MACC: a visual interactive knowledgebase of metabolite-associated cell communications.

Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/.

MVSF-AB: Accurate antibody-antigen binding affinity prediction via multi-view sequence feature learning.

MOTIVATION: Predicting the binding affinity between antigens and antibodies accurately is crucial for assessing therapeutic antibody effectiveness and enhancing antibody engineering and vaccine design. Traditional machine learning methods have been widely used for this purpose, relying on interfacial amino acids' structural information. Nevertheless, due to technological limitations and high costs of acquiring structural data, the structures of most antigens and antibodies are unknown, and sequence-based methods have gained attention. Existing sequence-based approaches designed for protein-protein affinity prediction exhibit a significant drop in performance when applied directly to antibody-antigen affinity prediction due to imbalanced training data and lacking design in the model framework specifically for antibody-antigen, hindering the learning of key features of antibodies and antigens. Therefore, we propose MVSF-AB, a Multi-View Sequence Feature learning for accurate Antibody-antigen Binding affinity prediction. RESULTS: MVSF-AB designs a multi-view method that fuses semantic features and residue features to fully utilize the sequence information of antibody-antigen and predicts the binding affinity. Experimental results demonstrate that MVSF-AB outperforms existing approaches in predicting unobserved natural antibody-antigen affinity and maintains its effectiveness when faced with mutant strains of antibodies. AVAILABILITY AND IMPLEMENTATION: Datasets we used and source code are available on our public GitHub repository https://github.com/TAI-Medical-Lab/MVSF-AB.

Downregulation of mesenteric afferent sensitivity following long-term systemic treatment of vincristine in mice.

AIMS: Gastrointestinal paresthesia and dysmotility are common side effects of vincristine (VCR) chemotherapy, which have become one of the factors for dose reduction, therapy delay or discontinuation. However, the mechanism is not entirely clear, whether it is related to autonomic nerves injury remains unknown. Therefore, we aimed to study whether VCR-induced gastrointestinal toxicity is related to changes in mesenteric afferent activity. METHODS: The effects of a single VCR stimulation and long-term systemic VCR treatment on mesenteric afferent activity were investigated by directly recording mesenteric afferent discharge in vitro. RESULTS: Our results showed that a single VCR (0.001-1 µmol/L) stimulation obviously increased the spontaneous, chemically evoked and mechanically evoked discharge of jejunal and colonic mesenteric afferents. This kind of hypersensitivity of VCR could be blocked by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. For the mice treated with VCR (0.1 mg/kg/d, i.p.) for 14 days, the abdominal withdrawal reflex and writhing response scores were reduced. Meanwhile, the spontaneous discharge of colonic mesenteric afferents and the afferent response to VCR was downregulated, and the afferent sensitivity to chemical and mechanical stimulation was reduced. Moreover, the expression of TRPV1 in colon was decreased. CONCLUSIONS: These results suggest that the direct stimulation by VCR increases the mesenteric afferent sensitivity by activating TRPV1, which may be the reason of VCR-induced abdominal pain; the long-term systemic treatment of VCR decreases mesenteric afferent sensitivity by reducing TRPV1, which may be the reason of VCR-induced constipation.

Probing PT-Symmetry Breaking of Non-Hermitian Topological Photonic States via Strong Photon-Magnon Coupling.

Light-matter interaction is crucial to both understanding fundamental phenomena and developing versatile applications. Strong coupling, robustness, and controllability are the three most important aspects in realizing light-matter interactions. Topological and non-Hermitian photonics have provided frameworks for robustness and control flexibility, respectively. How to engineer the properties of the edge state such as photonic density of state by using non-Hermiticity while ensuring topological protection has not been fully studied. Here we construct a parity-time-symmetric dimerized photonic lattice and probe the spontaneous PT-symmetry breaking of the edge states by utilizing the strong coupling between the photonic mode and a spin ensemble. Our Letter presents an accurate and almost noninvasive approach for investigating non-Hermitian topological states, while also offering methodologies for the implementation and manipulation of topological light-matter interactions.

Feasibility and safety of endoscopic resection for the jejunoileal lesions.

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

Transferability of Machine Learning Models for Predicting Raman Spectra.

Theoretical prediction of vibrational Raman spectra enables a detailed interpretation of experimental spectra, and the advent of machine learning techniques makes it possible to predict Raman spectra while achieving a good balance between efficiency and accuracy. However, the transferability of machine learning models across different molecules remains poorly understood. This work proposed a new strategy whereby machine learning-based polarizability models were trained on similar but smaller alkane molecules to predict spectra of larger alkanes, avoiding extensive first-principles calculations on certain systems. Results showed that the developed polarizability model for alkanes with a maximum of nine carbon atoms can exhibit high accuracy in the predictions of polarizabilities and Raman spectra for the n-undecane molecule (11 carbon atoms), validating its reasonable extrapolation capability. Additionally, a descriptor space analysis method was further introduced to evaluate the transferability, demonstrating potentials for accurate and efficient Raman predictions of large molecules using limited training data labeled for smaller molecules.

A dynamic prediction model for preeclampsia using the sFlt-1/PLGF ratio combined with multiple factors.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery remains the only available treatment for PE. This study aims to establish a dynamic prediction model for PE. METHODS: A total of 737 patients who visited our hospital from January 2021 to June 2022 were identified according to the inclusion and exclusion criteria, forming the primary dataset. Additionally, 176 singleton pregnant women who visited our hospital from July 2022 to November 2022 comprised the verification set. We investigated different gestational weeks of sFlt-1/PLGF (soluble FMS-like tyrosine kinase-1, placental growth factor) ratio combined with maternal characteristics and routine prenatal laboratory results in order to predict PE in each trimester. Multivariate logistic regression was used to establish the prediction model for PE at different gestational weeks. The discrimination, calibration, and clinical validity were utilized to evaluate predictive models as well as models in external validation queues. RESULTS: At 20-24 weeks, the obtained prediction model for PE yielded an area under the curve of 0.568 (95% confidence interval, 0.479-0.657). At 25-29 weeks, the obtained prediction model for PE yielded an area under the curve of 0.773 (95% confidence interval, 0.703-0.842)and 0.731 (95% confidence interval, 0.653-0.809) at 30-34 weeks. After adding maternal factors, uterine artery pulsation index(Ut-IP), and other laboratory indicators to the sFlt-1/PLGF ratio, the predicted performance of PE improved. It found that the AUC improved to 0.826(95% confidence interval, 0.748 ∼ 0.904) at 20-24 weeks, 0.879 (95% confidence interval, 0.823 ∼ 0.935) at 25-29 weeks, and 0.862(95% confidence interval, 0.799 ∼ 0.925) at 30-34 weeks.The calibration plot of the prediction model indicates good predictive accuracy between the predicted probability of PE and the observed probability. Furthermore, decision-curve analysis showed an excellent clinical application value of the models. CONCLUSION: Using the sFlt-1/PLGF ratio combined with multiple factors at 25-29 weeks can effectively predict PE, but the significance of re-examination in late pregnancy is not significant.

Alpinia officinarum Hance extract relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis.

Sepsis is generally triggered by a dysfunctional host response to infection, and it can result in life-threatening organ dysfunction. Alpinia officinarum Hance (AO) exhibits regulatory functions in some diseases. However, whether AO extract (AOE) plays a promoting role in sepsis--triggered myocardial injury is unclear. This study was aimed at investigating the regulatory effects of AOE on myocardial ferroptosis and inflammation in sepsis, and the regulation effects on the lncRNA MIAT/TRAF6/NF-κB axis. Lipopolysaccharide (LPS) was used to treat mice for establishing an in vivo sepsis model. The pathological changes in heart tissues were observed through hematoxylin-eosin (HE) staining. The levels of CK-MB, cTnl, MDA, SOD, IL-1ß, IL-18, IL-6, and TNF-α in serum were detected through enzyme-linked immunosorbent assay (ELISA). The level of Fe2+ was assessed, and the protein expressions (ACSL4, GPX4, TRAF6, p-P65, and P65) were examined through western blot. The expressions of lncRNA MIAT and TRAF6 were measured through real-time quantitative polymerase chain reaction (RT-qPCR). Our results demonstrated that AOE treatment ameliorated sepsis-triggered myocardial damage by reducing the disordered cardiomyocytes, the destroyed sarcolemma, and the CK-MB and cTnl levels. In addition, AOE treatment inhibited sepsis-induced myocardial ferroptosis and inflammation by regulating Fe2+, ACSL4, GPX4, IL-1ß, IL-18, IL-6, and TNF-α levels. Moreover, the improvement effect of AOE was strengthened with the increase in the dose of AOE (25, 50, 100 mg/kg). It was also revealed that AOE treatment retarded the lncRNA MIAT/TRAF6/NF-κB axis. Rescue assays manifested that overexpression of MIAT reduced the cardioprotective effect of AOE. In conclusion, AOE relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis. These findings may provide a potential therapeutic drug for the treatment of sepsis.

The effectiveness of various treatment approaches for laryngeal contact granulomas.

OBJECTIVES: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). METHODS: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. RESULTS: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). CONCLUSIONS: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG.

MTML: An Efficient Multitrait Multilocus GWAS Method Based on the Cauchy Combination Test.

Genome-wide association study (GWAS) by measuring the joint effect of multiple loci on multiple traits, has recently attracted interest, due to the decreased costs of high-throughput genotyping and phenotyping technologies. Previous studies mainly focused on either multilocus models that identify associations with a single trait or multitrait models that scan a single marker at a time. Since these types of models cannot fully utilize the association information, the powers of the tests are usually low. To potentially address this problem, we present here a multitrait multilocus (MTML) modeling framework that implements in three steps: (1) simplify the complex calculation; (2) reduce the model dimension; (3) integrate the joint contribution of single markers to multiple traits by Cauchy combination. The performances of MTML are evaluated and compared with other three published methods by Monte Carlo simulations. Simulation results show that MTML is more powerful for quantitative trait nucleotide detection and robust for various numbers of traits. In the meanwhile, MTML can effectively control type I error rate at a reasonable level. Real data analysis of Arabidopsis thaliana shows that MTML identifies more pleiotropic genetic associations. Therefore, we conclude that MTML is an efficient GWAS method for joint analysis of multiple quantitative traits. The R package MTML, which facilitates the implementation of the proposed method, is publicly available on GitHub https://github.com/Guohongping/MTML.

[Structural maintenance of chromosomes and associated genetic disorders].

Structural maintenance of chromosomes (SMC), including cohesin, condensin and the SMC5/6 complex, are protein complexes which maintain the higher structure and dynamic stability of chromatin. Such circular complexes, with similar structures, play pivotal roles in chromatid cohesion, chromosomal condensation, DNA replication and repair, as well as gene transcription. Despite extensive research on the functions of the SMCs, our understanding of the SMC5/6 complex has remained limited compared with the other two complexes. This article has reviewed the architecture and crucial physiological roles of the SMCs, and explored the associated phenotypes resulting from mutations of the SMC components such as Cornelia de Lange syndrome (CdLS) and microcephaly, with an aim to provide insights into their functions in eukaryotic cells and implications for human diseases.

[Daidzein attenuates high glucose-induced inflammatory injury in macrophages by regulating NLRP3 inflammasome signaling pathway].

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1ß secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1ß, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 µmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Iron Oxide Clusters as Electron Donors Under Light Enhance Oxygen Reduction Kinetics at Atomically Dispersed Fe for Photocatalytic CH4 Partial Oxidation.

Photocatalytic CH4 oxidation to CH3OH emerges as a promising strategy to sustainably utilize natural gas and mitigate the greenhouse effect. However, there remains a significant challenge for the synthesis of methanol by using O2 at low temperature. Inspired by the catalytic structure in soluble methane monooxygenase (MMO) and the corresponding reaction mechanism, we prepared a biomimetic photocatalysts with the decoration of Fe2O3 nanocluster and satellite Fe single atom immobilized on carbon nitride. The catalyst demonstrates an excellent CH3OH productivity of 5.02 mmol·gcat-1·h-1 with methanol selectivity of 98.5%. Mechanism studies reveal that the synergy between Fe2O3 nanocluster and Fe single atom establishes a dual-Fe site as MMO for O2 activation and subsequent CH4 partial oxidation. Moreover, the light excitation of Fe2O3 nanoclusters with a relative narrow bandgap could deliver the electrons and protons to atomic Fe that facilitating the oxygen reduction kinetics for the robust of methanol synthesis.

Atomically Dispersed Electron Traps in Cu Doped BiOBr Boosting CO2 Reduction to Methanol by Pure H2 O.

Overall photocatalytic conversion of CO2 and pure H2 O driven by solar irradiation into methanol provides a sustainable approach for extraterrestrial synthesis. However, few photocatalysts exhibit efficient production of CH3 OH. Here, BiOBr nanosheets supporting atomic Cu catalysts for CO2 reduction are reported. The investigation of charge dynamics demonstrates a strong built-in electric field established by isolated Cu sites as electron traps to facilitate charge transfer and stabilize charge carriers. As result, the catalysts exhibit a substantially high catalytic performance with methanol productivity of 627.66 µmol gcatal -1 h-1 and selectivity of ≈90% with an apparent quantum efficiency of 12.23%. Mechanism studies reveal that the high selectivity of methanol can be ascribed to energy-favorable hydrogenation of *CO intermediate giving rise to *CHO. The unfavorable adsorption on Cu1 @BiOBr prevents methanol from being oxidized by photogenerated holes. This work highlights the great potential of single-atom photocatalysts in chemical transformation and energy storage reactions.

Spatial multiplexing for robust optical vortex transmission with optical nonlinearity.

Optical vortex beams, with phase singularity characterized by a topological charge (TC), introduces a new dimension for optical communication, quantum information, and optical light manipulation. However, the evaluation of TCs after beam propagation remains a substantial challenge, impeding practical applications. Here, we introduce vortices in lateral arrays (VOILA), a novel spatial multiplexing approach that enables simultaneous transmission of a lateral array of multiple vortices. Leveraging advanced learning techniques, VOILA effectively decodes TCs, even in the presence of strong optical nonlinearities simulated experimentally. Notably, our approach achieves substantial improvements in single-shot bandwidth, surpassing single-vortex scheme by several orders of magnitude. Furthermore, our system exhibits precise fractional TC recognition in both linear and nonlinear regimes, providing possibilities for high-bandwidth communication. The capabilities of VOILA promise transformative contributions to optical information processing and structured light research, with significant potential for advancements in diverse fields.

Quantum Induced Coherence Light Detection and Ranging.

Quantum illumination has been proposed and demonstrated to improve the signal-to-noise ratio (SNR) in light detection and ranging (LiDAR). When relying on coincidence detection alone, such a quantum LiDAR is limited by the timing jitter of the detector and suffers from jamming noise. Inspired by the Zou-Wang-Mandel experiment, we design, construct, and validate a quantum induced coherence (QuIC) LiDAR which is inherently immune to ambient and jamming noises. In traditional LiDAR the direct detection of the reflected probe photons suffers from deteriorating SNR for increasing background noise. In QuIC LiDAR we circumvent this obstacle by only detecting the entangled reference photons, whose single-photon interference fringes are used to obtain the distance of the object, while the reflected probe photons are used to erase path information of the reference photons. In consequence, the noise accompanying the reflected probe light has no effect on the detected signal. We demonstrate such noise resilience with both LED and laser light to mimic the background and jamming noise. The proposed method paves a new way of battling noise in precise quantum electromagnetic sensing and ranging.

Quantum Control of a Single Magnon in a Macroscopic Spin System.

Nonclassical quantum states are the pivotal features of a quantum system that differs from its classical counterpart. However, the generation and coherent control of quantum states in a macroscopic spin system remain an outstanding challenge. Here we experimentally demonstrate the quantum control of a single magnon in a macroscopic spin system (i.e., 1 mm-diameter yttrium-iron-garnet sphere) coupled to a superconducting qubit via a microwave cavity. By tuning the qubit frequency in situ via the Autler-Townes effect, we manipulate this single magnon to generate its nonclassical quantum states, including the single-magnon state and the superposition of single-magnon state and vacuum (zero magnon) state. Moreover, we confirm the deterministic generation of these nonclassical states by Wigner tomography. Our experiment offers the first reported deterministic generation of the nonclassical quantum states in a macroscopic spin system and paves a way to explore its promising applications in quantum engineering.

Salvage peroral endoscopic myotomy is a promising treatment for achalasia after myotomy failure.

BACKGROUND AND AIMS: Reintervention modalities after myotomy failure in achalasia patients have yet to be established. The efficacy and safety of salvage peroral endoscopic myotomy (POEM) for treatment of achalasia after myotomy failure were evaluated in the study. METHODS: Between August 2011 and August 2021 at the Endoscopy Center of Zhongshan Hospital, 219 achalasia patients who had previously undergone a myotomy underwent a salvage POEM and were thus retrospectively enrolled in this study. After propensity score matching (PSM), operation-related parameters were compared between the salvage POEM group and the naïve POEM group. Subgroup analysis was performed between patients with previous Heller myotomy (HM) and patients with previous POEM. RESULTS: With similar baseline characteristics between both groups after PSM, the salvage POEM group presented with shorter tunnel length (11.8 ± 2.2 cm vs 12.8 ± .9 cm, P < .0001) and myotomy length (9.8 ± 2.0 cm vs 10.4 ± 1.0 cm, P < .0001) than the naïve POEM group. No significant differences were found in procedure-related adverse events between patients of salvage POEM and naïve POEM. The primary outcome of treatment success occurred in 175 of 193 patients (90.7%) in the salvage POEM group versus 362 of 374 patients (96.8%) in the naïve POEM group (P = .0046). At a 2- and 5-year follow-up, significantly higher rates of clinical failures were observed in the previous HM subgroup than in the previous POEM subgroup (P = .0433 and P = .0230, respectively). CONCLUSIONS: Salvage POEM after a previous myotomy failure, especially after a POEM failure, is a promising treatment option because it has a durable clinical relief rate.

Muscular injury as an independent risk factor for esophageal stenosis after endoscopic submucosal dissection of esophageal squamous cell cancer.

BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

Management of delayed bleeding of upper gastrointestinal endoscopic submucosal tunneling procedures: a retrospective single-center analysis and brief meta-analysis.

OBJECTIVES: Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE. METHOD: From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed. RESULTS: The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken-Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post-bleeding hospital stay was 10.0 ± 6.2 days. A brief meta-analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G-POEM was 0.4%. CONCLUSIONS: Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions.