Drug Design, Development and Therapy最新文献

{"title":"Minimum Effective Volume of 0.25% Ropivacaine for Ultrasound-Guided Superior Trunk Block with Dexmedetomidine Sedation in Shoulder Arthroscopy: A Biased Coin Up-and-Down Trial.","authors":"Kai Wang, Shuhan Zhang, Zhaoyu Lv, Wei Chen, Yonghua Li","doi":"10.2147/DDDT.S597074","DOIUrl":"https://doi.org/10.2147/DDDT.S597074","url":null,"abstract":"<p><strong>Background: </strong>Although interscalene brachial plexus block (ISB) remains the gold standard for shoulder arthroscopy, it is associated with a high incidence of hemidiaphragmatic paralysis (HDP). The superior trunk block (STB) offers comparable analgesia with a significantly reduced risk of HDP; however, the optimal local anesthetic dose for surgical anesthesia when STB is used alone has not been established. This study aimed to determine the minimum effective volume of 0.25% ropivacaine required to achieve surgical anesthesia in 90% of patients (MEV₉ ₀) under ultrasound-guided STB.</p><p><strong>Methods: </strong>We employed a biased coin design up-and-down method (BCD-UDM). Starting from an initial volume of 5 mL, the dose for each subsequent patient was determined by the previous patient's outcome: failure triggered a 2 mL increase, while success led to random assignment between a 2 mL decrease (11% probability) or the same volume (89% probability). Block success was defined as a composite sensory score ≥9 at 30 minutes and completion of surgery under STB with dexmedetomidine sedation (loading dose 0.8 μg/kg over 15 min before incision, followed by a maintenance infusion of 0.1-0.5 μg/kg/h), without conversion to general anesthesia.</p><p><strong>Results: </strong>A total of 52 patients were included. Using isotonic regression with bootstrapped confidence intervals, the MEV₉ ₀ of 0.25% ropivacaine for ultrasound-guided STB was estimated to be 9.1 mL (95% CI: 8.3-9.9 mL). No patient developed severe bradycardia (heart rate ≤40 bpm) attributable to dexmedetomidine sedation.</p><p><strong>Conclusion: </strong>The MEV₉ ₀ of 0.25% ropivacaine required to achieve surgical anesthesia for ultrasound-guided STB under dexmedetomidine sedation is 9.1 mL.</p><p><strong>Trial registration number: </strong>ChiCTR2200059042.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"597074"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Drug-Drug Interactions of DA-8010 with Clarithromycin or Rifampicin: Influence of CYP2D6 Phenotype on the Extent of These Interactions.","authors":"Sujong Lee, Heejae Won, Kyung-Sang Yu, Dae Young Lee, SeungHwan Lee","doi":"10.2147/DDDT.S592783","DOIUrl":"https://doi.org/10.2147/DDDT.S592783","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the pharmacokinetic (PK) drug-drug interactions (DDIs) of DA-8010 with clarithromycin or rifampicin, and to assess the influence of cytochrome P450 (CYP) 2D6 phenotype on the extent of these interactions.</p><p><strong>Methods: </strong>An open-label, fixed-sequence, three-period crossover study was conducted in healthy participants. Participants received a single dose of DA-8010 5 mg alone on Day 1 (Period 1); clarithromycin 500 mg twice daily from Day 6 to 11, with a concomitant single dose of DA-8010 5 mg on Day 10 (Period 2); and rifampicin 600 mg once daily from Day 16 to 25, with a concomitant single dose of DA-8010 5 mg on Day 25 (Period 3). Each treatment period was separated by a five-day washout. Serial blood samples for PK assessments of DA-8010 were collected up to 48 h post-dose. CYP2D6 genotyping was performed retrospectively, and phenotypes were assigned based on activity score.</p><p><strong>Results: </strong>Sixteen participants completed the study: eleven were classified as CYP2D6 extensive metabolizers (EMs) and five as CYP2D6 intermediate metabolizers (IMs). Co-administration of DA-8010 with clarithromycin had no significant effect on the PKs of DA-8010. In contrast, co-administration with rifampicin reduced the systemic exposure of DA-8010 by approximately 50% compared with DA-8010 alone. Across all treatment conditions, DA-8010 exposure was approximately two-fold higher in IMs than in EMs.</p><p><strong>Conclusion: </strong>DA-8010 showed no clinically meaningful PK interaction with clarithromycin, while rifampicin significantly reduced DA-8010 exposure. Although the CYP2D6 phenotype affected overall DA-8010 exposure, it did not alter the extent of the PK interaction observed with clarithromycin or rifampicin.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"592783"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulatory Landscape of Ferroptosis and Iron Homeostasis: Pathophysiological Mechanisms and Therapeutic Horizons in Cardiovascular Disease.","authors":"Tianqing Zhang, Sijie Xiao, Yanfu Xia, Kun Chen, Honglan Liu, Ping Zhang, Li Luo","doi":"10.2147/DDDT.S581236","DOIUrl":"https://doi.org/10.2147/DDDT.S581236","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent form of regulated cell death driven by unrestrained lipid peroxidation, morphologically and biochemically distinct from apoptosis, necrosis, and autophagy. It is increasingly recognized as a core pathophysiological mechanism across the full spectrum of cardiovascular diseases, including myocardial ischemia-reperfusion injury, heart failure, atherosclerosis, diabetic cardiomyopathy, and chemotherapy-induced cardiotoxicity. The initiation and progression of ferroptosis are governed by the dysregulation of iron homeostasis, lipid metabolic remodeling, and collapse of antioxidant defense systems, with extensive crosstalk with other regulated cell death modalities in cardiovascular pathophysiology. Preclinical studies have consistently demonstrated that targeting ferroptosis exerts robust cardioprotective effects via multiple mechanisms. However, clinical translation faces key hurdles, including the lack of specific biomarkers, off-target risks, and interindividual heterogeneity in therapeutic response. This review systematically summarizes the regulatory mechanisms of ferroptosis, its causal role in cardiovascular diseases, and the latest advances in targeted therapeutic strategies, with a focus on clinical translation prospects and challenges.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"581236"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Desflurane and Propofol General Anesthesia on Postoperative Recovery Quality in Elderly Patients Undergoing Spinal Surgery: A Randomized Non-Inferiority Trial.","authors":"Dongjing Shi, Xuan Liang, Chunhua Xi, Chunming Pei, Guyan Wang","doi":"10.2147/DDDT.S601299","DOIUrl":"https://doi.org/10.2147/DDDT.S601299","url":null,"abstract":"<p><strong>Purpose: </strong>Postoperative recovery quality is a key concern for elderly patients undergoing spinal surgery, yet evidence comparing different anesthetic techniques in this population remain limited. This study aimed to compare the quality of recovery between desflurane-based inhalational anesthesia and propofol-based total intravenous anesthesia in this population.</p><p><strong>Patients and methods: </strong>This randomized non-inferiority trial was conducted from July 1 to October 31, 2025. A total of 109 elderly patients scheduled for spinal surgery were randomly assigned to two groups: the desflurane group (group D), which received desflurane at a maintenance dose of 0.7 to 1.0 MAC, and the propofol group (group P), which received propofol at 4 to 6 mg/kg/h. Both groups received standard monitoring and invasive arterial blood pressure measurement. The primary outcome was the quality of recovery (QoR-15) scores on postoperative day 1 (POD1). Secondary outcomes include intraoperative remifentanil and vasopressors requirements, fluid volume, hemodynamic parameters, emergence profiles, duration of post-anesthesia care unit (PACU) stay, postoperative hospital length of stay, Activities of Daily Living (ADL) scale, Mini Montreal Cognitive Assessment (Mini-MoCA), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), incidence of postoperative nausea and vomiting (PONV), Numeric Rating Scale (NRS) of postoperative pain and subjective sleep quality on POD1 and POD2.</p><p><strong>Results: </strong>The total QoR-15 score on POD1 in group D was non-inferior to that in group P (117.0 ± 10.6 vs. 118.4 ± 12.0; mean difference: -1.4; 95% CI: -5.6-2.4; one-sided <i>P</i>=0.017 for non-inferiority). Compared with group P, group D had significantly shorter times to extubation, eye opening, limb movement, orientation recovery, and ability to state one's name, as well as significantly higher Riker Sedation-Agitation Scale scores. Intraoperative phenylephrine consumption and fluid volume were lower in group D than in group P. No significant differences were observed between the two groups in PACU stay duration, postoperative hospital length of stay, ADL scale, Mini-MoCA, CAM-ICU, PONV incidence, NRS pain scores, or subjective sleep quality.</p><p><strong>Conclusion: </strong>Desflurane-based inhalational anesthesia provided a non-inferior quality of recovery compared with propofol. Additionally, desflurane was associated with faster emergence and lower vasopressor requirements. Desflurane and propofol can be considered interchangeable for general anesthesia in elderly patients undergoing spinal surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"601299"},"PeriodicalIF":5.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum Computing and Quantum Technologies in Drug Discovery and Therapeutics: Evidence, Benchmarking, and Translational Integration.","authors":"Sarfaraz K Niazi","doi":"10.2147/DDDT.S590730","DOIUrl":"https://doi.org/10.2147/DDDT.S590730","url":null,"abstract":"<p><p>Quantum technologies-quantum computing, quantum sensing, and quantum-enabled materials-are increasingly proposed as tools to accelerate drug discovery. Yet \"quantum advantage\" is frequently asserted without standardized benchmarks, clinically meaningful endpoints, or controlled comparisons against modern classical workflows. This review separates (i) quantum computing for molecular simulation and optimization, (ii) quantum sensing for structural/biophysical characterization and diagnostics, and (iii) quantum nanotechnologies for imaging and sensing, and then extends the framework to include device-led and physical therapies that increasingly co-evolve with drug development: photobiomodulation (red/NIR), focused ultrasound for blood-brain barrier opening and delivery enhancement, noninvasive neuromodulation devices (tDCS/TMS), and optogenetic therapies. We summarize demonstrated capabilities and constraints of NISQ-era computing, outline algorithmic classes for quantum chemistry and hybrid variational methods, evaluate quantum error-mitigation strategies and their limits, and contrast claimed performance with classical baselines in computational chemistry and machine learning. We conclude that near-term translational value is most substantial for quantum sensing and for device/physical platforms with established clinical evidence. In contrast, quantum computing remains principally hypothesis-generating until fault tolerance and reproducible advantage are established. Device-based modalities-including transcranial photobiomodulation for neuropsychiatric indications, focused ultrasound enabling CNS drug delivery, and home-supervised neuromodulation-are already reshaping therapeutic landscapes and clinical trial design. For drug discovery, the central requirement is not quantum novelty but validated decision impact, demonstrated under controlled benchmarks aligned with reproducibility expectations comparable to those evolving for AI/ML-driven methods in regulated contexts.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"590730"},"PeriodicalIF":5.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Sex on the Median Effective Dose of Dexmedetomidine for Preoperative Sedation in Adults Undergoing Upper Limb Surgery: An Up-and-Down Sequential Allocation Study.","authors":"Gaofei Fan, Mingming Han, Shudong Wang, Min Zhang, Fang Kang, Juan Li","doi":"10.2147/DDDT.S576010","DOIUrl":"https://doi.org/10.2147/DDDT.S576010","url":null,"abstract":"<p><strong>Purpose: </strong>Prospective evidence on sex-based variability in the sedative potency of dexmedetomidine remains limited. This study aimed to estimate and compare the median effective dose (ED₅₀) of dexmedetomidine for preoperative sedation in adult men and women undergoing elective upper limb surgery.</p><p><strong>Patients and methods: </strong>In this prospective, single-center, assessor-blinded, dose-finding study, adult patients aged 18 to 60 years scheduled for upper limb surgery were allocated to male and female dexmedetomidine groups according to biological sex. Dexmedetomidine was administered intravenously over 15 minutes using a modified Dixon's up-and-down sequential method (initial dose 1.0 μg/kg; step size 0.05 μg/kg). Adequate sedation was defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale score < 3 at 26 minutes from infusion start. The primary endpoint was the Dixon-derived ED_50, with supportive analyses including probit regression, bootstrap validation, and multivariable logistic regression adjusted for baseline covariates. Secondary outcomes included sedation depth and adverse events.</p><p><strong>Results: </strong>Forty-six patients (23 per group) were enrolled. The Dixon-derived ED₅₀ (95% confidence interval) was 1.26 μg/kg (1.17-1.35) in men and 1.28 μg/kg (1.17-1.38) in women, with overlapping confidence intervals. Probit regression and bootstrap-validated ED₅₀ estimates were consistently similar between groups. In multivariable analysis, sex was not independently associated with adequate sedation (<i>P</i> = 0.275), whereas dexmedetomidine dose was a significant predictor. At 26 minutes, neither MOAA/S scores nor bispectral index (BIS) values differed significantly between sexes. Bradycardia occurred in 39.1% of males versus 34.8% of females, and hypertension in 13.0% versus 4.3%, respectively; all adverse events were transient and safely managed.</p><p><strong>Conclusion: </strong>No clinically meaningful sex-related difference was observed in dexmedetomidine ED₅₀ under standardized preoperative conditions. These findings do not support routine sex-based dose adjustment for preoperative sedation in relatively healthy adults.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"576010"},"PeriodicalIF":5.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor 21: Mechanisms, Therapeutic Potential, and Clinical Translation in Metabolic Dysfunction.","authors":"Kaanthi Rama, Vinay Jahagirdar, Arun J Sanyal","doi":"10.2147/DDDT.S560034","DOIUrl":"https://doi.org/10.2147/DDDT.S560034","url":null,"abstract":"<p><p>Fibroblast growth factor 21 (FGF21) is an endocrine hepatokine that coordinates systemic energy metabolism by linking hepatic nutrient sensing with adipose and central signalling pathways. Experimental and clinical studies identify FGF21 as a critical modulator of lipid oxidation, insulin sensitivity, and inflammatory balance, processes central to the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). Endogenous FGF21 rises in response to fasting, lipotoxicity, and mitochondrial stress, yet this compensatory increase is insufficient in chronic metabolic disease, reflecting target-tissue resistance. Pharmacologic augmentation with engineered FGF21 analogues demonstrates robust reductions in hepatic fat, serum transaminases, and fibrosis biomarkers, along with improvements in triglyceride and adiponectin levels as well as liver histology. In a Phase 2b trial, efruxifermin reversed cirrhosis in 39% of participants. These agents act across the MASH cascade, mitigating lipotoxic injury, inflammation, and stellate-cell activation while favorably modifying cardiometabolic risk. FGF21 therefore represents a unifying therapeutic axis that integrates hepatic and systemic metabolic correction. Ongoing Phase 3 studies will determine whether these biochemical and histologic improvements translate into long-term clinical benefit, positioning FGF21 analogues as cornerstone therapies for metabolic disease. This review aims to synthesize current evidence on the molecular mechanisms and therapeutic potential of FGF21 in metabolic dysfunction-associated steatohepatitis. It highlights emerging clinical data on FGF21 analogues and their role in targeting key pathways of disease progression, with implications for future therapeutic strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"560034"},"PeriodicalIF":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis in Sepsis: Cell Type-Specific Mechanisms and Clinical Prospects.","authors":"Shangping Fang, Wanning Li, Zhaorong Chang, Xiaoyu Tang, Xin Niu, Yongquan Chen, Xianwen Hu","doi":"10.2147/DDDT.S600729","DOIUrl":"https://doi.org/10.2147/DDDT.S600729","url":null,"abstract":"<p><p>Sepsis is a life-threatening clinical syndrome caused by a severely dysregulated host response to infection. As a major global health challenge, it continues to exhibit high mortality. Copper, an essential trace element crucial for biological homeostasis, is central to a recently defined form of cell death: cuprotosis. This novel, copper-dependent mitochondrial cell death pathway is mechanistically distinct from classical apoptosis and pyroptosis. In sepsis, cuprotosis contributes significantly to immune dysfunction and organ failure by mediating the death of both immune cells (e.g. macrophages, lymphocytes) and parenchymal cells (e.g. cardiomyocytes, renal tubular cells). Therefore, modulating this regulatory mechanism in a cell type-specific manner may represent a novel potential therapeutic avenue for sepsis, although substantial clinical validation is still required. This review systematically outlines the core mechanisms of cuprotosis, elucidates its pathophysiological role in sepsis, and evaluates the potential and challenges of targeting cuprotosis for sepsis therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"600729"},"PeriodicalIF":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linoleic Acid Reduces Paclitaxel Chemosensitivity in Colorectal Cancer.","authors":"Bingwen Zhou, Jinjin Pan, Mengjie Wang, Peng Zhou, Zhili Li, Jingwei Cui, Chuyue Huang, Lu Wang, Zhimin Fan","doi":"10.2147/DDDT.S577058","DOIUrl":"https://doi.org/10.2147/DDDT.S577058","url":null,"abstract":"<p><strong>Purpose: </strong>Paclitaxel, a natural diterpenoid compound derived from <i>Taxus</i> species, is one of the most successful plant-based anticancer drugs and has been widely applied in the treatment of various solid tumors. In recent years, emerging evidence has suggested its potential efficacy in refractory or advanced colorectal cancer (CRC), particularly in patients resistant to standard first-line chemotherapy such as 5-fluorouracil (5-FU). However, responses to paclitaxel in CRC are heterogeneous. This study aimed to elucidate the metabolic determinants underlying the heterogeneous response of CRC to paclitaxel and to identify serum metabolites associated with therapeutic response.</p><p><strong>Patients and methods: </strong>Integrated serum metabolomic profiling was performed in patient-derived tumor organoid (PDTOs, n=18), combined with drug sensitivity assays and in vivo validation using mouse xenograft models. An analysis was conducted to sensitivity of paclitaxel, followed by targeted metabolomic quantification and pathway enrichment to identify key metabolites influencing paclitaxel efficacy.</p><p><strong>Results: </strong>Linoleic acid (LA) was identified as a serum metabolite significantly correlated with reduced paclitaxel sensitivity. Elevated LA levels attenuated paclitaxel-induced G₂/M cell cycle arrest and reduced cytotoxicity by altering microtubule dynamics. Functional validation in CRC cell lines and animal models further confirmed that LA diminished the antitumor effect of paclitaxel, supporting a metabolism-mediated mechanism of chemoresistance.</p><p><strong>Conclusion: </strong>This study identifies serum linoleic acid as a metabolism-related candidate biomarker associated with paclitaxel resistance in CRC. These findings highlight the potential clinical relevance of metabolic factors in modulating chemotherapy response and suggest that LA may have potential relevance for patient stratification in future studies of paclitaxel response in CRC.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"577058"},"PeriodicalIF":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasopressor Regimens and Maternal Core Temperature During Cesarean Delivery: A Randomized, Double‑blind, Non‑inferiority Trial.","authors":"Wenhui Tao, Jinfeng Bao, Haifeng Cao, Yifei Dong, Quanlong Fang, Meng Jiang, YuLe Wu, Jie Song, Yufang Xie, Xin Wang, Wensheng He, Ye Zhang, Xianwen Hu","doi":"10.2147/DDDT.S598964","DOIUrl":"https://doi.org/10.2147/DDDT.S598964","url":null,"abstract":"<p><strong>Background: </strong>Norepinephrine (NE), a vasopressor commonly used during cesarean section, avoids the phenylephrine (PE)-induced decreases in heart rate and cardiac output. Conversely, PE reduces the incidence and severity of maternal shivering and hypothermia during cesarean section. Therefore, before recommending NE as a complete replacement for PE, their effects on maternal core temperature must be compared. This study aimed to determine whether prophylactic infusion of NE is non-inferior to PE in maintaining maternal core temperature.</p><p><strong>Materials and methods: </strong>One hundred and forty eligible women scheduled for cesarean section under spinal or combined spinal-epidural anaesthesia were randomly assigned to either the NE or PE group. All participants, caregivers, and outcome assessors were blinded. NE (8 μg/mL) or PE (100 μg/mL) was administered intravenously at a fixed rate of 15 mL/h (equivalent to NE 2 μg/min or PE 25 μg/min), starting concurrently with the subarachnoid injection, and continuing until the end of surgery. The primary outcome was postoperative maternal core temperature, with a non-inferiority margin set at 0.2°C.</p><p><strong>Results: </strong>Postoperative maternal core temperature was non-inferior in the NE group (mean, 36.35°C; 95% confidence interval [CI], 36.28-36.42) compared to the PE group (mean, 36.41°C; 95% CI, 36.34-36.49). The mean difference between the two groups was -0.06°C (95% CI, - 0.16 to 0.04), meeting the criterion for non-inferiority (one-sided <i>p</i> <b>=</b> 0.008). The incidence of bradycardia was significantly lower in the NE group than in the PE group (7.4% vs. 33.8%; <i>p</i> < 0.001). No significant differences were found between the groups in the incidence or severity of shivering, the incidence of hypothermia, or the thermal comfort score.</p><p><strong>Conclusion: </strong>NE was not inferior to PE regarding its effect on maternal core temperature, providing a rationale for its use during cesarean sections.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"598964"},"PeriodicalIF":5.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}