Molecular mechanisms of gut microbiota in diabetic nephropathy.

Diabetic nephropathy is a common complication of diabetes and a considerable contributor to end-stage renal disease. Evidence indicates that glucose dysregulation and lipid metabolism comprise a pivotal pathogenic mechanism in diabetic nephropathy. However, current treatment outcomes are limited, as they only provide symptomatic relief without preventing disease progression. The gut microbiota is a group of microorganisms that inhabit the human intestinal tract and play a crucial role in maintaining host energy balance, metabolism, and immune activity. Patients with diabetic nephropathy exhibit altered gut microbiota, suggesting its potential involvement in the onset and progression of the disease. However, how a perturbed microbiota induces and promotes diabetic nephropathy remains unelucidated. This article summarizes the evidence of the impact of gut microbiota on the progression of diabetic nephropathy, with a particular focus on the molecular mechanisms involved, aiming to provide new insights into the treatment of diabetic nephropathy.

METTL3-mediated pre-miR-665/DLX3 m6A methylation facilitates the committed differentiation of stem cells from apical papilla.

Methyltransferase-like 3 (METTL3) is a crucial element of N6-methyladenosine (m6A) modifications and has been extensively studied for its involvement in diverse biological and pathological processes. In this study, we explored how METTL3 affects the differentiation of stem cells from the apical papilla (SCAPs) into odonto/osteoblastic lineages through gain- and loss-of-function experiments. The m6A modification levels were assessed using m6A dot blot and activity quantification experiments. In addition, we employed Me-RIP microarray experiments to identify specific targets modified by METTL3. Furthermore, we elucidated the molecular mechanism underlying METTL3 function through dual-luciferase reporter gene experiments and rescue experiments. Our findings indicated that METTL3+/- mice exhibited significant root dysplasia and increased bone loss. The m6A level and odonto/osteoblastic differentiation capacity were affected by the overexpression or inhibition of METTL3. This effect was attributed to the acceleration of pre-miR-665 degradation by METTL3-mediated m6A methylation in cooperation with the "reader" protein YTHDF2. Additionally, the targeting of distal-less homeobox 3 (DLX3) by miR-665 and the potential direct regulation of DLX3 expression by METTL3, mediated by the "reader" protein YTHDF1, were demonstrated. Overall, the METTL3/pre-miR-665/DLX3 pathway might provide a new target for SCAP-based tooth root/maxillofacial bone tissue regeneration.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Application of artificial intelligence in the diagnosis and treatment of cardiac arrhythmia.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line.

BACKGROUND: Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. METHODS: In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. RESULTS: The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. CONCLUSIONS: The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.

Hydrolysis of Nerve Agent Simulants Accelerated by Stimuli-Responsive Dinuclear Catalysts.

The ability to control the catalytic activity of enzymes in chemical transformations is essential for the design and development of artificial catalysts. Herein, we report the synthesis and characterization of functional ligands featuring two 1,4,7,10-tetraazacyclododecane units linked by an azobenzene group and their corresponding dinuclear Zn(II) complexes. We show that the configuration switching (E/Z) of the azobenzene spacer in the ligands and their dinuclear Zn(II) complexes is reversibly controlled by irradiation with UV and visible light. The Zn(II)-metal complexes are light-responsive catalysts for the hydrolytic cleavage of nerve agent simulants, i.e., p-nitrophenyl diphenyl phosphate and methyl paraoxon. The catalytic activity of the Z-isomers of the dinuclear Zn(II) complexes outperformed that of the E-counterparts. Moreover, combining the less active E-isomers with gold nanoparticles induced an enhancement in the hydrolysis rate of p-nitrophenyl diphenyl phosphate. Kinetic analysis has shown that the catalytic site appears to involve a single metal ion. We explain our results by considering the different desolvation effects occurring in the catalyst's configurations in the solution and the catalytic systems involving gold nanoparticles.

Evaluation of 3D tablet-based stereoacuity test ASTEROID in children with normal and abnormal visual acuity.

PURPOSE: To assess the utility of 3D, tablet-based, glasses-free Accurate STEReotest (ASTEROID) in children compared with the Titmus test. METHODS: Children aged 5-13 years were enrolled in a single-center, nonrandomized, observational comparison study and analyzed by age (5-7 vs 8-13 years) and visual acuity (20/25 or better in both eyes vs abnormal). Each participant underwent both the ASTEROID and Titmus stereoacuity tests. Stereoacuity was defined as fine (≤60 arcsec), moderate (61-200 arcsec), coarse (201-1199 arcsec), or very coarse to nil (≥1200 arcsec). Agreement between the tests was assessed using a weighted kappa (κ) statistic based on all four categories. RESULTS: A total of 112 children were included: 28 aged 5-7 with normal visual acuity, 30 aged 5-7 with abnormal visual acuity, 34 aged 8-13 with normal visual acuity, and 20 aged 8-13 with abnormal visual acuity. Mean ASTEROID score was 688 ± 533 arcsec (range, 13-1200 arcsec). Agreement between ASTEROID and Titmus test scores for participants overall was moderate (κ = 0.52). By subgroup, agreement was fair for children 5-7 with abnormal visual acuity (κ = 0.31), moderate for children 5-7 with normal visual acuity (κ = 0.47) and children 8-13 with normal visual acuity (κ = 0.42), and substantial for children 8-13 with abnormal visual acuity (κ = 0.76). Where ASTEROID and Titmus score group varied, ASTEROID score was poorer in 94% (47/50) of cases. CONCLUSIONS: ASTEROID is a digital, tablet-based test that evaluates global stereopsis, does not require glasses, and provides a continuum of scores. Among children, ASTEROID has good agreement with the Titmus test; however, it may be more sensitive at detecting stereovision deficits. Further study is necessary to determine which test is more accurate.

Deselenylative Acylation and Nitration of Monoselenides.

A deselenylative protocol that enables the construction of the C-C and C-N bonds has been disclosed. By using acyl chloride/AgOTf as an efficient acylation reagent, diarylselenides smoothly undergo deselenylative acylation to produce a series of aroyl compounds. In addition, deselenylative nitration can be enabled by a mild nitration reagent consisting of TsCl and AgNO3, furnishing a diverse array of nitroaromatic compounds.

Complex Droplet Microreactor for Highly Efficient and Controllable Esterification and Cascade Reactions.

A highly efficient complex emulsion microreactor has been successfully developed for multiphasic water-labile reactions, providing a powerful platform for atom economy and spatiotemporal control of reaction kinetics. Complex emulsions, composing a hydrocarbon phase (H) and a fluorocarbon phase (F) dispersed in an aqueous phase (W), are fabricated in batch scale with precisely controlled droplet morphologies. A biphasic esterification reaction between 2-bromo-1,2-diphenylethane-1-ol (BPO) and perfluoro-heptanoic acid (PFHA) is chosen as a reversible and water-labile reaction model. The conversion reaches up to 100 % under mild temperature without agitation, even with nearly equivalent amounts of reactants. This efficiency surpasses all reported single emulsion microreactors, i. e., 84~95 %, stabilized by various emulsifiers with different catalysts, which typically necessitate continuous stirring, a high excess of one reactant, and/or extended reaction time. Furthermore, over 3 times regulation threshold in conversion rate is attained by manipulating the droplet morphologies, including size and topology, e. g., transition from completely engulfed F/H/W double to partially engulfed (F+H)/W Janus. Addition-esterification, serving as a model for triple phasic cascade reaction, is also successfully implemented under agitating-free and mild temperature with controlled reaction kinetics, demonstrating the versatility and effectiveness of the complex emulsion microreactor.

Expression of chiral molecular and supramolecular structure on enantioselective catalytic activity.

Understanding the structure-function relationships encoded on chiral catalysts is important for investigating the fundamental principles of catalytic enantioselectivity. Herein, the synthesis and self-assembly of naphthalene substituted bis-l/d-histidine amphiphiles (bis-l/d-NapHis) in DMF/water solution mixture is reported. The resulting supramolecular assemblies featuring well-defined P/M nanoribbons (NRs). With combination of the (P/M)-NR and metal ion catalytic centers (Mn+ = Co2+, Cu2+, Fe3+), the (P)-NR-Mn+ as chiral supramolecular catalysts show catalytic preference to 3,4-dihydroxy-S-phenylalanine (S-DOPA) oxidation while the (M)-NR-Mn+ show enantioselective bias to R-DOPA oxidation. In contrast, their monomeric counterparts bis-l/d-NapHis-Mn+ display an inverse and dramatically lower catalytic selectivity in the R/S-DOPA oxidation. Among them, the Co2+-coordinated supramolecular nanostructures show the highest catalytic efficiency and enantioselectivity (select factor up to 2.70), while the Fe3+-coordinated monomeric ones show nearly racemic products. Analysis of the kinetic results suggests that the synergistic effect between metal ions and the chiral supramolecular NRs can significantly regulate the enantioselective catalytic activity, while the metal ion-mediated monomeric bis-l/d-NapHis were less active. The studies on association constants and activation energies reveal the difference in catalytic efficiency and enantioselectivity resulting from the different energy barriers and binding affinities existed between the chiral molecular/supramolecular structures and R/S-DOPA enantiomers. This work clarifies the correlation between chiral molecular/supramolecular structures and enantioselective catalytic activity, shedding new light on the rational design of chiral catalysts with outstanding enantioselectivity.

Crystal Facet Controlled Metal-Support Interaction in Uricase Mimics for Highly Efficient Hyperuricemia Treatment.

The effect of strong metal-support interaction (SMSI) has never been systematically studied in the field of nanozyme-based catalysis before. Herein, by coupling two different Pd crystal facets with MnO2, i.e., (100) by Pd cube (Pdc) and (111) by Pd icosahedron (Pdi), we observed the reconstruction of Pd atomic structure within the Pd-MnO2 interface, with the reconstructed Pdc (100) facet more disordered than Pdi (111), verifying the existence of SMSI in such coupled system. The rearranged Pd atoms in the interface resulted in enhanced uricase-like catalytic activity, with Pdc@MnO2 demonstrating the best catalytic performance. Theoretical calculations suggested that a more disordered Pd interface led to stronger interactions with intermediates during the uricolytic process. In vitro cell experiments and in vivo therapy results demonstrated excellent biocompatibility, therapeutic effect, and biosafety for their potential hyperuricemia treatment. Our work provides a brand-new perspective for the design of highly efficient uricase-mimic catalysts.

Exploring the landscape of stem cell extracellular vesicle research for angiogenesis: A bibliometric analysis from 2003 to 2023.

BACKGROUND: Exosomes and other secretory membrane vesicles are collectively referred to as extracellular vesicles (EVs). Relevant data indicate that stem cell-derived extracellular vesicles (SC-EVs) play a critical role in angiogenesis by transmitting crucial information such as proteins, second messengers, and genetic material between cells. Therefore, this study aimed to map current trends on SC-EVs for angiogenesis and provide directions for future research to advance this important field. METHODS: We conducted a thorough search for relevant studies on SC-EVs for angiogenesis from 2003 to 2023 using the Web of Science database. Subsequently, we used VOSviewer and CiteSpace to analyze the collected data. RESULTS: A total of 2359 relevant publications, which included original articles and reviews, related to the role of SC-EVs in angiogenesis were screened in this study based on the search strategy. China and the United States were leading in this field, with China having a higher output in terms of publications and citations (1172, 43681). Also, the top five universities were located in China, with Shanghai Jiao Tong University having the highest output. Stem Cell Research & Therapy and International Journal of Molecular Sciences, are prominent platforms for researchers in this field to share their findings and advancements, and they had most of published studies on SC-EVs for angiogenesis. The results derived from the cluster analysis suggested that future investigations should predominantly prioritize studying the involvement of SC-EVs in angiogenesis across various diseases, with a specific emphasis on skin wound healing. CONCLUSION: In this comprehensive review, global trends in SC-EVs for angiogenesis were analyzed. The analysis of journals, institutions, references, and keywords could assist researchers in deciding on the direction of research. The role of SC-EVs in promoting angiogenesis during wound healing and repair represents an emerging research focus.

Na3V2(PO4)3-decorated Na3V2(PO4)2F3 as a high-rate and cycle-stable cathode material for sodium ion batteries.

Since Na3V2(PO4)3 (NVP) possesses modest volume deformation and three-dimensional ion diffusion channels, it is a potential sodium-ion battery cathode material that has been extensively researched. Nonetheless, NVP still endures the consequences of poor electronic conductivity and low voltage platforms, which need to be further improved. On this basis, a high voltage platform Na3V2(PO4)2F3 was introduced to form a composite with NVP to increase the energy density. In this study, the sol-gel technique was successfully used to synthesize a Na3V2(PO4)2.75F0.75/C (NVPF·3NVP/C) composite cathode material. The citric acid-derived carbon layer was utilized to construct three-dimensional conducting networks to effectively promote ion and electron diffusion. Furthermore, the composites' synergistic effect accelerates the quick ionic migration and improves the kinetic reaction. In particular, NVP as the dominant phase enhanced the structural stability and significantly increased the capacitive contribution. Therefore, at 0.1C, the discharge capacity of the modified NVPF·3NVP/C composite is 120.7 mA h g-1, which is greater than the theoretical discharge capacity of pure NVP (118 mA h g-1). It discharged 110.9 mA h g-1 of reversible capacity even at an elevated multiplicity of 10C, and after 200 cycles, it retained 64.1% of its capacity. Thus, the effort produced an optimized NVPF·3NVP/C composite cathode material that may be used in the sodium ion cathode.

Pan­immune­inflammation value as a novel prognostic biomarker in nasopharyngeal carcinoma.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

Phenylglycine amphiphile-metal ion chiral supramolecular nanozymes for enantioselective catalysis.

L/D-Phenylglycine amphiphiles and metal ions with peroxidase-like activity self-assembled into chiral nanoribbons, which act as efficient chiral supramolecular nanozymes for catalyzing the 3,4-dihydroxy-L/D-phenylalanine (L/D-DOPA) oxidation reactions. The catalytic efficiency and enantioselectivity are dominated by the chirality transfer and the synergistic effect between the metal ions and chiral nanoribbons.

Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer.

BACKGROUND: Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM: To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS: A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS: The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION: This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.