搜索结果：Therapeutic drug monitoring

Colorectal cancer (CRC) remains a major cause of cancer-related mortality, and the widespread occurrence of drug resistance constitutes a central bottleneck that constrains therapeutic efficacy and adversely affects long-term patient outcomes. Current therapeutic strategies, guided by the Tumor-Node-Metastasis (TNM) staging system, integrate chemotherapy, targeted therapy, and immunotherapy; however, resistance frequently limits their long-term efficacy. This review adopts a stage-oriented, pharmacology-driven framework to systematically integrate resistance mechanisms and corresponding counterstrategies across CRC management. We analyze resistance across major therapeutic modalities, including chemotherapeutics (5-fluorouracil, oxaliplatin, irinotecan), targeted agents (epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors), and immune checkpoint inhibitors, with mechanistic insights directly linked to actionable, mechanism-guided interventions-including novel targeted agents, rational combination strategies, nanomedicine-based delivery systems, and emerging immunotherapeutic approaches. We further highlight convergent mechanisms that transcend individual therapies, particularly cancer stem cell plasticity and epigenetic reprogramming, which collectively drive multidrug resistance (MDR). Finally, in conjunction with emerging resistance detection technologies such as circulating tumor DNA (ctDNA), this review explores future directions for resistance monitoring and precision treatment adaptation, aiming to provide a systematic reference for overcoming therapeutic resistance in CRC.

To develop an integrated system for tendon injury repair that combines electrical stimulation, drug iontophoresis, and electromyography (EMG) monitoring, and validate it in a rat Achilles tendon injury model. A flexible 16-channel acquisition and stimulation system was constructed based on field programmable gate array. The system had a sampling rate ranging from 250 SPS to 16 kSPS with a resolution of 5 μV, and the stimulation current was 2.55 mA with a resolution of 10 nA, enabling synchronous and stable stimulation and signal monitoring. Fifteen Sprague-Dawley rats with induced Achilles tendon injuries were randomly allocated to three groups ( n=5): blank control, electrical stimulation, and drug iontophoresis groups. The Achilles tendon injury model was established by injecting typeⅠcollagenase solution into the Achilles tendon of right hind limb. At 3 days after modeling, the electrical stimulation group and drug iontophoresis group received corresponding interventions with the self-developed system for 2 consecutive weeks, and aspirin was delivered via iontophoresis in the latter group. No treatment was performed in the blank control group. The survival status and limb motor function of rats were observed, and EMG signals were recorded throughout the intervention. Gross observation and histological examination (HE staining and Sirius red staining) of Achilles tendons were performed at 2 and 4 weeks since the initiation of intervention to evaluate the repair effect. All rats survived until the scheduled experimental time point. All animals presented postoperative limping, which recovered spontaneously within 2 weeks without obvious intergroup difference. EMG results demonstrated that all groups underwent a consistent three-stage recovery process, namely compensatory activation, collagen remodeling, and functional recovery. The electrical stimulation group exhibited the mildest EMG fluctuations, whereas the drug iontophoresis group showed the most significant early muscular compensatory activation. Obvious differences in EMG characteristics between the injured and contralateral healthy sides were observed in the early stage, which gradually diminished and finally achieved synchronization with the progression of tendon repair. The support vector machine (SVM) achieved a classification accuracy of 85.8% for recovery stage identification. Gross observation and histological examination revealed that both intervention groups displayed milder peritendinous adhesion and better tendon luster compared with the blank control group, and achieved superior tendon repair outcomes. The integrated system proves to be effective for both the assessment and intervention of tendon injury repair. EMG signals can reliably distinguish between different stages of Achilles tendon recovery. Furthermore, both electrical stimulation and iontophoretic drug delivery promote repair by effectively regulating collagen remodeling and modulating compensatory muscle activation patterns. 开发一套集电刺激、药物电渗与肌电监测于一体的肌腱损伤修复系统，并在大鼠跟腱损伤模型中验证效果。. 基于现场可编程门阵列构建一个16通道采集、16通道刺激系统，采样率250 SPS～16 kSPS（5 μV分辨率），刺激电流最大达2.55 mA（10 nA分辨率），实现同时稳定刺激与监测。将15只6～8周龄雄性SD大鼠随机分为空白组、电刺激组、药物电渗组，每组5只。于右后肢跟腱注射Ⅰ型胶原酶溶液构建跟腱损伤模型，3 d后电刺激组、药物电渗组采用设计的肌腱损伤修复系统分别行电刺激及电渗给药（阿司匹林），持续2周；空白组不作特殊处理。干预后观察各组大鼠存活及肢体运动情况，持续记录肌电信号；干预后2、4周行跟腱大体及组织学观察（HE和天狼猩红染色）评估修复效果。. 所有大鼠造模后均存活。造模后各组大鼠右后肢均出现跛行，2周后恢复自由活动，未见明显组间差异。肌电信号观测示，各组均呈现“代偿性激活-胶原重塑-功能恢复”的三阶段趋势，电刺激组波动最平缓，药物电渗组代偿激活最强；健患侧在术后早期存在较大差异，随恢复进程差异逐渐减小并趋于同步；支持向量机对肌电信号分类总体准确率达85.8%。大体及组织学观察示，与空白组相比，电刺激组与药物电渗组跟腱粘连程度轻、光泽度好，随时间延长整体修复质量更优。. 初步研究结果提示构建的肌腱损伤修复系统可用于肌腱损伤修复的评估与干预；肌电信号可以判别跟腱恢复阶段；电刺激与电渗给药可以调控胶原重塑与肌肉代偿性激活，促进跟腱修复。.

In contemporary clinical practice, novel tetracycline-class antimicrobial agents have been increasingly utilized due to their favorable pharmacological profiles. However, the potential association between novel tetracycline-class drugs and coagulation dysfunction is relatively underreported in the literature. This study utilizes the FDA Adverse Event Reporting System (FAERS) to identify and analyze risk signals for coagulation disorders associated with three commonly used the novel tetracyclines in clinical practice. The findings are expected to provide valuable references for clinicians in the targeted monitoring of adverse drug reactions. Coagulation dysfunction reports associated with the novel tetracycline-class drugs, submitted to the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2024, were collected. Data mining was performed using the ROR, PRR, BCPNN, and MGPS. All data extraction was conducted using R software (version 4.4.2).It should be noted that FAERS is a spontaneous reporting system without exposure denominators and is subject to reporting bias and confounding factors. A total of 346 coagulation dysfunction reports with the novel tetracycline-class drugs as suspected drugs were screened, including 327 for tigecycline, 6 for omadacycline, and 13 for eravacycline. Disproportionate reporting signals of coagulation dysfunction were detected for both tigecycline and eravacycline, with tigecycline showing the strongest signal [ROR = 46.85 (42.29-51.91)]. Subgroup analyses by age, gender, and dosage revealed a higher proportion of male patients receiving tigecycline and eravacycline. while tigecycline and eravacycline exhibited a stronger disproportionate reporting signal in male patients over 65 years old. Omadacycline showed stronger disproportionate reporting signal at a daily dose of 100 mg. The peak onset time for omadacycline was consistently 9 days. However, all subgroup findings for omadacycline and eravacycline should be interpreted with extreme caution due to the limited number of reports. These observations are considered exploratory rather than confirmatory. Disproportionality analysis identified prominent signals of coagulation dysfunction signals associated with tigecycline and eravacycline. Distinctive reporting patterns of coagulation abnormalities were observed across the three novel tetracyclines, with visible discrepancies in patient age, gender, therapeutic indications, daily dosage, clinical outcomes, and adverse event onset time. Based on the above findings, clinicians should maintain high vigilance against the potential coagulation abnormalities induced by novel tetracyclines, and implement standardized and rational therapeutic drug monitoring during clinical medication practice.

Therapeutic peptides represent an important class of biomolecules with great clinical and economic significance, however their structural complexity and susceptibility to degradation pose significant analytical challenges. This study aimed to evaluate the applicability of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy in combination with multivariate data analysis as a rapid, non-destructive tool for monitoring structural changes and degradation in formulations containing semaglutide and liraglutide as model compounds. Spectral data allowed the detection of subtle conformational changes, particularly in the amide region I, which is directly related to the secondary structure. The application of principal component analysis (PCA) enabled the identification of clustering patterns and classification of samples under different stress conditions, while the analysis of loading and contribution line plots allowed recognition of the main spectral features contributing most to the variance. Despite the relatively short incubation times and using a dry film approach which may introduce conformational changes, clear changes associated with early and advanced phases of degradation were detected. ATR-FTIR results were complemented by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), showing consistency between the spectroscopic, mass spectrometric and chromatographic data. As demonstrated in this proof-of-concept study, this integrated analytical approach indicates potential for application in stability monitoring, formulation studies, process control, and as part of a multi-analytical strategy for product authentication, particularly when structural alterations are expected. The results confirm the applicability of ATR-FTIR spectroscopy combined with multivariate data analysis as a powerful tool for rapid assessment of the behavior of peptide medicines under stress conditions.

Antibody-drug conjugates (ADCs) are covalently conjugated molecules composed of a monoclonal antibody, a payload, and a linker. They represent an innovative therapeutic approach that combines the precise targeting capability of target therapies with the cytotoxic effects of chemotherapeutic agents. Given the unique molecular structure of ADCs, drug-related adverse reactions have drawn a considerable attention. Based on the safety data of ADCs currently available in the field of lung cancer, the common adverse drug reactions primarily involve the digestive system, hematologic system, hepatobiliary system, pulmonary system, skin, eyes, sensory nervous system, and musculoskeletal system. Unlike other cancer types, lung cancer is characterized by complex disease subtypes and molecular pathological mechanisms, as well as diverse treatment modalities. Moreover, patients with advanced lung cancer often have comorbidities such as chronic obstructive pulmonary disease and pulmonary inflammation, making the comprehensive management of ADC-related adverse reactions even more challenging. To address this, the Precision Treatment Branch of Thoracic Oncology, Chinese Geriatric Health Association, has taken the lead in organizing a multidisciplinary panel of domestic experts in gastroenterology, dermatology, respiratory medicine, ophthalmology and oncology, to discuss and jointly formulate the "Consensus of Chinese experts on the multidisciplinary management of adverse reactions to antibody-drug conjugates in the treatment of Lung Cancer (2025 edition)". A total of 21 recommendations are proposed in this consensus, covering pre-ADC safety assessments, comprehensive monitoring and management of relevant adverse reactions during ADC treatment, patient education, and medication guidance for special populations. The consensus aims is to provide clinicians with practical guidelines for the application of ADC, thereby maximizing therapeutic benefits for patients with lung cancer. 抗体药物偶联物（ADC）由单克隆抗体、有效载荷和连接子3部分共价偶联组成，是将靶向药物的精准定位与化疗药物的细胞毒性杀伤作用相结合的创新疗法。鉴于ADC独特的分子结构，其药物相关的不良反应一直备受关注。根据已披露的肺癌领域ADC安全性数据，目前常见的药物不良反应主要涉及消化系统、血液系统、肝胆系统、肺部、皮肤、眼部、外周感觉神经系统及肌肉骨骼系统等。与其他癌种不同的是，肺癌不仅疾病亚型及分子病理学机制复杂，治疗模式多样，而且晚期肺癌患者常合并慢性阻塞性肺疾病、肺部炎症等多种共患病，致使ADC相关不良反应的全程化管理更具挑战。为此，由中国老年保健协会胸部肿瘤精准治疗分会专业委员会牵头，组织国内消化科、皮肤科、呼吸科、眼科及肿瘤科等多学科专家讨论并联合制定了《抗体药物偶联物治疗肺癌不良反应多学科管理专家共识（2025版）》，共提出21条推荐意见，贯穿ADC使用前安全评估、ADC治疗期间发生相关不良反应的全面监测管理、ADC治疗的患者教育以及特殊人群的用药指导，旨在为临床医师提供切实可行的ADC应用参考准则，确保肺癌患者治疗获益最大化。.

Alzheimer's disease (AD) is a multifactorial and progressive neurodegenerative disorder characterized by complex interactions among amyloid-β (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, metal dyshomeostasis, and impaired autophagy. Increasing evidence positions neuroinflammation not merely as a secondary response but as a central driver of disease progression, dynamically interacting with amyloid and tau protein pathology and contributing to synaptic dysfunction and neuronal loss. Among inflammatory mechanisms, microglial activation pathways-particularly TREM2 signaling, NLRP3 inflammasome activation, and complement cascade dysregulation-are currently the most clinically actionable targets, supported by genetic, biomarker, and therapeutic evidence. Emerging data suggest that modulation of innate immune pathways is most likely to confer benefit during the prodromal and early symptomatic stages of AD, when neuroinflammatory responses remain partially adaptive and neuronal networks retain functional reserve. Despite decades of drug development, many candidates have failed due to limited efficacy or safety concerns. Recent FDA approvals of anti-amyloid monoclonal antibodies, including aducanumab and lecanemab, represent important advances toward disease-modifying therapy, although their long-term clinical impact and safety profiles remain under evaluation. These developments underscore the importance of biomarker-guided patient selection, disease-stage stratification, and vigilant safety monitoring, particularly regarding amyloid-related imaging abnormalities. Therapeutic strategies are increasingly shifting toward multi-target approaches that integrate amyloid modulation, tau protein-directed interventions, and attenuation of maladaptive neuroinflammatory responses. Concurrently, inflammatory mediators and peripheral metabolic biomarkers are gaining recognition as tools for early detection, risk stratification, and therapeutic response monitoring, potentially enabling precision-based intervention. This review synthesizes current understanding of AD pathogenesis through an inflammation-centered framework, highlighting clinically actionable immune pathways and stage-specific therapeutic windows. By integrating mechanistic insights with biomarker-driven strategies, we aim to delineate translational paths toward more precise, safe, and clinically meaningful disease modification.

Posaconazole exhibits substantial pharmacokinetic variability, particularly with oral formulations. Real-world data on target attainment across formulations and on specific toxicity thresholds remain limited. This study aimed to evaluate posaconazole target attainment rates, identify independent predictors of subtherapeutic exposure, and explore potential hepatotoxicity exposure thresholds in a real-world Chinese cohort. This single-centre, retrospective observational study conducted at Nanjing Drum Tower Hospital, China, between January 2023 and August 2025 enrolled 148 patients with IPFI. Posaconazole was administered for prophylaxis with a target trough concentration of &#x2265;0.5 mg/L, or for treatment with a target of &#x2265;1.0 mg/L. Multivariable logistic regression was utilised to identify independent predictors of subtherapeutic exposure. Subtherapeutic trough concentrations were observed in 24.0% of the prophylaxis group and 23.3% of the treatment group. Concomitant proton pump inhibitor (PPI) use was the dominant independent risk factor for subtherapeutic exposure in both prophylaxis (OR 17.97, 95% CI 4.22-76.53, P<0.001) and treatment (OR 3.60, 95% CI 1.10-11.75, P=0.034) groups. Regarding regimen optimisation, switching to the intravenous formulation proved more effective than oral dose escalation for correcting subtherapeutic levels. Furthermore, an exposure-safety analysis revealed that hepatotoxicity rates increased significantly when trough concentrations exceeded 1.95 mg/L (P=0.015). Subtherapeutic posaconazole exposure remains common. PPI use is a critical risk factor that may not be fully overcome by delayed-release or intravenous formulations. Our findings suggest a potential exposure-hepatotoxicity relationship around 1.95 mg/L for Chinese patients, highlighting the need for individualised TDM.

Malaria remains a major public health challenge in Ethiopia, with Plasmodium falciparum and Plasmodium vivax accounting for most malaria cases. Continuous monitoring of antimalarial drug efficacy and safety is essential to ensure effective case management and to detect early signs of emerging drug resistance. In addition, understanding gametocyte clearance following treatment is important because persistent gametocytaemia can sustain malaria transmission. This study assessed the therapeutic efficacy, safety, and gametocyte clearance following antimalarial treatment among patients with uncomplicated P. falciparum and P. vivax malaria in Northeast Ethiopia. A prospective observational study was conducted from November 2024 to January 2026 among 159 patients with uncomplicated malaria, including 81 P. falciparum and 78 P. vivax infections. Patients received treatment according to national guidelines, with artemether-lumefantrine for P. falciparum and chloroquine for P. vivax, while a subset also received a single low dose of primaquine. Participants were followed for 28 days to assess therapeutic outcomes, fever clearance, asexual parasite clearance, haemoglobin recovery, gametocyte clearance and adverse events. Data were analysed using SPSS version 26.0. Kaplan-Meier survival analysis was used to evaluate fever, parasite, and gametocyte clearance. Statistical significance was considered at p&#x2009;<&#x2009;0.05. Therapeutic efficacy was high in both species, with adequate clinical and parasitological response rates of 88.9% among P. falciparum patients and 97.4% among P. vivax patients. Fever and asexual parasite clearance occurred more rapidly in P. vivax than in P. falciparum, with median fever clearance times of 2 and 3 days and median parasite clearance times of 2 and 4 days, respectively. Haemoglobin levels improved throughout follow-up in both groups, although P. falciparum infections were associated with lower baseline haemoglobin levels. Antimalarial treatments were generally well tolerated, with most adverse events being mild and no treatment discontinuations recorded. A transient increase in gametocyte carriage on day 3 was observed more frequently among participants who did not receive primaquine. Primaquine significantly accelerated gametocyte clearance, reducing the median clearance time from 11 to 7 days in P. falciparum and from 7 to 4 days in P. vivax. Higher baseline gametocyte density was associated with slower gametocyte clearance, particularly among P. falciparum patients. First-line antimalarial treatments remain highly effective and well tolerated for the management of uncomplicated P. falciparum and P. vivax malaria in Northeast Ethiopia. However, post-treatment gametocyte persistence may contribute to ongoing transmission, particularly in P. falciparum infections. The addition of low-dose primaquine significantly enhanced gametocyte clearance in both species, highlighting its potential role in reducing transmission and supporting malaria elimination efforts.

Human serum albumin (HSA), the most abundant plasma protein synthesized by hepatocytes, is vital for maintaining plasma colloid osmotic pressure, regulating redox balance, and transporting nutrients and metabolic wastes. Abnormal HSA levels correlate strongly with multiple diseases, especially liver disorders including cirrhosis, hepatocellular carcinoma and drug-induced liver injury (DILI), making HSA an essential biomarker for clinical diagnosis and prognosis. Although small-molecule fluorescent probes have been developed for HSA detection, major drawbacks persist: most work in the visible spectrum with poor tissue penetration, show low selectivity in complex biological environments, cannot realize subcellular localization or real-time in vivo monitoring. Herein, we fabricated a new near-infrared fluorescent probe TH from rhodamine derivatives for HSA detection. Relying on the twisted intramolecular charge transfer (TICT) mechanism, TH is weakly fluorescent in free form. When bound to the hydrophobic cavity of HSA, its molecular torsion is inhibited, producing prominent near-infrared fluorescence at 720 nm. TH possesses outstanding selectivity toward HSA, with a low detection limit of 2.3 &#x3bc;g/mL and favorable linear response. It also targets mitochondria, allowing real-time subcellular imaging of HSA in live cells. Further verified in a DILI mouse model, TH enables noninvasive real-time monitoring of hepatic HSA dynamics. This work offers a novel near-infrared probe for HSA analysis, holding great promise for auxiliary diagnosis and therapeutic assessment of DILI and other HSA-associated liver diseases.

Low success rates in clinical drug development can be largely attributed to the poor predictive power of existing preclinical models. Microphysiological systems (MPS) have greatly advanced in vitro modeling; however, current platforms do not adequately support long-term sampling and often fail to recapitulate nutrient and drug exposure dynamics. To address these limitations, we established a machine vision-guided MPS with real-time fluidic control that enables fully automated periodic sampling with high temporal resolution, media replenishment, and programmable dosing, allowing for the simulation of dynamic nutritional or pharmacological exposure scenarios. We showcase the system's capability by emulating physiological insulin profiles and repeated-dose pharmacokinetic exposures over multiple weeks. Furthermore, pharmacokinetically accurate acetaminophen exposure in 3D primary human liver spheroids mimicking an acute overdose rapidly induced liver toxicity, as evidenced by aminotransferase release, cytokine secretion and a drop in cellular ATP. In contrast, dose-equivalent constant exposure patterns did not elicit detectable hepatotoxicity. Mechanistically, targeted proteomics of sampled supernatants and Cell Painting revealed that toxicity was paralleled by disrupted lipid homeostasis, loss of tight junctions and extracellular matrix remodeling. These results demonstrate the robustness and versatility of the machine vision-guided automated microphysiological platform and underscore the importance of incorporating drug exposure dynamics for mechanistic toxicology.

Difelikefalin, a peripherally acting selective &#x3ba;-opioid receptor agonist, is approved for treating chronic kidney disease-associated pruritus (CKD-aP) in adults on hemodialysis. However, real-world data on its adverse drug events (ADEs) remain limited. This study aimed to systematically identify ADE signals associated with difelikefalin in hemodialysis patients using the FAERS database, to generate hypotheses for subsequent clinical validation and provide targeted evidence for safe clinical application of difelikefalin in this vulnerable population. ADE reports related to difelikefalin were extracted from the FAERS database (2022-2025). Drug names were standardized using Medex UIMA, and ADEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analyses, including the reporting odds ratio (ROR) and proportional reporting ratio (PRR), were employed to detect ADE signals. A total of 328 difelikefalin-related ADE reports were included, which is limited by the relatively recent approval and limited real-world use of this agent. Demographically, male patients (49.09%) outnumbered females (24.09%), and the vast majority of patients with clear age data were aged 65 years or older. Clinically, the most frequent outcomes were 'other serious' events (46.01%), hospitalization (33.46%), and death (15.59%). At the System Organ Class (SOC) level, Nervous system disorders (ROR&#xa0;=&#xa0;3.4) and Psychiatric disorders (ROR&#xa0;=&#xa0;2.99) showed the strongest ADE signals. At the Preferred Term (PT) level, high-risk signals included mental status changes (ROR&#xa0;=&#xa0;85.65), disorientation (ROR&#xa0;=&#xa0;33.62), electric shock sensation (ROR&#xa0;=&#xa0;32.09), somnolence (ROR&#xa0;=&#xa0;16.25), fall (ROR&#xa0;=&#xa0;8.46), and fracture (ROR&#xa0;=&#xa0;21.06). We also identified several rare ADE signals unreported in phase III clinical trials (e.g. electric shock sensation, disorientation) with significant disproportional reporting. This pharmacovigilance study identifies potential neuropsychiatric safety signals associated with difelikefalin, with a particularly elevated risk in elderly patients. These findings identify elderly hemodialysis patients as the high-risk group for difelikefalin-related ADEs, and suggest the need for targeted clinical monitoring strategies for this population; all signals require prospective cohort studies to validate potential causal relationships.

This Health Policy compares the current recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for new treatments in rheumatoid arthritis, highlighting where they align, where they differ, and how harmonisation could make drug development more efficient. We examined the EMA's Guidelines on Clinical Trials of Medicinal Products for the Treatment of rheumatoid arthritis and the FDA's draft guidance rheumatoid arthritis Development of Drugs for Treatment, together with relevant cross-indication FDA guidelines and labelling decisions in rheumatoid arthritis in the last two decades. The key aspects of trial design, including study populations, endpoints, safety requirements, and statistical considerations were analysed. The findings were reviewed and interpreted by a panel of rheumatologists, who proposed strategies for aligning regulatory expectations. The FDA and EMA agree on several core principles such as the use of composite clinical endpoints, validated patient-reported outcomes, the importance of preventing structural joint damage, need for adequate long-term safety exposure, and limits on placebo duration. The EMA, however, favours remission or low disease activity as the preferred primary endpoints, generally requires two pivotal trials in distinct rheumatoid arthritis populations, and background methotrexate unless contraindicated. The FDA offers more flexibility in primary endpoint selection, allows for a single pivotal trial if supported by strong confirmatory evidence, and places greater emphasis on early dose-response characterisation. Greater alignment between FDA and EMA requirements could help reduce duplication, streamline global data interpretation, and speed patient access to effective rheumatoid arthritis therapies globally.

DNA nanodevices have emerged as versatile tools for intracellular biosensing and imaging, yet their broader application is constrained by limited tumor specificity and insufficient subcellular precision. Here, we report a sequentially responsive DNA nanodevice (SRDN) for spatially selective imaging of mitochondrial microRNAs (miRNAs) in live tumor cells and early assessment of treatment efficacy. The sensing function of SRDN is initially silenced through the strategic integration of an abasic site and a blocking DNA element, but can be sequentially activated by human apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm and mitochondria-encoded ribosomal RNA, thereby achieving accurate mitochondrial miRNA imaging with improved spatial resolution. This cascade-activated mechanism significantly reduces off-site signals and enhances the tumor-to-background contrast, enabling tumor-specific mitochondrial miRNA imaging. Furthermore, we demonstrate the performance of SRDN in dynamically monitoring mitochondrial miRNA levels in tumor cells during therapeutic intervention, supporting reliable assessment of treatment efficacy. Collectively, this study provides a robust platform for detecting biomolecules at the subcellular level and investigating treatment-related signaling pathways, underscoring its prospective applications in disease diagnosis and drug development.

Sex-based differences in treatment-related adverse events (TRAEs) have been described across several anticancer therapies. However, sex-disaggregated safety data for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC) is lacking. We conducted a monocentric cohort study including patients with advanced NSCLC treated with developmental ADCs within phase I-II clinical trials at Gustave Roussy (2018-2023). Clinically significant TRAEs (grade &#x2265;2, Common Terminology Criteria for Adverse Events version 5.0), dose modifications, hospitalisations, and survival outcomes were analysed according to sex using univariate and multivariate analysis. Our population included 132 patients [women, 64 (48.5%); men, 68 (51.5%)] receiving ADCs targeting TROP2 (32.6%), ITGB6 (31.8%), HER2 (13.6%), CEACAM5 (13.6%), HER3 (5.4%), c-MET (2.3%), and Nectin-4 (0.7%). Overall, 100 (76%) and 39 (29%) patients experienced grade &#x2265;2 and grade &#x2265;3 TRAEs, respectively. Women had a higher incidence of grade &#x2265;2 TRAEs than men [82.8% versus 69.1%; adjusted odds ratio (OR) 2.8, 95% confidence interval (CI) 1.03-7.84, P = 0.04)] and a higher median number of TRAEs (2 versus 1, P = 0.04). Metabolic TRAEs (anorexia, weight loss, ion and lipid imbalances) were significantly more frequent in women (29.7% versus 10.3%; OR 3.68, 95% CI 1.42-9.49, P = 0.009), as were dose reductions (37.5% versus 19.1%; OR 3.35, 95% CI 1.24-9.01, P = 0.02). Women treated with developmental ADCs for advanced NSCLC experience a higher burden of clinically relevant TRAEs. Our data suggest that sex may represent a key variable to integrate into safety reporting and monitoring strategies for developmental ADCs in NSCLC.

Hydrophobins are small amphipathic proteins that self-assemble at hydrophobic-hydrophilic interfaces to form stable waterproof coatings over fungal spores. Class I hydrophobins form particularly stable "rodlets" containing ordered amyloid-like structures that coat surfaces. This unusual surface chemistry gives them potential applications in drug delivery, foam stabilization, emulsification, and surface modification. To produce hydrophobins, there is a need for comprehensive, high-yield protocols from simple expression systems. Furthermore, it is necessary to provide facile methods to characterize hydrophobin function following recombinant production and purification. Herein, we describe protocols for the production and characterization of SC16, a class IB hydrophobin produced by the fungus Schizophyllum commune, which can be recombinantly expressed in Escherichia coli and subsequently purified under non-reducing, native conditions. This involves transformation of an expression plasmid encoding SC16 fused to an N-terminal fusion protein into E. coli, induction of protein expression, cell lysis under native conditions, affinity chromatography, and protease cleavage to isolate the hydrophobin at yields of &#x2265;5 mg. The self-assembly of SC16 can then be monitored by end-point or kinetic fluorescence-based assays using thioflavin T. Both assays involve incubation of SC16 with prolonged mixing to promote self-assembly at air-water interfaces and are monitored by fluorescence measurements. Together, these approaches provide simplified protocols for purifying SC16 and monitoring its self-assembly and may be extended to other systems involving similar protein self-assembly.

This review summarizes recent evidence on continuous glucose monitoring (CGM) in adults with type 2 diabetes mellitus (T2D), focusing on clinical effectiveness, patient-reported outcomes, disparities in use, and policy and economic considerations. Studies from 2020 to 2025 show that CGM use in T2D is associated with consistent improvements in glycosylated hemoglobin (HbA1c), time in range, and diabetes self-management across insulin and non-insulin treatment regimens. Emerging observational data suggest reductions in mortality and health care utilization, and cost-effectiveness analyses consistently demonstrate that CGM represents a high-value intervention across payer settings. Despite these benefits, CGM uptake remains variable, with persistent disparities by age, race, and ethnicity, insurance coverage, and care setting. CGM is an effective and cost-effective tool for T2D management, but inequities in access limit its impact. Future research should address implementation in safety-net and primary care settings, evaluate over-the-counter CGM, and assess long-term clinical and health system outcomes.

Hyperbaric oxygen (HBO) therapy increases blood oxygen levels by exposing patients to 100% oxygen under elevated pressure and is used clinically for conditions such as decompression sickness, carbon monoxide poisoning, chronic wounds, and impaired tissue healing. However, real-time precise and quantitative measurement of tissue oxygen tension (pO2) under hyperbaric conditions remains technically very challenging. We developed a specialized small-animal hyperbaric chamber compatible with in vivo electron paramagnetic resonance (EPR) oximetry using customized OxyTrack oxygen detectors. Up to two detectors were implanted simultaneously to measure pO2 in skeletal muscle and tumor tissue in mice. Animals were exposed to air (21% O2) and 100% O2 at both normobaric pressure and 2 atmospheres absolute (ATA) in a stepwise protocol. The chamber operated safely and stably up to 2 ATA, enabling continuous real-time pO2 monitoring without adverse events and issues with the hardware for up to 90&#x2009;min. In B16-F10 melanoma, tumor pO2 increased from &#x223c;9&#x2009;mmHg at baseline to &#x223c;26&#x2009;mmHg at 100% O2 (1 ATA) and &#x223c;50&#x2009;mmHg at 2 ATA, with partial retention after decompression. In contrast, SCC7 tumors showed minimal responsiveness (&#x223c;9-10&#x2009;mmHg), whereas skeletal muscle demonstrated marked pressure-dependent increases (up to &#x223c;50&#x2009;mmHg). The small-animal HBO chamber enables real-time, tissue-specific assessment of oxygen dynamics under clinically relevant hyperbaric conditions. The approach could facilitate optimization of HBO protocols and support translational investigation of oxygen-modulated therapies, including radiation and drug responses in solid tumors.

Cryptococcosis is a severe invasive fungal infection with limited therapeutic options beyond fluconazole-based regimens. Isavuconazole, a broad-spectrum triazole antifungal, has emerged as a potential alternative, although clinical data supporting its use remain scarce. We aimed to evaluate the real-world effectiveness and safety of isavuconazole in patients with different forms of cryptococcosis. A retrospective observational study was conducted at a tertiary-care hospital, including patients with cryptococcosis who received isavuconazole at any treatment phase. Standard microbiological methods were used for pathogen identification and susceptibility testing. Demographic, clinical, and microbiological data were collected. Clinical and microbiological responses and tolerability were assessed at end of treatment or until death. Eight patients with cryptococcosis received isavuconazole, most of whom were immunocompromised. Clinical presentations included pulmonary and disseminated disease, with Cryptococcus neoformans as the predominant species. Isavuconazole was primarily used during the consolidation and maintenance phases, after induction therapy with amphotericin B and flucytosine for 2&#xa0;weeks in most cases, and as salvage therapy in two patients. It was well tolerated during prolonged treatment (6-12&#xa0;months). In the two patients with isavuconazole therapeutic drug monitoring, plasma total trough concentrations were within the therapeutic range (5 and 3.5&#xa0;&#xb5;g/mL, respectively), whereas cerebrospinal fluid total concentration levels were undetectable. A favorable clinical response was observed in four patients, while three remain on treatment with ongoing clinical improvement; one patient died early. Microbiological clearance was achieved in all culture-positive cases. Isavuconazole demonstrated clinical effectiveness in this cohort of patients across different presentations of cryptococcosis. Treatment was safe and well tolerated, supporting its role as an alternative antifungal option against Cryptococcus, particularly when fluconazole is limited by adverse effects or drug-drug interactions. However, data on central nervous system penetration were limited, and further studies are needed to better define its role in cryptococcal meningitis management.

Patients with malignancy are at increased risk of bleeding due to tumor-related vascular fragility, chemotherapy-induced thrombocytopenia, impaired hepatic function, malnutrition, and systemic inflammation. Anticoagulation management in this population is further complicated by frequent medication changes, drug-drug interactions, poor oral intake, and acute illness, making bridging anticoagulation a particularly high-risk transition. We report a case of a non-traumatic iliacus muscle hematoma occurring during therapeutic-dose enoxaparin bridging in a patient with active metastatic malignancy, illustrating how multiple concurrent risk factors can precipitate clinically significant hemorrhage even when the international normalized ratio (INR) appears subtherapeutic or within range. A 67-year-old man with metastatic squamous cell carcinoma of the lung and larynx, atrial flutter on chronic warfarin therapy, and concurrent thrombocytopenia developed progressive anemia during hospitalization. Warfarin was held for a planned procedure, and bridging anticoagulation with therapeutic-dose enoxaparin was initiated. Imaging subsequently identified a 3.5 &#xd7; 2.4 &#xd7; 5.5 cm left iliacus muscle hematoma without evidence of trauma or active extravasation. The patient was managed conservatively with serial monitoring and individualized anticoagulation adjustments, resulting in hemoglobin stabilization and clinical improvement. This case reinforces the multifactorial nature of bleeding risk in patients with malignancy receiving anticoagulation and highlights that INR alone does not fully capture hemorrhagic risk when additional anticoagulants, thrombocytopenia, renal impairment, and cancer-related hemostatic alterations are present.