Medical hypotheses最新文献_第2页

Iron chelators reduce prostaglandins and leukotrienes by inhibiting cyclooxygenase and lipoxygenase: A hypothesis to attenuate PPARγ transcriptional activity in prostate cancer 铁螯合剂通过抑制环氧合酶和脂氧合酶降低前列腺素和白三烯：一种削弱前列腺癌中PPARγ转录活性的假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-29 DOI: 10.1016/j.mehy.2026.111895

Egarit Noulsri , Surada Lerdwana

Aggressive prostate cancer (PC) relies on lipid metabolic reprogramming and pathological iron (Fe) accumulation to drive disease progression. While peroxisome proliferator-activated receptor-gamma (PPARγ) is a master regulator of this lipid-addicted phenotype, direct therapeutic targeting remains clinically limited by systemic toxicity. We propose a novel therapeutic framework: the Fe- cyclooxygenase (COX)/lipoxygenase (LOX)- prostaglandins (PGs)/leukotrienes (LTs)-PPARγ signaling axis. This hypothesis identifies intracellular iron bioavailability as the critical catalytic switch for oncogenic PPARγ activity. Within this axis, Fe serves as an essential cofactor for COX and LOX enzymes that synthesize activating eicosanoid ligands, PGs and LTs, required for receptor transactivation. This model shifts the paradigm of iron chelation from traditional nutritional starvation to a sophisticated signal-transduction interference strategy. By deactivating COX/LOX through active-site coordination and peroxide tone modulation, iron chelators e.g., deferoxamine, deferiprone induce a ligand deficit that forces PPARγ into an inactive apo-conformation, silencing pro-survival genes such as FASN and CD36. To validate this axis, we propose a multi-faced roadmap. This involves in vitro rescue experiments confirming that exogenous ligands bypass chelation-induced silencing, paired with in vivo transcriptomic RNA-seq and cistromic ChIP-seq mapping to verify the global attenuation of the PPARγ regulation. This signaling interference model provides a mechanistic rationale for using iron chelators as indirect transcriptional modulators. Such a strategy may provide a precision-guided approach for sensitizing castration-resistant disease to conventional therapeutic regimens.

侵袭性前列腺癌（PC）依赖于脂质代谢重编程和病理性铁（Fe）积累来驱动疾病进展。虽然过氧化物酶体增殖激活受体γ (PPARγ)是这种脂质成瘾表型的主要调节因子，但直接治疗靶向仍然受到全身毒性的限制。我们提出了一个新的治疗框架：铁-环氧合酶(COX)/脂氧合酶(LOX)-前列腺素(pg)/白三烯(lt)- ppar γ信号轴。这一假设确定了细胞内铁的生物利用度是致癌PPARγ活性的关键催化开关。在这个轴上，铁作为COX和LOX酶的必需辅因子，这些酶合成激活类二十烷配体、pg和lt，这些配体是受体转激活所必需的。该模型将铁螯合的范式从传统的营养饥饿转变为复杂的信号转导干扰策略。铁螯合剂（如去铁胺、去铁素）通过活性位点协调和过氧化物音调调节使COX/LOX失活，诱导配体缺陷，迫使PPARγ进入失活的apo构象，沉默促生存基因，如FASN和CD36。为了验证这个轴，我们提出了一个多方面的路线图。这包括体外救援实验，证实外源性配体绕过螯合诱导的沉默，并与体内转录组RNA-seq和囊性ChIP-seq图谱配对，以验证PPARγ调控的全局衰减。这种信号干扰模型为使用铁螯合剂作为间接转录调节剂提供了一个机制基础。这种策略可能为去势抵抗性疾病对传统治疗方案的敏感化提供一种精确的指导方法。

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引用次数: 0

The Stage 1 Plus hypothesis in status epilepticus: predicting resistance before it happens 癫痫持续状态的第1阶段假说：在耐药性发生之前预测耐药性

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-29 DOI: 10.1016/j.mehy.2026.111894

Giuseppe Magro

The traditional four-stage model of status epilepticus (SE) classifies treatment based on clinical response rather than underlying pathophysiology. However, growing evidence from experimental and clinical studies indicates that resistance to benzodiazepines (BDZs) can often be predicted, especially in patients experiencing prolonged SE, those with acute symptomatic causes, or nonconvulsive presentations with coma. This is why the author hypothesizes a Stage 1 Plus: an umbrella term to predict early BDZ resistance in treatment-naïve SE, as in any of the already-mentioned conditions.

Here, the author explores some of the mechanistic basis, preclinical validation, and emerging clinical support for SE’s Stage 1 Plus hypothesis. Time-dependent GABA-A receptor internalization and NMDA receptor upregulation drive BDZ resistance within minutes of SE onset, increasing over time. Preclinical models consistently demonstrate that simultaneous polytherapy, including midazolam and ketamine, is more effective than sequential drug administration.

Stage 1 Plus identifies SE patients who, although treatment-naïve, are likely to be BDZ-refractory. For these patients, early polytherapy may be essential. Future trials should be designed to test the hypotheses of early polytherapy rather than the current sequential drug administration approach in those situations.

传统的癫痫持续状态（SE）四阶段模型根据临床反应而不是基础病理生理来分类治疗。然而，来自实验和临床研究的越来越多的证据表明，对苯二氮卓类药物（BDZs）的耐药性通常是可以预测的，特别是那些经历长期SE的患者，那些有急性症状原因的患者，或有昏迷的非惊厥表现的患者。这就是为什么作者假设了一个阶段1 +：一个总括术语，用于预测treatment-naïve SE的早期BDZ抗性，就像在任何已经提到的条件下一样。在这里，作者探讨了一些机制基础，临床前验证，以及新兴的临床支持阶段1 +假说。时间依赖性GABA-A受体内化和NMDA受体上调可在SE发病数分钟内驱动BDZ耐药，并随时间增加。临床前模型一致表明，同时多重治疗，包括咪达唑仑和氯胺酮，比顺序用药更有效。阶段1 +确定SE患者，虽然treatment-naïve，可能是bdz难治性的。对于这些患者，早期综合治疗可能是必要的。未来的试验应该设计为测试早期多种治疗的假设，而不是目前在这些情况下的顺序给药方法。

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引用次数: 0

Hybrid GAN–P-TransUNet framework for alveolar bone regeneration in dental implant planning: A hypothesis 混合GAN-P-TransUNet框架在种植体规划中的牙槽骨再生：一个假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-27 DOI: 10.1016/j.mehy.2026.111892

S. Shyam Sundar , Sahith Kumar Shetty , K. Brindha

The long-term success of dental implants depends on adequate alveolar bone volume, often necessitating regenerative interventions such as guided bone regeneration and sinus augmentation. Accurate assessment of bone dimensions is critical for planning these procedures, yet manual methods are prone to operator variability and limited reproducibility. Artificial intelligence (AI) has shown promise in dental imaging, with systems such as Dental-YOLO and automated segmentation models achieving high precision in detecting anatomical landmarks. However, existing AI approaches are constrained by dataset diversity, generalizability, and interpretability. We hypothesize that a hybrid Generative Adversarial Network (GAN)–P-TransUNet framework could overcome these limitations by combining GAN-based synthetic data augmentation with transformer-enhanced segmentation for precise and reproducible alveolar bone measurement. This framework could standardize preoperative bone evaluation, optimize regenerative planning, minimize surgical risk, and provide educational value through synthetic datasets. If validated, it has the potential to transform precision-driven regenerative implantology, improving clinical outcomes and patient safety.

牙种植体的长期成功依赖于足够的牙槽骨体积，通常需要再生干预，如引导骨再生和窦增强。骨尺寸的准确评估对于这些手术的规划是至关重要的，然而手工方法容易受到操作人员的变化和重复性的限制。人工智能（AI）在牙科成像方面显示出前景，诸如dental - yolo和自动分割模型等系统在检测解剖标志方面实现了高精度。然而，现有的人工智能方法受到数据集多样性、泛化性和可解释性的限制。我们假设混合生成对抗网络(GAN) -P-TransUNet框架可以克服这些限制，将基于GAN的合成数据增强与变压器增强分割相结合，以实现精确和可重复的牙槽骨测量。该框架可以规范术前骨评估，优化再生计划，降低手术风险，并通过合成数据集提供教育价值。如果得到验证，它有可能改变精确驱动的再生植入，改善临床结果和患者安全。

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引用次数: 0

A novel hypothesis on the pathogenesis of traumatic temporomandibular joint ankylosis 外伤性颞下颌关节强直发病机制的新假说

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-27 DOI: 10.1016/j.mehy.2026.111891

Ning Li , Yumin Heng , Tianyang Lv , Xiaoyue Ge , Changkui Liu , Kaijin Hu

Traumatic temporomandibular joint ankylosis (TTMJA), with its high recurrence rate post-surgery, lacks a unifying pathogenesis theory, hindering effective prevention. We propose a novel four-stage cascade hypothesis that highlights early lymphatic dysfunction—rather than hematoma organization—as a key early determinant of pathological repair. High-energy trauma releases free fibrocartilage fragments into the joint space, where they may act as ’osteogenic seeds’. Subsequent mechanical zonation of the joint into micromotion and stable zones then drives spatially distinct osteogenic pathways (endochondral and intramembranous ossification), explaining the histopathological heterogeneity of the ankylotic mass. This process culminates in piezoelectric-guided vascular fusion and osteoclast-suppressed consolidation, forming a complete bony bridge. Empirically testable in established models, this hypothesis delineates clear therapeutic windows: early intervention targeting lymphatic repair and debris clearance (≤7 days), followed by mechanical modulation (7–21 days), and late osteoclast reactivation (>60 days). This framework reframes clinical management by advocating stage-specific interventions within defined therapeutic windows to shift from reactive surgery to mechanism-based prevention.

外伤性颞下颌关节强直（TTMJA）术后复发率高，发病机制缺乏统一的理论，阻碍了有效的预防。我们提出了一个新的四阶段级联假说，强调早期淋巴功能障碍-而不是血肿组织-是病理修复的关键早期决定因素。高能创伤将游离的纤维软骨碎片释放到关节间隙，在那里它们可能起到“成骨种子”的作用。随后关节的机械区分为微动区和稳定区，然后驱动空间上不同的成骨途径（软骨内和膜内骨化），解释了强直团块的组织病理学异质性。这个过程在压电引导的血管融合和破骨细胞抑制的巩固中达到高潮，形成一个完整的骨桥。在已建立的模型中进行了实证检验，该假设描绘了明确的治疗窗口：针对淋巴修复和碎片清除的早期干预（≤7天），随后进行机械调节（7 - 21天），以及晚期破骨细胞再激活（60天）。该框架通过提倡在确定的治疗窗口内进行阶段特异性干预，从反应性手术转向基于机制的预防，从而重新构建了临床管理。

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引用次数: 0

Molecular signaling between primary tumor and secondary tumor through tyrosine kinase 酪氨酸激酶在原发性肿瘤和继发性肿瘤之间的分子信号传导

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-27 DOI: 10.1016/j.mehy.2026.111893

Ayah Al-Qasrawi

Despite major advances in tumor cell biology, metastatic disease remains the principal cause of nearly 90% of cancer-related deaths. While the literature characterizes the pre-metastatic niche through processes such as angiogenesis and immune suppression, the molecular basis of organ-specific metastasis—the non-random spread of cancer—remains poorly understood. Traditional models focus on vascular or lymphatic dissemination; however, evidence suggests that biochemical communication between primary tumors and distant tissues is crucial for the selective colonization of metastases. This hypothesis proposes a novel molecular mechanism to explain organ-specific metastasis, mediated by tyrosine kinase (TK) signaling. We hypothesize that primary tumors secrete specific tyrosine kinase proteins in exosomes that interact with overexpressed receptors in secondary organs. This targeted signaling creates a molecular “pre-metastatic niche,” facilitating organ-specific metastasis beyond passive vascular models. Uncovering this signaling axis is essential for better understanding cancer pathophysiology and for developing more targeted therapeutic approaches. Clinical successes demonstrate the therapeutic relevance of TK pathways in managing organ-specific metastases. These include the CNS-penetrant EGFR inhibitor osimertinib in non–small cell lung cancer, the dabrafenib–trametinib combination in BRAF V600 mutant melanoma, and the HER2-targeted regimen incorporating tucatinib for metastatic breast cancers.

尽管肿瘤细胞生物学取得了重大进展，但转移性疾病仍然是近90%癌症相关死亡的主要原因。虽然文献通过血管生成和免疫抑制等过程描述了转移前生态位的特征，但器官特异性转移的分子基础-癌症的非随机扩散-仍然知之甚少。传统模型侧重于血管或淋巴传播；然而，有证据表明，原发肿瘤和远端组织之间的生化交流对于转移瘤的选择性定植至关重要。这一假说提出了一种新的分子机制来解释由酪氨酸激酶（TK）信号介导的器官特异性转移。我们假设原发性肿瘤在外泌体中分泌特异性酪氨酸激酶蛋白，这些蛋白与次要器官中过度表达的受体相互作用。这种靶向信号产生分子“转移前生态位”，促进器官特异性转移超越被动血管模型。揭示这一信号轴对于更好地理解癌症病理生理和开发更有针对性的治疗方法至关重要。临床成功证明了TK通路在管理器官特异性转移中的治疗相关性。其中包括用于非小细胞肺癌的cns渗透型EGFR抑制剂奥西替尼，用于BRAF V600突变型黑色素瘤的达非尼-曲美替尼联合治疗，以及用于转移性乳腺癌的靶向her2的联合图卡替尼治疗方案。

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引用次数: 0

Comment on: Refinements to the hypothesis of climate-driven decline in human core body temperature 点评：对气候导致人体核心体温下降假说的改进

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-27 DOI: 10.1016/j.mehy.2026.111890

Fèlix Faming Wang

引用次数: 0

The cheeky ape hypothesis: Is rosacea the evolutionary price of human buccal fat? 厚脸皮猿假说：酒糟鼻是人类颊脂肪的进化代价吗？

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-25 DOI: 10.1016/j.mehy.2026.111889

Mohammed Abrahim , Brittany Abrahim

Rosacea is a common, chronic inflammatory skin condition primarily affecting the human face. Clinical manifestations range from mild erythema to disfiguring phymatous changes, such as rhinophyma. Despite extensive research, its primary etiology remains unclear. Current evidence suggests that the disease may begin with an initial vascular insult, which then triggers an inflammatory cascade modulated by genetic, environmental, and microbial factors. However, the mechanisms underlying this initial vascular dysfunction have yet to be elucidated.

We propose the “Cheeky Ape Hypothesis,” which offers a novel evolutionary and anatomical potential contributor to the pathophysiology of rosacea. This hypothesis posits that impaired venous return within the facial vein and its tributaries—resulting from bilateral venous compression within the buccal fat pad, a uniquely human anatomical feature—could play a contributory role in initiating of the disease. As deep buccal fat is specific to humans, this anatomical specialization may represent an evolutionary trade-off, which could partly help explain the distinctive prevalence of rosacea in humans. The hypothesis suggests that the interplay between facial venous flow and adipose tissue distribution underpins the pathogenesis of rosacea. Rigorous experimental and clinical studies will be required to investigate and validate the proposed mechanism.

酒渣鼻是一种常见的慢性炎症性皮肤病，主要影响人的面部。临床表现从轻度红斑到毁容的肿变，如鼻肿。尽管进行了广泛的研究，其主要病因仍不清楚。目前的证据表明，该疾病可能始于最初的血管损伤，然后引发由遗传、环境和微生物因素调节的炎症级联反应。然而，这种初始血管功能障碍的机制尚未阐明。我们提出“厚脸皮猿假说”，这为酒渣鼻的病理生理提供了一种新的进化和解剖学上的潜在贡献者。这一假说认为，面部静脉及其分支内的静脉回流受损——由颊脂肪垫内的双侧静脉压迫引起，这是一种独特的人类解剖特征——可能在疾病的发病中起一定作用。由于深颊脂肪是人类特有的，这种解剖学上的特化可能代表了一种进化上的权衡，这可能部分地有助于解释人类中酒渣鼻的独特流行。该假说表明面部静脉流动和脂肪组织分布之间的相互作用是酒渣鼻发病的基础。需要严格的实验和临床研究来调查和验证所提出的机制。

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引用次数: 0

Endogenous Mirroring Phenomena (EMP): a paradigm shift in biological sciences 内生性镜像现象（EMP）：生物科学的范式转变

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-20 DOI: 10.1016/j.mehy.2026.111888

Mahdieh Emadi

The dynamic interaction between organisms and their environment has been a cornerstone of biological research, yet the mechanisms underlying this relationship remain incompletely understood. Recent advances in fields such as enactivism and ecological psychology have emphasized the active role organisms play in shaping their environments, suggesting that perception and action are deeply intertwined. However, existing theories often limit their focus to cognitive or passive reactive processes. This manuscript introduces Endogenous Mirroring Phenomena (EMP) as a novel theoretical framework, positing that biological systems possess intrinsic mechanisms that actively mirror environmental stimuli across the molecular, cellular, and systemic levels. Unlike biophotonic emissions or mirror neuron activity, which primarily address localized or specific reactive processes, EMP proposes a comprehensive, organized reflection of environmental cues that influences physiological regulation, adaptation, and evolution. This concept not only broadens our understanding of biological complexity but also offers new avenues for research on cellular communication, signaling, and evolutionary biology. By establishing EMP as a unifying principle, this work challenges traditional views and sets the stage for future interdisciplinary exploration.

生物与其环境之间的动态相互作用一直是生物学研究的基石，然而这种关系背后的机制仍然不完全清楚。在行动主义和生态心理学等领域的最新进展强调了生物体在塑造环境方面发挥的积极作用，这表明感知和行动是紧密交织在一起的。然而，现有的理论往往局限于认知或被动反应过程。本文介绍了内源性镜像现象（EMP）作为一个新的理论框架，假设生物系统具有内在机制，在分子、细胞和系统水平上积极反映环境刺激。与生物光子发射或镜像神经元活动不同，它们主要解决局部或特定的反应过程，EMP提出了影响生理调节、适应和进化的环境线索的全面、有组织的反映。这一概念不仅拓宽了我们对生物复杂性的理解，而且为细胞通讯、信号传导和进化生物学的研究提供了新的途径。通过建立EMP作为一个统一的原则，这项工作挑战了传统的观点，并为未来的跨学科探索奠定了基础。

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引用次数: 0

Hypoxia-induced mitochondrial silencing as a proposed third axis of apoptosis control in solid tumors: a dual hypothesis linking initiation–promotion transition to hypoxic niche maintenance 缺氧诱导的线粒体沉默作为实体肿瘤细胞凋亡控制的第三个轴：将启动-促进转变与缺氧生态位维持联系起来的双重假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-19 DOI: 10.1016/j.mehy.2026.111887

Masato Hiki

Cancer initiation and progression have traditionally been interpreted primarily through the accumulation of genetic mutations and the dysregulation of intracellular signaling pathways. At the same time, increasing evidence indicates that the tumor microenvironment—particularly hypoxia and pathological angiogenesis—plays a critical role in tumor cell survival, clonal selection, and therapeutic resistance. However, how genetic alterations and hypoxia-driven metabolic adaptation are functionally integrated during stepwise tumor progression remains incompletely understood.

In this manuscript, we propose a dual hypothesis framework in which hypoxia-induced mitochondrial silencing and hypoxic niches maintained by pathological angiogenesis cooperatively shape cancer progression in hypoxia-prone solid tumors. Mitochondrial silencing is defined here as a functional mitochondrial state in which oxidative metabolism is suppressed and the executional capacity of mitochondria-dependent apoptosis is attenuated, despite the structural persistence of mitochondria. We further propose that this state functions as a third regulatory layer of apoptosis control, distinct from classical pro- and anti-apoptotic signaling pathways.

As a second component of the hypothesis, we suggest that structurally and functionally abnormal tumor neovasculature generates spatially heterogeneous microenvironments characterized by limited red blood cell–mediated oxygen delivery but relatively preserved diffusion of glucose. Such hypoxic, glucose-accessible niches are predicted to preferentially select for and maintain cell populations adapted to mitochondrial silencing and glycolysis-dominant metabolism, thereby supporting clonal persistence, heterogeneity, and progression.

Although this work does not present experimental data, it provides a testable conceptual framework that repositions mitochondrial functional state as a central integrator of genetic alterations and microenvironmental constraints, and offers new perspectives on apoptosis resistance and metabolic adaptation in hypoxic solid tumors.

传统上，癌症的发生和发展主要通过基因突变的积累和细胞内信号通路的失调来解释。同时，越来越多的证据表明，肿瘤微环境，特别是缺氧和病理性血管生成，在肿瘤细胞存活、克隆选择和治疗抵抗中起着关键作用。然而，在逐步的肿瘤进展过程中，基因改变和缺氧驱动的代谢适应如何在功能上整合仍然不完全清楚。在这篇论文中，我们提出了一个双重假设框架，其中缺氧诱导的线粒体沉默和病理性血管生成维持的缺氧生态位共同塑造了易缺氧实体瘤的癌症进展。线粒体沉默在这里被定义为一种线粒体功能状态，在这种状态下，氧化代谢受到抑制，线粒体依赖性凋亡的执行能力减弱，尽管线粒体具有结构持久性。我们进一步提出，这种状态作为细胞凋亡控制的第三个调控层，不同于经典的促凋亡和抗凋亡信号通路。作为该假说的第二个组成部分，我们认为结构和功能异常的肿瘤新生血管产生了空间异质性的微环境，其特征是红细胞介导的氧气输送有限，但葡萄糖的扩散相对保留。据预测，这种低氧、葡萄糖可及的生态位会优先选择和维持适应线粒体沉默和糖酵解主导代谢的细胞群，从而支持克隆持久性、异质性和进展。虽然这项工作没有提供实验数据，但它提供了一个可测试的概念框架，将线粒体功能状态重新定位为遗传改变和微环境约束的中心整合者，并为缺氧实体瘤的细胞凋亡抵抗和代谢适应提供了新的视角。

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引用次数: 0

Species-specific biofilm traits and virulence gene expression in recurrent vulvovaginal candidiasis: a translational hypothesis 物种特异性生物膜特征和毒力基因表达在复发性外阴阴道念珠菌病：一个翻译假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-17 DOI: 10.1016/j.mehy.2026.111885

Nazia Hassan , Ayan K. Das , Asgar Ali

Recurrent Vulvovaginal Candidiasis (RVVC) is characterised as four or more symptomatic episodes of vulvovaginal candidiasis in a year, with partial resolution between episodes and microbiologic confirmation in at least two episodes. The prominent symptoms include vaginal-itching, discharge, erythema, oedema, and burning sensation. Biofilm development and antifungal resistance perpetuate RVVC symptoms by seeding Candida colonisation, infection relapse, and persistence. The microbial landscape of RVVC is predominantly C. albicans (90%) and emerging non-albicans Candida (NAC) species, including C. tropicalis, C. parapsilosis, C. krusei, and C. dubliniensis. The rare isolates, C. auris and S. cerevisiae, also contribute to ecological complexity in multi-species biofilms by enhancing resilience and interfering with quorum sensing. This hypothesis proposes that RVVC persistence is sustained not only by species-specific biofilm traits and virulence gene expression (ALS3, HWP1, EFG1, TUP1, BEM2), but also by interspecies interactions within multispecies vaginal biofilms that augment antifungal resistance and persistence. We propose that profiling clinical isolates could help reveal correlations between antifungal susceptibility, biofilm architecture, and gene-level regulation. The hypothesis highlights the translational importance of multispecies, multidrug-resistant, and rare Candida biofilms as key modulators of resistance and virulence traits. The proposed framework includes culture-based identification, antifungal susceptibility testing, in vitro biofilm assays, confocal microscopy, and qPCR analysis. These approaches will define biofilm-associated resistance patterns and establish quantitative molecular biomarkers to guide novel formulation designs, in vivo validation, and species-specific antifungal stewardship.

复发性外阴阴道念珠菌病（RVVC）的特征是一年内有四次或更多的外阴阴道念珠菌病症状发作，发作之间有部分缓解，微生物学证实至少有两次发作。主要症状包括阴道瘙痒、分泌物、红斑、水肿和灼烧感。生物膜发育和抗真菌耐药性通过播种念珠菌定植、感染复发和持续性使裂谷病毒感染症状永久化。RVVC的微生物景观主要是白色念珠菌（90%）和新兴的非白色念珠菌（NAC）物种，包括热带念珠菌、副念珠菌、克鲁塞念珠菌和dubliniensis。罕见的金黄色葡萄球菌（C. auris）和酿酒葡萄球菌（S. cerevisiae）也通过增强恢复力和干扰群体感应来增加多物种生物膜的生态复杂性。这一假设表明，RVVC的持久性不仅由物种特异性生物膜特征和毒力基因表达（ALS3, HWP1, EFG1, TUP1, BEM2）维持，而且还通过多物种阴道生物膜内的种间相互作用来增强抗真菌抗性和持久性。我们建议分析临床分离株可以帮助揭示抗真菌敏感性，生物膜结构和基因水平调控之间的相关性。这一假设强调了多物种、多耐药性和罕见的念珠菌生物膜作为耐药性和毒力性状的关键调节剂的翻译重要性。建议的框架包括基于培养的鉴定，抗真菌药敏试验，体外生物膜测定，共聚焦显微镜和qPCR分析。这些方法将定义生物膜相关的耐药模式，并建立定量的分子生物标志物，以指导新的配方设计、体内验证和物种特异性抗真菌管理。

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引用次数: 0