Linyi People's Hospital

Abstract Background Stroke guidelines recommend intravenous thrombolysis (IVT) within 4.5 hours of symptom onset for patients with minor acute ischemic stroke (AIS) but disabling symptoms. However, such patients are often overlooked for treatment, increasing their risk of stroke-related disability. Tenecteplase is endorsed as an alternative to alteplase for IVT in patients with AIS. More evidence is required regarding its efficacy and safety in the minor stroke population. Methods This post hoc analysis of the ORIGINAL randomized clinical trial aimed to evaluate the efficacy and safety of tenecteplase versus alteplase in the patient subgroup with minor (National Institutes of Health Stroke Scale [NIHSS] ≤5) disabling stroke. Primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 at Day 90. Results Data were analyzed for 299 patients treated with tenecteplase 0.25 mg/kg and 297 patients treated with alteplase 0.9 mg/kg. At Day 90, 86.3% of tenecteplase recipients and 82.8% of alteplase recipients achieved a mRS score of 0 or 1 (risk ratio=1.04 [95% confidence interval 0.971–1.114]; non-significant). No heterogeneity of treatment effect was observed across predefined subgroups according to baseline NIHSS score, time to drug administration, sex, age, presence (yes/no) of atrial fibrillation and diabetes and thrombectomy performed. No statistically significant differences were observed between tenecteplase and alteplase across secondary efficacy and safety outcomes. Conclusions The comparable efficacy and safety of tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg in the minor stroke population of the ORIGINAL randomized clinical trial suggests that tenecteplase is a suitable alternative to alteplase in this setting. Trial registration ClinicalTrials.gov NCT04915729 (ORIGINAL randomized clinical trial; https://clinicaltrials.gov/study/NCT04915729 ). Submitted 4 June 2021.

To investigate the association between monounsaturated fatty acids (MUFAs) intake and the prevalence of Parkinson’s disease (PD) among US adults using data from the National Health and Nutrition Examination Survey (NHANES) database. Cross-sectional data from the NHANES 2001–2018 were selected. PD cases were identified through self-reported PD medications. MUFAs intake was determined from dietary interview data for two 24-hour periods. To address severe outcome imbalance and improve covariate comparability, we conducted survey-weighted propensity score matching (PSM) incorporating NHANES sampling weights. In the matched sample, survey-weighted logistic regression was used to evaluate the association between MUFAs intake (quartiles) and PD prevalence, and a trend test was performed. Restricted cubic spline (RCS) models were applied to examine potential non-linear associations. A total of 12,122 participants were included, consisting of 84 PD patients and 12,038 participants without PD. MUFAs intake was significantly lower in the PD group than in matched controls after PSM (P = 0.010). Exploratory subgroup analyses suggested heterogeneity across some subpopulations. RCS analyses did not indicate a significant non-linear relationship between MUFAs intake and the prevalence of PD. Higher MUFAs intake was inversely associated with PD prevalence in this cross-sectional analysis. Given the study design, causality cannot be inferred; prospective studies are warranted to confirm these findings and clarify underlying mechanisms.

This study reveals that depression among disabled older adults in China is influenced by multiple interconnected factors. Greater attention should therefore be directed toward the mental health of this population, and targeted measures should be implemented to improve depressive conditions among disabled older adults.

Abstract Background TROP2 and HER3 are frequently overexpressed in HER2-negative breast cancer (BC). JSKN016 is a first-in-class bispecific ADC targeting TROP2/HER3, conjugated to a topoisomerase I inhibitor via a cleavable linker (average drug-to-antibody ratio 4). Glycan conjugation provided high stability and minimized off-target toxicity: In 217 patients treated with JSKN016 monotherapy, hematologic toxicity was uncommon, with grade (G) 3 neutropenia, anemia, and leukopenia observed in 2.8%, 2.3%, and 1.4%, respectively. The bispecific construct also demonstrated promising efficacy in HER2-negative BC. Method JSKN016-101 (NCT06592417) is a first-in-human, dose-escalation and expansion study in China, enrolling patients with advanced solid tumors to receive JSKN016 monotherapy. Tumor responses were assessed every 6 weeks per RECIST v1.1 by investigators (INV) and an independent review committee (IRC). This analysis focuses on the HER2-negative BC cohort. Results As of September 5, 2025, JSKN016 was escalated to 8 mg/kg IV Q3W without reaching the maximum tolerated dose. A total of 82 patients were enrolled: 50 TNBC and 32 HR+/HER2- BC patients treated at 4 mg/kg (n = 14), 6 mg/kg (recommended phase II dose [RP2D]; n = 65), and 8 mg/kg (n = 3). Overall, 98.8% (81/82) had stage IV disease and 13.4% (11/82) with brain metastases at baseline. Median age was 50 (TNBC) and 52 (HR+/HER2- BC); ECOG PS 1 was reported in 78.7% and 76.7%, respectively. All TNBC patients had prior taxane-based chemotherapy, and 28.0% had received ≥3 prior systemic regimens. All HR+/HER2- BC patients had progressed after ≥1 endocrine therapy with CDK4/6 inhibitors and ≥1 chemotherapy. Among 47 efficacy-evaluable TNBC patients, objective response rate (ORR) was 57.4% (INV) and 63.8% (IRC). At RP2D (n = 31), ORR was 61.3% (INV) and 64.5% (IRC), with disease control rates (DCR) of 83.9% and 90.3%. Among 30 efficacy-evaluable HR+/HER2- patients, ORR was 43.3% (INV) and 50.0% (IRC); at RP2D (n = 29), ORR was 44.8% (INV) and 51.7% (IRC), with DCR of both 100%. Notably, intracranial activity was observed: one patient with multiple brain metastases achieved a complete response and three patients showed intracranial tumor shrinkage. With median follow-up of 5.0 months, the most common treatment-related adverse events (TRAEs; ≥30%) included stomatitis, nausea, asthenia, weight loss, vomiting and leukopenia, mostly G1-2. No G4-5 TRAEs occurred. The most common G3 TRAEs included neutropenia (4.9%), stomatitis (3.7%), and amylase elevation, asthenia, lymphopenia, leukopenia (each 2.4%). No TRAEs led to treatment discontinuation. No interstitial lung disease (ILD) was reported. Conclusions JSKN016 demonstrated robust antitumor activity with a manageable safety profile in patients with HER2-negative BC, supporting further development. Citation Format: H. Yao, Z. Huang, H. Zong, M. Yan, Y. Zhao, Z. Tong, J. Liu, J. Wang, Y. Cao, Q. Zhang, X. Han, L. Sun, X. Wu, J. Shi, J. Tang, J. Wen, H. Yu, F. Su, H. Zhou, Q. Dang, H. Yang, Z. Yu, W. Li, R. Zhao, F. Wu, R. Xu, X. Tang, T. Xu. Jskn016, a first-in-class anti-TROP2/HER3 bispecific antibody drug conjugate (ADC) in patients with HER2-negative locally advanced or metastatic breast cancer: results from a phase I study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-09-05.

Abstract Objective To compare the patient-reported outcomes (PROs) and quality of life in patients with HR+/HER2- early breast cancer (EBC) treated with ribociclib (RIB) and abemciclib (ABE) as adjuvant therapy. Methods A multicenter, retrospective cohort study was conducted in Chinese patients receiving ribociclib or abemciclib as adjuvant therapy for HR+/HER2- EBC. PRO data were collected via an electronic questionnaire. The questionnaire was based on the PRO scale for breast cancer patients in China (NCC-BC-A scale), EQ-5D-5L and safety information of CDK4/6 inhibitors, including six dimensions of physiological function, psychological status, social support, treatment related symptoms, economic dimension and overall self-evaluation. The higher score of the questionnaire, the better quality of life. Results Between Mar 15, and May 12, 2025, 197 patients completed the survey, including 94 patients who received ribociclib and 103 patients who received abemciclib. Overall, 195 patients (99%) were female and two (1%) were male. No difference was observed in baseline characteristics such as age, employment status, medical insurance, and concomitant treatment. The total score of the PRO in ribociclib group was higher than that in abemciclib group (187.14±17.57 vs 180.66±22.26, p=0.024). In therapeutic domain, the score was significantly higher in ribociclib group (34.81±5.29 vs 32.77±5.51, p=0.009). Patients in ribociclib group were less affected by the treatment-related symptoms of diarrhea (3.88±0.53 vs 2.31±1.33, p<0.001), fatigue (2.29±0.91 vs 2.00±1.02, p=0.038) and hair loss (2.94±1.39 vs 2.49±1.24, p=0.018). The proportion of patients receiving ribociclib who discontinued due to the side effects of long-term treatment (28.6% vs 50%) or reduced the dose due to adverse events (22.2% vs 70%) was lower. The overall health status score of ribociclib group was higher (6.67±1.27 vs 5.83±1.45, p<0.001). Conclusion HR+HER2- EBC patients who received ribociclib had a better PRO score than those who received abemciclib. Patients in ribociclib group experienced less treatment-related adverse reactions, especially diarrhea, fatigue, and hair loss, and had a lower rate of discontinuation/reduction due to adverse events, a better self-evaluation of their overall health status. Citation Format: B. Cong, C. Hou, C. Shan, S. Sun, S. Sun, Y. Wang. Patient-reported outcomes of adjuvant therapy with CDK4/6 inhibitors for HR+/HER2- early breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-28.

ABSTRACTBackgroundDose exposure to supraventricular cardiac conduction system doses has been reported to be associated with distinct arrhythmia classes after thoracic radiotherapy, but its impact in esophageal squamous cell carcinoma (ESCC) remains unknown.Materials and MethodsLocally advanced ESCC treated with neoadjuvant chemoradiotherapy (nCRT) were included. The primary endpoint was grade ≥ 3 adverse cardiac arrhythmia events. Prediction performance was evaluated through time‐dependent receiver operating characteristic curves, and competing risk frameworks were implemented to quantify the cumulative incidence of distinct cardiac arrhythmia.ResultsOf 358 patients, 84.9% were men, with a median age of 66 years (range: 39–79 years). A total of 60 (16.8%) patients experienced at least 1 grade ≥ 3 arrhythmia, with a median time to first arrhythmia of 13 months (95% CI: 12–15 months). The 2‐year cumulative incidences of distinct cardiac arrhythmia were 8.89% for AF, 2.96% for atrial flutter, and 5.12% for other SVT. Baseline coronary heart disease was a risk factor for all types of arrhythmia (p < 0.05). After adjusting for baseline cardiovascular risk factors, Heart Dmax (sHR 3.69, p = 0.0024) was associated with AF, Heart volume receiving 5 Gy with atrial flutter (sHR: 9.35, p = 0.0077), and Heart volume receiving 40 Gy (sHR 5.72, p = 0.00078) with other SVT.ConclusionGrade ≥ 3 cardiac arrhythmia associated with thoracic radiation occurs in 16.7% of ESCC patients undergoing nCRT within a median time of 13 months. The radiation dose exposure of the supraventricular cardiac conduction system is not associated with increased cardiac arrhythmia. Specific arrhythmia subtypes exhibited differential associations with distinct dose‐volume parameters of whole heart irradiation.

ABSTRACTDihydroquercetin (DHQ) is a plant‐derived flavonoid with well‐documented antioxidant and anti‐inflammatory properties. This study aimed to elucidate the therapeutic mechanisms of DHQ in metabolic dysfunction‐associated steatotic liver disease (MASLD) by integrating network pharmacology with in vivo and in vitro experiments. Network pharmacology analysis identified potential DHQ targets associated with MASLD, followed by GO and KEGG enrichment analyses. A high‐fat diet‐induced murine MASLD model and a free fatty acid‐induced HepG2 cell steatosis model were employed to evaluate the effects of DHQ. Biochemical assays, ELISA, Oil Red O staining, RT‐qPCR, and Western blotting were used to assess lipid metabolism, inflammatory responses, and HIF‐1 signaling. Thirty‐seven overlapping targets between DHQ and MASLD were identified, with protein–protein interaction analysis highlighting key hub proteins and enrichment analyses implicating the HIF‐1 signaling pathway. In vivo, DHQ significantly reduced body and liver weight, improved serum lipid profiles and liver enzyme levels, and alleviated hepatic histopathological damage. Mechanistically, DHQ activated the LKB1–AMPK axis, inhibited ACC, reduced IL‐1β and TNF‐α production, and attenuated aberrant HIF‐1α/VEGF signaling. Consistently, DHQ decreased lipid accumulation and inflammatory cytokine expression in steatotic HepG2 cells, while CoCl2‐induced HIF‐1α stabilization partially reversed these protective effects. Collectively, these findings suggest that DHQ ameliorates lipid metabolic disorders and inflammation in MASLD by modulating the HIF‐1α/VEGF pathway, supporting its potential as a therapeutic candidate.