Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches.

Postoperative cognitive dysfunction or impairment,¹ as a particular format and important component of the broader concept of perioperative neurocognitive disorder,² is a common complication of surgery and anesthesia. With large variations by age and surgery type, the incidence rates of postoperative cognitive dysfunction are most marked in older patients after cardiac surgery (16.0%-39.0% at 3 months),^3,4 whereas the rates after major noncardiac surgery (9.9%-12.7%) or surgery in younger patients (5.6% of those aged 40-59 years)^5,6 are lower. On the basis of small studies, a comparable incidence of postoperative cognitive impairment was reported among older Chinese surgery patients (10.3%-18.2%).^7,8 However, data from middle-aged Chinese adults with cognitive function measured up to 12 months after surgery are lacking. In addition to direct impairments in perception, thinking, and memory ability, cognitive impairment has been found to be associated with increased medical costs after surgery,⁹ dismissal from work due to disabilities,¹⁰ and even increased premature deaths.⁶ Therefore, understanding the cognitive trajectories of surgery patients and identifying risk factors, particularly the modifiable ones that might contribute to postoperative cognitive deterioration, are crucial and have great clinical importance in terms of developing interventions for postoperative cognitive impairment prevention.

Myocardial ischemic/reperfusion (IR) injury is a global cardiovascular disease with high mortality and morbidity. Therapeutic interventions for myocardial ischemia involve restoring the occluded coronary artery. However, reactive oxygen species (ROS) inevitably impair the cardiomyocytes during the ischemic and reperfusion phases. Antioxidant therapy holds great promise against myocardial IR injury. The current therapeutic methodologies for ROS scavenging depend predominantly on administering antioxidants. Nevertheless, the intrinsic drawbacks of antioxidants limit their further clinical transformation. The use of nanoplatforms with versatile characteristics greatly benefits drug delivery in myocardial ischemic therapy. Nanoplatform‐mediated drug delivery significantly improves drug bioavailability, increases therapeutic index, and reduces systemic toxicity. Nanoplatforms can be specifically and reasonably designed to enhance molecule accumulation at the myocardial site. The present review initially summarizes the mechanism of ROS generation during the process of myocardial ischemia. The understanding of this phenomenon will facilitate the advancement of innovative therapeutic strategies against myocardial IR injury. The latest developments in nanomedicine for treating myocardial ischemic injury are then discussed. Finally, the current challenges and perspectives in antioxidant therapy for myocardial IR injury are addressed.

There is still debate over whether opioid-free anaesthesia (OFA) can improve the patient-reported quality of recovery (QoR). A search was conducted across Pubmed, Cochrane Library, and EMBASE until June 2024 for randomized controlled trials comparing the impact of OFA and opioid-based anaesthesia (OBA) on QoR in adult patients undergoing general anaesthesia. The primary outcome was the quality of recovery measured with the QoR scale. The secondary outcomes were the five dimensions of the QoR scale. The analysis included 15 studies, and showed that compared with OBA, OFA improved the global QoR score at postoperative 24 h (SMD 0.87; 95% CI, 0.48 to 1.27; I²: 92%; low-level evidence). Among them, 10 studies revealed a greater QoR-40 score at postoperative 24 h in the OFA than in the OBA (MD 6.59; 95% CI, 2.84 to 10.34; I²: 93%; moderate-level evidence), which exceeded the minimal clinically important difference of 6.3. Conversely, the synthetic data of 4 studies did not reveal an improvement in the global QoR-15 score at postoperative 24 h (MD 9.94; 95% CI, -0.15 to 12.35; I²: 97%; low-level evidence). Regarding different domains of scale, OFA had positive effects on physical comfort (SMD 0.75; 95% CI, 0.25 to 1.25; I²: 93%; moderate-level evidence) and pain (SMD 0.59; 95% CI, 0.15 to 1.03; I²: 91%; moderate-level evidence). The meta-analysis indicate OFA can improve the quality of recovery at postoperative 24 h, particularly in terms of enhancing physical comfort and reducing pain. However, due to significant heterogeneity and moderate-to-low level of evidence, the external validity of OFA for improving postoperative recovery remains to be further validated. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database on December 07, 2023 (CRD42023486235).

PANoptosis plays a crucial role in cancer initiation and progression. However, the roles of PANoptosis-related genes (PARGs) in the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC) remain unclear. Integrated bioinformatics analyses based on the data of HNSCC patients in the TCGA database were conducted. We extracted 48 PARGs expression profile and then conducted differentially expressed analysis, following building a Cox model to predict the survival of HNSCC patients. Subsequently, the relationships between the risk score, immune landscape, chemo-, and immune-therapy responses were analyzed, respectively. Moreover, we investigated the prognostic value, and further predicted the pathways influenced by PARGs. Finally, we identified the biological function of crucial PARGs. A total of 18 differentially expressed PARGs were identified in HNSCC, and a Cox model including CASP8, FADD, NLRP1, TNF, and ZBP1 was constructed, which showed that the risk score was associated with the prognosis as well as immune infiltration of HNSCC patients, and the risk score could be regarded as an independent biomarker. Additionally, patients with high-risk score might be an indicator of lymph node metastasis and advanced clinical stage. High-risk scores also contributed to the chemotherapy resistance and immune escape of HNSCC patients. In addition, FADD and ZBP1 played a crucial role in various cancer-related pathways, such as the MAPK, WNT, and MTOR signaling pathways. On the other hand, we suggested that FADD facilitated the progression and 5-fluorouracil (5-FU) resistance of HNSCC cells. A signature based on PANoptosis showed great predictive power for lymph node metastasis and advanced stage, suggesting that the risk score might be an independent prognostic biomarker for HNSCC. Meanwhile, FADD, identified as a prognostic biomarker, may represent an effective therapeutic target for HNSCC.