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INTRODUCTION: Chemotherapy is the standard second-line treatment option for advanced biliary tract cancer (BTC), but its therapeutic efficacy is suboptimal. Disitamab vedotin (RC48) and lenvatinib have demonstrated promising efficacy in human epidermal growth factor receptor 2 (HER2)-positive BTC and other malignancies. In this study, we aim to evaluate the efficacy and safety of RC48 in combination with lenvatinib in second-line or above treatment for HER2-positive advanced BTC. METHODS AND ANALYSIS: This is a single-centre, single-arm, open-label, exploratory phase II clinical study in patients with HER2-positive unresectable locally advanced or metastatic BTC who have failed prior therapy. 31 patients will be enrolled in this study to receive the combination of RC48 and lenvatinib. The primary study endpoint is objective response rate, and the secondary study endpoints are disease control rate, duration of response, progression-free survival and overall survival. ETHICS AND DISSEMINATION: The study has received approval from the Medical Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval No. (2023)0367-01). Results will be disseminated through publication in peer-reviewed journals and through other appropriate media channels. TRIAL REGISTRATION NUMBER: ChiCTR2300076406.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Compuestos de Fenilurea , Quinolinas , Receptor ErbB-2 , Humanos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/metabolismo , Receptor ErbB-2/metabolismo , Ensayos Clínicos Fase II como Asunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Anticuerpos Monoclonales , OligopéptidosRESUMEN
Furanocoumarins (FCMs) are a group of organic compounds abundantly found in citrus fruits. Excessive intake is closely associated with increased incidence of skin cancer. Consequently, the development of an efficient approach for in vivo determination of FCMs in citrus fruits is of critical importance. In this study, 1,3,5-tris (4-aminophenyl) benzene (TAPB) and 2,4-dihydroxybenzene-1,3,5-tricarbaldehyde (DHTA) were used to synthesize covalent organic framework (COF) as a solid phase microextraction (SPME) probe. The probe showed highly ordered porosity (1.49 nm), outstanding stability, and hydrophobicity. With respect to these superiorities, it was coupled with electrospray ionization mass spectrometry (ESI/MS) to achieve the detection of six FCMs with high enrichment factors (71.3-108.5), and low detection limits (0.003-0.160 µg L-1). The platform was used with great success for the in vivo analysis of FCMs in four citrus fruits, indicating that this platform had good prospects as a powerful instrument for in vivo monitoring fruits.
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RATIONALE: Ulcerative colitis (UC) and psoriasis are both chronic inflammatory diseases mediated by the immune system. Ixekizumab, used to treat psoriasis, carries a risk of inducing or exacerbating UC. Infliximab has also been reported to exacerbate psoriasis. Guselkumab (GUS) can be used to treat both UC and psoriasis. Currently, there are few case reports on the use of GUS for the treatment of UC-psoriasis comorbidity. Our observations support the rationale for IL-23-targeted agents in patients with overlapping psoriasis and inflammatory bowel disease, and they provide exploratory evidence that the psoriasis-labeled regimen of GUS may suffice for selected UC patients. PATIENT CONCERNS: A 51-year-old woman with a history of psoriasis for more than 20 years was diagnosed with ulcerative colitis due to abdominal pain, diarrhea, and mucous-bloody stools while using ixekizumab. During treatment with infliximab for ulcerative colitis, her psoriatic lesions worsened. Switching to guselkumab achieved complete skin clearance (PASI 0) and sustained endoscopic remission of UC (Mayo 1, UCEIS 1) without the need for additional biologic therapy. DIAGNOSES: Psoriasis has been previously diagnosed; ulcerative colitis was diagnosed based on the patient's clinical symptoms, colonoscopy, and pathological examination. INTERVENTIONS: The patient was given guselkumab (100 mg every 8 weeks) and mesalazine (4 g every day). OUTCOMES: Four months after starting guselkumab, the patient's psoriasis area and severity index score reached 0, and guselkumab therapy was continued thereafter. Since then, she has experienced no gastrointestinal symptoms, and her psoriasis has been well-controlled. On June 28, 2025, a follow-up colonoscopy was performed. The Mayo endoscopic score was 1, and the ulcerative colitis endoscopic index of severity score was 1. LESSONS: Dermatologists closely monitor gastrointestinal symptoms in patients with psoriasis who are receiving ixekizumab to ensure safe medication use. Patients with ulcerative colitis and psoriasis may actively consider using guselkumab.
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Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Fármacos Dermatológicos , Psoriasis , Humanos , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Psoriasis/complicaciones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéuticoRESUMEN
MOTIVATION: Drug synergy is crucial for developing effective combination therapies, but traditional screening methods suffer from inefficiency and high costs. While deep learning shows promise for predicting drug synergy, current approaches using Transformers and graph neural networks focus on combining drug and cell line features without modelling how genes causally influence drug responses. RESULTS: To address this limitation, we propose CADS (Causal Adjustment for Drug Synergy), a deep learning framework that integrates causal relationships between genes and drug responses. Leveraging multi-omics data, CADS uses a learnable mask mechanism to identify key causal genes while filtering out irrelevant genetic factors through backdoor adjustment. Our model achieves two key objectives simultaneously: accurate prediction of drug synergy and interpretable causal gene discovery. Experiments on multiple datasets show that CADS consistently outperforms state-of-the-art methods across multiple metrics. Case studies demonstrate that CADS can reduce unnecessary complexity while providing more biological insights through its gene importance scores, which help identify clinically validated cancer-related genes that mediate drug interactions. AVAILABILITY AND IMPLEMENTATION: Taken together, CADS advances combination therapy prediction by explicitly modelling drug synergy causal genes, offering enhanced interpretability for AI-based drug development. The source code can be found at https://github.com/HuaiwuZhang/causalDC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Glioblastoma multiforme (GBM) continues to pose a significant challenge in the field of neuro-oncology primarily because of the limited penetration of therapeutics across the blood-brain barrier (BBB) and the presence of immunosuppressive tumor microenvironments. To address these challenges, a HD-PEG2K@BM biomimetic nanoplatform (hereinafter referred to as HD-P@BM) is developed that cloaks the near-infrared II photosensitizer HD-PEG2K (HD-P) inside microglial membranes to enable enhanced BBB penetration and tumor-targeted delivery. In this study, it is found that the microglia-derived membranes enhanced the uptake of nanoparticles by both the glioma cells and tumor-associated microglia. Furthermore, irradiation with 808 nm laser induced a photodynamic effect that caused mitochondrial dysfunction and elicited immunogenic cell death. Notably, HD-P@BM reprogrammed the immunosuppressive microglia to pro-inflammatory M1 phenotypes, which promoted cytotoxic T-cell infiltration and remodeled the tumor immune landscape. In orthotopic GBM models, HD-P@BM significantly suppressed tumor growth, prolonged survival, and mitigated systemic toxicity. This multifunctional strategy synergized biomimetic delivery, photodynamic therapy (PDT), and immunotherapy is a promising therapeutic approach for GBM. Thus, this study establishes a multifunctional nanotherapeutic strategy that combines enhanced BBB penetration, precise tumor targeting, and synergistic PDT, showing high potential for effective clinical GBM treatment.
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Materiales Biomiméticos , Barrera Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Microglía , Nanopartículas , Fotoquimioterapia , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Fotoquimioterapia/métodos , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Microglía/metabolismo , Ratones , Humanos , Línea Celular Tumoral , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Nanopartículas/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismoRESUMEN
Immune checkpoint inhibitor (ICI) resistance in hepatocellular carcinoma (HCC) poses a major therapeutic challenge. Here we present a Phase 2 trial evaluating stereotactic body radiotherapy (SBRT) combined with sintilimab and bevacizumab biosimilar (PD-1/VEGF blockade) to overcome resistance in ICI-refractory HCC. Twenty-one patients with progressive HCC after ICI therapy receive SBRT followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks. The primary outcome, objective response rate in non-irradiated lesions is 33.3%, with a disease control rate of 66.7%. Median progression-free survival is 6.2 months, and estimated median overall survival is 24.4 months. SBRT achieves 100% local control, with 33.3% experiencing grade 3 or higher adverse events. Proteomic profiling reveals that responders exhibit lower baseline IFN-γ and elevated IL-6, while post-SBRT increases in IFN-γ, IL-2, and IL-6 correlate with improved outcomes. These results indicate that combination of SBRT in ICI-refractory HCC is effective, well-tolerated, and may be guided by cytokine assessment.
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This study evaluated the prognostic value of the C-PLAN index in advanced esophageal squamous cell carcinoma (ESCC) patients receiving immune checkpoint inhibitor (ICI) therapy. A retrospective analysis of 241 eligible patients treated during February 2020 to January 2023 was conducted. Based on the C-PLAN index, calculated from lactate dehydrogenase (LDH), C-reactive protein (CRP), performance status (PS), albumin (ALB), and derived neutrophil-to-lymphocyte ratio (dNLR), patients were categorized into Good (0-1 points) and Poor (2-5 points) groups. The Poor group exhibited more advanced clinical stages and larger tumor diameters (both p < 0.05). The Good group demonstrated a significantly higher objective response rate and disease control rate (both p < 0.05), lower progression/death incidence (both p < 0.001), and longer progression-free survival and overall survival (p < 0.001). Multifactorial Cox regression analysis revealed that PD-L1 CPS < 10%, clinical stage IV, and high C-PLAN score (2-5 points) were independent risk factors for disease progression or death following ICI therapy in patients with advanced ESCC. The C-PLAN index effectively stratifies prognosis and optimizes therapeutic decision-making for advanced ESCC. The C-PLAN index serves as a prognostic factor, providing an objective basis for survival assessment and treatment plan optimization in advanced ESCC patients.
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Background: Pituitary adenomas (PA) frequently compress the optic chiasm, leading to visual field defects (VFDs) and potentially affecting the function of brain networks. This cross-sectional study aimed to investigate alterations in brain networks in PA patients with chiasmal compression using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In this study, 35 PA patients with chiasmal compression and 33 healthy controls (HCs) were enrolled and underwent rs-fMRI scanning. Network-Based Statistic (NBS) and large-scale network analyses were performed. Additionally, correlations were analyzed between altered functional connectivity (FC) and suprasellar extension distance, duration of VFDs, as well as mean deviation (MD), reflecting the degree of VFDs. Results: Combining NBS and large-scale network analyses, we found that PA patients with chiasmal compression mainly showed significantly decreased intra- and inter-network connectivity, including the visual network (VN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), somatosensory-motor network (SMN), and subcortical network (SCN). Moreover, the decreased mean FC values within VN and between VN-VAN were negatively correlated with suprasellar extension distance, and the decreased mean FC within VN was positively correlated with MD. Conclusions: This study highlights the widespread dysfunction of brain networks in PA patients with chiasmal compression. These findings offer new insights into the brain dysfunction in PA patients with chiasmal compression and could also aid in the evaluation of therapeutic efficacy for the disease.
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Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the malignant proliferation of myeloid progenitor cells. Although the introduction of the B-cell lymphoma-2 (BCL-2) inhibitor Venetoclax (VEN) has significantly improved patient outcomes and established it as a first-line treatment, high rates of drug resistance and relapse remain major clinical challenges. We integrated RUNX3 chromatin immunoprecipitation sequencing (ChIP-seq) data with the GAPIA2 database to identify CRTC2 as a key candidate gene. Subsequently, we employed qRT-PCR to compare CRTC2 expression levels between donors and AML patients. The role of CRTC2 in apoptosis was further validated through knockdown and overexpression experiments in various cell lines. To investigate the impact of CRTC2 on AML progression, we established a cell line-derived xenograft (CDX) model. The proportion of human CD45-positive (hCD45+) cells in the bone marrow and liver was assessed, and histological examination was conducted using HE staining, along with peripheral blood smear analysis. In addressing VEN resistance, we analyzed CRTC2 expression patterns in clinical samples and explored the synergistic therapeutic effect of a CRTC2 inhibitor in combination with VEN. To further elucidate the underlying molecular mechanisms, we performed mitochondrial function assays and analyzed mitochondrial translation-related proteins. Clinical analyses have demonstrated that elevated expression levels of CRTC2, a downstream target of RUNX3, are significantly correlated with poor prognosis in patients with AML. Functional experiments have shown that CRTC2 plays a role in disease progression by modulating apoptosis in AML cells. The knockdown of CRTC2 was observed to delay disease progression in CDX mouse models. Additional investigations revealed a positive correlation between CRTC2 expression and resistance to VEN in AML cells, with CRTC2 inhibition synergistically enhancing VEN's cytotoxic effects. Mechanistic studies suggest that increased mitochondrial activity contributes to VEN resistance, thereby identifying a potential molecular target for overcoming drug resistance. CRTC2 is a key regulator in AML, with high expression levels promoting disease progression and resistance to VEN. Inhibiting CRTC2 reduces mitochondrial translation and energy reserves, increasing AML cell sensitivity to VEN. These results highlight CRTC2 as a promising therapeutic target and suggest a new strategy to overcome VEN resistance.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Mitocondrias , Sulfonamidas , Factores de Transcripción , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Animales , Ratones , Sulfonamidas/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Progresión de la Enfermedad , Apoptosis/efectos de los fármacos , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Antineoplásicos/farmacología , MasculinoRESUMEN
BACKGROUND: Cancer in the cervical region of the uterus is a major health issue for women. A live bacterial vector therapeutic vaccine is genetically engineered to stimulate a targeted immune response by integrating the target antigen gene into a live, attenuated vector. Listeria has become a focal point for bacterial vaccine vectors, owing to its distinctive intracellular parasitism and ability to process and present antigens. Antibiotic-resistant plasmids in vaccines present a dual risk, including the promotion of antibiotic resistance and in vivo instability. The implementation of a balanced lethal system can effectively mitigate both challenges. METHODS: We constructed therapeutic vaccinations for cervical cancer with dual-species Listeria vectors-attenuated Listeria monocytogenes (LM) with act A/plc B/dal/dat deletion (LM∆∆dd) and recombinant Listeria ivanovii (LI) whose hemolysin gene (ilo) is substituted with the hly gene of LM and with dal/dat deletion (LI∆ilo::hly∆∆dd). Recombinant Listeria-vectored therapeutic vaccines for cervical cancer, expressing HPV6/11/16/18 E6E7 proteins, were constructed based on the balanced lethal system. The basic biological characteristics of the vaccines were described. The vaccinations were evaluated for biosafety, stability, and immunogenicity in mice, and their efficacy was assessed in subcutaneous HPV16/18 E6/E7-expressing tumor models. RESULTS: This study demonstrates that recombinant Listeria expressing multivalent HPV E6/E7 proteins exhibit broad-spectrum anti-tumor effects against cervical cancer models. The study showed that the vaccination strains effectively expressed multivalent HPV antigen, exhibited plasmid stability in vitro, and had no significant impact on biochemical reactions and hemolytic activity. In mice, the vaccine strain was biologically safe, and the plasmid remained stable in vivo. A heterologous immunization strategy-LM prime-LI boost-LM final-was employed to immunize the mice, resulting in a robust, antigen-specific cellular immune response. In the subcutaneous HPV16/18 E6/E7-expressing tumor models, this vaccination protocol achieved complete tumor cure rates of 30% and 40%, respectively, and significantly extended the median survival time. CONCLUSIONS: Our objective was to evaluate the efficacy of the vaccine against subcutaneous HPV16/18 E6/E7-expressing tumor models, enhance its safety profile, and co-express multivalent HPV antigens to target a broader range of cervical cancer types.
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PD-1 inhibitors show efficacy in hepatocellular carcinoma (HCC), yet overall outcomes remain poor. In this retrospective study of 258 advanced HCC patients treated between 2019 and 2024, peripheral blood B-cell dynamics were evaluated. Patients with higher B-cell proportions or absolute counts had significantly longer overall survival (OS) and progression-free survival (PFS). Multivariate analysis confirmed elevated B-cell proportion as an independent protective factor for OS. These results suggest that peripheral blood B-cell levels may serve as prognostic biomarkers for PD-1-based immunotherapy in advanced HCC.
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While FLT3 inhibitors have significantly improved the treatment of aggressive FLT3-mutated acute myeloid leukemia (AML), the emergence of resistance remains as a major challenge. Here, we applied our recently developed single-cell lineage tracing method ReSisTrace to identify cells that are intrinsically resistant or sensitive to the FLT3 inhibitors midostaurin and quizartinib in AML with FLT3-ITD mutations. Comparison of the gene expression profiles of these cells revealed transcriptional resistance signatures, including upregulation of GSPT1. Depletion of GSPT1 with CRISPR-Cas9-mediated knockout resulted in increased sensitivity of AML cells to quizartinib treatment. Further, targeting GSPT1 with the small molecule CC-90009 exhibited strong synergistic effects when combined with FLT3 inhibitors in the FLT3-ITD cell lines and primary AML patient samples. In addition, in an FLT3-ITD-positive AML patient-derived xenograft (PDX) mouse model, the CC-90009 and quizartinib combination showed significantly higher anti-tumor efficacy and prolonged overall survival compared to either treatment alone. Furthermore, compounds that induced transcriptomic changes opposite to the resistance signatures prompted cells to acquire FLT3 inhibitor-sensitive states. Vistusertib (mTOR inhibitor), linsitinib (IGF1R and insulin receptor inhibitor), and meisoindigo (IGF1R and Src family kinase inhibitor), all inhibiting pathways parallel to or downstream of oncogenic FLT3 signaling, were predicted and validated to sensitize FLT3-mutated cell lines and primary cells to FLT3 inhibitors. Collectively, these findings demonstrate the ability of ReSisTrace to unveil pre-existing transcriptional features of treatment vulnerability in hematological cancers and elucidate strategies for enhancing FLT3 inhibitor treatment efficacy in FLT3-ITD-mutated AML.
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Ovarian high-grade serous cancer (HGSC) is the most aggressive ovarian cancer subtype with limited treatment options. We identify the PDPK1 inhibitor BX-912 as a promising candidate, showing strong single-agent activity and synergy with the PARP inhibitor olaparib, independent of BRCA status. Unexpectedly, BX-912 induces multinucleation, a phenotype not seen with other PDPK1 inhibitors. Proteome Integral Solubility Alteration (PISA) assay reveals HES1 as a functional off-target, while structural modeling suggested BX-912 acts as a protein-protein interaction modulator, driving nuclear accumulation of HES1 complexes and hence inducing mitotic catastrophe. Cell-cycle analyses confirm enhanced DNA damage response and G2/M arrest when combined with olaparib. These findings uncover a novel mechanism for BX-912, establish HES1 inhibition as a therapeutic strategy in HGSC, demonstrate proteomics' power to reveal hidden drug activities, and propose sequential cell-cycle targeting to improve treatment efficacy.
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Cistadenocarcinoma Seroso , Mitosis , Neoplasias Ováricas , Proteoma , Factor de Transcripción HES-1 , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/genética , Factor de Transcripción HES-1/metabolismo , Línea Celular Tumoral , Mitosis/efectos de los fármacos , Proteoma/metabolismo , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/metabolismo , Piperazinas/farmacología , Proteómica/métodos , Ftalazinas/farmacología , Antineoplásicos/farmacología , Daño del ADN/efectos de los fármacos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacologíaRESUMEN
Background: Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) exhibit a dismal prognosis, occurring in 44%-62.2% of cases at initial diagnosis. The optimal treatment for this population remains undefined. Methods: In this prospective, multicenter, single-arm phase II trial across three Chinese centers, eligible HCC patients with Vp3/4 PVTT received combined stereotactic body radiotherapy (SBRT), cadonilimab, and lenvatinib. Primary endpoint was objective response rate (ORR) in primary liver lesions (RECIST v1.1/mRECIST); secondary endpoints included ORR in PVTT, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Results: Of 24 enrolled patients, 21 were evaluable for efficacy. ORR for primary lesions was 38.1% (RECIST v1.1) and 47.6% (mRECIST), with a disease control rate (DCR) of 100% by both criteria. For PVTT, ORR and DCR were 76.2% and 100%, respectively. At a median follow-up of 19.7 months, median PFS was 6.8 months (95% CI: 4.6-12.9), DOR was 10.4 months (95% CI: 2.9-NE), and OS was 13.4 months (95% CI: 6.8-NE). Early biomarker declines (≥75% AFP reduction or ≥50% PIVKA-II decline at 6 weeks) correlated with superior outcomes: AFP reduction predicted longer PFS (HR=0.22, p=0.006) and OS (HR=0.25, p=0.024); PIVKA-II reduction similarly predicted PFS (HR=0.28, p=0.007) and OS (HR=0.18, p=0.002). Common treatment-related adverse events (TRAEs) included hypertension (50%), thrombocytopenia (42%), and fatigue (38%). Conclusions: The combination of SBRT, cadonilimab, and lenvatinib showed promising efficacy and manageable toxicity in HCC patients with Vp3/4 PVTT. Early AFP or PIVKA-II response at 6 weeks may serve as a prognostic biomarker. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT06040177.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Vena Porta , Quinolinas , Radiocirugia , Trombosis de la Vena , Humanos , Masculino , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Femenino , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Persona de Mediana Edad , Anciano , Vena Porta/patología , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Radiocirugia/efectos adversos , Estudios Prospectivos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trombosis de la Vena/terapia , Trombosis de la Vena/etiología , Resultado del Tratamiento , Terapia CombinadaRESUMEN
OBJECTIVE: To comparatively evaluate therapeutic outcomes and complications of percutaneous kyphoplasty (PKP) treatment for very severe osteoporotic vertebral compression fractures (vsOVCF) located in different segments, providing evidence-based recommendations for anatomical region-specific management. METHODS: Data of patients over 65 years old with vsOVCF, located in T5-L3 segments treated by PKP in our hospital during April 2015 and December 2021, were retrospectively analyzed. Fractures were stratified by anatomical location: upper/middle thoracic and thoraco/lumbar cohorts. Symptom improvement, imaging index changes, and complications were compared. RESULTS: This study included 79 patients (mean age 77.1 ± 6.4 years, 65 women) with vsOVCFs stratified by location: upper/middle thoracic (T5-T9, n = 22) and thoraco/lumbar (T10-L3, n = 57). The preoperative visual analog scale score of the upper/middle thoracic group was higher than that of the thoraco/lumbar group. But there was no significant difference in postoperative visual analog scale and Eastern Cooperative Oncology Group score at the last follow-up or height improvement between the 2 groups (P > 0.05). The thoraco/lumbar group exhibited significantly higher rates of low-energy injury and intravertebral clefts preoperatively (P < 0.05). Vertebral height was significantly lower postoperatively in the upper/middle thoracic group (P < 0.05), but comparable at final follow-up. The thoraco/lumbar group demonstrated significantly greater local kyphotic angle and a 4.4-fold higher recollapse rate (P < 0.05) at final follow-up. New fracture incidence was borderline higher in the thoraco/lumbar group (17 vs. 2 fractures, P = 0.053). Bone cement leakage showed no intergroup difference. CONCLUSIONS: PKP provides significant pain relief and functional improvement in vsOVCF, regardless of the lesion's location. However, thoraco/lumbar vsOVCF demonstrate substantially higher risk of augmented vertebral recollapse after PKP.
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BACKGROUND AND PURPOSE: Visual disturbance is a major complication in nonfunctioning pituitary adenoma (NFPA) due to chiasmal compression. While neuroimaging studies have established brain dysfunction in visually impaired patients from chiasmal compression, the brain dynamic features of spontaneous activity and functional connectivity remain underexplored. This cross-sectional study aims to explore changes in temporal variability of spontaneous activity and connectivity in visually impaired patients with NFPA by resting-state functional MRI. MATERIALS AND METHODS: Thirty-six patients with NFPA with visual impairment and 36 healthy controls were recruited and underwent resting-state fMRI scans. Dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic functional connectivity (dFC) analyses were performed to assess temporal variability in brain activity and interregional communication. Associations between altered dALFF/dFC and the severity and duration of chiasmal compression, as well as visual field defect severity (quantified by mean deviation), were further evaluated. RESULTS: Compared with healthy controls, patients with a nonfunctioning pituitary exhibited significantly reduced dALFF in the right lingual gyrus (LING) and bilateral calcarine fissure and surrounding cortex (CAL). Additionally, patients showed a significant reduction in dFC between the right LING and the bilateral precuneus. Our exploratory correlation analyses revealed that the altered dALFF values in the bilateral CAL and right LING were positively correlated with chiasmal volume, and the altered dALFF in the left CAL was negatively correlated with suprasellar extension distance. Additionally, the altered dALFF values in the bilateral CAL were positively correlated with mean deviation. CONCLUSIONS: Patients with NFPA with visual impairment exhibited decreased temporal variability in brain activity and functional connectivity within visual-related regions, offering new insights into the neuropathologic mechanisms underlying visual disturbance in nonfunctioning pituitary adenoma.
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Adenoma , Encéfalo , Imagen por Resonancia Magnética , Neoplasias Hipofisarias , Trastornos de la Visión , Humanos , Masculino , Femenino , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adenoma/fisiopatología , Adenoma/complicaciones , Adenoma/diagnóstico por imagen , Adulto , Estudios Transversales , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/etiología , Trastornos de la Visión/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , AncianoRESUMEN
We studied the protective effects of Radix Astragali (RA) on gastric ulcer (GU). A literature search was conducted using databases from Web of Science, PubMed, Springer, ScienceDirect, Science Direct Chinese National Knowledge Infrastructure (CNKI), and Wanfang. The inclusion criteria for this study were limited to reports on the effects of RA, AS-IV, cycloastragenol, astragalus polysaccharide (APS), and astragalosides (AST) in the treatment of gastric ulcers. Any studies involving gastric lesions that were precancerous or cancerous were eliminated. The search period was from database inception through June 2024. The results suggested RA hold promiseas potential novel therapeutics for the therapy of GU.
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Planta del Astrágalo , Medicamentos Herbarios Chinos , Úlcera Gástrica , Úlcera Gástrica/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Humanos , Planta del Astrágalo/química , Polisacáridos/farmacología , Polisacáridos/química , Animales , Estructura Molecular , Astragalus propinquus , Saponinas/farmacologíaRESUMEN
BACKGROUND: This study aimed to investigate the therapeutic potential of a combined low-dose propofol (PPF) and salvianolic acid A (SAA) regimen in mitigating lipopolysaccharide (LPS)-induced cardiac dysfunction and ferroptosis in diabetic contexts, and to explore the role of the sirtuin 1 (SIRT1)/forkhead box O1 (FoxO1) signaling pathway. METHODS: Type 2 diabetes (DM) was induced in mice, followed by LPS administration to induce cardiac injury. The mice were randomly assigned to six groups: control, DM, control + LPS, DM + LPS, DM + LPS + high-dose PPF, and DM + LPS + low-dose PPF + SAA. Cardiac function was assessed via echocardiography, while ferroptosis was evaluated with BODIPY staining and transmission electron microscopy. In vitro, H9c2 cardiomyocytes were treated with high glucose and LPS. Ferroptosis was assessed with FerroOrange and JC-1 staining. Oxidative stress and inflammatory cytokines were measured using ELISA or flow cytometry, and protein expression of key markers was analyzed. RESULTS: Diabetes aggravated LPS-induced cardiac injury in mice evidenced as impaired myocardial function, which was concomitant with decreased cardiac expression of SIRT1, FoxO1, and GPX4 proteins; increased production of oxidative stress, pro-inflammatory cytokines, oxidized lipids, and damaged mitochondrial cristae as compared to NC + LPS group. The combined use of PPF and SAA enhanced cardiac SIRT1 and FoxO1 and ameliorated LPS-mediated cardiac dysfunction in diabetic mice, but these beneficial effects were abolished by inhibition of SIRT1 or FoxO1. In vitro, hyperglycemia and LPS-induced cellular injuries were ameliorated by PPF and SAA, respectively. Low dose of PPF in combination with SAA reduced the production of ROS and ferroptosis that were concomitant with increased SIRT1 and FoxO1 expression, effects that were either comparable or superior to those achieved with high-dose PPF alone, but these protective effects were reversed by silencing SIRT1 or FoxO1. CONCLUSION: The combination of low-dose PPF and SAA effectively protects against LPS-induced cardiac dysfunction and ferroptosis in diabetic conditions by activating the SIRT1/FoxO1 pathway.
Asunto(s)
Ácidos Cafeicos , Diabetes Mellitus Tipo 2 , Ferroptosis , Lactatos , Animales , Sirtuina 1/metabolismo , Lipopolisacáridos/toxicidad , Ratones , Proteína Forkhead Box O1/metabolismo , Transducción de Señal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Masculino , Diabetes Mellitus Experimental/complicaciones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ácidos Cafeicos/farmacología , Ratas , Lactatos/farmacología , Ratones Endogámicos C57BL , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
PURPOSE: To develop and validate a multimodal deep-learning model for predicting postoperative vault height and selecting implantable collamer lens (ICL) sizes using anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) images combined with clinical features. SETTING: West China Hospital, Sichuan University, Chengdu, Sichuan, China. DESIGN: Deep-learning study. METHODS: 626 AS-OCT and 1309 UBM images from 209 eyes of 105 participants with ICL V4c implantation were used. Features were extracted using a convolutional neural network (ResNet50) and combined with clinical data for model training. Machine learning algorithms including Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting (XGBoost), and Random Forest (RF) were used to develop models for postoperative vault height prediction and ICL size selection. Models were validated using metrics such as mean absolute error (MAE), root mean squared error (RMSE), R2 , accuracy, sensitivity, specificity, and precision. RESULTS: The LightGBM, XGBoost, and RF models showed RMSE values below 150 µm, MAE values below 120 µm, and R2 values around 0.4 in predicting postoperative vault height. The LightGBM model achieved the best performance in ICL size selection, with an accuracy of 0.904, sensitivity of 0.935, specificity of 0.907, and precision of 0.873, outperforming traditional methods and nearing the performance of senior doctors. CONCLUSIONS: The multimodal deep-learning model significantly improved the accuracy of predicting postoperative vault height and selecting ICL sizes for ICL V4c implantation, overcoming the limitations of single-modal data analysis. Future studies should expand sample sizes and conduct multicenter validations to enhance model generalizability and clinical applicability.