北京若生智能科技有限公司
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isosorbide dinitrate + hydralazine (hydralazine + ISDN / BiDil / ISDN + hydralazine)

✓ Approved

Arbor Pharmaceuticals, LLC · CACNA1C · 小分子

什么是 isosorbide dinitrate + hydralazine？

isosorbide dinitrate + hydralazine 是一种小分子，由Arbor Pharmaceuticals, LLC研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名hydralazine + ISDN, BiDil, ISDN + hydralazine
公司Arbor Pharmaceuticals, LLC
药物类别小分子
分子靶点CACNA1C
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Arbor Pharmaceuticals, LLC

作用机制

分子靶点

isosorbide dinitrate + hydralazine 作用于 1 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

isosorbide dinitrate + hydralazine 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Cardiac disordersCardiac failure✓ Approved

相关研究文献

PubMedCardiovascular and interventional radiology2026-09-10

A Scoping Review of Interventional Radiology Curricula for Medical Students and Correlation with Kern's Six-Step Framework for Curriculum Development.

O'Carroll Jillian J, Temperley Hugo C HC, Bell Jack M JM, Deshwal Avinash A et al.

Interventional radiology (IR) plays an increasingly important role in modern healthcare; however, its integration into undergraduate medical education remains inconsistent. This scoping review evaluated IR teaching for medical students against Kern's six-step framework. A search of PubMed, EMBASE, Web of Science, and the Cochrane Library databases, through July 2026, identified 36 studies examining IR exposure, teaching strategies, and educational outcomes. IR teaching is consistently underrepresented. Educational interventions included didactic teaching, case-based learning, and digital platforms, but were typically implemented as isolated initiatives. Mapping to Kern's framework demonstrated predominant focus on problem identification and educational strategies, with limited attention to needs assessment, implementation, and evaluation. No study addressed all six steps. These findings highlight poor framework alignment and support the development of structured, systematically designed curricula.

PMID 42717108
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PubMedTherapeutic advances in endocrinology and metabolism2026-09-10

Association between HOMA-IR and coexisting MASLD and type 2 diabetes: Insights from NHANES and network pharmacology.

Heng Xian-Pei XP, Yang Liu-Qing LQ, Chen Qi-Wei QW, Jin Lin-Xi LX et al.

Insulin resistance is a common metabolic feature of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D), but its cross-sectional association with the coexistence of these conditions remains incompletely characterized. To evaluate the associations between the homeostasis model assessment of insulin resistance (HOMA-IR) and the concurrent presence of MASLD and T2D, and to explore potential demographic heterogeneity and generate hypotheses regarding candidate biological pathways. Population-based cross-sectional study using data from the National Health and Nutrition Examination Survey 2017-March 2020 pre-pandemic cycle. Adults with fasting glucose, fasting insulin, vibration-controlled transient elastography, and covariate data were included. Participants were classified as having neither condition, MASLD alone, T2D alone, or both. Multivariable logistic regression evaluated HOMA-IR continuously and by quartiles. Interaction and stratified analyses were conducted by sex and race/ethnicity. Secondary analyses examined concurrent MASLD and prediabetes among participants without T2D. Exploratory mediation analyses used fasting serum insulin as the exposure to assess whether glycemic and lipid indicators statistically accounted for part of the association. Network pharmacology was used as a hypothesis-generating approach to predict candidate targets and enriched pathways. Among 1,527 participants, each 1-unit increase in HOMA-IR was associated with 59.9% higher odds of concurrent MASLD and T2D versus neither condition (odds ratio [OR] 1.599, 95% confidence interval [CI] 1.491-1.715), 20.2% higher odds versus MASLD alone, and 14.5% higher odds versus T2D alone. When T2D alone was the reference, the association differed by race/ethnicity (P for interaction <0.01). Each 1-unit increase in HOMA-IR was also associated with 22.5% higher odds of concurrent MASLD and prediabetes versus prediabetes alone. Sex-related heterogeneity was observed in secondary comparisons involving concurrent MASLD and prediabetes. The odds of comorbidity were progressively higher across increasing HOMA-IR quartiles (P for trend <0.001). Fasting plasma glucose and hemoglobin A1c statistically accounted for 48.1% and 12.1%, respectively, of the total association between fasting serum insulin and concurrent MASLD and T2D. Hypothesis-generating network pharmacology predicted PRKACA, MAPK1/3, PIK3CA, and SRC as candidate hub targets and suggested candidate pathways related to PI3K-Akt, FOXO, and MAPK signaling. Higher HOMA-IR was associated with higher odds of concurrent MASLD and T2D. The magnitude of the associations varied by race/ethnicity and the selected reference group, while sex-related heterogeneity was observed in secondary analyses of concurrent MASLD and prediabetes.

PMID 42719461
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PubMedPediatric blood & cancer2026-09-10

Genomic Characterization of ETV6::RUNX1-Positive Childhood B-ALL in a Chinese Cohort: Novel Fusion Partners, Co-Occurring Mutations, and Risk-Stratifying Biomarkers.

Luo Hualei H, Zhou Guichi G, Li Qian Q, Yao Qiang Q et al.

ETV6::RUNX1 is the most common genetic abnormality in pediatric B-cell acute lymphoblastic leukemia (ALL; ∼25%), yet the comprehensive genetic architecture and molecular predictors of intermediate-risk (IR) stratification remain incompletely characterized. We performed whole-transcriptome sequencing (Illumina NovaSeq 6000, rRNA depletion, 41.70 Gb/sample) on bone marrow samples from 93 pediatric ETV6::RUNX1-positive B-ALL patients. Bioinformatics analysis included STAR alignment, MuTect2 variant calling, FusionCatcher fusion detection, and VEP annotation. The Jaccard index with permutation testing assessed mutation co-occurrence; logistic regression identified independent predictors of IR classification. Beyond ETV6::RUNX1, we identified 51 distinct fusion genes across the cohort, including the reciprocal RUNX1-ETV6 (73.1%), chr8::KLF1210 (38.7%), and KLF12-chr8 (34.4%). Somatic mutations in 249 genes were detected; the most frequent were KIAA1715 (17.2%), KRAS (11.8%), and NSD2 (10.8%). Network analysis revealed significant chromatin modifier co-occurrence (KIAA1715-KMT2C: J = 0.136, p = 0.015) and KRAS-NRAS mutual exclusivity (J = 0.000, p = 0.042). PTCH1 (OR = 3.50, 95% CI 0.21-58.49, p = 0.41) and GNB1 (OR = 6.5, 95% CI 1.2-34.8, p = 0.029) mutations independently predicted IR classification. chr8::KLF1210 fusion correlated with higher Day-19 MRD levels (p = 0.038). GNB1 mutation represents a novel independent predictor of IR stratification in ETV6::RUNX1-positive B-ALL. The chromatin modifier co-occurrence module and extensive fusion architecture reveal biological heterogeneity within this favorable-risk subtype, with potential implications for risk-adapted therapeutic strategies.

PMID 42720515
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PubMedFrontiers in immunology2026-09-10

Sequential conditioning in hematopoietic stem cell transplantation in elderly high-risk myeloid blood cancer patients: long-term survival, disease control, and immune recovery across donor types in a matched-pair analysis.

Haebe Sarah S, Stauffer Elena E, Drolle Heidrun H, Prevalsek Dusan D et al.

Sequential conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimens might offer improved disease control in high-risk myeloid patients. But concerns remain regarding toxicity, infection risk and delayed immune reconstitution (IR), particularly in older and HLA-haploidentical transplant recipients. To address these concerns, we comprehensively compared safety, feasibility and clinical outcome across HLA-matched related (MRD), matched unrelated (MUD) and haploidentical donor (Haplo) HSCT and longitudinally characterize IR patterns and their associations with post-transplant outcomes. We conducted a retrospective matched-pair analysis comparing MRD-, matched MUD- and Haplo-HSCT in elderly patients matched for (1) disease activity: p = 1.0; (2) disease status: p = 1.0; (3) modified disease risk index (DRI): p = 0.9; (4) hematopoietic cell transplantation comorbidity index (HCT-CI): p = 0.92; and (5) age: p = 0.95. Outcomes included disease-free (DFS) and overall survival (OS), relapse, non-relapse mortality (NRM), graft-versus-host disease (GvHD), toxicity, infections, and donor-specific IR dynamics and their impact on clinical outcomes. With a median follow-up of more than 9 years, no significant differences were observed in long-term disease control and survival among the three groups (5-y DFS/OS: MRD = 41%/41%, MUD = 56%/63%, Haplo = 58%/58%; p = 0.52/0.55). Cumulative incidences (CI) of 5-y-NRM and 1-y moderate and severe chronic GvHD (cGvHD) rates were comparable among the three groups (NRM/cGvHD: MRD = 19%/13%, MUD = 29%/6%, Haplo = 18%/19%; p = 0.3/0.57). Overall immune cell recovery after one year was comparable among groups, though early recovery of CD3+ T and NK cells was delayed after Haplo-HSCT. Subgroup analysis revealed that higher early CD4+ T and lower B cell counts were associated with increased CI of acute GvHD III-IV° (p = 0.04/0.03). Additionally, NK recovery at one year was associated with improved DFS and OS as well as lower relapse incidence. Sequential therapy is safe and feasible in elderly patients with high-risk or active disease across all three transplant platforms. The observed associations between IR and clinical outcomes highlight the relevance of immune monitoring for anticipating post-transplant complications and guiding individualized prophylactic and therapeutic strategies. Prospective studies are needed to further investigate these findings and define the underlying mechanisms.

PMID 42718553
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PubMedThe journal of physical chemistry. A2026-09-10

Elucidating Protomer Structures and Fragmentation Dynamics of Protonated Aminobenzoic and Aminocinnamic Acids via Cryo-Ion Mobility and Laser Spectroscopy.

Inokuchi Yoshiya Y, Tsunoda Kengo K, Ohata Amiru A, Kida Motoki M et al.

Biological and synthetic systems featuring coexisting amino and carboxy groups, such as amino acids and peptides, serve as vital models for understanding hydrogen-bonded proton transport networks. Unambiguously identifying protonation isomers (protomers) is crucial yet challenging, as their structures are heavily modulated by both intrinsic stabilities and extrinsic solvent environments. Here, we present a comprehensive investigation into the protonation sites and geometric structures of protonated 4-aminobenzoic acid (H+(4ABA)) and 4-aminocinnamic acid (H+(4ACA)) utilizing a synergistic combination of cryogenic ion mobility-mass spectrometry (Cryo-IM-MS), UV photodissociation (UVPD) and IR-UV double-resonance (IR-UV DR) spectroscopy, and quantum chemical calculations. Cryo-IM-MS demonstrates a pronounced solvent-dependent protomer distribution, where electrospray ionization from H2O/CH3OH = 1:1 and CH3CN solution predominantly yields the O- and N-protomers, respectively. Isomer-selective IR-UV DR spectroscopy successfully pins down the precise spatial orientations of the functional groups. Crucially, H+(4ABA) and H+(4ACA) exhibit markedly distinct photofragmentation pathways driven by the unsaturated alkenyl link in H+(4ACA). While the H+(4ABA) O-protomer undergoes competitive decarboxylation (CO2 loss) and dehydration (H2O loss), the extended π-conjugation in H+(4ACA) introduces a substantial kinetic bottleneck that completely suppresses CO2 elimination. In the case of the H+(4ACA) N-protomer, the alkenyl group acts as an active, structurally preorganized hydrogen source, facilitating highly efficient H2O loss via a tightly constrained transition state. These results provide profound fundamental insights into how structural modifications and local environments dictate competitive deactivation pathways, offering broader implications for the design and understanding of functional charge-transport materials.

PMID 42720385
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PubMedMovement disorders clinical practice2026-09-10

Lipid-Related Metabolic Dysregulation Affects Survival in Idiopathic Normal Pressure Hydrocephalus.

Bissacco Jacopo J, Mascioli Davide D, Simonetta Clara C, Mancini Maria M et al.

Idiopathic normal pressure hydrocephalus (iNPH) is associated with increased mortality and vascular-metabolic comorbidity, but prognostic biomarkers are lacking. To assess the triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, an insulin resistance (IR) marker, and its associations with MRI glymphatic markers and mortality in iNPH. We conducted a dual-center longitudinal study including 67 iNPH patients and 37 matched controls. Baseline lipid profiles were assessed, enlarged perivascular spaces (EPVS) were rated on 3 T MRI in a subgroup, differences were tested by ANCOVA, and mortality associations by adjusted Cox models. iNPH patients showed higher triglycerides and TG/HDL-C and lower HDL-C. High-grade centrum semiovale (CSO)-EPVS were associated with higher TG/HDL-C. TG/HDL-C showed the strongest mortality association. A model combining TG/HDL-C with CSO-EPVS showed the best fit, suggesting synergy. iNPH exhibits a lipid profile associated with IR linked to glymphatic alterations and mortality. Moreover, despite requiring large-scale validation, combined-marker models are promising.

PMID 42717528
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