Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Efficacy of intravenous thrombolysis beyond 4.5 to 24 hours in patients with isolated posterior circulation acute ischemic stroke].","authors":"Jianwei Wang, Shenqiang Yan, Yuting Lang, Tingyu Jin, Huan Tang, Shuxia Qian, Han Yu, Min Lou, Hongfang Chen","doi":"10.3724/zdxbyxb-2025-0434","DOIUrl":"10.3724/zdxbyxb-2025-0434","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the functional outcomes and safety of intravenous thrombolysis (IVT) administered within the standard 4.5-hour time window versus an extended time window of >4.5-24 h after symptom onset in patients with isolated posterior circulation acute ischemic stroke (AIS).</p><p><strong>Methods: </strong>Data from patients with isolated posterior circulation AIS who received IVT between January 2017 and December 2024 were extracted from the Acute Stroke Patients for Stroke Management Quality Evaluation online database (CASE-Ⅱ, NCT04487340). Patients were categorized into the standard time window group (within 4.5-hour) and the extended time window group (>4.5-24 h). The primary outcome was 3-month functional independence (modified Rankin Scale score 0-2). Multivariate logistic regression and propensity score matching were used to compare outcomes. Interaction tests assessed the consistency of the time window effect across subgroups predefined by age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, presence of large vessel occlusion, thrombolytic agent, and trial of ORG 10172 in acute stroke treatment (TOAST) subtype.</p><p><strong>Results: </strong>Among 3508 included patients, 3147 were in the standard time window group and 361 in the extended time window group. The rate of 3-month functional independence did not significantly differ between the two groups (80.1% <i>vs</i>. 78.7%, adjusted OR=0.896, 95%CI: 0.655-1.226, <i>P</i>>0.05). This finding remained consistent after propensity score matching (adjusted OR=1.122, 95%CI: 0.724-1.738, <i>P</i>>0.05). In the entire cohort, each 30-minute delay in ONT was associated with a 2.6% decrease in the probability of functional independence (OR=0.974, 95%CI: 0.952-0.996, <i>P</i>=0.02). This negative association was significant only within the standard time window group (OR=0.934, 95%CI: 0.887-0.984, <i>P</i>=0.01). Subgroup analysis indicated that the standard time window group had a higher rate of functional independence than the extended time window group (both interactions <i>P</i><0.05) among patients with a baseline NIHSS score >5 or those with large vessel occlusion. No significant differences were observed in safety outcomes, including 24 h symptomatic intracranial hemorrhage, early neurological deterioration, and 3-month all-cause mortality.</p><p><strong>Conclusions: </strong>For patients with isolated posterior circulation AIS, IVT administered within >4.5-24 h after onset demonstrates effectiveness and safety comparable to treatment within the standard 4.5-hour time window.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"95-104"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Spatial omics in pulmonary fibrosis: advancing mechanistic insights and therapeutic strategies].","authors":"Yunpeng Peng, Yunyun Xie, Fan Yang, Xin Qiao, Yange Tian","doi":"10.3724/zdxbyxb-2025-0785","DOIUrl":"10.3724/zdxbyxb-2025-0785","url":null,"abstract":"<p><p>Pulmonary fibrosis, a group of chronic interstitial lung diseases charac-terized by persistent inflammation and aberrant deposition of fibrous connective tissue, poses a significant therapeutic challenge, with idiopathic pulmonary fibrosis (IPF) being its most representative and severe form. Spatially resolved omics technologies-encompassing spatial metabolomics, transcriptomics, and proteomics-have emerged as transformative tools that preserve the architectural context of tissues while enabling high-throughput, visualization-capable analysis of metabolites, genes, and proteins. Spatial metabolomics facilitates the visualization and intelligent annotation of metabolic landscapes; spatial transcriptomics deciphers regional heterogeneity and refines the molecular timeline of early disease events; and spatial proteomics elucidates protein interaction networks and uncovers novel drug-resistance mechanisms. Collectively, spatial omics provides unprece-dented insights into disease pathogenesis, offering a powerful framework for advancing precision diagnosis, identifying therapeutic targets, and guiding drug development. This article synthesizes recent progress in applying spatial omics to pulmonary fibrosis research, underscoring its potential to translate into more effective clinical strategies.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"154-162"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Efficacy and safety of mechanical thrombectomy beyond 24 to 72 hours in acute ischemic stroke patients with large vessel occlusion].","authors":"Xuanfei Jiang, Yi Chen, Haidi Jin, Xinlong Huo, Qing Lin, En Wang, Hanming Tu, Min Lou, Bing Zhang","doi":"10.3724/zdxbyxb-2025-0556","DOIUrl":"10.3724/zdxbyxb-2025-0556","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the efficacy and safety of mechanical thrombectomy performed beyond 24 hours from symptom onset in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO).</p><p><strong>Methods: </strong>In this retrospective cohort study, patients with LVO-related AIS who underwent mechanical thrombectomy within 72 hours of onset were enrolled from the Acute Stroke Patients for Stroke Management Quality Evaluation online database (CASE-Ⅱ, NCT04487340) between January 2017 and December 2024. Patients were stratified into beyond 24-hour thrombectomy group and within 24-hour thrombectomy group based on the time from onset to mechanical thrombectomy. Propensity score matching (PSM) was used to balance baseline characteristics between the two groups. Binary logistic regression and generalized linear models were employed to compare 3-month functional and safety outcomes between the groups. Sensitivity analyses were conducted separately in patients undergoing mechanical thrombectomy within the extended time window (6-24 hours) and in those receiving mechanical thrombectomy alone (without prior intravenous thrombolysis). Subgroup analyses were performed based on age, presence of atrial fibrillation, use of oral anticoagulants, pre-stroke modified Rankin Scale (mRS) score, baseline National Institutes of Health Stroke Scale (NIHSS) score, and occlusion site.</p><p><strong>Results: </strong>Of the 9121 patients included, 277 underwent mechanical thrombectomy beyond 24 hours and 8844 within 24 hours. After PSM, 534 patients were analyzed (267 per group). No significant difference was found in the rate of 3-month functional independence (mRS score 0-2) between the beyond 24-hour and within 24-hour thrombectomy groups, both before and after matching (OR=0.977, 95%CI: 0.753-1.268, <i>P</i>=0.861; OR=1.151, 95%CI: 0.712-1.549, <i>P</i>=0.804, respectively). The rates of 24-hour symptomatic intracranial hemorrhage, 24-hour parenchymal hemorrhage, and 3-month all-cause mortality also showed no significant differences between the two groups (all <i>P</i>>0.05). Sensitivity analyses among patients in the extended time window (6-24 hours) and those receiving mechanical thrombectomy alone yielded similar results, with no significant differences in functional or safety outcomes (all <i>P</i>>0.05). Subgroup analyses revealed no significant heterogeneity in the 3-month functional independence across various baseline characteristics (all <i>P</i>>0.05).</p><p><strong>Conclusions: </strong>For AIS patients with LVO, the efficacy and safety of mechanical thrombectomy performed beyond 24 hours appear comparable to those of mechanical thrombectomy performed within 24 hours.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"113-120"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Efficacy and safety of intravenous thrombolysis in patients with mild acute ischemic stroke].","authors":"Xiaorong Li, Xuting Zhang, Anni Wang, Tinghuan Wang, Yi Yan, Jingjing Fu, Jing Zheng, Min Lou, Jin Hu","doi":"10.3724/zdxbyxb-2025-0730","DOIUrl":"10.3724/zdxbyxb-2025-0730","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the efficacy and safety of intravenous thrombolysis in patients with mild acute ischemic stroke (AIS).</p><p><strong>Methods: </strong>In this retrospective cohort study, adult patients with mild AIS within 4.5 hours of onset between July 2009 and December 2024 were enrolled from four hospitals in Zhejiang province. Mild AIS was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤5, with a limb motor NIHSS score of 0, and a NIHSS score ≥2 in any of the following items: gaze, visual fields, facial palsy, limb ataxia, sensation, language, dysarthria, or neglect. Logistic regression and general linear models were used to assess the impact of intravenous thrombolysis on 3-month functional outcomes and safety endpoints.</p><p><strong>Results: </strong>Among 347 enrolled patients, 206 (59.4%) received intravenous thrombolysis. The proportion of patients achieving a favorable functional outcome (modified Rankin Scale score 0-1) at 3 months was significantly higher in the thrombolysis group than that in the non-thrombolysis group (76.2% <i>vs</i>. 66.0%, adjusted OR=1.729, 95%CI: 1.016-2.940, <i>P</i><0.05). The thrombolysis group also had a significantly lower all-cause mortality rate (1.0% <i>vs.</i> 12.8%, adjusted OR=0.074, 95%CI:0.015-0.379, <i>P</i><0.01). Safety analysis showed hemorrhagic transformation in 5.8%, parenchymal hemorrhage in 1.9%, and symptomatic intracranial hemorrhage in 2.9% within 24 hours in the thrombolysis group, compared with 3.5% hemorrhagic transformation in the non-thrombolysis group, with no statistically significant differences between the two groups (all <i>P</i>>0.05).</p><p><strong>Conclusions: </strong>Intravenous thrombolysis can significantly improve 3-month functional outcomes and reduce mortality in patients with mild AIS, without increasing the risk of hemorrhagic transformation.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"105-112"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Functional characterization of double-negative T cells isolated from leukoreduction filter residues].","authors":"Zhiqiang Xiang, Yue Wu, Kaiyu Huang, Fuqiang Wu, Ju Lin, Lieyong Sang, Liming Yang","doi":"10.3724/zdxbyxb-2025-0625","DOIUrl":"10.3724/zdxbyxb-2025-0625","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To characterize the biological properties of double-negative T (DNT) cells isolated from leukoreduction filter residues.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Leukoreduction filters containing residues from 400 mL whole blood units (&lt;i&gt;n&lt;/i&gt;=6) were collected from a blood center. Filters were back-flushed with normal saline, and the eluate was concentrated to obtain leukoreduction filter residues. Leukocytes in the residues were counted by dual-fluorescence staining. DNT cells were then isolated from the residues using antibody-mediated adsorption and density gradient centrifugation. Both cryopreserved-thawed and non-cryopreserved DNT cells derived from the residues were subjected to &lt;i&gt;in vitro&lt;/i&gt; culture. Cells were assessed for expansion fold, viability, immunophenotype, differentiation status, and cytotoxicity against target cells using dual-fluorescence staining and flow cytometry, with comparisons made to DNT cells derived from whole blood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The leukocyte recovery rate achieved through reverse flushing of the leukocyte reduction filter was (41.9±14.7)%. Compared to whole blood, the DNT cells starting material obtained from filter residues showed no significant difference in total T-cells content (&lt;i&gt;P&lt;/i&gt;&gt;0.05). However, the viability and purity of the resulting DNT cells starting materials were significantly lower (both &lt;i&gt;P&lt;/i&gt;&lt;0.05). After 17 days of culture, DNT cells from filter residues and whole blood showed no significant differences in expansion fold, immunophenotype, differentiation status, or cytotoxicity toward target cells (all &lt;i&gt;P&lt;/i&gt;&gt;0.05). However, the viability of DNT cells from residues was significantly lower than that of whole blood-derived DNT cells [(86.0±4.2)% &lt;i&gt;vs.&lt;/i&gt; (92.2±1.2)%, &lt;i&gt;P&lt;/i&gt;&lt;0.05]. After thawing (post 3 or 15 days of cryopreservation) and 17 days of culture, DNT cell starting materials from residues showed comparable immunophenotype, expansion fold, and differentiation status to their non-cryopreserved counterparts from the same source (all &lt;i&gt;P&lt;/i&gt;&gt;0.05). However, the viability of the 3-day cryopreservation recovery group [92.4% (91.8%, 92.8%) &lt;i&gt;vs&lt;/i&gt;. 87.8% (82.0%, 89.0%)] and the cytotoxicity against target cells of the 15-day cryopreservation recovery group [91.3% (89.4%, 95.1%) &lt;i&gt;vs&lt;/i&gt;. 70.9% (67.3%, 80.2%)] were both significantly higher than those of non-cryopreserved DNT cells (all &lt;i&gt;P&lt;/i&gt;&lt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;DNT cells derived from leukoreduction filter residues exhibited highly comparable characteristics to those from whole blood in terms of expansion, purity, differentiation, and biological potency. Furthermore, their biological activity post-cryopreservation and revival remained largely similar to non-cryopreserved cells. These findings suggest that leukoreduction filter residues represent a promising alternative source of starting material for manufacturing off-the-shelf, allogeneic DNT cell therapeutic","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"145-153"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Construction of a prognosis forecasting model for breast cancer based on lipid metabolism-related genes and functional verification of <i>ALDH2</i>].","authors":"Zirong Lu, Yufeng Lu, Ji Zhou, Yichao Zhu","doi":"10.3724/zdxbyxb-2025-0567","DOIUrl":"10.3724/zdxbyxb-2025-0567","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the expression patterns and prognostic value of lipid metabolism-related genes in breast cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas breast cancer-related gene (TCGA-BRCA) cohort, including 1100 breast cancer tissue samples and 112 normal breast tissue samples. Differentially expressed lipid metabolism-related genes were screened from a predefined set of 2043 genes using Bioconductor in R, with a false discovery rate &lt;0.05 and |log&lt;sub&gt;2&lt;/sub&gt;(fold change)|&gt;2. Breast cancer tissue samples were randomly divided into a training cohort (&lt;i&gt;n&lt;/i&gt;=651) and a validation cohort (&lt;i&gt;n&lt;/i&gt;=431) at a 6∶4 ratio. Prognostic lipid metabolism-related genes were identified using univariate Cox regression (&lt;i&gt;P&lt;/i&gt;&lt;0.01) and further refined via least absolute shrinkage and selection operate (LASSO) regression. A risk score model was constructed using multivariate Cox regression, and patients were stratified into high- and low-risk groups based on the median risk score. The model's performance was evaluated using Kaplan-Meier survival analysis with the log-rank test and time-dependent receiver operator characteristic (ROC) curves. A nomogram integrating age, TNM stage, clinical grade, and risk score was developed and validated using calibration curves and the concordance index. Immune cell infiltration was quantified using an immune scoring algorithm, and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with immune cell infiltration. Finally, to validate the function of the key gene &lt;i&gt;ALDH2&lt;/i&gt;, small interfering RNA targeting &lt;i&gt;ALDH2&lt;/i&gt; was transfected into breast cancer cells (MDA-MB-231), and its effects on invasion and migration were assessed using Transwell invasion and wound healing assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 185 differentially expressed lipid metabolism-related genes were identified. Univariate Cox and LASSO regression analyses identified three genes-&lt;i&gt;ALDH2, CYP21A2,&lt;/i&gt; and &lt;i&gt;IL24&lt;/i&gt;-which were incorporated into the multivariate Cox model. The prognosis forecasting model based on these genes demonstrated good predictive performance in both cohorts: patients in the high-risk group had significantly shorter overall survival (both &lt;i&gt;P&lt;/i&gt;&lt;0.01), and the areas under the ROC curve for predicting 1-, 3-, and 5-year survival rates were all greater than 0.64. Analysis of the tumor microenvironment revealed a dysfunctional state in the high-risk group, characterized by reduced infiltration of several anti-tumor immune cells and downregulation of key immune checkpoint molecules such as PDCD1 and CTLA-4. WGCNA suggested an association between &lt;i&gt;ALDH2&lt;/i&gt; and immune cell infiltration. Functional experiments confirmed that &lt;i&gt;ALDH2&lt;/i&gt; knockdown significantly enhanced the migration and invasion abilities of breast cancer cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"77-86"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Application and progress of artificial intelligence agents in drug development].","authors":"Donghai Zhao, Changyu Hsieh","doi":"10.3724/zdxbyxb-2025-0697","DOIUrl":"10.3724/zdxbyxb-2025-0697","url":null,"abstract":"<p><p>Drug discovery faces formidable challenges including high technology, high costs, substantial risks, and prolonged development timelines, necessitating disruptive technologies capable of systematically improving efficiency, enhancing predictive accuracy, and reducing failure rates. Artificial intelligence (AI) agent-an emerging intelligent paradigm powered by large language models-holds significant potential to transform the entire drug development pipeline. Their core capability lies in performing autonomous reasoning, planning, and tool utilization directed at complex scientific objectives, thereby integrating and orchestrating multiple research stages and transitioning AI from a mere \"tool\" to an \"active collaborator\". Through knowledge integration and hypothesis generation, AI agents can identify underexplored therapeutic targets and novel mecha-nisms of action. In parallel, they can automate complex tasks such as molecular design, optimization, and synthesis planning, and further close the loop between virtual design and physical experimentation by interfacing with automated experimental platforms. Moreover, AI agents are evolving toward higher-level paradigms, including the development of integrated drug design platforms and general-purpose biomedical agents. This review systematically summarizes the core architectures of AI agents, highlights their applica-tions across key stages of drug development, and discusses current limitations along with future directions, providing a reference for researches in related fields.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"4-15"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Advances in injectable and transdermal glucose-responsive insulin delivery systems].","authors":"Kaihui Li, Xiuwen Zhang, Zhen Gu, Jinqiang Wang","doi":"10.3724/zdxbyxb-2025-0656","DOIUrl":"10.3724/zdxbyxb-2025-0656","url":null,"abstract":"<p><p>To address the core limitations of conventional insulin therapy, including delayed glycemic control and the frequent risk of hypoglycemia, the development of glucose-responsive insulin delivery systems capable of dynamically sensing blood glucose levels and releasing insulin on demand has emerged as a pivotal strategy. Based on their underlying sensing mechanisms, these systems are generally classified into three categories: those utilizing glucose oxidase, glucose-binding molecules, and phenylboronic acid. From the perspective of administration routes, injectable and transdermal delivery are the two primary approaches for glucose-responsive insulin. Injectable glucose-responsive insulin delivery systems are highly compatible with existing clinical practices, primarily relying on glucose-responsive carriers to regulate the insulin release rate and achieve stable and efficient bioavailability. Transdermal glucose-responsive insulin delivery systems utilize glucose-responsive microneedle arrays to penetrate the skin stratum corneum and precisely control the rate of insulin release, allowing for sufficient insulin delivery under almost painless conditions. This review systematically summarizes recent advances in both injectable and transdermal glucose-responsive insulin delivery systems, with a focus on carrier design strategies, glucose-responsive release mechanisms, and evolutionary pathways of preparation techniques. It also highlights the contributions of these systems toward improved glucose-responsiveness, therapeutic safety, biocompatibility, and patient adherence. Furthermore, challenges and future prospects for clinical translation are discussed. This overview is expected to provide valuable insights for further research and development in this field.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"16-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Construction of a prognosis forecasting model for immuno-therapy response in cancer patients by integrating routine clinical parameters and tumor mutational burden].","authors":"Xudong Zhu, Shuqiang Hao, Zhen Cheng, Weijia Fang","doi":"10.3724/zdxbyxb-2025-0205","DOIUrl":"10.3724/zdxbyxb-2025-0205","url":null,"abstract":"<p><strong>Objectives: </strong>To develop a machine-learning model that integrates routine clinical parameters with tumor mutational burden (TMB) and to evaluate its performance in predicting responses to programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) inhibitors across various cancer types.</p><p><strong>Methods: </strong>We conducted a retrospective study of 146 patients with advanced solid tumors who were treated with PD-1/PD-L1 inhibitors. The cohort was randomly divided into a training set (<i>n</i>=116) and a validation set (<i>n</i>=30) at a 4:1 ratio. Using the PyTorch framework, we constructed a neural network model (designated NNT9) incorporating age, sex, body mass index (BMI), TMB, history of systemic therapy, neutrophil-to-lymphocyte ratio (NLR), and other routine blood parameters. The model employed a multilayer perceptron architecture. Hyperparameters were automatically optimized using AutoGluon, and the model was refined via 5-fold cross-validation. SHapley Additive exPlanations (SHAP) was used to perform feature importance analysis on the optimal model in the training set. Predictive performance was compared against TMB alone using metrics including the area under the receiver operating characteristic curve (AUC), accuracy, F1 score, sensitivity, and specificity. Confusion matrices were generated, and the association between model-predicted response groups and progress free survive (PFS) was analyzed.</p><p><strong>Results: </strong>NNT9 was identified as the optimal model, and the history of systemic therapy, TMB, platelet count, and BMI were the four most important predictive features. NNT9 achieved AUCs of 0.949 and 0.851 in the training and validation sets, respectively, outperforming TMB alone (AUCs: 0.747 and 0.720). In the validation set, NNT9 also demonstrated superior sensitivity (0.571), accuracy (0.867), F1 score (0.667), positive predictive value (0.800), and negative predictive value (0.880). The confusion matrix revealed that NNT9 misclassified only half as many patients as TMB alone in the validation set. Kaplan-Meier analysis showed that patients predicted to be responders by NNT9 had significantly longer PFS than non-responders in both training and validation sets (both <i>P</i><0.01).</p><p><strong>Conclusions: </strong>The NNT9 model, which integrates readily available clinical parameters with TMB, represents an accurate and clinically feasible tool for predicting immunotherapy benefit in a pan-cancer cohort, and shows promise for clinical translation.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"36-45"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[U-shaped association between hematocrit and resting pulse oxygen saturation in Tibetan plateau population].","authors":"Yimei Guo, Ronghui Li, Ciren Laba, Qi Yan","doi":"10.3724/zdxbyxb-2025-0617","DOIUrl":"10.3724/zdxbyxb-2025-0617","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the relationship between hematocrit (HCT) and low resting oxygen saturation in Tibetan plateau population.</p><p><strong>Methods: </strong>This retrospec-tive cohort study included 3075 Tibetan adult inpatients who underwent elective non-cardiac, non-thoracic surgery at Tibet Autonomous Region People's Hospital between January 2023 and October 2024. Multivariate logistic regression was used to assess the association between HCT and low resting oxygen saturation (SpO₂<88%). Restricted cubic splines were employed to model non-linear relationships, and piecewise logistic regression, in combination with maximum likelihood estimation, was used to identify the HCT threshold.</p><p><strong>Results: </strong>Multivariate logistic regression analysis showed that elevated HCT was an independent risk factor for low oxygen saturation in the patients. For every 5-percentage-point increase in HCT, the risk of low oxygen saturation increased by 12% (<i>P</i><0.01). The restricted cubic spline model revealed a significant U-shaped association between HCT and the risk of low oxygen saturation (<i>P</i><0.01). The HCT threshold for the total population was 42.8%. When HCT was below 42.8%, each 5% increase in HCT was associated with a 22% reduction in the risk of low oxygen saturation in the patients (OR=0.780, 95%CI: 0.619-0.982, <i>P</i><0.05). When HCT was 42.8% or above, the risk increased by 27.2% (OR=1.272, 95%CI: 1.132-1.429, <i>P</i><0.01). Stratified analysis indicated that the HCT threshold was 40.4% for female patients and 46.6% for male patients.</p><p><strong>Conclusions: </strong>There is a U-shaped association between HCT and low resting oxygen saturation in the Tibetan plateau population. An HCT level exceeding the population-specific threshold suggests that the adaptive erythropoietic response to high-altitude hypoxia may transition from being compensatory to potentially detrimental.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"87-92"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}