Xiyuan Hospital

• First mechanistic elucidation of glycosylation-dependent HSA binding divergence: Crocetin exhibits 43 % higher affinity ( K a = 3.49×10 5 M -1 ) via bidentate H-bonding (LYS199/HIS242), while crocin-1 suffers glycosyl entropy penalty. • Clinically critical displacement risk : >99 % plasma protein binding and >100 % increased free warfarin ( P < 0.001) validated by multispectral/computational approaches. • Albumin-based solutions : Proposed formulations overcome crocin-1′s bioavailability limits and stabilize crocetin’s gut microbiota-dependent variability. Human serum albumin (HSA) serves as a critical carrier for systemic drug delivery.This study elucidates the competitive binding dynamics of the main active component of saffron, crocin-1, and its aglycone metabolite crocetin to HSA through integrated multispectral and computational analyses. Ultracentrifugation revealed high plasma protein binding (PPB) rates for both compounds (crocin-1: 90 %; crocetin: >99 %), indicating susceptibility to displacement by high-affinity drugs like warfarin. Static quenching dominated HSA interactions, confirmed by temperature-dependent K SV decay, K q exceeding diffusion limits, and UV–Vis spectral shifts. Crocetin exhibited 43 % higher affinity ( K a = 3.49×10 5 M -1 ) than crocin-1 ( K a = 2.44 × 10 5 M -1 ) at 310 K, driven by bidentate hydrogen bonding (LYS199/HIS242) and deeper hydrophobic pocket penetration, as evidenced by molecular docking. Thermodynamically, crocin-1 binding was enthalpy-driven (Δ H = −38.55 kJ/mol) but hindered by glycosyl conformational entropy loss, whereas crocetin leveraged strong exothermicity (Δ H = − 65.15 kJ/mol) to overcome entropy penalties. Structurally, crocin-1 reduced HSA α-helix content by 5.2 %, while crocetin preserved integrity. Critically, co-incubation with crocin-1/crocetin doubled free warfarin concentrations ( P < 0.001), highlighting clinical risks for anticoagulant co-therapy. These findings provide a foundation for developing albumin-based delivery systems for saffron-derived neuroprotectants while highlighting clinical risks in co-therapy.

Osteosarcoma, the most common primary malignant bone tumour, presents significant treatment challenges due to its complex tumour microenvironment and the development of chemoresistance. This study employs single-cell transcriptomics to investigate chemotherapy-induced changes in osteosarcoma at both the cellular and molecular levels. Single-cell RNA sequencing data were analysed to identify cell subpopulations and their responses to chemotherapy. Differential gene expression and pathway enrichment analyses were performed to elucidate chemotherapy-induced changes. Additionally, we developed and validated a predictive model based on pyroptosis-related genes, named Pyroscore, using 101 different machine-learning algorithms. Chemotherapy led to an increased proportion of osteoclasts, endothelial cells, mesenchymal stem cells and pericytes, while decreasing T and NK cells, B cells, chondroblasts, monocytes and macrophages. Chemotherapy markedly upregulates the pyroptosis pathway in tumour cells, suggesting that chemotherapy induces programmed cell death in cancer cells through the activation of pyroptosis. Metabolic pathway analysis revealed significant inhibition of sulphur metabolism, starch and sucrose metabolism, pentose phosphate pathway, inositol phosphate metabolism, nitrogen metabolism and fatty acid metabolism. The Pyroscore model, which incorporates BAK1, CASP1, CASP5 and CASP6, demonstrated robust prognostic value across multiple data sets, with high scores correlating with improved survival outcomes. This study highlights the impact of chemotherapy on osteosarcoma cell subpopulations and the tumour microenvironment. The activation of the pyroptosis pathway and the development of the pyroscore prognostic model provide new insights into the mechanisms of chemotherapy response and potential therapeutic targets. These findings underscore the importance of personalized treatment strategies in improving outcomes for osteosarcoma patients.

To evaluate the efficacy and safety of Linggui Yangyuan Paste (LG) in treating male infertility caused by asthenozoospermia (AZS) and oligoasthenozoospermia (OAZS) associated with the Chinese medicine (CM) pattern of Shen (Kidney) deficiency and blood stasis. This randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial enrolled 162 male infertility patients at 5 hospitals in China from June 2023 to February 2024. Using block randomization within strata, participants were assigned (1:1) to LG + Wuzi Yanzong Oral Solution (WZ) placebo or WZ + LG placebo for 12 weeks (each LG 1 sachet and WZ 1 vial, twice daily), with a 12-week follow-up. The primary outcome was the change in total progressive motile sperm count (TPMSC) from baseline to week 12. Secondary outcomes included pregnancy rate, CM symptom score (CMSS), and semen parameters including semen volume (SV), sperm concentration (SC), total sperm count (TSC), progressive motility (PR), and PR + non-progressive motility (NP). Prespecified subgroup analyses on cumulative pregnancy rate and semen parameters were performed for participants with AZS and OAZS. Safety was monitored throughout the trial. Of 162 randomized participants, 145 completed the trial (75 in the LG group and 70 in the WZ group) and were included in the per-protocol analysis. At week 12, the LG group showed significantly greater improvement in TPMSC compared to the WZ group, with an adjusted between-group difference of 8.81 × 106 sperm (P<0.05, 95% confidence interval 2.75-14.87). The cumulative pregnancy rate at week 24 was significantly higher in the LG group than the WZ group [24.0% (18/75) vs. 10.0% (7/70), P<0.05)]. CMSS decreased significantly in both groups, with greater reduction in the LG group (P<0.05). Subgroup analysis showed that cumulative pregnancy rates were higher in the LG group than in the WZ group in the AZS subgroup at both weeks 12 and 24 (both P<0.05). In the AZS subgroup analysis, PR and PR+NP showed significantly greater improvements in the LG group (P<0.05). In the OAZS subgroup, SV, SC, TSC, PR, and PR+NP all showed greater improvements in the LG group (P<0.05). No adverse events or adverse drug reactions were reported in either group. LG demonstrates significant efficacy and safety in treating male infertility associated with Shen deficiency and blood stasis syndrome, supporting its clinical application as an integrative therapy for male infertility. (Registration No. ITMCTR2023000009).

BackgroundMyocardial infarction (MI) is a leading cause of cardiovascular mortality worldwide and requires timely treatment and accurate public awareness of risk factors, warning signs, and first aid. In China, short-video platforms such as TikTok (Douyin, Chinese mainland version) and Bilibili have become major health information sources, yet the quality and reliability of MI-related content remain inadequately evaluated.ObjectiveThis cross-sectional study systematically assessed and compared the quality, reliability, and educational value of MI-related videos on TikTok and Bilibili.MethodsUsing the keyword “心肌梗死” (myocardial infarction), we retrieved the top 100 videos from TikTok and Bilibili on September 1, 2025. After exclusions, 137 videos were included. Uploaders were classified as clinicians, patients, or traditional Chinese medicine practitioners. Quality was evaluated using GQS, mDISCERN, JAMA benchmarks, and PEMAT-U/A. Statistical analyses included Spearman correlation, Mann–Whitney U, Kruskal–Wallis, and chi-square tests.ResultsBilibili videos were significantly longer but had much lower engagement than TikTok videos. Only mDISCERN scores differed significantly between platforms: Bilibili contained a higher proportion of high-reliability videos than TikTok, while JAMA, GQS, and PEMAT-U/A scores did not differ significantly. Uploader background significantly influenced quality outcomes. Clinicians and TCM practitioners achieved higher JAMA scores than patients, indicating greater formal credibility, whereas patients had a higher proportion of high mDISCERN scores, reflecting more detailed experiential content. Correlation analysis revealed a bidirectional effect of video length: longer duration was positively associated with mDISCERN and GQS scores but negatively associated with JAMA scores. Interaction metrics showed strong internal synergy but almost no correlation with professional quality scores, demonstrating a clear “quality popularity paradox.”Content analysis showed an imbalanced pattern: particularly regarding emergency measures and medication safety information were severely lacking.ConclusionMI-related content on Chinese short-video platforms is of moderate quality but characterized by a significant disconnect between popularity and educational value, as well as critical deficiencies in emergency response information. These findings underscore the urgent need for coordinated interventions, including platform-level quality control, collaborative content creation between professionals and platform, and enhanced public health literacy to ensure the safe and effective use of these platforms for health education.