adiponectin in gingival crevicular fluid in the experimental group was significantly higher than that in the control group (P＜0.05), MMP-13 and IL-1ß in the experimental group were significantly higher than that in the control group (P＜0.05). After treatment, procollagenⅠtype N-terminal peptide (PINP), cross linked C-telopeptide of type Ⅰ collagen(CXT) and bone glaprotein (BGP) were significantly higher than those before treatment (P＜0.05), and the experimental group was significantly higher than the control group (P＜0.05). The total effective rate of the experimental group was significantly higher than that of the control group (P＜0.05). CONCLUSIONS: Laser combined with periodontal basic treatment can effectively improve periodontal indexes, reduce subgingival flora, increase the levels of adiponectin and bone metabolic factor in gingival crevicular fluid, reduce the levels of MMP-13 and IL-1ß in gingival crevicular fluid, and improve the clinical therapeutic effect in patients with periodontitis.

Effects of whole-body vibration on bone mineral density in postmenopausal women: an overview of systematic reviews.

OBJECTIVE: The aim of this study is to evaluate the findings of existing systematic reviews (SRs) and provide scientific evidence on the efficacy and safety of whole-body vibration (WBV) in improving bone mineral density (BMD) in postmenopausal women, to provide recommendations and guidance for future high-quality clinical research and SRs. METHODS: We conducted searches in six databases (SinoMed, CNKI, Cochrane Library, Embase, PubMed, Web of Science) from the inception of the databases until July 31, 2023. The language was limited to Chinese or English. The methodological quality, risk of bias, and evidence grade of outcomes were evaluated using AMSTAR-2, ROBIS, and GRADE, respectively. Additionally, the degree of overlap in randomized controlled trials (RCTs) among the SRs was calculated using corrected covered area (CCA). Furthermore, we performed quantitative synthesis or descriptive analysis of the relevant data. All relevant operations were independently conducted by two individuals. RESULTS: A total of 15 SRs were included in the analysis, out of which three were qualitative descriptions and 12 were meta-analyses. According to AMSTAR-2, only two SRs were rated as low or moderate, while the remaining 13 SRs were rated as critically low quality. The ROBIS assessment indicated that seven SRs had a low risk of bias, while 8 SRs had a high risk of bias. The overall findings suggest that WBV does not have a significant advantage in improving BMD in postmenopausal women. Furthermore, the CCA results revealed a high overlap in RCTs across five outcomes among the 15 SRs. Only five SRs reported specific adverse reactions/events experienced by participants after WBV interventions, and none of the SRs reported any severe adverse events. CONCLUSION: The existing evidence cannot establish definitive advantages of WBV in improving BMD in postmenopausal women. Therefore, we do not recommend the use of WBV for improving BMD in postmenopausal women. However, WBV may have potential value in maintaining BMD in postmenopausal women, further research is needed to confirm these findings.

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023.

Background: Donepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy. Methods: We retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age. Results: Of the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment. Conclusion: Our study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

[Cluster Analysis and Ablation Success Rate in Atrial Fibrillation Patients Undergoing Catheter Ablation]. / æˆ¿é¢¤å°„é¢‘æ¶ˆèžæ‚£è€ çš„èšç±»åˆ†æžåŠæ¶ˆèžæˆåŠŸçŽ‡è¯„ä»·.

Objective: Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes. Methods: The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t2 index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy. Results: Five statistically driven clusters were identified: 1) the younger age cluster (n=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (n=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (n=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (n=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (n=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant. Conclusions: This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.

The effect and potential mechanism of inulin combined with fecal microbiota transplantation on early intestinal immune function in chicks.

Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-ß secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.

DSN signal amplification strategy based nanochannels biosensor for the detection of miRNAs.

MiRNA-21 is recognized as an important biological marker for the diagnosis, treatment, and prognosis of breast cancer. Here, we have created a nanochannel biosensor utilizing the duplex-specific nuclease (DSN) signal amplification strategy to achieve the detection of miRNAs. In this system, DNA as the capture probe was covalently immobilized on the surface of nanochannels, which hybridized with the target miRNA and forms RNA/DNA duplexes. DSN could cleave the probe DNA in RNA/DNA duplexes, recycling target miRNA, which may again hybridized with other DNA probes. After N cycles, most of the DNA probes had been cleaved, and the content of miRNA could be quantified by detecting changes in surface charge density. This biosensor can distinguish miR-21 from non-complementary miRNAs and one-base mismatched miRNAs, with reliable detection limits as low as 1 fM in PBS. In addition, we had successfully applied this method to analysis of total RNA samples in MCF-7 cells and HeLa cells, and the nanochannels had also shown excellent responsiveness and strong anti-interference ability. This new method is expected to contribute to miRNA detection in clinical diagnostics, providing a unique approach to detecting and distinguishing disease-associated molecules.