A novel method for precise implantation of tracheal Y-shaped stent.

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

Impact of exercise training and diet therapy on the physical fitness, quality of life, and immune response of people living with HIV/AIDS: a randomized controlled trial.

BACKGROUND: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA. METHODS: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy. RESULTS: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition. CONCLUSIONS: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA.

An Evidence-Based Medical Review on Promoting Gastrointestinal Function Recovery After Colorectal Cancer Surgery.

Objective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC. Methods: Based on the hierarchical "6S" evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria. Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management. Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.

Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.

Chronic obstructive pulmonary disease trajectory: severe exacerbations and dynamic change in health-related quality of life.

BACKGROUND: The life trajectory of chronic obstructive pulmonary disease (COPD) remains unknown. PATIENTS AND METHODS: We collected data from two populations. In the first cohort, we recruited 375 patients with COPD from our hospital, and 1440 repeated assessments of quality of life (QoL) using the European Quality of Life-5 Dimensions questionnaire from 2006 to 2020. We analysed their dynamic changes using the kernel-smoothing method. The second cohort comprised 27 437 patients from the National Health Insurance (NHI) dataset with their first severe acute exacerbations (AEs) requiring hospitalisation from 2008 to 2017 were analysed for their long-term course of AEs. We employed a Cox hazard model to analyse the predictors for mortality or AEs. RESULTS: Cohorts from our hospital and NHI were male predominant (93.6 and 83.5%, respectively). After the first severe AE, the course generally comprised three phases. The first was a 1-year period of elevated QoL, followed by a 2-year prolonged stable phase with a slowly declining QoL. After the second AE, the final phase was characterised by a rapid decline in QoL. For NHI cohort, 2712 died during the 11-year follow-up, the frequency of the first AE was approximately 5 per 10 000 per day. The median time from the first to the second AE was 3 years, which decreased to less than 6 and 3 months from 4th to 5th and 8th to 9th AE, respectively. The frequency of AE was increased 10-fold and 15-fold and risk of subsequent AE was increased 12-fold and 20-fold after the 6th and the 10th AE, relative to the first. Male gender, heart failure comorbidities were associated with the risk of subsequent AE and death. CONCLUSIONS: The life trajectory of COPD includes the accelerated frailty phase, as well as elevated health and prolonged stable phase after the first AE.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Pleiotropic effects of different exonic nucleotide changes at the same position contribute to hemophilia B phenotypic variation.

BACKGROUND: The disease-causing effects of genetic variations often depend on their location within a gene. Exonic changes generally lead to alterations in protein production, secretion, activity, or clearance. However, owing to the overlap between proteins and splicing codes, missense variants can also affect messenger RNA splicing, thus adding a layer of complexity and influencing disease phenotypes. OBJECTIVES: To extensively characterize a panel of 13 exonic variants in the F9 gene occurring at 6 different factor IX positions and associated with varying severities of hemophilia B (HB). METHODS: Computational predictions, splicing analysis, and recombinant factor IX assays were exploited to characterize F9 variants. RESULTS: We demonstrated that 5 (38%) of 13 selected F9 exonic variants have pleiotropic effects. Although bioinformatic approaches accurately classified effects, extensive experimental assays were required to elucidate and deepen the molecular mechanisms underlying the pleiotropic effects. Importantly, their characterization was instrumental in developing tailored RNA therapeutics based on engineered U7 small nuclear RNA to mask cryptic splice sites and compensatory U1 small nuclear RNA to enhance exon definition. CONCLUSION: Overall, albeit a multitool bioinformatic approach suggested the molecular effects of multiple HB variants, the deep investigation of molecular mechanisms revealed insights into the HB phenotype-genotype relationship, enabling accurate classification of HB variants. Importantly, knowledge of molecular mechanisms allowed the development of tailored RNA therapeutics, which can also be translated to other genetic diseases.

Cell-cycle-linked growth reprogramming encodes developmental time into leaf morphogenesis.

How is time encoded into organ growth and morphogenesis? We address this question by investigating heteroblasty, where leaf development and form are modified with progressing plant age. By combining morphometric analyses, fate-mapping through live-imaging, computational analyses, and genetics, we identify age-dependent changes in cell-cycle-associated growth and histogenesis that underpin leaf heteroblasty. We show that in juvenile leaves, cell proliferation competence is rapidly released in a "proliferation burst" coupled with fast growth, whereas in adult leaves, proliferative growth is sustained for longer and at a slower rate. These effects are mediated by the SPL9 transcription factor in response to inputs from both shoot age and individual leaf maturation along the proximodistal axis. SPL9 acts by activating CyclinD3 family genes, which are sufficient to bypass the requirement for SPL9 in the control of leaf shape and in heteroblastic reprogramming of cellular growth. In conclusion, we have identified a mechanism that bridges across cell, tissue, and whole-organism scales by linking cell-cycle-associated growth control to age-dependent changes in organ geometry.

[Source Appointment and Assessment of Heavy Metal Pollution in Surface Dust in the Main District Bus Stops of Tianshui City].

In this study, a PMF model was used to identify the sources and pollution level of heavy metals in the surface dust of a bus station. On the basis of the traditional heavy metal pollution evaluation methods, the Hakanson toxicity response coefficient was used to modify the traditional weight. The matter-element extension theory was introduced to reflect the toxicological properties and hazard degree of the heavy metals, and the matter-element extension model was established to evaluate the pollution level of heavy metals in the surface dust of the study area. The results were compared with Igeo, PN, and RI. ① Except for Co and V, the other heavy metals were higher than the Gansu soil background values by 1.29-9.30 times. The points of Cu and Pb exceeded the rate by 100%, and Cr, Ni, and As exceeded the rate by 96.15%, 94.23%, and 96.15%, respectively. ② PMF showed that source 1 was a natural source, and its contribution rate to V was 32.12%. Source 2 was natural-traffic pollution sources, contributing 51.50% and 33.37% to Cu and Co, respectively. Source 3 was a construction waste pollution source, with contribution rates of 45.06% and 44.70% for Cr and Ni, respectively, and source 4 was a coal-traffic mixed source, with contribution rates of 49.89% and 75.25% for As and Pb, respectively. ③ The matter-element evaluation results showed that the surface dust of the bus stops was mainly class IV (moderately polluted), and 13% of sample points were still clean, 37% were moderately polluted, and 25% were slightly and heavily polluted. The results of this method were quite different from the PN results and were more consistent with the RI results, indicating that its evaluation results were more sensitive and can be used for heavy metal pollution assessment.

Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides.

Emerging data have shown that previously defined noncoding genomes might encode peptides that bind human leukocyte antigen (HLA) as cryptic antigens to stimulate adaptive immunity1,2. However, the significance and mechanisms of action of cryptic antigens in anti-tumour immunity remain unclear. Here mass spectrometry of the HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human breast cancer samples identified HLA-I-binding cryptic antigenic peptides that were noncanonically translated by a tumour-specific circular RNA (circRNA): circFAM53B. The cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and induced anti-tumour immunity. Clinically, the expression of circFAM53B and its encoded peptides was associated with substantial infiltration of antigen-specific CD8+ T cells and better survival in patients with breast cancer and patients with melanoma. Mechanistically, circFAM53B-encoded peptides had strong binding affinity to both HLA-I and HLA-II molecules. In vivo, administration of vaccines consisting of tumour-specific circRNA or its encoded peptides in mice bearing breast cancer tumours or melanoma induced enhanced infiltration of tumour-antigen-specific cytotoxic T cells, which led to effective tumour control. Overall, our findings reveal that noncanonical translation of circRNAs can drive efficient anti-tumour immunity, which suggests that vaccination exploiting tumour-specific circRNAs may serve as an immunotherapeutic strategy against malignant tumours.

Salvirrane A-F, six undescribed nordrimane sesquiterpene derivatives from Salvia castanea Diels f. tomentosa Stib and their cytotoxic activities.

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.

A novel GATA1 variant p.G229D causing the defect of procoagulant platelet formation.

INTRODUCTION: GATA1 is one of the master transcription factors in hematopoietic lineages development which is crucial for megakaryocytic differentiation and maturation. Previous studies have shown that distinct GATA1 variants are associated with varying severities of macrothrombocytopenia and platelet dysfunction. OBJECTIVE: To determine the underlying pathological mechanisms of a novel GATA1 variant (c. 686G > A, p. G229D) in a patient with recurrent traumatic muscle hematomas. METHODS: Comprehensive phenotypic analysis of the patient platelets was performed. Procoagulant platelet formation and function were detected using flow cytometry assay and thrombin generation test (TGT), respectively. The ANO6 expression was measured by qPCR and western blot. The intracellular supramaximal calcium flux was detected by Fluo-5N fluorescent assay. RESULTS: The patient displayed mild macrothrombocytopenia with defects of platelet granules, aggregation, and integrin αIIbß3 activation. The percentage of the procoagulant platelet formation of the patient upon the stimulation of thrombin plus collagen was lower than that of the healthy controls (40.9 % vs 49.0 % ± 5.1 %). The patient platelets exhibited a marked reduction of thrombin generation in platelet rich plasma TGT compared to the healthy controls (peak value: ∼70 % of the healthy controls; the endogenous thrombin potential: ∼40 % of the healthy controls). The expression of ANO6 and intracellular calcium flux were impaired, which together with abnormal granules of the patient platelets might contribute to defect of procoagulant platelet function. CONCLUSIONS: The G229D variant could lead to a novel platelet phenotype characterized by defective procoagulant platelet formation and function, which extended the range of GATA1 variants associated platelet disorders.

Effects of different chronic restraint stress periods on anxiety- and depression-like behaviors and tryptophan-kynurenine metabolism along the brain-gut axis in C57BL/6N mice.

Chronic restraint stress (CRS) is a widely used stimulus to induce anxiety- and depression-like behaviors, linked to alterations in tryptophan-kynurenine (TRP-KYN) metabolism in animals. This study assessed the effects of different CRS periods on anxiety- or depression-like behaviors and TRP-KYN metabolism along brain-gut axis in C57BL/6N mice. Results showed that one-week CRS decreased the open arm entries of mice in elevated plus maze and delayed latency of feeding in novelty suppressed feeding test. Four-week CRS reduced sucrose preference, increases forced swimming immobility time, and also induced anxiety-like behaviors of mice. UPLC-MS/MS analysis revealed decreased levels of the neurotoxic 3-hydroxykynurenine (3-HK) and quinolinic acid (QA), and an increase in the neuroprotective kynurenic acid (KA) in the hippocampus of one-week CRS mice; meanwhile, four-week CRS mice displayed a reduction in KA and increases in 3-HK and QA. In the colon, both one-week and four-week CRS mice exhibited significant reductions in 3-HK and QA, with a marked increase of KA exclusively in four-week CRS mice. Briefly, one-week CRS only induced anxiety-like behaviors with hippocampal neuroprotection in TRP-KYN metabolism, whereas four-week CRS caused anxiety- and depression-like behaviors with neurotoxicity. In the colon, during both CRS periods, KYN was metabolized in the direction of NAD+ production. However, four-week CRS triggered intestinal inflammation risk with increased KA. Summarily, slightly short-term stress has beneficial effects on mice, while prolonged chronic stress can lead to pathological changes. This study offers valuable insights into stress-induced emotional disturbances.

Low-intensity pulsed ultrasound enhances neurite growth in serum-starved human neuroblastoma cells.

Introduction: Low-intensity pulsed ultrasound (LIPUS) is a recognized tool for promoting nerve regeneration and repair; however, the intracellular mechanisms of LIPUS stimulation remain underexplored. Method: The present study delves into the effects of varying LIPUS parameters, namely duty cycle, spatial average-temporal average (SATA) intensity, and ultrasound amplitude, on the therapeutic efficacy using SK-N-SH cells cultured in serum-starved conditions. Four distinct LIPUS settings were employed: (A) 50 mW/cm2, 40%, (B) 25 mW/cm2, 10%, (C) 50 mW/cm2, 20%, and (D) 25 mW/cm2, 10%. Results: Immunochemistry analysis exhibited neurite outgrowth promotion in all LIPUS-treated groups except for Group D. Further, LIPUS treatment was found to successfully promote brain-derived neurotrophic factor (BDNF) expression and enhance the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) signaling pathways, as evidenced by western blot analysis. Discussion: The study suggests that the parameter combination of LIPUS determines the therapeutic efficacy of LIPUS. Future investigations should aim to optimize these parameters for different cell types and settings and delve deeper into the cellular response mechanism to LIPUS treatment. Such advancements may aid in tailoring LIPUS treatment strategies to specific therapeutic needs.

Effects of Resistance Training with Blood Flow Restriction on Explosive Power of Lower Limbs: A Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to compare changes in explosive power between blood flow restriction training and traditional resistance training protocols. Searches of PubMed, Scopus, Web of Science, and OVID Medline were conducted for studies. Inclusion criteria were: (a) healthy people; (b) randomized controlled or controlled trials; (c) outcome measures of explosive performance (peak power, rate of force development, jump performance, sprint performance, etc.); (d) involving a comparison between blood flow restriction training and traditional resistance training. Quality assessment was conducted using the Physiotherapy Evidence Database (PEDro) scale. A total of 12 studies (262 subjects) were finally included for analysis. The PEDro scale score had a median of 5 of 10 points (range: 3-6 points). Significant small to moderate improvements were observed in blood flow restriction training [jump: standard mean difference (SMD) of 0.36 (95% CI: 0.02; 0.69); sprint: SMD of 0.54 (95% CI: 0.00; 1.07); power: SMD of 0.72 (95% CI: 0.17; 1.27)] when compared to traditional resistance training. The findings indicate that blood flow restriction training is more effective in improving explosive power of lower limbs compared to traditional resistance training in healthy people. In addition, blood flow restriction with a wide cuff (≥ 10 cm) during training improved explosive power better than with a narrow cuff or during the rest interval. Blood flow restriction training is very suitable for athletes in short competitive seasons and those who are not able to tolerate high loads (i.e., rehabilitators and the elderly).

Beta-blockers reduce severe exacerbation in patients with mild chronic obstructive pulmonary disease with atrial fibrillation: a population-based cohort study.

BACKGROUND AND OBJECTIVE: Beta-blockers (BBs) decrease mortality and acute exacerbation (AE) rates in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease; however, information on their effects in patients with COPD and atrial fibrillation (AF) is limited. We aimed to assess the AE risk in patients with different severities of COPD and AF receiving BBs compared with that in patients receiving calcium channel blockers (CCBs). METHODS: This retrospective cohort study used data from the Taiwan National Health Insurance Database from 2009 to 2018. Outcomes included AE-related emergency room visits and hospitalisation. HRs and 95% CIs were estimated using the Cox proportional hazards model. COPD severity was classified as mild or severe based on exacerbation history. Sensitivity analyses included treatment and subgroup analyses, and competing risk adjustment. RESULTS: After propensity score matching, 4486 pairs of BB and CCB users from 13 462 eligible patients were included. The exacerbation risk for BB users was lower (HR 0.80; 95% CI 0.72 to 0.89) than that of CCB users. After stratification, BB benefits persisted in the mild COPD group (HR 0.75; 95% CI 0.66 to 0.85), unlike the severe COPD group (HR 0.95; 95% CI 0.75 to 1.20). The results of the subgroup analysis showed consistent protective effects even in patients without heart failure or myocardial infarction (adjusted HR 0.82; 95% CI 0.71 to 0.94). CONCLUSION: We found that BB use in patients with mild COPD and AF was associated with a lower exacerbation risk than CCB use, and that close monitoring of BB use in patients with severe COPD and AF is warranted.

HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA.

PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.

Analysis of Correlation Between Coronary Heart Disease and Genetic Polymorphism Detected by Gold Magnetic Nanoparticles Chromatography.

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD.

Intensive Lipid-Lowering Therapy as per the Latest Dyslipidemia Management Guideline in Predicting Favorable Long-Term Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Grafting: A Retrospective Cohort Study.

Background There are limited data on low-density lipoprotein cholesterol (LDL-C) goal achievement per the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia management guidelines and its impact on long-term outcomes in patients undergoing coronary artery bypass grafting (CABG). We investigated the association between LDL-C levels attained 1 year after CABG and the long-term outcomes. Methods and Results A total of 2072 patients diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were included. Patients were categorized by lipid levels at 1 year after CABG, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was evaluated. The goal of LDL-C <1.40 mmol/L was attained in only 310 patients (14.9%). During a mean follow-up of 4.2 years after the index 1-year assessment, 25.0% of the patients experienced MACCEs. Multivariable-adjusted hazard ratios (95% CIs) for MACCEs, cardiac death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and cardiac rehospitalization were 1.94 (1.41-2.67), 2.27 (1.29-3.99), 2.45 (1.55-3.88), 1.17 (0.63-2.21), 2.47 (1.31-4.66), and 1.87 (1.19-2.95), respectively, in patients with LDL-C ≥2.60 mmol/L, compared with patients with LDL-C <1.40 mmol/L. The LDL-C levels at 1-year post-CABG were independently associated with long-term MACCEs. Conclusions This retrospective analysis demonstrates that lipid goals are not attained in the vast majority of patients at 1 year after CABG, which is independently associated with the increased risk of long-term MACCEs. Further prospective, multicenter studies are warranted to validate if intensive lipid management could improve the outcomes of patients undergoing CABG.