Frontiers in Pharmacology最新文献

{"title":"Dysregulated bile acid metabolism drives lipid peroxidation and ferroptosis in NAFLD: therapeutic potential for traditional Chinese medicine.","authors":"Jing Liu, Fuxing Li, Qianru Zeng, Wenxiao Hu, Le Yang, Shengping Luo, Dingxiang Li, Yihui Deng","doi":"10.3389/fphar.2025.1669805","DOIUrl":"https://doi.org/10.3389/fphar.2025.1669805","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD), characterized by abnormal lipid accumulation in hepatocytes, is prevalent in conditions such as type 2 diabetes mellitus and obesity, which are associated with dysregulated glucose and lipid metabolism. Bile acids (BAs) are critical regulators of lipid and glucose homeostasis. Emerging research suggests that disturbances in BA metabolism not only exacerbate metabolic imbalance but also promote ferroptosis via lipid peroxidation. This review differs by systematically linking BA regulation, ferroptosis, and TCM, highlighting the multi-component and multi-target advantages of TCM in preventing and treating NAFLD. We summarize the mechanisms by which BAs regulate hepatic lipid synthesis and oxidation, and how lipid peroxidation connects to ferroptosis through glutathione/glutathione disulfide (GSH/GSSG) and reactive oxygen species (ROS). Finally, we review studies on TCM modulation of BA metabolism and ferroptosis to improve lipid peroxidation and metabolic disorders, providing timely insights into innovative therapeutic strategies for NAFLD.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1669805"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232031","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":"Higher prevalence of <i>NUDT15</i> rs116855232 compared to <i>TPMT</i> rs1142345 in a Chinese cohort and its implications for thiopurine therapy.","authors":"Chenyu Zhao, Hui Huang","doi":"10.3389/fphar.2025.1660719","DOIUrl":"https://doi.org/10.3389/fphar.2025.1660719","url":null,"abstract":"<p><strong>Background: </strong>Thiopurine drugs are widely used as immunosuppressants and chemotherapeutic agents in clinical practice, but their adverse effects significantly limit their clinical application. <i>TPMT</i> c.719A>G (rs1142345) and <i>NUDT15</i> c.415C>T (rs116855232) are the most common genetic polymorphisms influencing thiopurine drug toxicity, with notable differences in allele frequencies across diverse populations. However, there remains a paucity of research on the <i>NUDT15</i> c.415C>T polymorphism in the Chinese population.</p><p><strong>Methods: </strong>This study enrolled 571 Chinese patients. DNA samples were isolated, and polymerase chain reaction (PCR) was performed to amplify the <i>TPMT</i> c.719A>G and <i>NUDT15</i> c.415C>T in each sample. PCR products were genotyped via Sanger sequencing to identify the allelic frequencies of these polymorphisms. Additionally, we compared the detection rate of <i>NUDT15</i> c.415C>T and <i>TPMT</i> c.719A>G for thiopurine drug toxicity in the cohort.</p><p><strong>Results: </strong>The minor allele frequencies of <i>NUDT15</i> c.415C>T and <i>TPMT</i> c.719A>G were determined to be 12.52% and 2.36%, respectively. The detection rate of the <i>NUDT15</i> c.415C>T polymorphism was significantly higher than that of <i>TPMT</i> c.719A>G (23.47% vs. 4.55%, P < 0.001).</p><p><strong>Conclusion: </strong><i>NUDT15</i> c.415C>T yielded a higher carrier rate than <i>TPMT</i> c.719A>G in this cohort. And broader panels could shift absolute yields. These findings highlight the critical role of <i>NUDT15</i> c.415C>T genotyping in guiding precision therapy with thiopurine drugs.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1660719"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232100","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":"Shufeng Jiedu Capsules for treating wind-heat syndrome respiratory diseases: a systematic review and meta-analysis.","authors":"Jia-Min Liu, Lu Wang, Gui-Xiang Zhao, Hai-Long Zhang","doi":"10.3389/fphar.2025.1602563","DOIUrl":"https://doi.org/10.3389/fphar.2025.1602563","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This study systematically evaluates the efficacy and safety of Shufeng Jiedu Capsules in treating respiratory diseases with wind-heat syndrome patterns, providing clinical guidance and a reference for developing new \"syndrome-dominating disease management\" medications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search of CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Embase, Web of Science, and trial registries identified randomized controlled trials (RCTs) assessing Shufeng Jiedu Capsules for wind-heat syndrome respiratory diseases (from inception to December 2024). Two researchers independently screened studies and extracted data using predefined criteria. Methodological quality was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 and Stata 18 were used for data analysis, and evidence quality was graded using the GRADE system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-five RCTs involving 2681 patients were included, with 1339 in the experimental group and 1342 in the control group. The GRADE assessment indicated predominantly low or very low evidence certainty, mainly due to methodological flaws such as unclear allocation concealment, lack of blinding, and absence of protocol registration, which increased the risk of bias. Meta-analysis showed that Shufeng Jiedu Capsule combined with conventional biomedical therapy outperformed biomedical therapy alone. It improved the effective rate of traditional Chinese medicine syndromes (risk ratio [RR] = 1.17, 95% CI 1.10 to 1.24, &lt;i&gt;P&lt;/i&gt; &lt; 0.00001) and shortened the resolution time of cough (mean difference [MD] = -0.97, 95% CI -1.09 to -0.85, &lt;i&gt;P&lt;/i&gt; &lt; 0.00001) and phlegm (MD = -0.48, 95% CI -0.96 to -0.17, &lt;i&gt;P&lt;/i&gt; = 0.002). These outcomes were supported by high-quality GRADE evidence. Moderate-quality evidence supported improvements in imaging absorption rates (RR = 1.15, 95% CI 1.06 to 1.25, &lt;i&gt;P&lt;/i&gt; = 0.0009) and shorter resolution time for pulmonary rales (MD = -1.48, 95% CI -2.86 to -0.10, &lt;i&gt;P&lt;/i&gt; = 0.04). In contrast, apparent benefits in the clinical effective rate (RR = 1.16, 95% CI 1.12 to 1.19, &lt;i&gt;P&lt;/i&gt; &lt; 0.00001), fever resolution time (MD = -1.31, 95% CI -2.07 to -0.55, &lt;i&gt;P&lt;/i&gt; = 0.0007), C-reactive protein levels (standardized MD [SMD] = -0.99, 95% CI -1.55 to -0.43, &lt;i&gt;P&lt;/i&gt; = 0.0005), and procalcitonin levels (SMD = -2.06, 95% CI -3.62 to -0.49, &lt;i&gt;P&lt;/i&gt; = 0.01) were based on low or very low certainty evidence. These results should be interpreted cautiously and require confirmation in rigorously designed trials. There was no significant difference in the incidence of adverse events between groups (RR = 0.88, 95% CI 0.34 to 2.31, &lt;i&gt;P&lt;/i&gt; = 0.80). The adverse events were minor and controllable, and no serious adverse events were reported.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Shufeng Jiedu Capsule combined with biomedicine may offer advantages in treating respiratory diseases with wind-heat syndrome. The adverse events were minor and contro","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1602563"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232271","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":"Licochalcone D reduces H₂O₂-induced SH-SY5Y cell neurotoxicity by regulating reactive oxygen species.","authors":"Ah-Won Kwak, Seungmin Park, Ha-Na Oh, Jung-Hyun Shim, Goo Yoon, Woo-Keun Kim","doi":"10.3389/fphar.2025.1573882","DOIUrl":"https://doi.org/10.3389/fphar.2025.1573882","url":null,"abstract":"<p><p>Oxidative stress, one of the primary pathogenic factors in neurodegenerative diseases, plays a key role in neuronal damage via various apoptotic mechanisms. Using natural antioxidants to counteract oxidative stress may be a useful approach to slow the progression of neurodegenerative diseases. Licochalcone D (LCD), a root extract of <i>Glycyrrhiza inflata</i>, has various pharmacological activities; nonetheless, its neuroprotective effects and cellular mechanisms against oxidative damage in neuronal cells remain to be elucidated. To address this, we examined the neuroprotective effects and mechanisms of LCD in H₂O₂-induced cytotoxicity and neurotoxicity in the SH-SY5Y human neuroblastoma cell line. SH-SY5Y human neuroblastoma cells were differentiated using retinoic acid and subsequently treated with LCD and H₂O₂. Cell viability and cytotoxicity were evaluated using cell counting kit-8 and lactate dehydrogenase assays, respectively. Intracellular reactive oxygen species levels were quantified using 2',7'-dichlorofluorescein diacetate, while mitochondrial membrane potential was assessed using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazol-carbocyanine iodide dye. Gene expression analysis was performed by real-time qPCR, and neurite outgrowth was examined using high-content imaging. Protein expression levels were determined by Western blotting. All experiments were conducted in triplicate, and statistical analyses were performed to determine the significance of the results. LCD improved cell viability, reduced reactive oxygen species and lactate dehydrogenase levels, and protected SH-SY5Y cells from oxidative stress. High-content screening confirmed that LCD rescued the oxidative stress-induced inhibition of neurite outgrowth. LCD upregulated the mRNA expression of the neurodevelopmental genes <i>βIII-tubulin</i>, <i>GAP43</i>, <i>Nestin</i>, and <i>MAP2</i>. Mechanistically, LCD reduced p-p38 MAPK protein expression and inhibited H₂O₂-induced cell death by regulating the expression of apoptosis-related proteins. These findings confirm that LCD protects against H₂O₂-induced cytotoxicity, neurotoxicity, and p38 MAPK pathway-related apoptosis by mitigating reactive oxygen species production.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1573882"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232209","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":"<i>DPYD</i>-guided fluoropyrimidine dose adjustment in colorectal cancer <i>DPYD</i> carriers: start slower to finish stronger.","authors":"Rocío Rosas-Alonso, Nuria Rodríguez Salas, Pablo Perez Wert, Angela Hoyo, Susana Martin-López, Daniel Martínez-Pérez, Iciar Ruiz-Gutiérrez, Diego Jiménez-Bou, Jesús Peña, Pedro Arias, Ana Custodio, Itsaso Losantos-García, Alberto M Borobia, Jaime Feliu, Ismael Ghanem","doi":"10.3389/fphar.2025.1645188","DOIUrl":"https://doi.org/10.3389/fphar.2025.1645188","url":null,"abstract":"<p><strong>Introduction: </strong>Fluoropyrimidines (FP) are the mainstay of colorectal cancer (CRC) treatment, but can cause severe toxicity in up to 40% of patients. Variants in the <i>DPYD</i> gene are associated with these adverse events. A <i>DPYD</i>-guide dose adjustment is now recommended in Europe. This ambispective study aims to analyze the FP-related severe toxicity and the FP dose adjustment in heterozygous <i>DPYD</i> variant carriers with colorectal cancer, comparing a <i>DPYD</i>-guided FP dose adjustment (DA) approach to the non-<i>DPYD</i>-guided FP dose adjustment (NDA).</p><p><strong>Methods: </strong>1.279 <i>DPYD</i> genotyping reports were issued. Sixty patients were identified with <i>DPYD</i> variants. Twenty-five CRC patients (17 in the DA cohort and 8 in the NDA cohort) were included in the analysis. Thirty-five patients were excluded from the analysis because they did not satisfy any of the study's inclusion criteria. Reasons for exclusion included having a diagnosis other than colorectal cancer, not receiving fluoropyrimidine treatment, participation in a clinical trial, or insufficient follow-up.</p><p><strong>Results: </strong>Of the twenty-five patients included, sixteen patients (94%) started with a 50% FP dose reduction in the DA cohort while 7 out of 8 patients (87%) in the NDA cohort received 100% of dose in cycle 1. In the DA cohort, 12% of patients experienced severe fluoropyrimidines-related adverse events, compared to 50% in the NDA cohort (OR = 0.13; 95%CI: 0.01-0.93; p = 0.05). FP discontinuation due to severe toxicity occurred in 6% of patients in the DA cohort versus 50% in the NDA cohort (OR = 0.06; 95%CI: 0.003-0.55, p = 0.02).</p><p><strong>Discussion: </strong>These findings suggest that <i>DPYD</i>-guided dose adjustment significantly reduces both the incidence of severe toxicity and the rate of treatment discontinuation in CRC patients. Initiating treatment with a 50% FP reduction allows for dose escalation in patients who exhibit good tolerance and avoid the discontinuation for those patients intolerant to higher doses thereby improving overall treatment adherence and completion.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1645188"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232057","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":"Multifunctional PLGA nanosystems: enabling integrated diagnostic and therapeutic strategies.","authors":"Yue Li, Tao Tao, Yao Xiong, Weiyu Guo, Yangbiao Liang","doi":"10.3389/fphar.2025.1670397","DOIUrl":"https://doi.org/10.3389/fphar.2025.1670397","url":null,"abstract":"<p><p>In the past decades, biodegradable polymers have been widely used in pharmaceutical and medical engineering materials. Poly (lactic-co-glycolic acid) (PLGA) copolymer, renowned for its exceptional biocompatibility, inherent non-toxicity, and superior encapsulation and film-forming capabilities, has been widely acknowledged as one of the foremost candidate materials among next-generation biodegradable polymers with remarkable application potential. PLGA nanoparticles exhibit demonstrated versatility in accommodating hydrophobic or hydrophilic substances, which can be either encapsulated within their core matrix or adsorbed onto the surface. This includes chemical drugs, nucleic acids, peptides, and proteins. Upon entering the systemic circulation, the size-tunable characteristics of PLGA nanoparticles synergize with surface ligand-receptor interactions to confer dual-targeting capabilities: passive targeting through enhanced permeability and retention (EPR) effects, and active targeting <i>via</i> specific molecular recognition at pathological sites. Moreover, the integration of multimodal imaging capabilities into PLGA-based nanoparticles enables <i>in vivo</i> imaging-guided drug delivery, which paves the way for more precise and enhanced approaches to disease diagnosis and therapeutic intervention. This review systematically examines the fabrication strategies, structural variants of PLGA-based nanostructures, and their applications in both diagnostic and therapeutic domains of biomedicine.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1670397"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232216","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":"Severe skin toxicity and early progression following neoadjuvant ensartinib and surgery in anaplastic lymphoma kinase-positive locally advanced lung cancer: a case report.","authors":"Hongming Wang, Shiyan Li, Zhijun Wu, Wei Xu, Nuoni Wang, Zemin Xiao","doi":"10.3389/fphar.2025.1673086","DOIUrl":"https://doi.org/10.3389/fphar.2025.1673086","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic lymphoma kinase (ALK) fusion mutations exhibit exceptional sensitivity to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). Ensartinib, a second-generation ALK-TKI, represents a promising therapeutic option for ALK mutation-associated NSCLC; however, its clinical application in perioperative therapy remains to be elucidated.</p><p><strong>Case description: </strong>We report the case of a 45-year-old female diagnosed with stage IIIA (cT2N2M0, AJCC eighth edition) adenocarcinoma of the right lung harboring an EML4-ALK fusion (E6:A20) and a TP53 mutation. Following 3-month neoadjuvant therapy with ensartinib, surgical conversion from R(un) to R0 resection was achieved, accompanied by histopathological assessment and confirmation of a major pathological response (MPR) (<10% viable tumor cells) and negative postoperative molecular residual disease (MRD) surveillance. Despite effective neoadjuvant targeted therapy and the absence of significant adverse events, the patient experienced drug-refractory grade 3 cutaneous toxicity (CTCAE v5.0) 4 weeks after surgery and was subsequently found to have a T12 vertebral metastasis on 3-month surveillance imaging. After multidisciplinary evaluation and considering the patient's refusal to undergo local therapies, treatment was switched to lorlatinib. The patient subsequently experienced complete resolution of skin toxicity, sustained disease control, and a significantly improved quality of life.</p><p><strong>Conclusion: </strong>This case report describes a patient with an MPR subsequent to neoadjuvant ensartinib, who nonetheless developed early postoperative progression. Our case cautions that although MPR and MRD negativity can strongly predict lower recurrence risk, these markers may not universally guarantee long-term remission in every individual. The case underscores the need for continued vigilance and individualized surveillance strategies even once favorable pathological responses are achieved. Additionally, the perioperative evolution of skin toxicity highlights the importance of continuous adverse event monitoring and management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1673086"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232267","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":"Drug-induced agranulocytosis: a disproportionality analysis and umbrella review.","authors":"Yajie Lu, Bin Wu, Kunyu Li, Zhonglin Liu, Yuxi Chen, Ting Xu","doi":"10.3389/fphar.2025.1641747","DOIUrl":"10.3389/fphar.2025.1641747","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced agranulocytosis (DIA) is a rare but life-threatening hematologic disorder that demands increased clinical and research attention. This study aimed to provide the current overview of DIA for clinical guidance.</p><p><strong>Methods: </strong>Using real-world data from FDA Adverse Event Reporting System (FAERS), we performed a disproportionality analysis to identify the drugs associated with agranulocytosis, employing the information component and reporting odds ratio algorithms. Logistic analysis was conducted to explore the confounding factors of DIA. Time-to-onset analysis was implemented to compare the adverse event onset time among different drugs. To comprehensively supplement and corroborate our disproportionality findings, we further conducted an umbrella review of systematic reviews (SRs). Five electronic databases were searched with SRs addressing DIA as an included adverse event. Two independent reviewers performed literature screening, data extraction, and quality assessment according to the preferred reporting items for systematic reviews and meta-analysis statement. The results of the included SRs were synthesized using qualitative analysis.</p><p><strong>Results: </strong>The disproportionality analysis revealed that most identified DIA signals were for anticancer drugs. The top-five drugs with DIA signals by case number were methotrexate (6,462 cases), lenalidomide (5,722 cases), rituximab (5,691 cases), doxorubicin (4,391 cases), and carboplatin (4,371 cases). High-risk drugs (e.g., deferiprone), old age, and abnormal weight were strongly associated with DIA based on multivariate logistic regression. Time-to-onset analysis showed that clozapine has the longest median of onset time (1,121.3 days), while azithromycin has the shortest time (8.1 days). The umbrella review included seven systematic reviews, with five focusing on anticancer therapy. Their findings on DIA-associated drugs, including protein kinase inhibitors and immune checkpoint inhibitors, were consistent with those from the disproportionality analysis. Antibiotics, antithyroid drugs, and psychotropic drugs were also identified as causative drugs of DIA.</p><p><strong>Conclusion: </strong>This study systematically reviewed the FAERS database and existing literature on DIA to identify a spectrum of associated drugs. Anticancer drugs were predominant, with targeted therapies comprising a large proportion, while non-chemotherapy drugs were also identified as suspect drugs. These findings underscored the need for heightened clinical vigilance toward suspected drugs and highlighted the importance of future efforts to validate high-risk mechanisms and explore DIA monitoring strategies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1641747"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211995","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":"Esketamine versus fentanyl as adjuncts to hepatic hilar nerve block for ambulatory percutaneous liver tumor ablation focusing on respiratory safety: protocol for a randomized controlled trial.","authors":"Xiao Wang, Lijuan Yan, Jiaying Cai, Jianfei Wei, Zuobing Zhang, Bin Yang","doi":"10.3389/fphar.2025.1644029","DOIUrl":"10.3389/fphar.2025.1644029","url":null,"abstract":"<p><strong>Background: </strong>Opioid-induced respiratory depression (OIRD) is a critical safety concern during ambulatory percutaneous liver tumor thermal ablation. Esketamine has been shown to offer a promising opioid-sparing alternative with the potential to provide respiratory stability benefits. We hypothesize that hepatic hilar nerve block (HHNB) combined with esketamine will reduce the incidence of respiratory depression when compared to HHNB in conjunction with fentanyl in this particular context.</p><p><strong>Methods: </strong>This single-center, prospective, double-blind, randomized controlled trial (RCT) will enroll patients undergoing ambulatory ultrasound-guided percutaneous liver thermal ablation. Patients will be randomly assigned to receive either intravenous esketamine 0.37 mg kg^-1 (Intervention group) or intravenous fentanyl 1 μg·kg^- (Control group). All subjects will receive a standardized premedication consisting of midazolam 0.03 mg kg^-1 IV, followed by ultrasound-guided HHNB.</p><p><strong>Results and analysis: </strong>The primary outcome is the incidence of respiratory depression, defined as SpO₂ <90% or EtCO₂ >55 mmHg. Secondary outcomes include the rate of anesthesia success, postoperative pain scores, and the consumption of remedial analgesia at 2, 6, and 24 h post-surgery. Additionally, satisfaction scores from both the sonographer and the patient are considered, along with any adverse events that may occur. The statistical analysis will utilize appropriate parametric/non-parametric tests for continuous data and chi-square/Fisher's exact tests for categorical data (significance p < 0.05), using SPSS (v20.0) and R (v4.4.3; R Foundation) within the RStudio environment (v2024.12.1 + 563).</p><p><strong>Conclusion and discussion: </strong>This trial aims to provide Level I evidence comparing the respiratory depression risk between esketamine-based and fentanyl-based analgesia during HHNB-guided liver ablation. Should esketamine prove to be demonstrably superior in terms of respiratory safety, HHNB-esketamine has the potential to be a viable treatment option.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1644029"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212192","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":"Digital multicriteria evaluation of negotiated medicines using Chinese mini-HTA: application of structured methodologies in assessing once-weekly GLP-1 RAs for improved clinical decision-making.","authors":"Xiao Li, Zhihong Qiu, Chaojun Xue, Xiaokai Ren, Zhanjun Dong","doi":"10.3389/fphar.2025.1588056","DOIUrl":"10.3389/fphar.2025.1588056","url":null,"abstract":"<p><strong>Background: </strong>Systematic and transparent evaluation of medicines remains a global challenge. In China, structured frameworks for clinical value assessment are underutilized despite improved access to negotiated medicines. Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were selected as a representative case for their reimbursement status and clinical and economic relevance. This study applied a quantitative mini-health (mini-HTA) technology assessment to support rational drug selection.¹.</p><p><strong>Methods: </strong>A structured, three-stage methodology was employed to evaluate four once-weekly GLP-1 RAs. First, a weighted scoring system was established for five dimensions-pharmaceutical properties, effectiveness, safety, economy, and other considerations-based on expert consensus using the Quantitative Record Form for Drug Evaluation and Selection in Medical Institutions. Second, evidence for each dimension was systematically collected using a PICO-based search strategy across guideline databases, literature sources, and official documents. Third, each drug was quantitatively scored in each dimension according to predefined criteria and expert-assigned weights; the total scores were used to classify drugs into recommendation levels (\"strongly recommended,\" \"weakly recommended,\" or \"not recommended\") to guide evidence-based selection in medical institutions.</p><p><strong>Results: </strong>Semaglutide (77.8) and dulaglutide (76.3) achieved the highest totals, driven by superior HbA1c reduction and proven cardiovascular benefit, and were strongly recommended. Exenatide microspheres scored 70.2, mainly owing to favourable acquisition cost, and was also strongly recommended. PEG loxenatide scored 62.9, limited by narrower reimbursement coverage and lower international uptake, and received a weak recommendation. Safety profiles were comparable across agents.</p><p><strong>Conclusion: </strong>The study demonstrates that a structured, expert-informed mini-HTA framework can be feasibly applied for quantitative evaluation and selection of once-weekly GLP-1 RAs in Chinese medical institutions. Key differentiators among agents were efficacy (notably cardiovascular benefit) and economic/policy factors, while safety differences were minimal. This replicable approach improves transparency, consistency, and evidence-based decision-making in clinical pharmacy and institutional formulary management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1588056"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212185","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}