The research and development of innovative drug have progressed remarkably, but the long development circle and high failure rate have become the bottleneck. Drug repurposing, discovering new indications of approved drugs, is a strategy to overcome these obstacles. By exploring new indications for approved drugs, rapid progress has been made in basic research and clinical translation in recent years. Rich resources of drugs, proven security, efficient development workflow and reduced cost are core advantages of this strategy, making the strategy a crucial direction of optimizing the pipeline of drug research and development. This review systematically summarizes drug repurposing cases that have received clinical approval over the past five years, and proposes core strategies for drug repurposing, including approaches based on targets, pathways, drug similarity, post-treatment phenotypes, and clinical side effects, aiming to provide some strategic guidance for drug repurposing efforts.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

There is controversy over the specific and non-specific components in the efficacy evaluation of acupuncture therapy.The placebo effect,as a key non-specific factor,needs to be clarified in terms of its mechanism and clinical value.This article reviewed the research progress in the placebo effect of acupuncture from three aspects:cognitive process,influencing factors,and mechanism.It focused on the regulatory effects of patient expectations,doctor-patient interaction,and individual differences on the effect,summarized key mechanisms such as endogenous opioid system,dopamine reward pathway,and neural projection of rostral anterior cingulate cortex to pontine nucleus,and pointed out the methodological limitations of current comfort acupuncture designs,in order to provide theoretical basis for the optimization of acupuncture clinical research models and the deepening of the effect mechanism.

Objective:To detect the expression levels of long non-coding RNAs(lncRNA)in elderly patients with pulmonary tuberculosis(PTB)and those with non-tuberculous lung diseases(non-TB), and to assess the performance of these lncRNA in the differential diagnosis of PTB.Methods:A total of 300 elderly patients with suspected PTB were recruited from Beijing Chest Hospital between January 2024 and September 2024, and were further divided into the PTB group and the non-TB lung disease group based on the results of mycobacterium tuberculosis(MTB)pathogenicity testing.Peripheral blood mononuclear cells were isolated using a lymphocyte separation solution, and RNA was extracted using the TRIzol method.Nine lncRNAs, previously identified as differentially expressed in PTB through our group's microarray analysis, were selected and detected by real-time fluorescence quantitative polymerase chain reaction to evaluate the expression levels of these lncRNAs between the PTB and non-TB lung disease groups.The overall patients were randomly divided into training and validation sets in a 7∶3 ratio.Lasso regression was employed to select the characteristic variables, and a random forest algorithm was then used to construct the lncRNA diagnostic portfolio.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of individual lncRNAs and the combined panel in differentiating elderly patients with PTB from those with other non-TB lung diseases.Results:A total of 201 cases were included, with 105 confirmed elderly patients diagnosed with PTB(52.2%)and 96 elderly patients suffering from non-TB lung disease(47.8%).Compared to the elderly patients with non-TB lung disease, the expression levels of ENST00000417346.1, ENST00000620744.1, lncRNA PWP1, ENST00000583184.1, lncRNA ABHD17B, ENST00000607464.1, ENST00000516057.1, and NR_003000 were significantly downregulated in the PTB patients, whereas the expression level of lncRNA BCL2L10 was significantly upregulated in the PTB patients.ROC analysis revealed that the area under the curve(AUC)for each lncRNA ranged from 0.659 to 0.848.The diagnostic panel, which included NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1 as determined by Lasso analysis, exhibited AUC values of 0.917 and 0.906 in the training and validation sets, respectively.The performance of this panel was superior to that of each individual lncRNA.Conclusions:The random forest model, which incorporates NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1, demonstrates potential in differentiating between PTB and non-TB lung diseases.

Objective:To explore the effect of transcranial direct current stimulation (tDCS) on dysphagia in hemispheric stroke patients.Methods:Sixty-two hemispheric stroke patients with dysphagia were randomized into an ipsilateral group, a contralateral group and a bilateral group with 20 in each group. The ipsilateral and contralateral groups received tDCS over their ipsilesional and contralesional hemispheres, respectively, while in the bilateral group it was over both hemispheres. That was followed by conventional swallowing therapy. Before and after 2 weeks of the treatment, swallowing function was assessed using the modified Mann Assessment of Swallowing Ability (MMASA) and a Swallow Severity scale (SSS). Linear regressions were evaluated to highlight the factors most influencing recovery from post-stroke hemispheric dysphagia.Results:After the treatments, the average MMASA and SSS scores had increased significantly in all three groups. There was no significant difference in the average post-treatment MMASA and SSS scores between the ipsilateral and contralateral groups, but the bilateral group showed significantly better average post-treatment MMASA and SSS scores compared to the other two groups. Linear regression analysis confirmed that the tDCS protocol (group allocation) was a significant predictor of recovery.Conclusion:Bilateral tDCS can effectively promote the recovery of swallowing function after a hemispheric stroke. It demonstrates greater therapeutic benefits than unilateral tDCS.

Objective:To evaluate the association between triglyceride-glucose(TyG) index level, their variability, and the risk of incident hyperuricemia(HUA).Methods:A total of 1 583 cases with good compliance who underwent follow-up at the health examination center of a tertiary hospital physical in Zhengzhou were enrolled. The TyG index mean(TyG-mean) and variability indexes, including standard deviation(TyG-SD), coefficient of variation(TyG-CV), and adjusted standard deviation(adj-TyG-SD), were calculated based on TyG index values from three consecutive annual health check-ups. Cox proportional risk regression model was used to assess the relationship between the variability of TyG index and the risk of new-onset HUA; the dose-response relationship between different TyG indexes and HUA was examined using restricted cubic spline(RCS). Results:After a 3-year follow-up, 146 participants developed incident HUA. Both TyG-mean and TyG index variability indicators were significantly higher in the HUA group compared to the non-HUA group( P<0.05). After adjusting for multiple confounders, each standard deviation σincrease in TyG-SD, TyG-CV, and adj-TyG-SD was associated with a 1.23-fold(95% CI 1.06-1.43), 1.22-fold(95% CI 1.05-1.42), and 1.26-fold(95% CI 1.08-1.45) higher risk of incident HUA, respectively. RCS analysis revealed a nonlinear association between adj-TyG-SD and HUA risk( P<0.05), with a critical threshold of 0.55 at a hazard ratio( HR) of 1. Conclusions:Increased TyG index variability is associated with a higher risk of incident HUA, with adj-TyG-SD showing the strongest correlation with HUA risk.

Objective:To address the challenges in cultivating young medical researchers, including the lack of initial research funding, insufficient interdisciplinary collaboration, absence of academic exchange platforms, and inadequate talent incentives, this study analyzes the specific practical measures of the new model(Fund-Alliance-Academic activities-Award Model, hereinafter referred to as ″FAAA model″) of A certain medical college in enhancing the innovative capabilities and interdisciplinary research proficiency of young medical talents in initial stage, and evaluates the practical significance of these initiatives.Methods:Through literature review, the inevitability of interdisciplinary integration was examined in the context of China′s developmental needs and medical discipline advancement. Innovative practices under the FAAA model of A certain medical college were retrospectively analyzed, focusing on the construction of a medical youth scientific innovation and development platform.Results:The FAAA model had achieved effective outcomes in improving young researchers′ capabilities, fostering interdisciplinary achievements, expanding academic influence, and advancing talent echelon development, yet required further refinement.Conclusions:The FAAA model effectively addresses critical bottlenecks in the growth of young medical researchers through systematic support mechanisms, significantly enhancing their scientific competitiveness and interdisciplinary innovation capacity. Its practical measures offer referential value for peer institutions. Future efforts should optimize the ″early funding-achievement incubation-national project linkage″ chain, strengthen institutionalized interdisciplinary collaboration, and build a data-driven ecosystem to provide sustainable talent support for medical science and technology innovation.

Objective:To establish a modified one-stage clotting assay (mOSA) based on the STA-R Evolution coagulation analyzer for quantifying emicizumab (EMI) concentration and to preliminarily evaluate its analytical performance; meanwhile to explore the clinical utility of the standard one-stage clotting assay (sOSA) in indirectly predicting EMI levels through surrogate factor Ⅷ (FⅧ) activity.Methods:A total of 30 pediatric patients with hemophilia A (HA) treated with EMI in the Hemophilia Treatment Center of Shenzhen Children′s Hospital from January 2023 to March 2025 were enrolled, and 48 post-treatment plasma samples were collected. EMI standards (2.5~100 μg/ml) were prepared using FⅧ-deficient plasma to establish the mOSA detection system. The linearity, accuracy, and precision of the method were evaluated. Surrogate FⅧ activity was measured by sOSA to estimate EMI concentrations, and its correlation with mOSA-derived EMI concentrations was analyzed using Spearman correlation analysis. The equivalent FⅧ activity in patient plasma samples was measured using a human chromogenic substrate assay-based FⅧ activity detection reagent, and Spearman correlation analysis was employed to evaluate its correlations with both the EMI concentrations measured by the mOSA method and estimated by the sOSA method respectively.Results:The established mOSA method for EMI detection showed excellent linearity in the range of 2.5?100 μg/ml ( Y=1.047 X?1.033, R 2=0.995, P<0.001). Average spike recovery rates at 25, 50, and 75 μg/ml were 101.55%(25.39/25.00), 105.31%(52.66/50.00), and 98.20%(73.65/75.00), respectively. Coefficients of variations of within-and inter-batch were 3.47%?4.80% and 6.30%?8.96%, respectively. A prediction model for EMI concentration was established as follows: estimated EMI concentration (μg/ml)=0.095×[alternative FⅧ activity (%) measured by sOSA]+2.652 ( R2=0.999, P<0.001). Validation demonstrated a strong correlation between the EMI concentration measured by the mOSA method and the EMI concentration estimated by the sOSA method ( r=0.989, P<0.001), with good consistency ( Y=1.014 X+0.684, R2=0.972, P<0.001). Both the EMI concentration measured by the mOSA method and the EMI concentration estimated by the sOSA method showed extremely strong correlations with the equivalent FⅧ activity ( r=0.986 and 0.987, respectively; P<0.001 for both). Conclusions:The mOSA system established on the STA-R Evolution analyzer demonstrates robust linearity, accuracy, and reproducibility, fulfilling clinical requirements for therapeutic drug monitoring of EMI. The sOSA method provides reliable indirect estimation of EMI concentrations through surrogate FⅧ activity, offering critical support for emergency decision-making.

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.