With the deepening application of artificial intelligence (AI) technology in the field of medical devices, pre-trained models have increasingly become a crucial engine driving innovation in intelligent healthcare due to their efficiency, generalization capability, and transfer learning performance. However, potential risks associated with pre-trained models—such as issues related to source diversity and quality controllability —pose new challenges to the safety and effectiveness of AI-based medical devices. Against this background, the National Medical Products Administration (NMPA) released the sectoral standard YY/T 1833.5-2024 Artificial Intelligence Medical Devices—Quality Requirements and Evaluation-Part 5: Pre-trained Models in September 2024. This standard provides essential technical guidance and a regulatory framework for standardizing the application of pre-trained models in medical devices, marking a milestone in ensuring the safety and efficacy of AI-powered medical products. This article offers an in-depth interpretation and analysis of the standard's background, orientation, and key technical consideration. It elucidates specific requirements regarding documentation for pre-trained models, definitions of critical quality attributes, and conformity assessment pathways. Furthermore, the practical and far-reaching implications of the standard are discussed, including its role in enhancing quality assurance throughout the entire lifecycle of AI-based medical devices and guiding technological innovation and healthy development within the industry. Additionally, by dissecting the standard, this article aims to support the industry in conducting prudent evaluations during model selection phases, thereby reducing the application of low-quality and high-risk models.

BACKGROUND: The achievement of an optimal return to sport (RTS) has remained a key goal after sports-related injuries, with the ongoing debate on the effectiveness of different surgical approaches for anterior cruciate ligament (ACL) rupture. This study aims to assess clinical outcomes and RTS across various surgical methods, such as anatomical single-bundle reconstruction (ASBR), central-axial single-bundle reconstruction (CASBR), and double-bundle reconstruction (DBR). METHODS: A randomized clinical trial was conducted, comprising 191 patients who underwent ACL rupture. These patients were divided into three groups based on the ACL reconstruction techniques they received (ASBR, CASBR, DBR). Over the 2-year follow-up period, the study assessed RTS through four single-hop tests, isokinetic extension tests, and limb asymmetry indices. Postoperative graft status was determined using the signal-to-noise quotient (SNQ), while knee function was evaluated using the International Knee Documentation Committee 2000 (IKDC-2000) score, Lysholm score, Tegner score, and degree of knee laxity. A binary logistic regression model was developed to forecast the factors influencing ideal RTS. RESULTS: DBR (67.63%) and CASBR (58.00%) exhibited higher RTS passing rates compared to ASBR (30.39%; χ2 = 19.57, P <0.05). Quadriceps strength symmetry in the lower limbs was identified as the key determinant of RTS ( χ2 = 17.08, P <0.05). The RTS rate was influenced by SNQs of the graft's tibial site (odds ratio: 0.544) and quadriceps strength of the reconstructed knee joint at 60°/s (odds ratio: 6.346). Notably, the DBR group showed enhanced knee stability, evidenced by superior results in the Lachman test ( χ2 = 13.49, P <0.01), objective IKDC-2000 ( χ2 = 27.02, P = 0.002), and anterior instability test ( χ2 = 9.46, P <0.01). Furthermore, DBR demonstrated superior clinical outcomes based on the Lysholm score (DBR: 89.57 ± 7.72, CASBR: 83.00 ± 12.71, ASBR: 83.21 ± 11.95; F = 10.452, P <0.01) and IKDC-2000 score (DBR: 90.95 ± 7.00, CASBR: 84.64 ± 12.68, ASBR: 83.63 ± 11.41; F = 11.78, P <0.01). CONCLUSION: For patients with ACL rupture, more ideal RTS rate and clinical outcomes were shown in the DBR group than in the ASBR and CASBR groups. Autograft status and quadriceps strength are postively related to RTS. TRIAL REGISTRATION ClinicalTrials.gov (NCT05400460).
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Return to Sport ; Adolescent ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Objective : To evaluate the coverage and spatial clustering of 13-valent pneumococcal conjugate vaccine(PCV13) among the 2017—2023 birth cohorts in Anhui Province. Methods : Obtained vaccination data of PCV13 for children born in 2017—2023 from the Anhui Immunization Information Management System.We estimated coverage levels and described characteristics of coverage.The spatial autocorrelation analysis of coverage was conducted. Results : Cumulative coverage,cumulative primary immunization coverage and cumulative full-series coverage of PCV13 were 17.19%,12.12% and 9.09% among the 2017—2023 birth cohort in Anhui Province.The coverage of PCV13 increased from 1.14% in the 2017 birth cohort to 41.59% in the 2022 birth cohort.The first dose of PCV13 at ages under 3,3—6,7—11,12—23 and not less than 24 months were 45.35%,29.84%,5.52%,10.75% and 8.53%,respectively.There were significant differences in the ages of the first dose between children of different years of born and kinds of PCV13(P<0.001).Significant differences were also observed in the cumulative coverage,cumulative primary immunization coverage,cumulative full-series coverage of PCV13 and ages of the first dose among children from various residence regions(P<0.001).From 2018 to 2023 birth cohort,the coverage of PCV13 in Anhui Province showed obvious positive spatial autocorrelation.Local spatial autocorrelation analysis showed that the "high-high" agglomeration areas were concentrated in the central area of Anhui. Conclusion The coverage of PCV13 was low in Anhui Province with significant regional differences.

Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.

Objective: To evaluate the effect of Tai Chi and Qigong on patients with lumbar disc herniation (LDH). Methods: Relevant data were retrieved from nine English and Chinese databases, including Cochrane Library, PubMed, and Wanfang Data, etc. from inception to June 2024. All published randomized controlled trials assessing the effect of Tai Chi and Qigong on visual analog scale (VAS), Japanese Orthopedic Association (JOA) score, and other health indicators in participants with LDH compared to usual medical care or other treatments were included. Grey literature, trials involving the pushing of hands (Tui Shou) or Tai Chi with weapons, and trials with co-interventions (Tai Chi/Qigong plus another treatment) were excluded. Methodological quality was analyzed using the Cochrane risk of bias tool, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: Fourteen trials (954 patients) were included in this study. Tai Chi and Qigong were associated with lower VAS pain scores (standardized mean difference −0.55, 95% confidence interval [CI] −0.95 to −0.15, P = .01), higher JOA scores (mean difference [MD] 4.40, 95% CI 2.62 to 6.18, P < .001) and straight leg raise test results (MD 9.40°, 95% CI 7.64 to 11.15, P < .001) in patients with LDH. Furthermore, compared with usual care, Tai Chi and Qigong showed enhanced effects on pain and JOA scores. When compared to other exercises or massage, the effect on pain scores was similar but that on JOA scores was significant. Conclusions Tai Chi and Qigong may have favorable effects on VAS pain and JOA scores compared with usual care, and on JOA scores compared with other exercises or massage in patients with LDH. Given the overall poor quality of the evidence, the results of current study should be interpreted cautiously.