Effects of Renal Denervation on Gap Junction in High-Pacing-Induced Heart Failure Dogs.

BACKGROUND: Gap junction remodeling is an important cause of ventricular arrhythmia in heart failure. However, it remains unclear whether renal denervation (RDN) regulates gap junction remodeling in heart failure. To explore the effect of RDN on gap junction remodeling in dogs with high-pacing-induced heart failure. METHODS: Fifteen dogs were randomly divided into control (n = 5), heart failure (HF) (n = 5), and RDN+HF (n = 5) group. A high-pacing-induced-heart failure model was established using rapid right ventricular pacing for 4 weeks. The RDN+HF group underwent surgical and chemical ablation of both renal arteries before 4 weeks rapid right ventricular pacing. After 4 weeks, echocardiography, High-Performance Liquid Chromatography-Mass Spectrometry test for norepinephrine and epinephrine, and pathological analysis were performed in the above 3 groups. Further, immunohistochemical staining was used to detect tyrosine hydroxylase, ChaT, connexin 43 (Cx43), and connexin 40 (Cx40). Connexin 43 and Cx40 expression was detected by western blotting. Transmission electron microscopy was used to observe the gap junction. RESULTS: Compared to the control group, myocardial fibrosis and sympathetic hyperactivity were observed in the HF group. Immunohistochemical staining and western blotting showed that Cx40 expression and Cx43 expression was significantly reduced in the HF group. Compared with the HF group, the RDN+HF group showed reduced sympathetic hyperactivity, Cx40 expression, Cx40/Cx43 ratio, and increased Cx43 expression. CONCLUSION: Renal denervation alleviates gap junction remodeling in high-pacing-induced heart failure dogs.

A fast visual onsite method for detection and quantitation of food additives using an engineered metal nanohybrid-based catalyst.

Unsafe food additives pose a significant threat to global health, especially in developing countries. Many existing methods rely on clean laboratories, complicated optics equipment, trained personnel and lengthy detection time, which are not suitable for onsite food safety inspections in emergency situations, peculiarly in impoverished areas. In this paper, a fast and visual onsite method is designed for the detection and quantification of additives in food safety by engineering a nanohybrid (MoS2/SDBS/Cu-CuFe2O4)-based catalysis. Interestingly, the nanohybrid presents peroxidase-like mimetic activity toward the substrate containing 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), which are then integrated simply into a detection kit. The blue oxidated TMB in this kit can be converted completely to colorless by some bio-molecule additives in commercial food, such as glutathione (GSH), cysteine (Cys), and ascorbic acid (AA). Remarkably, this process takes just less than 2 min and the detection limits are 2.8 nM, 5.5 nM and 47 nM, respectively. These results show excellent repeatability with a statistical analysis with (*P < 0.05) over 30 tests. Next, the images of the color changes can be captured clearly using a smartphone by red-green-blue (RGB) channels, which provides an opportunity for the development of field-operation device. Additionally, our approach is applied to some targets-indicative foods, showing a recovery range between 95.8 % and 104.2 %, offering an attractive and promising pathway for future practical food safety inspection applications. More importantly, this method can easily be extended to the detection of reducing substances in other analytical fields.

Portable Detection of Lysine Acetyltransferase Activity in Lung Cancer Cells Based on a Miniature Electrochemical Sensor.

The detection of lysine acetyltransferases is crucial for diagnosing and treating lung cancer, highlighting the necessity for highly efficient detection methods. We developed a portable, highly accurate, and sensitive technique using fast-scan cyclic voltammetry (FSCV) to determine the activity of the lysine acetyltransferase TIP60, employing a novel miniature electrochemical sensor. This approach involves a compact electrochemical cell, merely 3 mm in diameter, that holds solutions up to 50 µL, equipped with a conductive indium tin oxide working electrode. Uniquely, this system operates on a two-electrode model compatible with the FSCV, obviating the traditional requirement for a reference electrode. The system detects TIP60 activity through the continuous generation of CoA molecules that engage in reactions with Cu(II), thereby significantly improving the accuracy of the acetylation analysis. Remarkably, the detection limit achieved for TIP60 is notably low at 3.3 pg/mL (S/N = 3). The results show that the reversible dynamic acetylation can be effectively regulated by inhibitor incubation and glucose stimulation. This cutting-edge strategy enhances the analysis of a broad spectrum of biomarkers by modifying the responsive unit, and its miniaturization and portability significantly amplify its applicability in biomedical research, promising it to be a versatile tool for early diagnostic and therapeutic interventions in lung cancer.

A case of endocardial dissection caused by Micra implantation.

BACKGROUND: Leadless pacemakers are a recent technological advancement. It has many advantages, but there are still a few serious complications. CASE PRESENTATION: This article reports the case of a patient with an endocardial tear and dissection caused by contact with the tip of the Micra cup during surgery and summarises the relevant data. CONCLUSIONS: This case report details the occurrence and management of the incident and provides some guidance for future clinical management.

Neuroimmune modulation mediated by IL-6: A potential target for the treatment of ischemia-induced ventricular arrhythmias.

BACKGROUND: Neural remodeling in the left stellate ganglion (LSG), as mediated by neuroimmune reactions, promotes cardiac sympathetic nerve activity (SNA) and thus increases the incidence of ventricular arrhythmias (VAs). Interleukin-6 (IL-6) is an important factor of the neuroimmune interaction. OBJECTIVE: The present study explored the effects of IL-6 on LSG hyperactivity and the incidence of VAs. METHODS: Eighteen beagles were randomly allocated to a control group (saline with myocardial infarction [MI], n = 6), adeno-associated virus (AAV) group (AAV with MI, n = 6), and IL-6 group (overexpression of IL-6 via AAV vector with MI, n = 6). Ambulatory electrocardiography was performed before and 30 days after AAV microinjection into the LSG. LSG function and ventricular electrophysiology were assessed at 31 days after surgery, and a canine MI model was established. Samples of the LSG were collected for immunofluorescence staining and molecular biological evaluation. Blood samples and 24-hour Holter data were obtained from 24 patients with acute MI on the day after they underwent percutaneous coronary intervention to assess the correlation between IL-6 levels and SNA. RESULTS: IL-6 overexpression increased cardiac SNA and worsened postinfarction VAs. Furthermore, sustained IL-6 overexpression enhanced LSG function, promoted expression of nerve growth factor, c-fos, and fos B in the LSG, and activated the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway. Clinical sample analysis revealed a correlation between serum IL-6 levels and heart rate variability frequency domain index as well as T-wave alternans. CONCLUSION: IL-6 levels are correlated with cardiac SNA. Chronic overexpression of IL-6 mediates LSG neural remodeling through the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway, elevating the risk of VA after MI.

Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia.

The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.

A sensitive AAV transduction inhibition assay assists evaluation of critical factors for detection and concordance of pre-existing antibodies.

Pre-existing antibodies to viral capsids may have a negative impact on the efficacy and safety of adeno-associated virus (AAV)-based gene therapies. Total antibody (TAb) and/or cell-based transduction inhibition (TI) assays have been used to exclude seropositive individuals in clinical studies. Published AAV seroprevalence and patient enrollment criteria regarding antibody status lack comparability between assay formats, hindering a direct cross-study comparison. To identify critical factors impacting TI assay detection of AAV neutralizing antibodies (NAbs), we created a reporter construct expressing NanoLuc® luciferase (Nluc) that enabled a more sensitive and robust detection of AAV6 NAbs than using firefly luciferase. Assessment of additional factors including multiplicity of infection, cell lines, viral production, and capsid purity revealed the reporter is the major determinant of assay sensitivity impacting NAb detection. The Nluc reporter was further used to assess seroprevalence to AAV5, 8, and 9. Last, we compared AAV6 Nluc TI with two TAb assay formats. A higher correlation of Nluc TI was observed with direct binding (90%) than with the more sensitive bridging TAb assay (65%), suggesting both assay sensitivity and TAb formats contribute to AAV seropositivity concordance. Our results support a need to standardize assay formats to ensure proper assessment of pre-existing AAV immunity.

Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine.

Nasopharyngeal immune responses are vital for defense against SARS-CoV-2 infection. Although vaccination via muscle immunization has shown a high efficacy in reducing severity and death in COVID-19 infection, breakthrough infection frequently happens because of mutant variants and incompletely established mucosal immunity, especially in the upper respiratory tract. Here, we performed a single-cell RNA and T-cell receptor repertoire sequencing and delineated a high-resolution transcriptome landscape of nasopharyngeal mucosal immune and epithelial cells in vaccinated persons with breakthrough infection and non-vaccinated persons with natural infection as control. The epithelial cells showed anti-virus gene expression diversity and potentially recruited innate immune cells into the nasopharyngeal mucous of vaccinated patients. Upon infection, they released significant pro-inflammatory cytokines and chemokines by macrophages and monocytes and expressed antigen-presenting relevant genes by dendritic cells. Such immune responses of nasopharyngeal innate immune cells would facilitate the strengthened expression of cytotoxic genes in virus-specific T-cell or B-cell differentiation into antibody-secreting cells at the early stage of breakthrough infection through cell interaction between innate and adaptive immune cells. Notably, these alterations of nasopharyngeal immune cells in breakthrough infection depended on the activated Nuclear factor-κB (NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) signaling rather than type I interferon responses due to the general reduction in interferon-stimulated gene expression. Our findings suggest that vaccination potentially strengthens innate immune barriers and virus-specific memory immune cell responses, which could be quickly activated to defend against variant breakthrough infection and maintain nasopharyngeal epithelial cell integrity. Thus, this study highlights the necessity of a boost via nasal mucous after intramuscular immunization.

Desmosomal Junctions and Connexin-43 Remodeling in High-Pacing-Induced Heart Failure Dogs.

BACKGROUND: While desmosomal junctions and gap junction remodeling are among the arrhythmogenic substrates, the fate of desmosomal and gap junctions in high-pacing-induced heart failure remains unclear. This aim of this study was to determine the fate of desmosomal junctions in high-pacing-induced heart failure. METHODS: Dogs were randomly divided into 2 equal groups, a high-pacing-induced heart failure model group (heart failure group, n = 6) and a sham operation group (control group, n = 6). Echocardiography and cardiac electrophysiological examination were performed. Cardiac tissue was analyzed by immunofluorescence and transmission electron microscopy. The expression of desmoplakin and desmoglein-2 proteins was detected by western blot. RESULTS: A significant decrease in ejection fraction, significant cardiac dilatation, diastolic and systolic dysfunction, and ventricular thinning occurred after 4 weeks in high-pacing-induced dog model of heart failure. Effective refractory period action potential duration at 90% repolarization was prolonged in the heart failure group. Immunofluorescence analysis and transmission electron microscopy demonstrated connexin-43 lateralization accompanies desmoglein-2 and desmoplakin remodeling in the heart failure group. Western blotting showed that the expression of desmoplakin and desmoglein-2 proteins was higher in heart failure than in normal tissue. CONCLUSION: Desmosome (desmoglein-2 and desmoplakin) redistribution and desmosome (desmoglein-2) overexpression accompanying connexin-43 lateralization were parts of a complex remodeling in high-pacing-induced heart failure.

Case clustering, contact stratification, and transmission heterogeneity of SARS-CoV-2 Omicron BA.5 variants in Urumqi, China: An observational study.

Background: From August to September 2022, Urumqi, the capital of the Xinjiang Uygur Autonomous Region in China, faced its largest COVID-19 outbreak caused by the emergence of the SARS-CoV-2 Omicron BA.5.2 variants. Although the superspreading of COVID-19 played an important role in triggering large-scale outbreaks, little was known about the superspreading potential and heterogeneity in the transmission of Omicron BA.5 variants. Methods: In this retrospective observational, contact tracing study, we identified 1139 laboratory-confirmed COVID-19 cases of Omicron BA.5.2 variants, and 51 323 test-negative close contacts in Urumqi from 7 August to 7 September 2022. By using detailed contact tracing information and exposure history of linked case-contact pairs, we described stratification in contact and heterogeneity in transmission across different demographic strata, vaccine statuses, and contact settings. We adopted beta-binomial models to characterise the secondary attack rate (SAR) distribution among close contacts and modelled COVID-19 transmission as a branching process with heterogeneity in transmission governed by negative binomial models. Results: After the city lockdown, the mean case cluster size decreased from 2.0 (before lockdown) to 1.6, with decreased proportions of contacts in workplace and community settings compared with household settings. We estimated that 14% of the most infectious index cases generated 80% transmission, whereas transmission in the community setting presented the highest heterogeneity, with 5% index cases seeding 80% transmission. Compared with zero, one, and two doses of inactivated vaccine (Sinopharm), index cases with three doses of vaccine had a lower risk of generating secondary cases in terms of the reproduction number. Contacts of female cases, cases with ages 0-17 years, and household settings had relatively higher SAR. Conclusions: In the context of intensive control measures, active case detection, and relatively high vaccine coverage, but with an infection-naive population, our findings suggested high heterogeneity in the contact and transmission risks of Omicron BA.5 variants across different demographic strata, vaccine statuses, and contact settings. Given the rapid evolution of SARS-CoV-2, investigating the distribution of transmission not only helped promote public awareness and preparedness among high-risk groups, but also highlighted the importance of continuously monitoring the transmission characteristics of genetic variants of SARS-CoV-2.

A Woman With Recurrent Syncope and Malar Flush in the Setting of a Left Atrial Echogenic Mass.

This case report discusses a diagnosis of myxomatous left atrial tumor in a middle-aged woman who presented for evaluation of syncope.

Postcardiac injury syndrome caused by radiofrequency catheter ablation of persistent atrial fibrillation: severe pulmonary arterial hypertension with severe tricuspid regurgitation: a rare case report and literature review.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an easy-to-miss diagnosis, but it is not an uncommon complication. The phenomenon of echocardiography (ECHO) showing both severe pulmonary arterial hypertension (PAH) and severe tricuspid regurgitation (TR) is indeed rare in PCIS after extensive radiofrequency ablation. CASE PRESENTATION: A 70-year-old male was diagnosed with persistent atrial fibrillation. The patient received radiofrequency catheter ablation due to his atrial fibrillation being refractory to antiarrhythmic drugs. After the anatomical three-dimensional models were created, ablations were performed on the left and right pulmonary veins, roof linear and bottom linear of the left atrium, and the cavo-tricuspid isthmus. The patient was discharged in sinus rhythm (SR). After 3 days, he was admitted to the hospital for gradually worsening dyspnea. Laboratory examination showed a normal leukocyte count with an increased percentage of neutrophils. The erythrocyte sedimentation rate, C-reactive protein concentration, interleukin-6, and N-terminal pro-B-type natriuretic peptide were elevated. ECG exhibited SR, V1-V4 of precordial lead P-wave amplitude which was increased but not prolonged, PR segment depression, and ST-segment elevation. Computed tomography angiography of the pulmonary artery revealed that the lung had scattered high-density flocculent flakes and a small amount of pleural and pericardial effusion. Local pericardial thickening was seen. ECHO showed severe PAH with severe TR. Diuretics and vasodilators did not relieve the symptoms. Tumors, tuberculosis, and immune system diseases were all excluded. Considering the patient's diagnosis of PCIS, the patient was treated with steroids. The patient recovered on the 19th day post ablation. The patient's condition was maintained until 2 years of follow-up. CONCLUSIONS: The phenomenon of ECHO showing severe PAH with severe TR is indeed rare in PCIS. Due to the lack of diagnostic criteria, such patients are easily misdiagnosed, leading to a poor prognosis.

Transmission Characteristics and Inactivated Vaccine Effectiveness Against Transmission of SARS-CoV-2 Omicron BA.5 Variants in Urumqi, China.

Importance: In 2022, Omicron variants circulated globally, and Urumqi, China, experienced a COVID-19 outbreak seeded by Omicron BA.5 variants, resulting in the highest number of infections in the city's record before the exit of the zero COVID-19 strategy. Little was known about the characteristics of Omicron variants in mainland China. Objective: To evaluate transmission characteristics of Omicron BA.5 variants and the effectiveness of inactivated vaccine (mainly BBIBP-CorV) against their transmission. Design, Setting, and Participants: This cohort study was conducted using data from an Omicron-seeded COVID-19 outbreak in Urumqi from August 7 to September 7, 2022. Participants included all individuals with confirmed SARS-CoV-2 infections and their close contacts identified between August 7 and September 7, 2022 in Urumqi. Exposures: A booster dose was compared vs 2 doses (reference level) of inactivated vaccine and risk factors were evaluated. Main Outcomes and Measures: Demographic characteristics, timeline records from exposure to laboratory testing outcomes, contact tracing history, and contact setting were obtained. The mean and variance of the key time-to-event intervals of transmission were estimated for individuals with known information. Transmission risks and contact patterns were assessed under different disease-control measures and in different contact settings. The effectiveness of inactivated vaccine against the transmission of Omicron BA.5 was estimated using multivariate logistic regression models. Results: Among 1139 individuals diagnosed with COVID-19 (630 females [55.3%]; mean [SD] age, 37.4 [19.9] years) and 51 323 close contacts who tested negative for COVID-19 (26 299 females [51.2%]; mean [SD] age, 38.4 [16.0] years), the means of generation interval, viral shedding period, and incubation period were estimated at 2.8 days (95% credible interval [CrI], 2.4-3.5 days), 6.7 days (95% CrI, 6.4-7.1 days), and 5.7 days (95% CrI, 4.8-6.6 days), respectively. Despite contact tracing, intensive control measures, and high vaccine coverage (980 individuals with infections [86.0%] received ≥2 doses of vaccine), high transmission risks were found in household settings (secondary attack rate, 14.7%; 95% CrI, 13.0%-16.5%) and younger (aged 0-15 years; secondary attack rate, 2.5%; 95% CrI, 1.9%-3.1%) and older age (aged >65 years; secondary attack rate, 2.2%; 95% CrI, 1.5%-3.0%) groups. Vaccine effectiveness against BA.5 variant transmission for the booster-dose vs 2 doses was 28.9% (95% CrI, 7.7%-45.2%) and 48.5% (95% CrI, 23.9%-61.4%) for 15-90 days after booster dose. No protective outcome was detected beyond 90 days after the booster dose. Conclusions and Relevance: This cohort study revealed key transmission characteristics of SARS-CoV-2 as they evolved, as well as vaccine effectiveness against variants. These findings suggest the importance of continuously evaluating vaccine effectiveness against emerging SARS-CoV-2 variants.

Increased ß1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.

BACKGROUND: Autoimmune disorder is the emerging mechanism of atrial fibrillation (AF). The ß1-adrenergic receptor antibody (ß1-AAb) is associated with AF progress. Our study aims to investigate whether ß1-AAbs involves in atrial vulnerable substrate by mediating Ca2+ mishandling and atrial fibrosis in autoimmune associated AF. METHODS: Active immunization models were established via subcutaneous injection of the second extracellular loop (ECL2) peptide for ß1 adrenergic receptor (ß1AR). Invasive electrophysiologic study and ex vivo optical mapping were used to evaluate the changed electrophysiology parameters and calcium handling properties. Phospho-proteomics combined with molecular biology assay were performed to identify the potential mechanisms of remodeled atrial substrate elicited by ß1-AAbs. Exogenous ß1-AAbs were used to induce the cellular phenotypes of HL-1 cells and atrial fibroblasts to AF propensity. RESULTS: ß1-AAbs aggravated the atrial electrical instability and atrial fibrosis. Bisoprolol alleviated the alterations of action potential duration (APD), Ca2+ transient duration (CaD), and conduction heterogeneity challenged by ß1-AAbs. ß1-AAbs prolonged calcium transient refractoriness and promoted arrhythmogenic atrial alternans and spatially discordant alternans, which were partly counteracted through blocking ß1AR. Its underlying mechanisms are related to ß1AR-drived CaMKII/RyR2 activation of atrial cardiomyocytes and the myofibroblasts phenotype formation of fibroblasts. CONCLUSION: Suppressing ß1-AAbs effectively protects the atrial vulnerable substrate by ameliorating intracellular Ca2+ mishandling and atrial fibrosis, preventing the process of the autoimmune associated AF.

Clinical enrollment assay to detect preexisting neutralizing antibodies to AAV6 with demonstrated transgene expression in gene therapy trials.

Recombinant adeno-associated virus (AAV) vectors are the leading platform for gene delivery for a variety of clinical applications. Patients with preexisting antibodies to AAV are currently excluded from most AAV gene therapy trials to avoid vector neutralization and ensure response to therapy. Anti-AAV neutralizing antibodies (NAbs) are typically assessed by in vitro cell-based transduction inhibition (TI) assays. However, clinical relevance of the determined enrollment cutoff and the inherent variability of a cell-based assay present challenges for use as an enrollment screening test. Here, we describe an enrollment cutoff that was clinically validated and strategies to overcome assay challenges to enable long-term stable performance. A validated anti-AAV6 cell-based TI assay was used to support clinical enrollment across multiple investigational gene therapies and to evaluate AAV6 seroprevalence in healthy and disease populations. The clinical enrollment cutoff was determined statistically using samples collected from healthy donors, applying a 0.1% false error rate with the inclusion of a minimum significant ratio (MSR) metric and in consideration of results from in vivo mouse passive transfer studies. Our strategy for long-term monitoring and control of assay performance employed plate quality control samples flanking the predefined cutoff. An approach using donor samples was implemented to bridge different lots of critical reagents without the need to redefine the cutoff.

Right ventriculography improves the accuracy of leadless pacemaker implantation in right ventricular mid-septum.

BACKGROUND: Implanting leadless pacemakers in the right ventricular (RV) apex is prone to causing pericardial tamponade and myocardial perforation. OBJECTIVE: To investigate the feasibility and safety of right ventriculography-guided implantation of Micra™ leadless pacemaker (Micra™, Medtronic, Minneapolis, MN, USA) in the RV mid-septum. METHODS: One hundred eight consecutive patients who underwent Micra™ implantation intended in the mid-septum were enrolled and randomized (3:1) into the radiography group (n = 81) with assistance of right ventriculography to illustrate the RV septum and the non-radiography group (n = 27). All subjects underwent a postoperative computed tomography (CT) scan to determine the Micra™ location. The Micra™ location assessed by CT image was compared between the two groups to confirm the accuracy of the intended pacing site. The duration of the procedure, X-ray radiation dose, and time were also compared between the two groups. RESULTS: Reconstructed CT 3-D cardiac images found the Micra™ location in the intended mid-septum in 13 patients (48.1%, 13/27) in the non-radiography group and 76 patients (93.8%, 76/81) in the radiography group (P < 0.0001 between two groups). There was no significant difference in procedure interval between the two groups while the X-ray radiation dose (564.86 ± 112.44 vs. 825.85 ± 156.12 mGy, P < 0.0001), X-ray exposure time (7.79 ± 1.43 vs. 12.03 ± 2.86 min, P < 0.0001), and the number of fluoroscopy re-positioning (2.79 ± 1.03 vs. 6.41 ± 1.82, P < 0.0001) were significantly less in the radiography group than in the non-radiography group. No implantation-related complications were observed in both groups. CONCLUSION: Right ventriculography increases the accuracy of Micra™ implantation in the mid-septum and reduces X-ray exposure. TRIAL REGISTRATION: The trial registration number (ChiCTR2100051374) and date (09/22/2021).

Establishing a glutamine metabolism-based model for predicting the prognosis of low-grade glioma.

Background: The natural history of patients with low-grade glioma (LGG) varies widely, but most patients eventually deteriorate, leading to poor prognostic outcomes. We aim to develop biological models that can accurately predict the outcome of LGG prognosis. Methods: Prognostic genes for glutamine metabolism were searched by univariate Cox regression, and molecular typing was constructed. Functional enrichment analysis was done to evaluate potential prognostic-related pathways by analyzing differential genes in different subtypes. Enrichment scores of specific gene sets in different subtypes were measured by gene set enrichment analysis. Different immune infiltration levels among subtypes were calculated using algorithms such as CIBERSORT and ESTIMATE. Gene expression levels of prognostic-related gene signatures of glutamine metabolism phenotypes were used to construct a RiskScore model. Receiver operating characteristic curve, decision curve and calibration curve analyses were used to evaluate the reliability and validity of the risk model. The decision tree model was used to determine the best predictor variable ultimately. Results: We found that C1 had the worst prognosis and the highest level of immune infiltration, among which the highest macrophage infiltration can be found in the M2 stage. Moreover, most of the pathways associated with tumor development, such as MYC_TARGETS_V1 and EPITHELIAL_MESENCHYMAL_TRANSITION, were significantly enriched in C1. The wild-type IDH and MGMT hypermethylation were the most abundant in C1. A five-gene risk model related to glutamine metabolism phenotype was established with good performance in both training and validation datasets. The final decision tree demonstrated the RiskScore model as the most significant predictor of prognostic outcomes in individuals with LGG. Conclusion: The RiskScore model related to glutamine metabolism can be an exceedingly accurate predictor for LGG patients, providing valuable suggestions for personalized treatment.