Stabilizing High-Valence Copper(I) Sites with Cu-Ni Interfaces Enhances Electroreduction of CO2 to C2+ Products.

In this study, the copper-nickel (Cu-Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu-Ni, PIL-Cu and PIL-Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen-PIL@Ni(NO3)2 and Cu@Salen-PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu-Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen-PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC 2+) of 262.9 mA cm-2 at -0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen-PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm-2 at -0.78 V. Mechanistic studies indicates that the presence of Cu-Ni interfaces in Cu@Salen-PIL@Ni(NO3)2 accounts for the preserve of high-valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2-to-CO conversion and C-C coupling while inhibition of the competitive HER.

A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Cardiac Resynchronization Therapy for Patients with Mild to Moderately Reduced Ejection Fraction and Left Bundle Branch Block.

BACKGROUND: It is unknown if CRT would improve or halt the progression of heart failure (HF) in patients with mild-moderately reduced LVEF (HFmmrEF) and LBBB. OBJECTIVE: To investigate the outcomes of CRT in patients with HFmmrEF and LV conduction delay. METHODS: A prospective, randomized clinical trial sponsored by NHLBI included 76 patients who met the study inclusion criteria (LVEF 36-50% and LBBB). Patients received CRTP and were randomized to CRT-OFF (RV pacing 40bpm) or CRT-ON (BIV pacing 60-150bpm). At a 6-month follow-up, pacing programming was changed to the opposite settings. NYHA class, NT pro-BNP levels, and echocardiography were collected at baseline, 6-month, and 12-month. The primary study endpoint was the LV end-systolic volume (LVESV) change from baseline, and the primary randomized comparison was the comparison of 6-month to 12-month changes between randomized groups. RESULTS: The mean patient age was 68.4±9.8 years (male 71%). Baseline characteristics were similar between 2 randomized groups (all P>0.05). In patients randomized to CRT-OFF first, then ON, LVESV was reduced from baseline only after CRT-ON (baseline 116.1±36.5 mL, CRT-ON 87.6±26.0 mL, P<0.0001). The randomized analysis of LVEF showed a significantly better change from 6 to 12 months in the "OFF-ON" group, P=0.003. LVEF was improved by CRT (baseline 41.3±4.7%, CRT-ON 46.0±8.0%, P=0.002). In patients randomized to CRT-ON first, then OFF, LVESV was reduced both after CRT-ON and CRT-OFF (baseline 109.8±23.5 mL, CRT-ON 91.7±30.5 mL, P<0.0001; CRT-OFF 99.3±28.9 mL, P=0.012). However, the LVESV reduction effect became smaller between CRT-ON and OFF (P=0.027). LVEF improved both after CRT-ON and CRT-OFF (baseline 42.7±4.3%, CRT-ON 48.5±8.6%, P<0.001; CRT-OFF 45.9±7.7%, P=0.025). CONCLUSION: CRT for patients with HFmmrEF significantly improves LVEF and ventricular remodeling after 6 months of CRT. The study provides novel evidence that early CRT benefits patients with HFmmrEF with LBBB.

[Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia: based on clinical metabolomics and proteomics].

This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.

Evaluation of biological markers for the risk assessment of carbon black in epidemiological studies.

Background/objectives: Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis, cardiovascular disease, and other conditions. As a result, the risk assessment of biological markers as early-stage indicators has the potential to improve translation from experimental toxicologic findings to identifying evidence in human studies. The study aims to review the possible early biological changes in workers exposed to carbon black (CB), followed by an evidentiary quality evaluation to determine the predictive value of the biological markers. Methods: We conducted a literature search to identify epidemiological studies that assessed biological markers that were involved in the inflammatory process at early stages among workers with exposure to CB. We reviewed the studies with specific reference to the study design, statistical analyses, findings, and limitations. Results: We identified five Chinese studies that investigated the potential impact of exposure to CB on inflammatory markers, bronchial wall thickening, genomic instability, and lung function impairment in CB production workers. Of the five Chinese studies, four were cross-sectional; another study reported results at two-time points over six years of follow-up. The authors of all five studies concluded positive relationships between exposure and the inflammatory cytokine profiles. The weak to very weak correlations between biomarkers and early-stage endpoints were reported. Conclusion: Most inflammatory markers failed to satisfy the proposed evidentiary quality criteria. The significance of the results of the reviewed studies is limited by the cross-sectional study design, inconsistency in results, uncertain clinical relevance, and high occupational exposures. Based on this review, the risk assessment relying on inflammatory markers does not seem appropriate at this time. Nevertheless, the novel research warrants further exploration in assessing exposure to ENMs and corresponding potential health risks in occupational settings.

Elevated nitrogen loadings facilitate carbon dioxide emissions from urban inland waters.

Carbon dioxide (CO2) production and emissions from inland waters play considerable roles in global atmospheric CO2 sources, while there are still uncertainties regarding notable nutrient inputs and anthropogenic activities. Urban inland waters, with frequently anthropogenic modifications and severely nitrogen loadings, were hotspots for CO2 emissions. Here, we investigated the spatiotemporal patterns of partial pressure of CO2 (pCO2) and CO2 fluxes (FCO2) in typical urban inland waters in Tianjin, China. Our observation indicated that pCO2 values were oversaturated in highly polluted waters, particularly in sewage rivers and urban rivers, exhibiting approximately 9 times higher than the atmosphere equilibrium concentration during sampling campaigns. Obviously, the spatiotemporal distributions of pCO2 and FCO2 emphasized that the water environmental conditions and anthropogenic activities jointly adjusted primary productivity and biological respiration of inland waters. Meanwhile, statistically positive correlations between pCO2/FCO2 and NH4+-N/NO3--N (p < 0.05) suggested that nitrogen biogeochemical processes, especially the nitrification, played a dominant role in CO2 emissions attributing to the water acidification that stimulated CO2 production and emissions. Except for slight CO2 sinks in waters with low organic contents, the total CO2 emissions from the urban surface waters of Tianjin were remarkable (286.8 Gg yr-1). The results emphasized that the reductions of nitrogen loadings, sewage draining waters, and agricultural pollution could alleviate CO2 emissions from urban inland waters.

Machine Learning for Prediction of Ventricular Arrhythmia Episodes from Intracardiac Electrograms of Automatic Implantable Cardioverter-Defibrillators.

BACKGROUND: Despite the implantable cardioverter defibrillator's (ICD) effectiveness in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA following ICD implantation is unpredictable. OBJECTIVE: Apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs. METHODS: The study included 13,516 patients who received BIOTRONIK ICDs and enrolled in the CERTITUDE registry between 01/01/2010 to 12/31/2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long- (baseline or first scheduled remote recording), mid-(scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed. RESULTS: Of 13,516 patients (male 72%, age 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained VT/VF were observed in 4,467 patients (33.0%). Neural networks based on CNN using ResNet-like architectures on far-field IEGMs yielded an AUC of 0.83 with a 95% confidence interval of [0.79, 0.87] in the short-term, while the long- and mid-range analyses had minimal predictive value for VA events. CONCLUSION: In this study, applying ML to ICD-acquired IEGMs predicted impending VT/VF events seconds before they occurred, whereas mid- to long-term predictions were not successful. This could have important implications for future device therapies.

Left bundle branch pacing vs ventricular septal pacing for cardiac resynchronization therapy.

Background: The outcomes of left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) in patients with heart failure remain to be learned. Objective: The objective of this study was to assess the echocardiographic and clinical outcomes of LBBP, LVSP, and deep septal pacing (DSP). Methods: This retrospective study included patients who met the criteria for cardiac resynchronization therapy (CRT) and underwent attempted LBBP in 5 Mayo centers. Clinical, electrocardiographic, and echocardiographic data were collected at baseline and follow-up. Results: A total of 91 consecutive patients were included in the study. A total of 52 patients had LBBP, 25 had LVSP, and 14 had DSP. The median follow-up duration was 307 (interquartile range 208, 508) days. There was significant left ventricular ejection fraction (LVEF) improvement in the LBBP and LVSP groups (from 35.9 ± 8.5% to 46.9 ± 10.0%, P < .001 in the LBBP group; from 33.1 ± 7.5% to 41.8 ± 10.8%, P < .001 in the LVSP group) but not in the DSP group. A unipolar paced right bundle branch block morphology during the procedure in lead V1 was associated with higher odds of CRT response. There was no significant difference in heart failure hospitalization and all-cause deaths between the LBBP and LVSP groups. The rate of heart failure hospitalization and all-cause deaths were increased in the DSP group compared with the LBBP group (hazard ratio 5.10, 95% confidence interval 1.14-22.78, P = .033; and hazard ratio 7.83, 95% confidence interval 1.38-44.32, P = .020, respectively). Conclusion: In patients undergoing CRT, LVSP had comparable CRT outcomes compared with LBBP.

Recent Advances in Biopolymer-Based Hydrogel Electrolytes for Flexible Supercapacitors.

Growing concern regarding the impact of fossil fuels has led to demands for the development of green and renewable materials for advanced electrochemical energy storage devices. Biopolymers with unique hierarchical structures and physicochemical properties, serving as an appealing platform for the advancement of sustainable energy, have found widespread application in the gel electrolytes of supercapacitors. In this Review, we outline the structure and characteristics of various biopolymers, discuss the proposed mechanisms and assess the evaluation metrics of gel electrolytes in supercapacitor devices, and further analyze the roles of biopolymer materials in this context. The state-of-the-art electrochemical performance of biopolymer-based hydrogel electrolytes for supercapacitors and their multiple functionalities are summarized, while underscoring the current technical challenges and potential solutions. This Review is intended to offer a thorough overview of recent developments in biopolymer-based hydrogel electrolytes, highlighting research concerning green and sustainable energy storage devices and potential avenues for further development.

Electrical storm after left ventricular assist device (LVAD) implantation.

INTRODUCTION: Ventricular tachycardia storm or electrical storm (ES) is a common complication following left ventricular assist device (LVAD) implantation. The factors contributing to ES and outcomes are less studied. The study aimed to determine the factors associated with ES and the probability of survival in patients undergoing LVAD in three tertiary centers over a span of 15 years. METHODS: We performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2006 to December 31, 2020. ES was defined as ≥3 episodes of sustained ventricular tachycardia over a period of 24 h with no identifiable reversible cause. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed. RESULTS: A total of 883 patients who underwent LVAD implantation were included in our study. ES occurred in 7% (n = 61) of patients with a median of 13 days (interquartile range [IQR]: 5-297 days) following surgery. We found 57% of patients (n = 35) developed ES within 30 days, while 43% (n = 26) patients developed ES at a median of 545  (IQR 152-1032) days after surgery. Following ES, 26% of patients died within 1 year. Patients with ES had a significant association with a history of ventricular arrhythmias and implantable cardioverter defibrillator (ICD) shocks before the procedure. ES was significantly associated with reduced survival compared to patients without ES (hazards ratio [HR]: 1.92, 95% CI: 1.39-2.64, p < .001). CONCLUSION: Following LVAD implantation, the rate of ES was 7% with majority of ES occurring within 30 days of LVAD. Risk factors for ES included pre-implant history of ventricular arrhythmias and ICD shock. ES was significantly associated with reduced survival compared to patients without ES.

Paenibacillus thermotolerans sp. nov., isolated from a hot spring in Yunnan Province, south-west China.

Two Gram-positive, rod-shaped, endospore-forming strains, YIM B05601 and YIM B05602T, were isolated from soil sampled at Hamazui hot spring, Tengchong City, Yunnan Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences suggested that the two strains fell within the genus Paenibacillus, appearing most closely related to Paenibacillus alkalitolerans YIM B00362T (96.9 % sequence similarity). Genome-based phylogenetic analysis confirmed that strains YIM B05601 and YIM B05602T formed a distinct phylogenetic cluster within the genus Paenibacillus. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strains YIM B05601 and YIM B05602T with the related species P. alkalitolerans YIM B00362T were within the ranges of 74.43-74.57 % and 12.1-18.5 %, respectively, which clearly indicated that strains YIM B05601, YIM B05602T represented a novel species. Strains YIM B05601 and YIM B05602T exhibited 99.6 % 16S rRNA gene sequence similarity. The ANI and dDDH values between the two strains were 99.8 and 100 %, respectively, suggesting that they belong to the same species. Optimum growth for both strains occurred at pH 7.0 and 45 °C. The diagnostic diamino acid in the cell-wall peptidoglycan of strains YIM B05601 and YIM B05602T was meso-diaminopimelic acid. MK-7 was the predominant menaquinone. The polar lipids of strain YIM B05602T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, four unidentified glycolipids, an unidentified polarlipid and phosphatidylinositol mannoside. The major fatty acids of the two stains were iso-C15 : 0 and anteiso-C15 : 0. Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strains YIM B05601 and YIM B05602T could be classified as a novel species of the genus Paenibacillus, for which the name Paenibacillus thermotolerans sp. nov. is proposed. The type strain is YIM B05602T (=CGMCC 1.60051T=KCTC 43460T=NBRC 115924T).

Trends in the 30-year span of noninfectious cardiovascular implantable electronic device complications in Olmsted County.

Background: Cardiac implantable electronic devices (CIEDs), such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. Objectives: We sought to describe trends in noninfectious CIED complications over the past 3 decades in Olmsted County. Methods: The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966 to present. CIED implantations between 1988 and 2018 were determined. Trends in noninfectious complications within 30 days of implantation were analyzed. Results: A total of 157 (6.2%) of 2536 patients who received CIED experienced device complications. A total of 2.7% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.8%), followed by hematoma (1.7%). Complications went up from 1988 to 2005, and then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (P < .01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity index has trended up over the 30 years. Conclusion: Our study describes a real-world trend of CIED complications over 3 decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.

Increased serum asprosin is correlated with diabetes mellitus-induced erectile dysfunction.

OBJECTIVE: Asprosin, a newly identified adipokine, is pathologically increased in type 2 diabetes. The aim of this study is to see whether serum asprosin concentrations are linked to diabetes mellitus-induced erectile dysfunction (DMED). METHODS: 90 male patients with type 2 diabetes were included. According to the International Index of Erectile Function (IIEF-5) score, they were classified into two groups: 45 type 2 diabetes patients without erectile dysfunction (DM group) (IIEF-5 > 21),45 patients with diabetes induced erectile dysfunction (DMED group) (IIEF-5 ≤ 21)0.45 healthy male volunteers with normal blood glucose, IIEF-5 score > 21 points, and age matched with the DMED group were included as the control group. Anthropometric and biochemical variables were determined in all participants. RESULTS: When compared to the controls, T2DM ( Type 2 Diabetes Mellitus)patients had higher serum asprosin levels. The DMED group had significantly higher serum asprosin than the T2DM groups(p < 0.001). After adjusting for multiple variables considered traditional risk factors for ED(erectile dysfunction), Asprosin can still be used as an independent risk factor for ED; The ROC(Receive Operating Characteristic Curve) indicates that asprosin has good sensitivity (97.8%) and specificity (62.2%) in predicting ED, with an area under the curve of 0.843.Correlation analysis shows that asprosin is negatively correlated with SOD(superoxide dismutase ) and positively correlated with MDA (malondialdehyde). CONCLUSION: Serum asprosin concentrations are increased in patients with DMED. Also, asprosin is correlated with oxidative stress indexes (MDA, SOD).

DNMT1-mediated epigenetic suppression of FBXO32 expression promoting cyclin dependent kinase 9 (CDK9) survival and esophageal cancer cell growth.

Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT1-mediated methylation is still unclear. FBXO32 expression was examined in EC cells with high DNMT1 expression using GSE163735 dataset. RT-qPCR assessed FBXO32 expression in normal and EC cells, and impact of higher FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with EMT-related proteins. The xenograft model established by injecting EC cells transfected with FBXO32 was used to evaluate tumor growth, apoptosis, and tumor cells proliferation and metastasis. Chromatin immunoprecipitation (ChIP) assay was employed to study the interaction between DNMT1 and FBXO32. HitPredict, co-immunoprecipitation (Co-IP), and Glutathione-S-transferase (GST) pulldown assay analyzed the interaction between FBXO32 and cyclin dependent kinase 9 (CDK9). Finally, the ubiquitination assay identified CDK9 ubiquitination, and its half-life was measured using cycloheximide and confirmed through western blotting. DNMT1 negatively correlated with FBXO32 expression in esophageal cells. High FBXO32 expression was associated with better overall survival in patients. Knockdown of DNMT1 in EC cells increased FBXO32 expression and suppressed malignant phenotypes. FBXO32 repressed EC tumor growth and metastasis in mice. Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.

TYM-3-98, a novel selective inhibitor of PI3Kδ, demonstrates promising preclinical antitumor activity in B-cell lymphomas.

AIMS: PI3Kδ is expressed predominately in leukocytes and is commonly found to be aberrantly activated in human B-cell lymphomas. Although PI3Kδ has been intensively targeted for discovering anti-lymphoma drugs, the application of currently approved PI3Kδ inhibitors has been limited due to unwanted systemic toxicities, thus warranting the development of novel PI3Kδ inhibitors with new scaffolds. MAIN METHODS: We designed TYM-3-98, an indazole derivative, and evaluated its selectivity for all four PI3K isoforms, as well as its efficacy against various B-cell lymphomas both in vitro and in vivo. KEY FINDINGS: We identified TYM-3-98 as a highly selective PI3Kδ inhibitor over other PI3K isoforms at both molecular and cellular levels. It showed superior antiproliferative activity in several B-lymphoma cell lines compared with the approved first-generation PI3Kδ inhibitor idelalisib. TYM-3-98 demonstrated a concentration-dependent PI3K/AKT/mTOR signaling blockage followed by apoptosis induction. In vivo, TYM-3-98 showed good pharmaceutical properties and remarkably reduced tumor growth in a human lymphoma xenograft model and a mouse lymphoma model. SIGNIFICANCE: Our findings establish TYM-3-98 as a promising PI3Kδ inhibitor for the treatment of B-cell lymphoma.

Impact of infective versus sterile transvenous lead removal on 30-day outcomes in cardiac implantable electronic devices.

BACKGROUND: Transvenous lead removal (TLR) is associated with increased mortality and morbidity. This study sought to evaluate the impact of TLR on in-hospital mortality and outcomes in patients with and without CIED infection. METHODS: From January 1, 2017, to December 31, 2020, we utilized the nationally representative, all-payer, Nationwide Readmissions Database to assess patients who underwent TLR. We categorized TLR as indicated for infection, if the patient had a diagnosis of bacteremia, sepsis, or endocarditis during the initial admission. Conversely, if none of these conditions were present, TLR was considered sterile. The impact of infective vs sterile indications of TLR on mortality and major adverse events was studied. RESULTS: Out of the total 25,144 patients who underwent TLR, 14,030 (55.8%) received TLR based on sterile indications, while 11,114 (44.2%) received TLR due to device infection, with 40.5% having systemic infection and 59.5% having isolated pocket infection. TLR due to infective indications was associated with a significant in-hospital mortality (5.59% vs 1.13%; OR = 5.16; 95% CI 4.33-6.16; p < 0.001). Moreover, when compared with sterile indications, TLR performed due to device infection was associated with a considerable risk of thromboembolic events including pulmonary embolism and stroke (OR = 3.80; 95% CI 3.23-4.47, p < 0.001). However, there was no significant difference in the conversion to open heart surgery (1.72% vs. 1.47%, p < 0.111), and infection was not an independent predictor of cardiac (OR = 1.12; 95% CI 0.97-1.29) or vascular complications (OR = 1.12; 95% CI 0.73-1.72) between the two groups. CONCLUSION: Higher in-hospital mortality and rates of thromboembolic events associated with TLR resulting from infective indications may warrant further pursuing this diagnosis in patients.

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.