Drug Design, Development and Therapy最新文献

{"title":"Association of Dexmedetomidine Exposure with Long-Term Mortality in Patients with Dialysis-Requiring Acute Kidney Injury: A Propensity Score-Matched Retrospective Cohort Study.","authors":"Kuo-Chuan Hung, Li-Chen Chang, Ying-Jen Chang, Yi-Chen Lai, Chien-Ming Lin, I-Wen Chen","doi":"10.2147/DDDT.S598443","DOIUrl":"https://doi.org/10.2147/DDDT.S598443","url":null,"abstract":"<p><strong>Purpose: </strong>Patients surviving dialysis-requiring acute kidney injury (AKI-D) have high long-term mortality, yet effective pharmacologic interventions are limited. Dexmedetomidine (DEX) has demonstrated organ-protective properties, but its association with long-term outcomes in patients with AKI-D remains unclear.</p><p><strong>Methods: </strong>We conducted a propensity score-matched retrospective cohort study using the TriNetX database. Adults with AKI-D during intensive care unit (ICU) stay were classified into DEX exposure (within 1 month after AKI) or control groups. A 90-day landmark design was applied to reduce immortal time bias and reverse causation, with follow-up initiated thereafter. The primary outcome was 2-year mortality; secondary outcomes included end-stage renal disease (ESRD), eGFR decline <30 mL/min/1.73m², ICU readmission, pneumonia, and sepsis.</p><p><strong>Results: </strong>After matching, 6,354 patients remained per group. DEX exposure was associated with lower 2-year mortality (10.0% vs 14.6%; Hazard ratio[HR] 0.64, 95% CI 0.58-0.71, p<0.001), reduced ESRD progression (14.1% vs 16.2%; HR 0.80, 95% CI 0.73-0.88, p<0.001), and lower eGFR decline (19.4% vs 21.8%; HR 0.83, 95% CI 0.77-0.90, p<0.001). No significant differences were observed for ICU readmission (HR 0.97, 95% CI 0.89-1.06, p=0.55), pneumonia (HR 1.05, 95% CI 0.94-1.16, p=0.414), or sepsis (HR 1.07, 95% CI 0.97-1.18, p=0.199). The mortality benefit persisted during 2-5 year follow-up (HR 0.81, 95% CI 0.69-0.96, p=0.012). Sensitivity analyses using contemporary data, medical center restriction, and a benzodiazepine active comparator, along with subgroup analyses by age and sex, demonstrated consistent associations. Early DEX initiation (within 1 week) showed stronger associations with favorable outcomes compared with delayed exposure (1-4 weeks).</p><p><strong>Conclusion: </strong>DEX exposure following AKI-D in critical care settings was associated with reduced long-term mortality and lower risks of renal deterioration. These findings provide a strong rationale for prospective randomized controlled trials to evaluate the causal effects of dexmedetomidine in this high-risk population.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"598443"},"PeriodicalIF":5.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812384","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":"Comparison of the Effect of Different Administration Sequence of Propofol and Remifentanil on Sedation/Anesthesia During Gastroscopy in Obese Patients.","authors":"Jieke Tang, Zhao Zhong, Hongxue Jiang, Jinying Li, Jingwen Liu, Shan'e Duan, Shuqing Liang, Zhenpeng Wu, Mengxia Wang, Donghua Hu","doi":"10.2147/DDDT.S594697","DOIUrl":"https://doi.org/10.2147/DDDT.S594697","url":null,"abstract":"<p><strong>Purpose: </strong>Obesity is associated with an elevated risk of hypoxemia during endoscopic procedures performed under anesthesia. However, whether the sequence of drug administration - specifically the order of propofol and remifentanil - affects the incidence of hypoxemia remains unclear. This study was designed to evaluate whether a novel administration sequence, in which propofol precedes remifentanil, can decrease the incidence of hypoxemia in obese individuals during endoscopy.</p><p><strong>Patients and methods: </strong>This prospective, single center, randomized controlled clinical trial recruited 296 obese patients scheduled for sedative/anesthesia gastroscopy prior to bariatric surgery. Patients were randomly assigned to either novel administration sequence with propofol-remifentanil (P-R) group or conventional administration of remifentanil-propofol (R-P) group. The primary outcome was the incidence of hypoxemia. Secondary outcomes included the lowest peripheral oxygen saturation (L-SpO₂) during the procedure, hemodynamic parameters at six time points, and additional perioperative events.</p><p><strong>Results: </strong>284 patients were included in the analysis with 142 in each group. Hypoxemia occurred in 22 patients (15.5%) in the P-R group, and 42 patients (29.6%) in the R-P group (Relative Risk [RR], 1.44; 95% confidence interval [CI], 1.13 to 1.79; P = 0.007). The L-SpO₂ during the procedure was significantly higher in the P-R group than in the R-P group (median [interquartile range, IQR], 94.0% [91.0 to 97.0] vs 93.0% [87.7 to 95.0]; P < 0.001). The P-R sequence technique was also associated with more stable hemodynamic profiles, shorter induction time, the start of drug administration to scope insertion and recovery time, improved patient's satisfaction. Particularly, minimal respiratory depression was observed in subgroups such as body mass index (BMI) ≥ 40 kg/m².</p><p><strong>Conclusion: </strong>Propofol first and followed by remifentanil administration sequence significantly decreased the incidence of hypoxemia and increased the L-SpO₂ in obese patients for their anesthesia/sedation gastroscopy.</p><p><strong>Clinical trial registration: </strong>ChiCTR2400084998.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"594697"},"PeriodicalIF":5.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812431","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":"Beyond Symptom Suppression: The Multitargeted Reversal of Chronic Pain by Maresin1.","authors":"Fuquan Wang, Yang Yang, Wen Wang, Qing Shi, Bifa Fan","doi":"10.2147/DDDT.S585597","DOIUrl":"https://doi.org/10.2147/DDDT.S585597","url":null,"abstract":"<p><p>The transition from acute inflammation to chronic pain represents a significant clinical challenge, often driven by a failure of endogenous resolution programs. Specialized pro-resolving mediators (SPMs), derived from polyunsaturated fatty acids, are crucial for actively terminating inflammation and restoring tissue homeostasis. Maresin 1 (MaR1), a prototypical SPM biosynthesized from docosahexaenoic acid (DHA), has emerged as a powerful modulator of pain. This review comprehensively synthesizes the current preclinical evidence, primarily derived from preclinical animal models, detailing the analgesic effects of MaR1 across a spectrum of pain models, including inflammatory, neuropathic, postoperative, osteoarthritis-related pain, etc. We dissect the multifaceted mechanisms underlying its efficacy, which extend beyond simple anti-inflammation. MaR1 exerts its effects by: (1) attenuating neuroinflammation including the suppression of glial (microglia and astrocyte) activation and reprogramming macrophage phenotypes; (2) directly modulating neuronal function by inhibiting nociceptive ion channels (e.g. TRPV1) and reversing central synaptic plasticity; and (3) promoting robust tissue repair, including peripheral nerve regeneration. These actions are mediated through potential specific receptors, notably G-protein-coupled receptor 37-like 1 (GPR37L1) on glial cells and retinoic acid-related orphan receptor α (RORA) on neurons. While MaR1 demonstrates significant therapeutic potential, challenges related to its pharmacokinetic instability and observed sex-dependent analgesic effects must be addressed for successful clinical translation. This review provides a comprehensive mechanistic framework supporting MaR1 as a next-generation therapeutic candidate for pain management, and outlines the core research directions to overcome key translational barriers for MaR1-based therapies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"585597"},"PeriodicalIF":5.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812424","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":"Atorvastatin Attenuates Vancomycin-Induced Nephrotoxicity via PPARα-Associated Regulation of SLC Transporters.","authors":"Kexin Lin, Tingyu Li, Xiaorui Kong, Tong Li, Yawen Zuo, Deshi Dong, Shilei Yang, Yanna Zhu","doi":"10.2147/DDDT.S571916","DOIUrl":"https://doi.org/10.2147/DDDT.S571916","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin (VCM) is a first-line antibiotic for severe infections, but its clinical utility is limited by nephrotoxicity. Atorvastatin (ATO), a widely used lipid-lowering agent, has shown renoprotective potential. However, whether ATO mitigates vancomycin-induced nephrotoxicity (VIN) remains unclear.</p><p><strong>Methods: </strong>We investigated the effects of ATO on VIN using male C57BL/6 mice and HK-2 cells. Renal function, histopathology, inflammation, oxidative stress, and apoptosis were assessed. Transcriptome sequencing of renal tissue was performed to explore underlying mechanisms.</p><p><strong>Results: </strong>In vivo, ATO significantly improved VCM-induced renal dysfunction and renal pathological damage in mice. It significantly suppressed the release of inflammatory cytokines, enhanced renal antioxidant capacity, and reduced renal cell apoptosis. In vitro, ATO significantly increased HK-2 cell viability while reducing inflammation, reactive oxygen species (ROS) production, and renal cell apoptosis. Transcriptomic analysis revealed that ATO modulated peroxisome proliferator-activated receptor α (PPARα) signaling activity, which was accompanied by upregulated expression of solute carrier (SLC) transporters.</p><p><strong>Conclusion: </strong>This preclinical study demonstrates for the first time that ATO attenuates VIN by a PPARα-associated signaling pathway that orchestrates the upregulation of SLC transporters (including OAT1, OAT3, OCT2, and MATE1) to promote the excretion of endogenous toxins, with concomitant integrated protective effects against inflammation, oxidative stress, and apoptosis. These findings identify a novel mechanism and potential therapeutic strategy for VIN.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"571916"},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812449","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":"Structure-Based Discovery of Glyoxalase-I Inhibitors: Evaluating the Role of Active Site Water Molecules.","authors":"Reema Anaam, Israa H Isawi, Qosay Al-Balas","doi":"10.2147/DDDT.S575242","DOIUrl":"https://doi.org/10.2147/DDDT.S575242","url":null,"abstract":"<p><strong>Background: </strong>Glyoxalase-I (GLO-I) is a zinc-dependent metalloenzyme and a promising target for anticancer drug discovery. It catalyzes the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis, a metabolic shift commonly observed in cancer cells. GLO-I overexpression in tumor cells promotes multidrug resistance and tumor progression. However, the role of conserved water molecules within the GLO-I active site remains insufficiently explored, and understanding their influence on ligand binding may improve structure-based inhibitor design.</p><p><strong>Purpose: </strong>This study aimed to identify potential GLO-I inhibitors by examining the effect of conserved active site water molecules on ligand binding and activity predictions using a structure-based drug design approach.</p><p><strong>Materials and methods: </strong>Three human GLO-I crystal structures were used to generate structure-based pharmacophore models under two conditions: with and without crystallographic active site water molecules. The models were applied to virtually screen the OTAVA Lead-Like library (commercial lead-like compound library). Molecular docking of the resulting hits was then performed under both hydration conditions to evaluate effects on ligand binding affinity and pose orientation. Top-ranked compounds were purchased and evaluated in vitro for GLO-I inhibition. The most active hit was further evaluated by 1000 ns molecular dynamics (MD) simulations (± crystallographic waters), including analysis of pose stability and binding-site water behavior.</p><p><strong>Results: </strong>Among the 22 compounds tested in vitro, five showed inhibitory activity, with IC₅₀ values ranging from 12.07 to 25.36 μM. The most potent compound (hit <b>19</b>) demonstrated an IC₅₀ of 12.07 ± 0.31 μM and 85.63% inhibition at 50 μM. Docking analysis indicated that including crystallographic water molecules often increased docking scores but could distort binding orientations, whereas docking without conserved active site water molecules more consistently produced plausible poses and better agreement with experimental activity trends.</p><p><strong>Conclusion: </strong>For GLO-I, docking without conserved active site water molecules provided more accurate results and may represent a more reliable approach for studying ligand binding and guiding inhibitor design.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"575242"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765357","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":"Perioperative Flurbiprofen Axetil Administration and Acute Kidney Injury After Non-Cardiac Surgery: A Retrospective Cohort Study.","authors":"Shuang Wang, Yu-Qi Zhong, Bing-Cheng Zhao, Xiao-Min Hou, Bin-Yan Yin, Ke-Xuan Liu, Hua-Min Liu","doi":"10.2147/DDDT.S597928","DOIUrl":"https://doi.org/10.2147/DDDT.S597928","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the impact of different timing of flurbiprofen axetil (FA) administration on postoperative acute kidney injury (AKI) and other adverse events in non-cardiac surgery patients.</p><p><strong>Patients and methods: </strong>This retrospective cohort study included 45,062 adult patients undergoing non-cardiac surgery from January 1, 2019, to October 31, 2023. Perioperative FA analgesia records were extracted from electronic medical records. The primary outcome was AKI within 7 days after surgery. Secondary outcomes included postoperative adverse cardiovascular events (ACE), postoperative length of stay (LOS), and in-hospital mortality.</p><p><strong>Results: </strong>The incidences of AKI, ACE, and mortality were 6.0% (2,683/45,062), 8.5% (3,809/45,062), and 0.1% (48/45,062), respectively. Intraoperative [odds ratio (OR), 0.71; 95% confidence interval (CI), 0.62-0.82] and postoperative (OR, 0.73; 95% CI, 0.66-0.79) FA administration was associated with lower odds of AKI compared with non-use. Compared to patients who did not receive FA analgesia at any point, those who received FA both during and post-surgery had a significantly lower odds of AKI (OR, 0.61; 95% CI, 0.51-0.73). Subgroup analysis indicated a greater reduction in AKI odds for intraoperative FA administration in patients with a high inflammatory status (OR and 95% CI: 0.58 [0.47-0.72] vs 0.84 [0.59-1.20], <i>P</i> for interaction = 0.010). Postoperative, but not intraoperative FA administration, was associated with a lower odds of ACE (OR, 0.85; 95% CI, 0.79-0.91), with this association was significant in patients without preoperative hypertension (OR and 95% CI: 0.81 [0.74-0.88] vs 0.96 [0.81-1.13], <i>P</i> for interaction<0.05). Accelerated failure time model showed that both intraoperative and postoperative FA use was inversely correlated with postoperative LOS.</p><p><strong>Conclusion: </strong>Perioperative FA analgesia was associated with a lower odds of postoperative AKI and shorter postoperative LOS, whereas only postoperative FA analgesia was linked to a lower odds of postoperative ACE.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"597928"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765381","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":"Biomarker Variants of Dopamine Receptor Genes Influence the Binding Interaction Between Dopamine Receptor and Risperidone.","authors":"Noor B Almandil, Sayed AbdulAzeez, Mohamed S Gomaa, Abdallah M Ibrahim, Sherlin John John, Selvaraj Prathas, Tharmathass Stalin Dhas, Jesu Francis Borgio","doi":"10.2147/DDDT.S587705","DOIUrl":"https://doi.org/10.2147/DDDT.S587705","url":null,"abstract":"<p><strong>Introduction: </strong>Risperidone is atypical antipsychotic medication commonly used to control behavioral symptoms in children with autism and widely considered a first-line treatment for acute and maintenance treatment of schizophrenia and bipolar mania. However, the response to risperidone is varied between patients due to genetic factors such as dopamine receptor genes.</p><p><strong>Methods: </strong>Using state-of-the-art tools, the current study designed to predict the most deleterious SNPs of the five (<i>DRD1, DRD2, DRD3, DRD4</i> and <i>DRD5</i>) dopamine receptors genes, and their impact on the function and structure of dopamine receptor protein and the binding with risperidone. In-silico tools such as SIFT, PolyPhen2, PANTHER, PROVEAN, SNPs & GO, CRAVAT-VEST score, Mutation Assessor, FannsDB-CONDEL score, predict SNP and SNAP2 were subjected to predicting the deleterious nature of 1581 non-synonymous SNPs (nsSNP) of dopamine receptors genes.</p><p><strong>Results: </strong>The analysis predicted the most deleterious nsSNPs in each dopamine receptor: rs759268810 in <i>DRD1</i>, rs866976053 in <i>DRD2</i>, rs1274871399 in <i>DRD3</i>, rs745604469 in <i>DRD4</i>, and rs778635010 in <i>DRD5</i>. Significant reduction in the binding free energy in the mutant (F198C: S score = -7.29 kcal/mol) in the D2 subtype of the dopamine receptor compared to the wild (F198: S score = -8.73 kcal/mol) at the interaction analysis with risperidone. Cumulative analysis of the interaction between risperidone and dopamine receptor protein revealed the rs866976053 as the most deleterious nsSNP among the 1581 nsSNPs of the dopamine receptor genes.</p><p><strong>Conclusion: </strong>The observation of the state-of-the-art tools-based analysis and observations of MD simulations prioritized the F198C of <i>DRD2</i> as a candidate variant for wet lab studies to find its impact on drug efficacy for managing autism, schizophrenia and bipolar mania.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"587705"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765560","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":"Optimized UPLC-MS/MS Method for the Simultaneous Quantification of Pazopanib and GSK-1268997 and Its Application to Drug-Drug Interaction Studies.","authors":"Lu Cao, Peiqi Wang, Ruibin Li, Haoxin Fu, Jun Wu, Hailun Xia, Saili Xie, Congcong Zeng","doi":"10.2147/DDDT.S589066","DOIUrl":"https://doi.org/10.2147/DDDT.S589066","url":null,"abstract":"<p><strong>Introduction: </strong>Pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), is approved for treating advanced renal cell carcinoma (RCC). However, pazopanib can cause hypertension, often necessitating co-administration with antihypertensives like nicardipine. Given their shared metabolic pathway via cytochrome P450 3A4 (CYP3A4), this study investigated their potential drug-drug interaction (DDI).</p><p><strong>Methods: </strong>An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of pazopanib and its metabolite, GSK-1268997. This method was applied to in vitro inhibition studies using rat liver microsomes (RLM) and human liver microsomes (HLM), as well as to an in vivo pharmacokinetic study in rats, to evaluate the impact of nicardipine on pazopanib metabolism.</p><p><strong>Results: </strong>The assay was linear over the concentration ranges of 20-60,000 ng/mL for pazopanib and 10-30,000 ng/mL for GSK-1268997. The intra- and inter-day precision (relative standard deviations, RSD%) for the analytes ranged from 1.5% to 14.5%, with accuracy (relative errors, RE%) within ± 10.2%. The method also demonstrated acceptable selectivity, stability, matrix effect, and recovery. In vitro, nicardipine inhibited the metabolism of pazopanib in both RLM and HLM. In rats, co-administration of nicardipine significantly increased pazopanib exposure. The AUC_(0-t) and AUC_(0-∞) of pazopanib were increased by 4.03- and 4.31-fold, respectively, while the maximum plasma concentration (C_max) was increased by 1.60-fold. Conversely, the plasma clearance (CLz/F) was decreased by 78.26%.</p><p><strong>Discussion: </strong>The findings demonstrated that nicardipine significantly inhibited the metabolism of pazopanib both in vitro and in vivo, leading to substantially increased systemic exposure of pazopanib. This clinically significant finding suggests that, when these two drugs are used in combination, plasma drug concentrations should be closely monitored and the need for dose adjustment should be considered.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"589066"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765365","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":"Feedback-Regulated versus Constant-Rate Sufentanil Patient-Controlled Analgesia for Postoperative Nausea and Vomiting After Laparoscopic Myomectomy: A Randomized Controlled Trial.","authors":"Qian Ma, Mingming Wang, Weiqiao Zhang, Linfang Chen, Xiaowen Guo, Zhong Mei, Ting Ma","doi":"10.2147/DDDT.S597391","DOIUrl":"https://doi.org/10.2147/DDDT.S597391","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) remains a common and distressing side effect of opioid-based patient-controlled analgesia (PCA). Although continuous background infusion stabilizes analgesia, it often induces excessive opioid exposure and related adverse events. This study evaluates a novel smart PCA system featuring feedback-regulated background infusion (FRBI) designed to dynamically adjust opioid delivery based on real-time pain feedback, aiming to reduce PONV without compromising analgesia.</p><p><strong>Methods: </strong>In this prospective, randomized, controlled, single-center trial, 132 patients undergoing laparoscopic myomectomy were assigned in a 1:1 parallel-group design to either constant-rate background infusion (CRBI) at 2 mL/h (Group A) or FRBI with adjustable rates of 1-4 mL/h (Group B). Both groups received a standardized sufentanil-flurbiprofen solution via PCA. The FRBI algorithm dynamically adjusted the infusion rate: a 20% increase was triggered by ≥2 bolus demands within 30 minutes, and a 20% decrease followed 4 consecutive demand-free hours. The primary outcome was the incidence of PONV (defined as nausea and/or vomiting) within 48 hours postoperatively. Secondary outcomes included pain scores (NRS), total opioid consumption, occurrence of other adverse events, and patient satisfaction.</p><p><strong>Results: </strong>The FRBI group demonstrated a significantly lower incidence of PONV (nausea and/or vomiting) compared to the CRBI group (41.7% vs 62.7%, risk difference: -21.0% [95% CI: -38.1% to -3.9%]; risk ratio: 0.66 [95% CI: 0.46 to 0.96], P = 0.022). Total sufentanil consumption was reduced by approximately 30% in the FRBI group (P < 0.01). Pain scores were comparable between groups at all time points. Patient satisfaction was significantly higher in the FRBI group (P < 0.01). No cases of respiratory depression were observed in either group.</p><p><strong>Conclusion: </strong>The feedback-regulated background infusion mode significantly reduces the incidence of PONV and total opioid consumption while maintaining effective analgesia in patients undergoing laparoscopic myomectomy. This strategy suggests a favorable safety profile in this specific surgical population and may represent a promising strategy for opioid-sparing analgesia. Further studies are needed to validate these findings in broader patient populations and to assess economic feasibility.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"597391"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765126","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":"Cellular and Molecular Mechanisms of Hyperglycemia-Induced Atherosclerosis and Intervention Strategies of Chinese Herbal Medicine.","authors":"Shengping Luo, Jiayu Zhu, Qianru Zeng, Le Yang, Jing Liu, Yihui Deng","doi":"10.2147/DDDT.S602453","DOIUrl":"https://doi.org/10.2147/DDDT.S602453","url":null,"abstract":"<p><p>Diabetes is a significant global public health issue, and atherosclerosis serves as the primary pathological basis for the occurrence and progression of cardiovascular and cerebrovascular events. Studies have shown that hyperglycemia can promote the occurrence and progression of atherosclerosis by damaging vascular endothelial cells, macrophages, and vascular smooth muscle cells. In recent years, Chinese herbal medicines and their active ingredients have demonstrated unique advantages in preventing and treating high-glucose-induced vascular cell damage. Their mechanisms of action primarily encompass two aspects: firstly, regulating blood glucose through multiple pathways such as modulating the insulin signaling pathway, enhancing peripheral glucose uptake and utilization, and delaying intestinal carbohydrate absorption; secondly, intervening in key pathological processes such as high-glucose-induced vascular cell inflammation, cell death, phenotypic transformation, and metabolic reprogramming. This, in turn, slows down the progression of diabetes-related atherosclerosis. This article systematically elucidates the molecular mechanisms underlying hyperglycemia-induced damage to vascular endothelial cells, macrophages, and vascular smooth muscle cells. It also summarizes the protective mechanisms of Chinese herbal medicine active ingredients (albiflorin, salvianolic acid B, scutellarin, vitexin, hydroxysafflor yellow A, ginsenoside Rb1, maslinic acid, paeonol, citronellal, matrine, Panax notoginseng saponins, astragalus polysaccharides, 6-gingerol, and sodium tanshinone IIA sulfonate) and traditional Chinese medicine compounds (buyang huanwu decoction, guanxining tablets, and fufang zhenzhu tiaozhi) against vascular endothelial cells, macrophages, and vascular smooth muscle cells. The aim is to provide a theoretical basis for the prevention and treatment of diabetes-related atherosclerosis, as well as the development of related therapeutic drugs.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"602453"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765635","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}