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BACKGROUND: Medical treatment for Crohn's disease (CD) has continuously improved, which has led to a decrease in surgical recurrence rates. Despite these advancements, 25% of patients will undergo repeat intestinal surgery. Recurrence of CD commonly occurs on the mesentery side of the anastomosis site. AIM: To compare the new anti-mesenteric side-to-side delta-shaped stapled anastomosis (DSA) with the conventional stapled functional end-to-end anastomosis (CSA). METHODS: This retrospective study included CD patients who underwent ileo-ileal or ileo-colic anastomosis between January 2020 and December 2023. The DSA technique employed a stapler to maintain the concept of anti-mesentery side-to-side anastomosis by performing a 90° vertical closure of the open window compared with the CSA technique. At the corner where the open window is closed, the DSA avoids forming a pouch and creates an anastomosis resembling a delta shape within the intestinal lumen. We compared demographics, preoperative condition, operative findings, and operative outcomes for the two techniques. RESULTS: The study included 175 patients, including 92 in the DSA group and 83 in the CSA group. The two groups were similar in baseline characteristics, preoperative medical treatment, and operative findings except for the Montreal classification location. The 30-days postoperative complication rate was significantly lower in the DSA group compared with the CSA group (16.3% vs 32.5%, P = 0.009). Ileus incidence was significantly lower in the DSA group than in the CSA group (4.3% vs 14.5%, P = 0.033), and the hospital stay was shorter in the DSA group than in the CSA group (5.67 ± 1.53 days vs 7.39 ± 3.68 days, P = 0.001). CONCLUSION: The DSA technique was feasible and showed comparable postoperative outcomes with lower short-term complications compared with the CSA technique. Further studies on CD recurrence and long-term complications are warranted.

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2,5-Furandicarboxylic acid (FDCA), a critical polymer platform molecule that can potentially replace terephthalic acid, coupled hydrogen coproduction holds great prospects via electrolysis. However, the electrosynthesis of FDCA faces challenges in product separation from complex electrolytes and unclear electrochemical and nonelectrochemical reactions during the 5-hydroxymethylfurfural (HMF) oxidation. Herein, an electrochemical/chemical integrated system of alkaline HMF-H2O co-electrolysis is proposed, achieving distillation-free synthesis of high-purity FDCA by acidic separation/purification and hydrogen coproduction. This system achieves ampere-level current densities of 812 and 1290 mA cm-2 at potentials of 1.50 and 1.60 V, with nearly 100% FDCA yield and HMF conversion in only 6 min at 1.50 V. The electrooxidation of HMF involves a coupling of electrochemical and nonelectrochemical reactions, wherein the aldehyde group is dehydrogenated and oxidized, followed by dehydrated and oxidized of the hydroxyl group, ultimately forming FDCA. Concurrently, nonelectrochemical reactions of intermolecular electron transfer occur in HMF and aldehyde group-containing intermediates.

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Circular RNA (circRNA)-microRNA (miRNA) interaction (CMI) plays crucial roles in cellular regulation, offering promising perspectives for disease diagnosis and therapy. Therefore, it is necessary to employ computational methods for the rapid and cost-effective prediction of potential circRNA-miRNA interactions. However, the existing methods are limited by incomplete data; therefore, it is difficult to model molecules with different attributes on a large scale, which greatly hinders the efficiency and performance of prediction. In this study, we propose an effective method for predicting circRNA-miRNA interactions, called RBNE-CMI, and introduce a framework that can embed incomplete multiattribute CMI heterogeneous networks. By combining the proposed method, we integrate different data sets in the CMI prediction field into one incomplete network for modeling, achieving superior performance in 5-fold cross-validation. Moreover, in the prediction task based on complete data, the proposed method still achieves better performance than the known model. In addition, in the case study, we successfully predicted 18 of the 20 potential cancer biomarkers. The data and source code can be found at https://github.com/1axin/RBNE-CMI.

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A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features, the degree of malignancy, and the response to treatment. Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)-based lineage tracking are profiled in TETs at single-cell resolution. An original subpopulation of KRT14+ progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper-rearrangement state is revealed, due to the lack of CCL21+ medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn-infiltrating mature T cells. These common features based on the single-cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9-SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC-based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1+ CFTR- ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment.

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BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

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P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.

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Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

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Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

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BACKGROUND: Neoadjuvant chemoimmunotherapy has a promising effect on locally advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers robustly predicting therapeutic response are still lacking. METHODS: Formalin-fixed and paraffin-embedded pre-neoadjuvant chemoimmunotherapy biopsy samples from locally advanced ESCC patients were collected. Cohort 1 composed of 66 locally advanced ESCC patients from a prospective clinical trial (NCT04506138) received two cycles of camrelizumab in combination with nab-paclitaxel and carboplatin every 3 weeks. Cohort 2 included 48 patients receiving various types of immune checkpoint inhibitors with (nab-)paclitaxel and platinum-based chemotherapy as neoadjuvant therapy. Cohort 3 consisted of 27 ESCC patients receiving neoadjuvant treatment of toripalimab with chemotherapy and was used as the external validation dataset. Targeted RNA sequencing, immunohistochemistry for programmed death ligand 1 (PD-L1), and multiplex immunofluorescence (mIF) imaging were performed. RESULTS: Integration of targeted RNA sequencing, PD-L1 immunohistochemistry, and mIF revealed a significant immune-suppressive microenvironment with higher neutrophil infiltration, enriched TGF-ß, and cell cycle pathways in non-pathological complete response (non-pCR) patients. NK, activated CD4+ T cell infiltration, interferon-gamma, antigen processing and presentation, and other immune response signatures were significantly associated with pCR. Based on discovered tumor microenvironmental characteristics and their closely related genes were screened. Consequently, a seven-gene neoadjuvant chemoimmunotherapy risk prediction signature (NCIRPs) model, was constructed. In addition to cohort 1, this model alone or with PD-L1-combined positive score (CPS) demonstrated a higher prediction accuracy of pathological response than PD-L1 CPS or other routinely used immune signatures, such as IFN-γ, in cohorts 2 and 3. Neither prognostic association nor correlation with response to chemoradiotherapy was observed in The Cancer Genome Atlas Program ESCC dataset or in ESCC patients in the neoadjuvant chemoradiotherapy cohort (cohort 4). CONCLUSION: The NCIRPs model that was developed and validated using treatment-naïve endoscopic samples from the largest ESCC neoadjuvant chemoimmunotherapy dataset represents a robust and clinically meaningful approach to select a putative responder for neoadjuvant chemoimmunotherapy in locally advanced ESCC patients.

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BACKGROUND: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. METHODS: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. RESULTS: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. CONCLUSIONS: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.

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BACKGROUND: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo. METHODS: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture (CLP) model was used to detect neutrophil migration, neutrophil extracellular traps (NETs) level, and organ damage. RESULT: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of NETs, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multi-organ damage and lethality resulting from CLP. CONCLUSIONS: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.

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Purpose: The aim of this study was to examine the prognosis and associated risk factors, including adjuvant chemotherapy (CTx), in elderly patients with colon cancer. Methods: This retrospective study included patients who underwent radical resection for colon cancer between January 2010 and December 2014 at Asan Medical Center. The effects of stage, risk factors, and chemotherapy on overall survival (OS) and recurrence-free survival (RFS) were compared in patients aged ≥70 and <70 years. Results: Of 3,313 patients, 933 (28.1%) was aged ≥70 years. Of the 1,921 patients indicated for adjuvant CTx, 1,294 of 1,395 patients (92.8%) aged <70 years and 369 of 526 patients (70.2%) aged ≥70 years received adjuvant CTx. Old age (≥70 years) was independently associated with RFS in overall cohort. Among patients aged ≥70 years indicated for adjuvant CTx, the 5-year OS (81.6% vs. 50.4%, P<0.001) and RFS (82.9% vs. 67.4%, P=0.025) rates were significantly higher in those who did than did not receive adjuvant CTx. Additionally, adjuvant CTx was confirmed as independent risk factor of both OS and RFS in patients aged ≥70 years indicated for adjuvant CTx. Conclusion: Old age was associated with poor RFS and adjuvant CTx had benefits in OS as well as RFS in elderly patients eligible for adjuvant CTx.

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Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

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PURPOSE: This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy. RESULTS: In this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD. CONCLUSION: Integrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.

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BACKGROUND: Delirium is a common complication in intensive care unit (ICU) patients. It can lead to various adverse events. In this study, we investigated the effectiveness of combining the use of the PREdiction of DELIRium (PRE-DELIRIC) model for delirium risk assessment and the use of a multicomponent care bundle for delirium assessment, prevention, and care in terms of reductions in the incidence of delirium among surgical ICU patients. METHODS: This retrospective study included surgical ICU patients who had received PRE-DELIRIC-guided SMART/SmART care (SMART care: SmART bundle plus multidisciplinary team; SmART care: Sleep/sweet sense of home (creating a comforting and restful environment for patients), Assessment (regular and thorough evaluation of patient needs and conditions), Release (revised endotracheal tube care/removal, restraint device care, and immobility reduction for patient comfort), and Time (reorientation of time to optimize patient care schedules) in our hospital between May 2022 and March 2023 (intervention group) and individuals who had received usual care between January 2021 and April 2022 (historical control group). The SmART intervention involves providing care in the following domains: sleep/sweet sense of home, assessment, release, and time. Patients with a PRE-DELIRIC score of >30% received SMART care, which includes multidisciplinary (physicians, pharmacists, respiratory therapists, and physiotherapists) care in addition to SmART care. For the control group, usual care was provided following the guidelines for the prevention and management of pain, agitation, delirium, immobility, and sleep disruption. The primary outcome was delirium incidence during ICU stay, which was assessed using the Intensive Care Delirium Screening Checklist. The secondary outcomes were the duration of ICU stay, rate of unplanned self-extubation, and status of ICU discharge. RESULTS: The intervention and control groups comprised 184 and 197 patients, respectively; their mean ages were 63.7 ± 18.4 years and 62.4 ± 19.5 years, respectively. The incidence of delirium was significantly lower (p = 0.001) in the intervention group (22.3%) than in the control group (47.7%). CONCLUSION: Our findings suggest that the PRE-DELIRIC-guided SMART/SmART care intervention is effective in preventing and managing delirium among surgical ICU patients.

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Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

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Improving the nutrient content of red soils in southern China is a priority for efficient rice production there. To assess the effectiveness of oilseed rape as green manure for the improvement of soil phosphorus nutrient supply and rice yield in red soil areas, a long-term field plot experiment was conducted comparing two species of rape, Brassica napus (BN) and Brassica juncea (BJ). The effects of returning oilseed rape on soil phosphorus availability, phosphorus absorption, and yield of subsequent rice under rice-green manure rotation mode were analyzed, using data from the seasons of 2020 to 2021. The study found that compared with winter fallow treatment (WT) and no-tillage treatment (NT), the soil available phosphorus content of BN was increased, and that of BJ was significantly increased. The content of water-soluble inorganic phosphorus of BJ increased, and that of BN increased substantially. Compared with the WT, the soil organic matter content and soil total phosphorus content of BN significantly increased, as did the soil available potassium content of BJ, and the soil total phosphorus content of BJ was significantly increased compared with NT. The soil particulate phosphorus content of BJ and BN was significantly increased by 14.00% and 16.00%, respectively. Compared with the WT, the phosphorus activation coefficient of BJ was significantly increased by 11.41%. The rice plant tiller number under the green manure returning treatment was significantly increased by 43.16% compared with the winter fallow treatment. The green manure returning measures increased rice grain yield by promoting rice tiller numbers; BN increased rice grain yield by 9.91% and BJ by 11.68%. Based on these results, returning oilseed rape green manure could augment the phosphorus nutrients of red soil and promote phosphorus availability. Rice-oilseed rape green manure rotation could increase rice grain yield.

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The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

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BACKGROUND: The role of diverse antibodies in mediating peripheral nerve injury in Guillain-Barré syndrome (GBS) is becoming clearer, but positivity for multiple antibodies in one case is uncommon. To our knowledge, this is the first case involving GBS with positive anti-sulfatide, anti-GT1a, and anti-GT1b antibodies. CASE SUMMARY: A 20-year-old female patient was admitted to the hospital due to weakness of limbs for 5 d, and deterioration of the weakness and muscle aches for 1 d. The patient's limbs were weak, but the tendon reflexes in the part of the limbs were normal. There was no comorbid peripheral nociception or deep sensory dysfunction. She was diagnosed with GBS and was discharged after receiving intravenous human immunoglobulin pulse therapy. CONCLUSION: In this article, the clinical manifestations, neurophysiological examination, and auxiliary examination findings of a GBS patient positive for multiple antibodies were analyzed to improve the identification of the disease by clinical physicians at an early stage.

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Background: The global status of women's health is underestimated, particularly the burden on women of child-bearing age (WCBA). We aim to investigate the pattern and trend of female cancers among WCBA from 1990 to 2021. Methods: We retrieved data from the Global Burden of Disease Study (GBD) 2021 on the incidence and disability-adjusted life-years (DALYs) of four major female cancers (breast, cervical, uterine, and ovarian cancer) among WCBA (15-49 years) in 204 countries and territories from 1990 to 2021. Estimated annual percentage changes (EAPC) in the age-standardised incidence and DALY rates of female cancers, by age and socio-demographic index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the correlation between age-standardised rates and SDI. Findings: In 2021, an estimated 1,013,475 new cases of overall female cancers were reported globally, with a significant increase in age-standardised incidence rate (EAPC 0.16%), and a decrease in age-standardised DALY rate (-0.73%) from 1990 to 2021. Annual increase trends of age-standardised incidence rate were observed in all cancers, except for that in cervical cancer. Contrary, the age-standardised DALY rate decreased in all cancers. Breast and cervical cancers were prevalent among WCBA worldwide, followed by ovarian and uterine cancers, with regional disparities in the burden of four female cancers. In addition, the age-standardised incidence rates of breast, ovarian, and uterine cancers basically showed a consistent upward trend with increasing SDI, while both the age-standardised incidence and DALY rates in cervical cancer exhibited downward trends with SDI. Age-specific rates of female cancers increased with age in 2021, with the most significant changes observed in younger age groups, except for uterine cancer. Interpretation: The rising global incidence of female cancers, coupled with regional variations in DALYs, underscores the urgent need for innovative prevention and healthcare strategies to mitigate the burden among WCBA worldwide. Funding: This study was supported by the Science Foundation for Young Scholars of Sichuan Provincial People's Hospital (NO. 2022QN44 and NO. 2022QN18); the Key R&D Projects of Sichuan Provincial Department of Science and Technology (NO. 2023YFS0196); the National Natural Science Foundation of China (No. 82303701).