Lanzhou University Second Hospital

Hepatocellular carcinoma (HCC) is one of the most common and poor prognosis digestive malignant tumors with high morbidity and mortality worldwide. Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer metabolism and plays a pivotal role in the genesis, development, metastasis and drug resistance of HCC. Exosomes are nanoscale membrane vesicles secreted by cells and widely found in various body fluids, capable of carrying a variety of bioactive molecules, such as proteins, nucleic acids, lipids, etc, and mediating intercellular communication. Increasing evidence indicates that exosomes regulate metabolic reprogramming in HCC by transferring specific bioactive molecules or modulating key signaling pathways. Through these mechanisms, exosomes influence the expression and activity of glycolysis-related enzymes, ultimately affecting the proliferation, invasion, migration, and chemosensitivity of HCC cells. This review focuses on the exosome-mediated regulation of aerobic glycolysis in HCC and highlights the therapeutic potential of targeting exosome-mediated metabolic pathways, offering new perspectives for combination treatment strategies in HCC.

Dear Editor, We recently read with great interest the article entitled “FANS-UAS under local anesthesia for urinary stones with high risk postoperative urosepsis” by Zhang et al in your prestigious journal[1]. In this study, nephrolithiasis accompanied by asymptomatic bacteriuria (ASB) or asymptomatic pyuria (ASP) are considered urinary stones associated with a high risk of postoperative urosepsis (HR-POU). They found that retrograde intrarenal surgery (RIRS) assisted by flexible and navigable suction ureteral access sheath (FANS-UAS) under local anesthesia (LA) is feasible and safe for these HR-POU patients, and preliminary results indicate it may reduce the incidence of postoperative fever. These findings provide an attractive new option for stones with HR-POU. However, several issues merit further discussion. This study is compliant with the TITAN Guidelines 2025 – governing declaration and use of AI[2]. For patients with stone obstruction complicated by pyonephrosis or perinephric abscess, clinical priority is given to drainage methods such as ureteral stent placement or percutaneous nephrostomy[3]. Stone management is deferred to a second-stage procedure once the local infection has improved. However, this study performed first-stage FANS-UAS assisted RIRS on all 28 patients with kidney stones complicated by pyonephrosis without any discussion. Given the potential increased risk of infection following first-stage surgery, preoperative risk assessment and personalized treatment are particularly critical for these patients when opting for a primary surgery treatment plan. Based on the above, we recommend conducting a detailed analysis and discussion of the preoperative assessment and postoperative outcomes for patients with renal calculi complicated by pyonephrosis in this study. In most studies, general anesthesia (GA) is the preferred anesthetic type for RIRS[4]. The advantages of GA in kidney stone surgery include high patient compliance, controlled duration of anesthesia, and control over patient respiratory movements[5]. However, there are few studies evaluating the efficacy of LA during RIRS. This study found no significant differences between the two types of anesthesia in terms of surgical success rate, intraoperative bleeding, and operating time; however, patients in the LA group had a lower risk of postoperative fever. Furthermore, through comparative analysis of postoperative blood immune cells, the authors speculate that the cause may be attributed to the lack of significant impairment in immune function. It is our view that analyzing postoperative immune cells alone cannot fully elucidate the impact of primary surgical treatment under different anesthetic modalities on the immune function of patients with kidney stones. Instead, preoperative immune status should serve as the baseline, and different anesthetic techniques should be evaluated by comparing the degree of change in immune function before and after surgery between the two patient groups. During procedures performed under non-general anesthesia, unstable spontaneous breathing, uncontrollable coughing and sneezing reflexes, or patient movement that cannot be prevented during surgery due to inadequate analgesia may all negatively impact the successful completion of the surgical procedure. According to a study by Sahan et al, mucosal tears and hemorrhage occurred in 4.4% and 2.2% of patients in the regional anesthesia group, respectively[4]. In this study, three cases (0.8%) of patients undergoing LA experienced ureteral perforation. It is conceivable that the surgeon’s comfort level during procedures under local anesthesia would also be significantly reduced. Therefore, the safety and efficacy of RIRS assisted by FANS-UAS under LA require further discussion. In conclusion, this study pioneers an attractive new treatment option for patients with HR-POU kidney stones, but further prospective randomized controlled trials are needed to evaluate its safety and efficacy.

Metabolic reprogramming alters the processes by which tumor cells generate energy and synthesize products, affecting their growth and survival. It also reshapes the tumor microenvironment by influencing immune cell function and interaction. Current literature suggests that the metabolic characteristics of gastric malignancies are closely associated with tumor immune evasion and inflammatory responses, thereby influencing immune cell infiltration, tumor progression, and patient prognosis. Despite some progress, research on metabolic reprogramming in gastric cancer (GC) is challenging, particularly in understanding the specific mechanisms involved and their clinical applications. This review aims to comprehensively explore the mechanisms of metabolic reprogramming in GC and analyze its impact on the tumor immune microenvironment. We also propose potential metabolic-immune therapeutic strategies, such as glutaminase inhibitors, lactate transport blockers, and immune checkpoint therapy combined with metabolic regulators, providing new ideas and directions for immunotherapy in GC.

Introduction: Ischemic stroke (IS) is a major global health challenge, associated with high mortality and long-term disability. Current treatment strategies, including pharmacotherapy and acute reperfusion therapy, have significant limitations, underscoring the urgent need for novel neuroprotective agents. Andrographolide (AG), a bioactive compound derived from Andrographis paniculata, has demonstrated potent neuroprotective effects in various neurological disorders; however, the precise mechanisms underlying its efficacy in IS remain incompletely understood. This review aims to provide a comprehensive summary of the pharmacological effects of AG in IS, with the goal of identifying potential therapeutic avenues. Methods: A systematic literature search was conducted using PubMed, ScienceDirect, Web of Science, and Google Scholar, focusing on in vitro and in vivo studies that evaluated AG as a neuroprotective agent in the context of IS. Results: IS is a complex disease resulting from cerebral ischemia, which disrupts neural networks and triggers pathological processes including inflammation, blood-brain barrier (BBB) injury, and cell death. AG exhibits neuroprotective properties through multiple mechanisms, including antiinflammatory activity, endothelial cell protection, anti-apoptotic effects, and inhibition of platelet aggregation. Conclusion: AG represents a promising neuroprotective candidate for IS, acting via diverse mechanisms and pathways. Further research is warranted to elucidate its molecular targets and to explore its clinical potential in IS therapy.

Gliomas exhibit considerable molecular heterogeneity and immunological complexity, emphasizing the need for effective biomarkers and therapeutic targets. In this study, the Chinese Glioma Genome Atlas (CGGA-325/693) and The Cancer Genome Atlas (TCGA-LGG/GBM) cohorts were used to explore the pathological role of PHD finger protein 23 (PHF23) in gliomas. Machine learning algorithms were performed to construct a PHF23-related prognosis signature (PHF23-RPS). Our analysis revealed significant upregulation of PHF23 in high-grade gliomas, while the PHF23-RPS exhibited strong predictive performance (AUC = 0.853). Two molecular subtypes were identified; Cluster 2 was characterized as “inflamed yet immunosuppressive”. This subtype displayed a tumor mutational burden (TMB) paradox, where elevated TMB failed to translate into survival benefits due to extensive M2 macrophage infiltration and checkpoint-mediated immune exhaustion. Pharmacogenomic screening and molecular dynamics simulations identified Entospletinib as a potential candidate targeting this immunosuppressive barrier, showing a stable binding affinity (−7.7 kcal/mol). Functional assays, including in vitro experiments and in vivo experiments via a male BALB/c nude mouse orthotopic glioma model (n = 6/group), confirmed that PHF23 silencing inhibited glioma malignancy. Our results identify PHF23 as a critical oncogenic driver in glioma and support the PHF23-RPS for risk stratification. Entospletinib may offer a potential immunomodulatory option for high-risk gliomas.