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.

Objective:To investigate the clinical efficacy of autologous ear cartilage biomimetic nasal tip framework construction combined with dermal fat dorsal grafting in rhinoplasty.Methods:A retrospective analysis was conducted on clinical data of patients who underwent rhinoplasty at the Department of Plastic Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to May 2023. Autologous ear cartilage with preserved perichondrium was harvested from patients, and fashioned into a nasal tip framework simulating the natural nasal tip structure. Dermal fat grafts were harvested from the lateral gluteal crease region where the dermis was thicker, and implanted into the nasal dorsum for augmentation rhinoplasty. Postoperative follow-up included observation of incision healing, nasal tip morphology, and complications. Pre- and postoperative photographs were taken to measure nasal length and nasal tip height. Ultrasound was used to measure subcutaneous fat thickness at the nasal root before and after surgery, and absorption rates were calculated. The absorption rate at 6, 12, and 24 months postoperatively = (1 -subcutaneous fat thickness at 6 or 12 or 24 months postoperatively/subcutaneous fat thickness at 1 month postoperatively) × 100%. Aesthetic satisfaction was evaluated based on surgeon assessment, patient self-evaluation, and third-party physician evaluation (satisfaction by all three parties was rated as markedly effective, by two parties as effective, by one party as fair, and by none as poor). The aesthetic satisfaction rate = (markedly effective + effective) cases/total cases × 100%. Comparisons of preoperative and postoperative nasal tip height and nasal length were performed using paired t-tests, with P<0.05 considered statistically significant. Comparisons of subcutaneous fat thickness at the nasal root at different time points and absorption rates at different postoperative time points were performed using repeated measures ANOVA, with post-hoc pairwise comparisons using Bonferroni correction. For subcutaneous fat thickness comparisons, P<0.007 was considered statistically significant; for absorption rate comparisons, P<0.017 was considered statistically significant. Results:A total of 38 patients were included, consisting of 5 males and 33 females, with a mean age of 29.42 years (range 20-38 years). All patients were followed up for 24 months postoperatively. All incisions healed well; nasal appearance was aesthetically pleasing; nasal dorsal height was satisfactory; nasal tip mobility was good; the framework was stable; and no complications occurred. At 24 months postoperatively, nasal tip height [(22.87±0.52) mm vs. (19.94±0.53) mm] and nasal length [(47.18±0.61) mm vs. (44.20±0.55) mm] were significantly increased compared to preoperative measurements (both P<0.01). Comparison of subcutaneous fat thickness at the nasal root between preoperative and postoperative time points (1, 6, 12, and 24 months) showed statistically significant differences ( P<0.007). Post-hoc comparisons revealed statistically significant differences between: postoperative 1 month and 6 months vs. preoperative; postoperative 12 months vs. postoperative 1 and 6 months; and postoperative 24 months vs. postoperative 1 and 6 months (all P<0.007). However, the comparison between postoperative 24 months and 12 months showed no statistically significant difference ( P>0.007). Comparison of absorption rates at postoperative time points (6, 12, and 24 months) showed statistically significant differences ( P<0.017). Comparisons between postoperative 12 months vs. 6 months, and postoperative 24 months vs. 6 months showed statistically significant differences (both P<0.017), while the comparison between postoperative 24 months and 12 months showed no statistically significant difference ( P>0.017). In the aesthetic satisfaction survey, 37 cases were markedly effective and 1 case was fair, achieving an aesthetic satisfaction rate of 97%. Conclusion:The use of autologous ear cartilage for constructing a biomimetic nasal tip framework combined with dermal fat dorsal grafting in rhinoplasty results in natural postoperative appearance and high patient satisfaction, demonstrating significant value for extensive clinical use.

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.

Due to the high prevalence of periodontitis, the control of periodontal inflammation, as well as the regeneration and repair of periodontal tissues have attracted extensive attentions. To better understand the mechanism of periodontal diseases, in vivo and in vitro models are usually required. With the rapid development of tissue engineering, in vitro models with the advantages of easy observation, high controllability, low cost, and high efficiency has become a unique choice for current research. In vitro models of periodontitis are no longer limited to cellular models, researchers are increasingly inclined to develop simple, effective, and realistic models to simulate the periodontal microenvironment. This article reviews in vitro models of periodontitis that have been successfully established, aiming to provide researchers with new ideas to simulate the human periodontitis microenvironment in vitro, which is helpful to explore the pathogenesis of periodontitis.

Objective:Ménière's disease（MD） is a common disorder of the inner ear. The fluctuating clinical symptoms and the absence of gold standards for diagnosis have posed serious problems for clinical diagnosis and treatment over the years. With the development of science and technology, artificial intelligence （AI） has been widely used in the field of medicine, and the potential of AI application to MD is demonstrated. The purpose of this review is to outline the use of AI in MD. Initially, specific instances where AI aids in differentiating MD from other causes of vertigo are presented. Furthermore, the role of AI in the evaluation of Endolymphatic Hydrops （EH）, particularly through imaging and biochemical assays, is highlighted due to its correlation with MD. Additionally, the effectiveness of AI in managing MD patients and forecasting disease progression is examined. In conclusion, the prevalent challenges hindering the clinical integration of AI in MD treatment are discussed, alongside potential strategies to surmount these barriers.
Humans ; Meniere Disease/diagnosis* ; Artificial Intelligence ; Endolymphatic Hydrops/diagnosis*

Objective To investigate whether aberrant DNA methylation of ubiquinol-cytochrome C reductase core protein 1(UQCRC1)is related to cognitive impairment caused by neonatal sevoflurane exposure.Methods A total of 94 SPF C57 mice of either sex,aged 6 d,and weighing 4～6 g,were randomly divided into 7 groups:control group(Con,n=6),sevoflurane-6 and-24 h exposure groups(Sev-6 and-24 h,n=6),control+DMSO group(Con+DMSO,n=19),control+5-aza-2'-deoxycytidine(5-AZA,methylation inhibitor)group(Con+5-AZA,n=19),sevoflurane+DMSO group(Sev+DMSO group,n=19),and sevoflurane+5-AZA group(Sev+5-AZA group,n=19).From 6 to 8 d after birth,the mice of the Sev-6 and-24 h exposure groups were exposed to 3％sevoflurane daily(with 97％oxygen,2 L/min,2 h per day),while those from the Con groups were given exposure of 100％oxygen(2 L/min,2 h per day).For the mice of the 5-AZA and DMSO groups,1 mg/kg of 5-AZA or an equal volume of DMSO was injected intraperitoneally 30 min before daily exposure.In 6 and 24 h after the last exposure to sevoflurane,6 mice from the Con,Sev-6 h,and Sev-24 h groups were euthanized for biochemical analysis,and in 24 h post-exposure,6 mice from the Con+DMSO,Con+5-AZA,Sev+DMSO,and Sev+5-AZA groups were randomly selected for biochemical analysis,while another 3 mice from above each group were also randomly selected for morphological analysis.The remaining 10 mice in these groups underwent behavioral testing(open field test,novel object test,and Y-maze test)at 30～33 d after birth to assess cognitive function,and were euthanized in 24 h after the final behavioral test.RT-qPCR and Western blotting were used to detect the hippocampal expression of UQCRC1,DNA methyltransferases(Dnmts),and methyl CpG binding protein 2(Mecp2)at mRNA and protein levels,respectively.Immunofluorescence assay was employed to observe the distribution and expression of UQCRC1 in the hippocampus.Bisulfite sequencing PCR(BSP)was applied to measure the methylation in the UQCRC1 promoter region.Results Compared with the Con group,the mRNA and protein levels of UQCRC1 were down-regulated(P<0.05),and the mRNA level of Dnmts was up-regulated(P<0.05)in both the Sev-6 h and Sev-24 h exposure groups,while the methylation level in the UQCRC1 promoter region was enhanced in the Sev-24 h exposure group(P<0.05).Additionally,the Sev+5-AZA group had obviously increased mRNA and protein levels of UQCRC1(P<0.05),and notable improvement in cognitive impairment(P<0.05)when compared with the Sev+DMSO group.Conclusion Hypermethylation of UQCRC1 promoter region and thus down-regulating its mRNA and protein expression might be the main mechanism by which repeated neonatal sevoflurane exposure induces cognitive impairment later in life.

Bronchopulmonary dysplasia（BPD）is a chronic respiratory disease characterized by developmental disorders and abnormal repair of lung tissue in premature infants.Its clinical manifestations are characterized by persistent respiratory distress syndrome，which can cause progressive lung function damage and significantly affect the quality of life and long-term prognosis of the affected children.Vitamin D has been proven to have multiple lung protective effects in recent years.It not only participates in regulating normal lung development，but also effectively inhibits inflammatory reactions，promotes the biosynthesis of pulmonary surfactant，regulates cell apoptosis，and maintains lung tissue function and structural integrity.The above physiological functions are significantly correlated with the pathophysiology of BPD，providing a new theoretical perspective for further elucidating the pathogenesis of BPD.Based on existing evidence，vitamin D may provide new treatment and research directions for BPD.