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.

AIM: To investigate the association between dyslipidemia and macular hard exudates(HEs)in non-proliferative diabetic retinopathy(NPDR)secondary to type 2 diabetes mellitus(T2DM).METHODS: NPDR patients attending the outpatient ophthalmology clinic from January 2021 to December 2023 were selected and divided into three groups according to the severity of macular HEs. Group A: None or minimal HEs; Group B: Definite HEs; Group C: Prominent HEs. Total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), lipoprotein(a)[Lp(a)] levels and other lipid-related indicators were routinely measured. The correlation between these indicators and HEs was analyzed.RESULTS:Group A(24 eyes)consisted of 9 males and 15 females with the mean age of 54.71±6.15 y, group B(52 eyes)consisted of 20 males and 32 females with the mean age of 55.08±6.27 y, group C(14 eyes)consisted of 9 males and 5 females with the mean age of 53.93±6.08 y. The concentration of TC, TG, LDL-C and Lp(a)was highest in group C, followed by group B and lowest in group A with statistically significant differences(P<0.001). There were no statistically significant differences between the three groups for fasting plasma glucose(FPG), glycated hemoglobin A1c(HbA1c), creatinine(Cr), and HDL-C(P>0.05). The results of multivariate Logistic regression analysis showed that elevated levels of TC, TG, LDL-C, and Lp(a)were associated with the presence of macular HEs. Receiver operating characteristiccurve analysis showed that the area under the curve(AUC)for TC, TG, LDL-C, Lp(a), and their combination in predicting macular HEs in NPDR were 0.785, 0.718, 0.784, 0.742, and 0.911, respectively, with the combined model demonstrating the highest predictive performance.CONCLUSION: Dyslipidemia is closely associated with the development and progression of macular HEs in patients with NPDR and T2DM. The levels of TC, TG, LDL-C, and Lp(a)were correlated with the severity of macular HEs, suggesting that dyslipidemia may be involved in the pathological process of macular HEs formation.

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.

ObjectiveTo investigate the ameliorating effect of Xiao Chaihutang combined with Erchen Tang （XAE） on metabolic-associated fatty liver disease （MAFLD） in mice and the influence of this therapy on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/peroxisome proliferator-activated receptor α （PPARα） signaling pathway. MethodsForty-eight C57BL/6 mice were randomized into six groups： normal （CHOW）， atorvastatin （ATO， 0.05 g·kg^-1）， high-fat diet （HFD）， low-dose XAE （XAE-L， 10 g·kg^-1）， medium-dose XAE （XAE-M， 20 g·kg^-1）， and high-dose XAE （XAE-H， 40 g·kg^-1）. Each group contained 8 mice. Except the CHOW group， the other groups of mice were fed a HFD for the modeling of MAFLD. The experiment lasted for 20 weeks. Starting from the 13th week， mice were administered corresponding agents daily by gavage， and the mice in both the CHOW and HFD groups received equal volumes of purified water. At the end of the experiment， cardiac blood， liver， and adipose tissue samples were collected. Pathological staining was performed on the liver and adipose tissue separately. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglycerides （TG）， and total cholesterol （TC） in the serum， as well as TG and TC in the liver， were determined. Additionally， the mRNA levels of fatty acid synthetase （FASN）， stearoyl-CoA desaturase 1 （SCD1）， sterol regulatory element-binding protein 1c （SREBP-1c）， SIRT1， PPARα， PGC-1α， interleukin 6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the liver were measured by real-time PCR. The protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the mouse liver tissue were determined by Western blot. ResultsCompared with the CHOW group， the HFD group exhibited increased body weight， liver weight， and white adipose tissue weight （P<0.01）. After XAE intervention， these parameters were reduced compared with those in the HFD group （P<0.01）. Pathological section results showed that the morphology of hepatocytes and epididymal white adipocytes in the model mice was significantly improved after XAE intervention， with decreases in both the number and volume of lipid droplets. Furthermore， the XAE groups had lower levels of AST， ALT， HDL-C， LDL-C， TG， and TC in the serum and TG and TC in the liver than the HFD group （P<0.05，P<0.01）. Moreover， XAE administration downregulated the mRNA levels of lipid synthesis-related genes （FASN and SCD1） （P<0.05） and upregulated the mRNA levels of lipid oxidation-related genes （SIRT1， PPARα， and PGC-1α） （P<0.05，P<0.01）. Additionally， the protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the liver were upregulated after XAE treatment compared with those in the HFD group （P<0.05，P<0.01）. ConclusionXAE exerts a therapeutic effect on MAFLD by activating the SIRT1/PGC-1α/PPARα signaling pathway.

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*