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

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. This review highlights how these technologies are reshaping our understanding of pulmonary fibrosis. 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 unprecedented insights into disease pathogenesis, offering a powerful framework for advancing precision diagnosis, identifying therapeutic targets, and guiding drug develop-ment. This article synthesizes recent progress in applying spatial omics to pulmonary fibrosis research, underscoring its potential to translate into more effective clinical strategies.

Chronic spontaneous urticaria (CSU) is a common dermatologic disorder marked by significant patient heterogeneity. Existing treatment strategies often fall short of adequately addressing patients' clinical needs. In the past decade, insights into the pathophysiology of CSU have catalyzed the development of novel targeted therapies, which can be categorized into three main approaches: targeting mast cells, targeting cytokines, and targeting Janus kinase (JAK) signaling. Mast cell-targeted strategies focus on surface receptors (e.g., activating receptors, the KIT receptor governing mast cell proliferation/survival, and inhibitory receptors) and intracellular pathways such as Bruton's tyrosine kinase (BTK). Cytokine-targeted therapies aim at specific mediators including IL-4, thymic stromal lymphopoietin (TSLP), IL-17, IL-23, and IL-5. Regarding JAK-targeted therapy, besides approved JAK inhibitors, several novel agents, including dual-target inhibitors, are under investigation. This review systematically delineates recent advances in targeted therapies for CSU, comparing the features and clinical potential of different agents, to inform evidence-based and personalized management of this condition.

Objectives: 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).

Methods: In this retrospective cohort study, patients with LVO-related AIS who underwent mechanical thrombectomy within 72 hours of onset were enrolled from the multicenter Chinese Acute Stroke Evaluation and Management (CASE-Ⅱ) online database (January 2017 to December 2024). Patients were stratified into the beyond 24-hour thrombectomy group and the 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 neurological functional outcomes 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.

Results: 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, P=0.861; OR=1.151, 95%CI: 0.712-1.549, P=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 P>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 P>0.05). Subgroup analyses revealed no significant heterogeneity in the 3-month functional outcome across various baseline characteristics (all P>0.05).

Conclusions: 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.

Objectives: To compare the functional outcomes and safety of intravenous thrombolysis (IVT) administered within the standard 4.5-hour time window versus an extended window of 4.5 to 24 hours after onset in patients with acute ischemic stroke (AIS) isolated to the posterior circulation.

Methods: 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 window group (onset-to-needle time [ONT] ≤4.5 h) and the extended window group (ONT >4.5 to ≤24 h). The primary outcome was 3-month functional independence (modified Rankin Scale score ≤2). Multivariate logistic regression and propensity score matching were used to compare outcomes. Interaction tests assessed the consistency of the time-window effect across predefined subgroups (age, sex, baseline NIHSS score, presence of large vessel occlusion, thrombolytic agent, TOAST subtype).

Results: Among 3508 included patients, 3147 were in the standard window group and 361 in the extended window group. The rate of 3-month functional independence did not differ significantly between the extended and standard window groups (80.1% vs. 78.7%; adjusted OR=0.896, 95%CI: 0.655-1.266). This finding remained consistent after propensity score matching (adjusted OR=1.122, 95%CI: 0.724-1.738). 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). This negative association was significant only within the standard window group (OR=0.934, 95%CI: 0.887-0.984). Subgroup analysis indicated that the standard window group had a higher rate of functional independence than the extended window group (both interaction P<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 symptomatic intracranial hemorrhage, early neurological deteriora-tion, and 3-month all-cause mortality.

Conclusions: For patients with isolated posterior circulation AIS, IVT administered within 4.5 to 24 hours after onset demonstrates effec-tiveness and safety comparable to treatment within the standard 4.5-hour window.

External cervical resorption (ECR) is a progressive, osteoclast-mediated destructive disease of dental hard tissues that originates at the cervical region of the root. Characterized by its insidious onset and diagnostic challenges at early stages, ECR can lead to severe tooth structure loss and even tooth extraction. Although the precise patho-genesis remains unclear, it is thought to be associated with local stimuli, certain medications, and systemic conditions. Cone-beam computed tomography (CBCT) is currently the key imaging modality for three-dimensional assessment and accurate staging of ECR. Treatment should be based on such three-dimensional evaluation and follow a stepwise strategy tailored to the extent, depth, and pulpal involvement of the lesion: minimally invasive restoration with bioactive materials for early or localized defects; comprehensive manage-ment including root canal treatment, intentional replantation, or combined guided tissue regeneration for lesions involving the pulp or exhibiting extensive spread; and extraction with site preservation as a final restorative-oriented option for non-retainable teeth. This review systematically elaborates on the etiological factors, pathological mechanisms, clinical manifestations, image-based classification systems, diagnosis, and management of ECR, aiming to provide insights for precise clinical decision-making. Future research directions, such as early biomarker identification and targeted pharmacological intervention, are also discussed.

Objectives: To develop and validate a multimodal radiomics model based on machine learning for predicting central lymph node metastasis (CLNM) in patients with clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC).

Methods: A retrospective analysis was conducted on clinical data of 532 consecutive cN0 PTMC patients who underwent surgery at the Department of Thyroid Surgery of the First People's Hospital of Changzhou and the Department of Thyroid and Breast Surgery of Suzhou Municipal Hospital between January 2022 and June 2024. Among them, 487 patients from the First People's Hospital of Changzhou were randomly assigned to a training set (n=352) or an internal validation set (n=135), while 45 patients from Suzhou Municipal Hospital served as an external validation set. Clinical feature screening involved collinearity analysis using variance inflation factors, followed by logistic regression to identify independent risk factors for CLNM. Radiomics features were extracted separately from ultrasound and CT images. An initial feature screening was performed using statistical tests (t-test or Mann-Whitney U test, P<0.05) along with mutual information analysis (score >0.015), followed by LASSO regression for key feature selection. Using the optimized feature set, four machine learning models were constructed: Random Forest, Gradient Boosting Machine (GBM), Support Vector Machine, and K-Nearest Neighbors. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), decision curve analysis, and SHapley Additive exPlanations (SHAP) method.

Results: Logistic regression identified five clinical features independently associated with CLNM: age <55 years (OR=2.391, 95%CI: 1.072-5.334, P<0.05), coexisting Hashimoto's thyroiditis (OR=3.084, 95%CI: 1.474-6.453, P<0.01), maximum tumor diameter (OR=11.086, 95%CI: 2.881-48.378, P<0.01), monocyte count (OR=0.005, 95%CI: 0.001-0.044, P<0.01), and the lymphocyte-to-monocyte ratio (OR=0.564, 95%CI: 0.486-0.654, P<0.01). LASSO regression selected two ultrasound and six CT radiomics features. Among the four models, the GBM model based on multimodal feature fusion performed best, with AUC values of 0.975, 0.833, and 0.916, accuracies of 0.925, 0.748, and 0.863, specificities of 0.950, 0.800, and 0.881, and sensitivities of 0.900, 0.720, and 0.804 in the training, internal validation, and external validation sets, respectively. Decision curve analysis showed that the GBM model provided the highest net clinical benefit within the threshold probability range of 0.1-0.8.

Conclusions: The multimodal radiomics model based on GBM can accurately predict the risk of CLNM in patients with cN0 PTMC, which may facilitate individualized preoperative risk assessment.

Objectives: To evaluate the feasibility and effectiveness of replacing manual auscultation with artificial intelligence (AI)-assisted cardiac auscultation within the dual-indicator screening strategy for early detection of congenital heart disease (CHD) in neonates in a real-world clinical setting.

Methods: Using data from the provincial CHD treatment network led by the Children's Hospital of Zhejiang University School of Medicine, we retrospectively enrolled 41 320 neonates born between July 2020 and March 2023. All neonates underwent pulse oximetry (POX), AI-assisted auscultation, and manual auscultation. The traditional screening strategy was defined as "POX+manual auscultation," and the intelligent strategy as "POX+AI-assisted auscultation." A positive screening result was defined as a positive finding in either POX or the corresponding auscultation method (manual or AI). Echocardiography served as the gold standard for CHD diagnosis. True positive, false positive, true negative, and false negative results were determined, and the missed-diagnosis rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. To assess the consistency of screening performance across institutions, analyses were also conducted separately in the four hospitals with the highest screening volumes.

Results: A total of 354 neonates were diagnosed with CHD. Compared with the traditional strategy, the intelligent strategy significantly reduced the missed-diagnosis rate (67.23% vs. 34.75%, P<0.01) and increased sensitivity (32.77% vs. 65.25%, P<0.01) and NPV (99.41% vs. 99.67%, P<0.01). However, specificity, PPV, and diagnostic accuracy were lower (all P<0.01). Across the four high-volume institutions, the intelligent strategy consistently showed a significant reduction in missed-diagnosis rate and increased sensitivity, along with decreased specificity and diagnostic accuracy, indicating robust performance across diverse clinical settings.

Conclusions: In multicenter real-world practice, the intelligent screening strategy significantly reduces the missed-diagnosis rate of CHD and demonstrates stable screening performance across different institutions. Although diagnostic accuracy is moderately lower, AI-assisted auscultation is a feasible and clinically valuable alternative to manual auscultation in neonatal CHD screening, particularly when minimizing missed diagnoses is a priority.

Objective To evaluate the efficacy and safety of intravenous thrombolysis in patients with minor acute ischemic stroke (AIS). Methods In this retrospective cohort study, adult patients with minor AIS within 4.5 hours of onset between May 2009 and December 2024 were enrolled from four hospitals in Zhejiang province. Minor AIS was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤5, with a limb motor subscore of 0, and a score ≥2 in any of the following items: best gaze, visual fields, facial palsy, limb ataxia, sensation, best 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. Results 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 signifi-cantly higher in the thrombolysis group than in the non-thrombolysis group (76.2% vs. 66.0%; adjusted OR=1.729, 95%CI: 1.016-2.940, P=0.043). The thrombolysis group also had a significantly lower all-cause mortality rate (1.0% vs. 12.8%; adjusted OR=0.074, 95%CI:0.015-0.379, P=0.002). Safety analysis showed hemorrhagic transformation in 5.8%, parenchymal hemorrhage in 1.9%, and symptomatic intracranial hemorrhage in 2.9% of the thrombolysis group, compared with 3.5% hemorrhagic transformation in the non-thrombolysis group, with no statistically significant differences between the two groups (all P>0.05). Conclusion Intravenous thrombolysis can significantly improve 3-month functional outcomes and reduce mortality in patients with minor AIS without increasing the risk of hemorrhagic transformation.

Objectives: To compare the efficacy and safety of tenecteplase versus alteplase as bridging intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO).

Methods: In this retrospective cohort study, data were extracted from the multicenter Chinese Acute Stroke Evaluation and Management Ⅱ (CASE-Ⅱ) database (NCT04487340). Patients with AIS and large vessel occlusion who received tenecteplase or alteplase followed by mechanical thrombectomy within 24 hours of symptom onset from December 2022 to March 2025 were included. The patients were divided into the tenecteplase group and the alteplase group. Propensity score matching (1∶4) was performed based on age, sex, door-to-needle time (DNT), door-to-puncture time (DPT), and onset-to-door time. Binary logistic regression and general linear models were used to compare 3-month functional and safety outcomes. Sensitivity analysis was conducted for patients with onset-to-needle time (ONT)≤4.5 h, and subgroup analyses were performed based on age, sex, baseline NIHSS score, occlusion site, DNT, and DPT.

Results: Among 1505 enrolled patients, 250 received tenecteplase and 1255 received alteplase. After matching, 224 tenecteplase-treated and 767 alteplase-treated patients were included. No significant differences were observed in 3-month functional outcomes between the two groups (all P>0.05). However, the tenecteplase group had lower 3-month all-cause mortality before matching (OR=0.676, 95%CI: 0.470-0.972, P=0.032). After matching, there were no significant differences in functional or safety outcomes (all P>0.05). Sensitivity and subgroup analyses also showed no significant differences in 3-month functional independence (all P>0.05).

Conclusions: In patients with AIS and large vessel occlusion undergoing bridging thrombolysis before mechanical thrombectomy, tenecteplase and alteplase showed comparable 3-month functional outcomes and safety profiles.

Objectives: To investigate the association between in-hospital dynamic elevation of high-sensitivity cardiac troponin T (hs-cTnT) and both early neurological deterioration (END) and 3-month functional outcomes in patients with acute ischemic stroke (AIS).

Methods: Data of AIS patients who underwent two hs-cTnT measurements during hospitalization between March 2017 and November 2024 were extracted from the CIPPIS database for retrospective analysis. Based on whether hs-cTnT increased by more than 20% from the baseline level, patients were categorized into a dynamic elevation group and a non-elevation group. The incidences of END [defined as a ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days of onset] and 3-month functional independence [defined as a modified Rankin Scale (mRS) score of 0-2] were compared between the two groups. Binary logistic regression was used to analyze the relationship between hs-cTnT dynamic elevation and the outcomes. Sensitivity analysis (after excluding patients with acute myocardial infarction or severe renal dysfunction) and subgroup analyses were performed to assess the robustness of the findings.

Results: A total of 1049 patients were included (median age 73 years). Among them, 406 patients (38.7%) were female, 226 patients (21.5%) exhibited hs-cTnT dynamic elevation. Compared with the non-elevation group, the dynamic elevation group had a significantly higher incidence of END (9.71% vs. 15.42%, P<0.05) and lower proportions of patients with 3-month mRS scores of 0-1 (37.75% vs. 26.57%, P<0.01), 0-2 (48.71% vs. 36.71%, P<0.01), and 0-3 (63.87% vs. 55.56%, P<0.05). The 3-month all-cause mortality was also higher in the dynamic elevation group (9.20% vs. 14.01%, P<0.05). After adjusting for confounders (including age, sex, baseline NIHSS score, baseline hs-cTnT level, TOAST classification, and reperfusion therapy), dynamic elevation of hs-cTnT remained independently associated with a higher risk of END (adjusted OR=1.73, 95%CI: 1.07-2.82, P<0.05) and lower odds of achieving 3-month mRS scores of 0-1 (adjusted OR=0.65, 95%CI: 0.44-0.96, P<0.05) and 0-2 (adjusted OR=0.67, 95%CI: 0.48-0.94, P<0.05). The results were consistent in sensitivity analysis, and no significant interactions were observed across various subgroups (all interaction P>0.05).

Conclusions: In patients with AIS, in-hospital dynamic elevation of hs-cTnT is independently associated with an increased risk of early neurological deterioration and poorer 3-month functional outcomes. This association may reflect the adverse impact of acute myocardial injury on stroke prognosis.