Cancer Cell-Mimicking Prussian Blue Nanoplatform for Synergistic Mild Photothermal/Chemotherapy via Heat Shock Protein Inhibition.

Combined mild-temperature photothermal/chemotherapy has emerged as a highly promising modality for tumor therapy. However, its therapeutic efficacy is drastically compromised by the heat-induced overexpression of heat shock proteins (HSPs) by the cells, which resist heat stress and apoptosis. The purpose of this study was to downregulate HSPs and enhance the mild-temperature photothermal/chemotherapy effect. In detail, the colon cancer cell membrane (CT26M)-camouflaged HSP90 inhibitor ganetespib and the chemotherapeutic agent doxorubicin (DOX)-coloaded hollow mesoporous Prussian blue (HMPB) nanoplatform (named PGDM) were designed for synergistic mild photothermal/chemotherapy via HSP inhibition. In addition to being a photothermal agent with a high efficiency of photothermal conversion (24.13%), HMPB offers a hollow hole that can be filled with drugs. Concurrently, the cancer cell membrane camouflaging enhances tumor accumulation through a homologous targeting mechanism and gives the nanoplatform the potential to evade the immune system. When exposed to NIR radiation, HMPB's photothermal action (44 °C) not only causes tumor cells to undergo apoptosis but also causes ganetespib to be released on demand. This inhibits the formation of HSP90, which enhances the mild photothermal/chemotherapy effect. The results confirmed that the combined treatment regimen of mild photothermal therapy (PTT) and chemotherapy showed a better therapeutic efficacy than the individual treatment methods. Therefore, this multimodal nanoparticle can advance the development of drugs for the treatment of malignancies, such as colon cancer, and has prospects for clinical application.

The value of machine learning based on CT radiomics in the preoperative identification of peripheral nerve invasion in colorectal cancer: a two-center study.

BACKGROUND: We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). METHODS: A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. RESULTS: The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the "one standard error" rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the "one standard error" rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. CONCLUSIONS: Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. CRITICAL RELEVANCE STATEMENT: The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. KEY POINTS: • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients.

SAFB restricts contact domain boundaries associated with L1 chimeric transcription.

Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.

Use of Three-dimensional Electroanatomic Mapping for Epicardial Access: Needle Tracking, Elctrographic Characteristics and Clinical Application.

BACKGROUND AND AIMS: Pericardiocentesis is usually completed under fluoroscopy. The electroanatomic mapping (EAM) system allows visualizing puncture needle tip (NT) while displaying the electrogram recorded from NT, making it possible to obtain epicardial access (EA) independent of fluoroscopy. This study was designed to establish and validate a technique by which EA is obtained under guidance of 3-dimensional (3D) EAM combined with NT electrogram. METHODS: 3D shell of the heart was generated and the NT was made trackable in the EAM system. Unipolar NT electrogram was continuously monitored. Penetration into pericardial sac was determined by an increase in NT potential amplitude and an injury current. A long guidewire of which the tip was also visible in the EAM system was advanced to confirm EA. RESULTS: EA was successfully obtained without complication in 13 pigs and 22 patients. In the animals, NT potential amplitude was 3.2± 1.0 mV when it was located in mediastinum, 5.2±1.6 mV when in contact with fibrous pericardium and 9.8±2.8 mV after penetrating into pericardial sac (all p≤0.001). In human subjects, it measured 1.54±0.40 mV, 3.61±1.08 mV and 7.15±2.88 mV respectively (all p<0.001). Fluoroscopy time decreased in every 4-5 cases (64±15, 23±17 and 0 second for animals 1-4, 5-8, 9-13 respectively, p=0.01; 44±23, 31±18; 4±7 seconds for patients 1-7, 8-14, 15-22 respectively, p<0.001). In 5 pigs and 7 patients, EA was obtained without X-ray exposure. CONCLUSIONS: By tracking NT in the 3D EAM system and continuously monitoring the NT electrogram, it is feasible and safe to obtain EA with minimum or no fluoroscopic guidance.

AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. METHODS: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. RESULTS: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. CONCLUSIONS: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Mitochondria-Targeted Prodrug Nanoassemblies for Efficient Ferroptosis-Based Therapy via Devastating Ferroptosis Defense Systems.

Ferroptosis is a form of regulated cell death accompanied by lipid reactive oxygen species (ROS) accumulation in an iron-dependent manner. However, the efficiency of tumorous ferroptosis was seriously restricted by intracellular ferroptosis defense systems, the glutathione peroxidase 4 (GPX4) system, and the ubiquinol (CoQH2) system. Inspired by the crucial role of mitochondria in the ferroptosis process, we reported a prodrug nanoassembly capable of unleashing potent mitochondrial lipid peroxidation and ferroptotic cell death. Dihydroorotate dehydrogenase (DHODH) inhibitor (QA) was combined with triphenylphosphonium moiety through a disulfide-containing linker to engineer well-defined nanoassemblies (QSSP) within a single-molecular framework. After being trapped in cancer cells, the acidic condition provoked the structural disassembly of QSSP to liberate free prodrug molecules. The mitochondrial membrane-potential-driven accumulation of the lipophilic cation prodrug was delivered explicitly into the mitochondria. Afterward, the thiol-disulfide exchange would occur accompanied by downregulation of reduced glutathione levels, thus resulting in mitochondria-localized GPX4 inactivation for ferroptosis. Simultaneously, the released QA from the hydrolysis reaction of the adjacent ester bond could further devastate mitochondrial defense and evoke robust ferroptosis via the DHODH-CoQH2 system. This subcellular targeted nanoassembly provides a reference for designing ferroptosis-based strategy for efficient cancer therapy through interfering antiferroptosis systems.

Elucidating phylogenetic relationships within the genus Curcuma through the comprehensive analysis of the chloroplast genome of Curcuma viridiflora Roxb. 1810 (Zingiberaceae).

Curcuma viridiflora Roxb., a plant species of significant pharmaceutical interest, has been the subject of limited chloroplast genomic research. In this study, we present the sequencing and assembly of the C. viridiflora chloroplast genome, which is characterized by a circular chromosome spanning 162,212 base pairs and a GC content of 36.20%. The genome encodes 87 protein-coding genes (PCGs), 38 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. A phylogenetic analysis was conducted, incorporating eight related species, and based on the complete chloroplast genome and protein-coding DNA sequences of six related taxa within the genus. Outgroup species Zingiber zerumbet and Zingiber officinale were also included in the analysis. The results indicate a close relationship between C. viridiflora and Curcuma phaeocaulis, Curcuma sichuanensis, and Curcuma yunnanensis. This study provides the first chloroplast genome of C. viridiflora, thereby contributing a valuable genomic resource for future research on medicinal plants within the Curcuma genus.

A Dual-Mode Triboelectric Nanogenerator for Efficiently Harvesting Droplet Energy.

Triboelectric nanogenerator (TENG) is a promising solution to harvest the low-frequency, low-actuation-force, and high-entropy droplet energy. Conventional attempts mainly focus on maximizing electrostatic energy harvest on the liquid-solid surface, but enormous kinetic energy of droplet hitting the substrate is directly dissipated, limiting the output performance. Here, a dual-mode TENG (DM-TENG) is proposed to efficiently harvest both electrostatic energy at liquid-solid surface from a droplet TENG (D-TENG) and elastic potential energy of the vibrated cantilever from a contact-separation TENG (CS-TENG). Triggered by small droplets, the flexible cantilever beam, rather than conventional stiff ones, can easily vibrate multiple times with large amplitude, enabling frequency multiplication of CS-TENG and producing amplified output charges. Combining with the top electrode design to sufficiently utilize charges at liquid-solid interface, a record-high output charge of 158 nC is realized by single droplet. The energy conversion efficiency of DM-TENG is 2.66-fold of D-TENG. An array system with the specially designed power management circuit is also demonstrated for building self-powered system, offering promising applications for efficiently harvesting raindrop energy.

Combining Traditional Chinese Herbs and csDMARDs for the Treatment of Rheumatoid Arthritis Involves Tapering and Discontinuing Glucocorticoids: Protocol for a Two-Stage Non-Randomized Controlled Trial.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors.

BACKGROUND: Ferroptosis plays an important role in enhancing the efficacy of anti-programmed cell death 1 (PD-1) immunotherapy; however, the molecular mechanisms by which tumor ferroptosis sensitizes melanoma and lung cancer to anti-PD-1 immunotherapy have not been elucidated. METHODS: Cytotoxicity assays, colony formation assays, flow cytometry and animal experiments were used to evaluate the effects of mefloquine (Mef) on survival and ferroptosis in melanoma and lung cancer. RNA sequencing, Real-time quantitative PCR (qRT-PCR), western blotting, chromatin immunoprecipitation-qPCR and flow cytometry were used to determine the molecular mechanisms by which Mef regulates lysophosphatidylcholine acyltransferase 3 (LPCAT3). The relationship between LPCAT3 and the efficacy of anti-PD-1 immunotherapy was verified via a clinical database and single-cell RNA sequencing (ScRNA-Seq). RESULTS: In this study, we discovered that Mef induces ferroptosis. Furthermore, treatment with Mef in combination with T-cell-derived interferon-γ (IFN-γ) enhanced tumor ferroptosis and sensitized melanoma and lung cancer cells to anti-PD-1 immunotherapy. Mechanistically, Mef upregulated the expression of LPCAT3, a key gene involved in lipid peroxidation, by activating IFN-γ-induced STAT1-IRF1 signaling, and knocking down LPCAT3 impaired the induction of ferroptosis by Mef+IFN-γ. Clinically, analysis of the transcriptome and single-cell sequencing results in patients with melanoma showed that LPCAT3 expression was significantly lower in patients with melanoma than in control individuals, and LPCAT3 expression was positively correlated with the efficacy of anti-PD-1 immunotherapy. CONCLUSIONS: In conclusion, our study demonstrated a novel mechanism by which LPCAT3 is regulated, and demonstrated that Mef is a highly promising new target that can be utilized to enhance the efficacy of anti-PD-1 immunotherapy.

Chalcogen Atom-Modulated Croconaine for Efficient NIR-II Photothermal Theranostics.

Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.

Effect of Bi on the Performance of Al-Ga-In Sacrificial Anodes.

Cathodic protection is widely used for metal corrosion protection. To improve their performance, it is necessary and urgent to study the influence of metal oxides on the microstructure and performance of aluminum alloy sacrificial anodes. Taking an Al-Ga-In sacrificial anode as the research object, the dissolution morphology and current efficiency characteristics were studied by means of electrochemical testing and microstructural observation, and the influence of varying Pb and Bi contents on the performance of an aluminum alloy sacrificial anode was investigated. The test results reveal that: (1) The Al-Ga-In sacrificial anode with 4% Pb and 1% Bi contents exhibits the best sacrificial anode performance. (2) The inclusion of an appropriate Bi element content shifts the open-circuit potential in a negative direction and promotes activation dissolution. Conversely, excessive Bi content leads to uneven dissolution, resulting in the shedding of anode grains and greatly reducing the current efficiency. (3) During the activation dissolution of the aluminum alloy, the second phase preferentially dissolves, and the activation point destroys the oxide film, resulting in the dissolution of the exposed aluminum matrix. Consequently, the concentration of dissolved metal ions is reduced and deposited back on the surface of the anode sample, promoting the continuous dissolution of the anode.

A Cyclical Magneto-Responsive Massage Dressing for Wound Healing.

Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.

Unveiling the molecular regulatory mechanisms underlying sucrose accumulation and oil reduction in peanut kernels through genetic mapping and transcriptome analysis.

Sucrose content is a key factor for the flavor of edible peanut, which determines the sweet taste of fresh peanut and also attribute to pleasant flavor of roasted peanut. To explore the genetic mechanism of the sucrose content in peanut, an F2 population was created by crossing the sweet cultivar Zhonghuatian 1 (ZHT1) with Nanyangbaipi (NYBP). A genomic region spanning 28.26 kb on chromosome A06 was identified for the sucrose content through genetic mapping, elucidating 47.5% phenotypic variance explained. As the sucrose content had a significantly negative correlation with the oil content, this region was also found to be related to the oil content explaining 37.2% of phenotype variation. In this region, Arahy.42CAD1 was characterized as the most likely candidate gene through a comprehensive analysis. The nuclear localization of Arahy.42CAD1 suggests its potential involvement in the regulation of gene expression for sucrose and oil contents in peanut. Transcriptome analysis of the developing seeds in both parents revealed that genes involved in glycolysis and triacylglycerol biosynthesis pathways were not significantly down-regulated in ZHT1, indicating that the sucrose accumulation was not attributed to the suppression of triacylglycerol biosynthesis. Based on the WGCNA analysis, Arahy.42CAD1 was co-expressed with the genes involved in vesicle transport and oil body assembly, suggesting that the sucrose accumulation may be caused by disruptions in TAG transportation or storage mechanisms. These findings offer new insights into the molecular mechanisms governing sucrose accumulation in peanut, and also provide a potential gene target for enhancing peanut flavor.

The effect of the mitochondria-targeted antioxidant Mito-tempo during sperm ultra-rapid freezing.

During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.

Evaluation of an algorithm-guided photoplethysmography for atrial fibrillation burden using a smartwatch.

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Efficacy of functional magnetic resonance imaging-guided personalized repetitive transcranial magnetic stimulation (fMRI-rTMS) in depressive patients with emotional blunting: study protocol for a randomized controlled trial.

BACKGROUND: Emotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials. METHODS: This study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment. DISCUSSION: This trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future. TRIAL REGISTRATION: ClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .