Migraine is a very common chronic neurological disorder associated with severe disability and significant social burden worldwide. Beyond recurrent headache attacks, increasing evidence indicates that migraine often coexists with a broad range of systemic disorders, forming complex and often bidirectional relationships. These overlapping conditions complicate clinical management and suggest the presence of shared pathophysiological mechanisms extending beyond the central nervous system. Epidemiological studies have consistently shown strong associations between migraine and multiple comorbidities, including epilepsy, psychiatric disorders, sleep disturbances, cardio-cerebrovascular diseases, multiple sclerosis, asthma, other chronic pain syndromes, gastrointestinal disorders, and metabolic‒endocrine abnormalities. The presence of these conditions is generally associated with increased disease severity, higher rates of migraine chronification, poorer treatment responses, and increased healthcare utilization. Emerging mechanistic evidence indicates that migraine and its comorbidities share common biological pathways, including dysregulation of neurovascular signaling, neuroinflammation, central sensitization, alteration in autonomic nervous system and brain function, and disturbances in immune and metabolic homeostasis. Importantly, the presence of comorbid conditions may affect the efficacy, tolerance and safety of treatment, highlighting the limitations of symptom-oriented treatment strategies that fail to address these shared mechanisms. This review synthesizes current evidence on the epidemiological associations, shared pathophysiological mechanisms, and clinical implications of migraine and its common comorbidities. By elucidating these interrelated pathways, we aim to inform the development of comprehensive, personalized management strategies that transcend symptom-oriented treatment towards mechanism-based, comorbidity-informed approaches. Future research should prioritize the identification of biomarkers and the refinement of patient stratification tools to facilitate precision medicine in migraine and its associated conditions.

IntroductionPulsed radiofrequency (PRF) is a pivotal neuromodulation strategy for zoster-associated pain (ZAP); however, clinical outcomes exhibit significant interindividual heterogeneity. This study aimed to identify robust predictors and develop a transparent machine learning (ML) framework to forecast treatment response, thereby facilitating individualized pain management.MethodsWe conducted a retrospective analysis of a large-scale cohort comprising 1773 patients with ZAP treated with PRF. Patients were stratified into "responders" and "nonresponders" on the basis of clinical outcomes at a 3-month follow-up. To handle an initial pool of 47 multidimensional clinical and laboratory variables, a tripartite feature selection pipeline-incorporating least absolute shrinkage and selection operator (LASSO), Boruta, and multivariable logistic regression-was implemented. We benchmarked eight ML architectures. The optimal model was interpreted using Shapley additive explanations (SHAP) to ensure biological transparency and subsequently deployed as an interactive point-of-care tool.ResultsThe favorable clinical response rate for PRF was 68.0%. A parsimonious set of five core predictors was identified: age, baseline Numerical Rating Scale (NRS) score, preoperative opioid use, apolipoprotein B (ApoB), and neutrophil-to-monocyte ratio (NMR). Among the candidate algorithms, the CatBoost architecture was selected for its robust performance, achieving the highest F1 score (0.853) and an area under the receiver operating characteristic curve (AUROC) of 0.834. SHAP analysis revealed that preoperative opioid use was the most potent determinant of suboptimal response, followed by advanced age and high baseline pain intensity. Notably, elevated ApoB levels emerged as a novel metabolic indicator of favorable prognosis, whereas an increased NMR suggested a systemic pro-inflammatory state associated with diminished PRF efficacy.ConclusionsWe developed and internally validated a high-performance CatBoost-based model for predicting PRF outcomes in ZAP. By integrating novel metabolic (ApoB) and immunoinflammatory (NMR) biomarkers with established clinical metrics, this model provides a granular approach to risk stratification. The deployment of a Streamlit-based calculator translates complex algorithmic insights into an accessible clinical decision-support system.

Postoperative pain is a common complication caused by surgical trauma. Epidemiological studies indicate that the incidence of moderate to severe acute postoperative pain ranges from 41% to 85%, with approximately 10% to 50% of patients potentially progressing to chronic pain. This progression not only significantly impairs patients' quality of life, but also imposes substantial medical and socioeconomic burdens. The mechanisms underlying chronic postoperative pain are highly complex, involving the activation and sensitization of peripheral nociceptors, central sensitization of spinal dorsal horn neurons, and maladaptive alterations in higher-order cortical neural circuits. Additionally, local and systemic inflammatory responses induced by surgical injury, and psychosocial factors, such as anxiety, depression, and sleep disturbances, have all been shown to play critical roles in the transition from acute to chronic postoperative pain. This article systematically reviews the latest advances in risk factors, animal models, pathophysiological mechanisms, and therapeutic strategies of postoperative pain, with particular emphasis on key processes and potential intervention targets involved in the transition from acute to chronic pain, aiming to offer a more solid theoretical foundation and evidence-based guidance for clinical practice.

MicroRNA-126 (miR-126) has emerged as a potential key regulator in ischemic stroke. Yet, its exact mechanism of action is still unexplored. This study aims to investigate whether miR-126 targets and regulates the low-density lipoprotein receptor-related protein (LRP6), an important co-receptor in the Wnt/(3-catenin signaling pathway, to reduce ischemic brain injury in mice. C57BL/6 J mice were randomly divided into Sham group, Middle Cerebral Artery Occlusion (MCAO) group, MCAO+miR-126 antagomir group, MCAO+ antagomir NC group, MCAO+miR126 agomir group and MCAO + agomir NC group. The Garcia nervous system score assessed the neurobehavior of the mice. Infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the extent of cerebral ischemia-reperfusion injury was assessed by Nissl staining. The miR-126 level was detected by real-time PCR, and the apoptosis index was detected by Western blot. A luciferase reporter assay was applied to demonstrate that LRP6 is the target protein of miR-126. The increased expression of miR-126 in MCAO mice inhibits the Wnt/LRP6/(3-catenin pathway and enhances neuronal apoptosis. Inhibition of miR-126 alleviates the infarct area, motor ability damage, and apoptosis in MCAO mice. Additionally, Western blot results and luciferase reporter assay showed that inhibition of miR-126 activates the Wnt/(3-catenin signaling pathway via LRP6. Our data suggest that inhibition of microRNA-126 attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/(3-catenin signaling pathway.

Intestinal localized inflammations are recognized as key contributors to the incidence and progression of diverse extraintestinal disorders. Probiotic colonization has been increasingly highlighted for its potential to modulate susceptibility and progression of such diseases. Considering the adhesion- and colonization-related challenges posed by multiple physiological and pathological characteristics in the intestine, a microenvironment self-adaptive nanoarmor is developed. Partially acetylated chitosan oligosaccharides (CS) were employed to tune the adaptability and responsiveness of nanoarmor, enabling efficient interaction with the intestinal interface under dynamic conditions. Notably, Chitinase-3-like protein 1 (CHI3L1), an inflammation-related secreted glycoprotein, served as a colonized niche to facilitate probiotics colonization in pathological microenvironments by leveraging the specific interaction between chitin-like fragment and CHI3L1. By combining the intestinal microenvironment self-adaptive nanoarmor with the inherent anti-inflammatory properties of Lactobacillus plantarum ST-III (L. plantarum), the nanocoated bacteria demonstrated significantly improved performance in alleviating intestinal mucosal inflammation, restoring gut barrier integrity, and reestablishing microbial homeostasis. Furthermore, the nanocoated bacteria showed significant therapeutic potential in treating Parkinson's disease (PD), a model for extraintestinal disorders, as evidenced by their ability to improve motor behavior disorders, reduce dopaminergic neuronal death, and mitigate neuroimmune responses. This approach proposes new insights into the living therapeutics for the treatment of extraintestinal diseases.

Weber syndrome, characterized by ipsilateral oculomotor palsy and contralateral hemiplegia, frequently occurs in ischemic stroke cases and is difficult to recover from. Hydroxysafflor yellow A (HSYA), a bioactive component present in Carthamus tinctorius L. and the standardized preparation Danhong injection, has shown protective effects in animal models of various neurological diseases. This research was conducted to evaluate the therapeutic potential of HSYA in ischemic stroke-associated Weber syndrome, while elucidating its mechanistic basis. A rat MCAO model was induced to detect the effects of HSYA on motor dysfunction, ipsilateral ptosis and neuronal death in the right cerebral peduncle. By western blot, immunohistochemistry staining and immunofluorescence staining, we explored the involvement of oxidative stress and DNA damage in HSYA's neuroprotective action. HSYA treatment for consecutive 7 days significantly improved neurological function, grip strength, and asymmetry of bilateral eye clefts in CI/R-injured rats. HSYA also reduced cerebral infarction, preserved neuronal survival, and mitigated histopathological damage in the cerebral peduncle. Mechanistically, HSYA alleviated oxidative stress by preserving CAT, GSH, and SODM levels while inhibiting iNOS overexpression. Furthermore, CI/R injury triggered substantial DNA damage in the cerebral peduncle, as indicated by upregulated levels of 53BP1 and γ-H2A.X. Contents of PARP1, AIF, and MIF were also significantly elevated, accompanied by obvious upregulation of apoptotic cell death, while HSYA treatment effectively attenuated these deleterious effects. HSYA protects against CI/R injury and associated Weber syndrome, and the mechanism involves suppressing oxidative stress and limiting DNA injury.

OBJECTIVES:To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS:Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS:The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

MicroRNA-126 (miR-126) has emerged as a potential key regulator in ischemic stroke. Yet, its exact mechanism of action is still unexplored. This study aims to investigate whether miR-126 targets and regulates the low-density lipoprotein receptor-related protein (LRP6), an important co-receptor in the Wnt/β-catenin signaling pathway, to reduce ischemic brain injury in mice. C57BL/6 J mice were randomly divided into Sham group, Middle Cerebral Artery Occlusion (MCAO) group, MCAO+miR-126 antagomir group, MCAO+ antagomir NC group, MCAO+miR-126 agomir group and MCAO + agomir NC group. The Garcia nervous system score assessed the neurobehavior of the mice. Infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the extent of cerebral ischemia-reperfusion injury was assessed by Nissl staining. The miR-126 level was detected by real-time PCR, and the apoptosis index was detected by Western blot. A luciferase reporter assay was applied to demonstrate that LRP6 is the target protein of miR-126. The increased expression of miR-126 in MCAO mice inhibits the Wnt/LRP6/β-catenin pathway and enhances neuronal apoptosis. Inhibition of miR-126 alleviates the infarct area, motor ability damage, and apoptosis in MCAO mice. Additionally, Western blot results and luciferase reporter assay showed that inhibition of miR-126 activates the Wnt/β-catenin signaling pathway via LRP6. Our data suggest that inhibition of microRNA-126 attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE:Danhong injection (DI), a standardized traditional Chinese medicine injection prepared from Salvia miltiorrhiza Bge. and Carthamus tinctorius L., has been validated in clinical studies for its therapeutic efficacy and is widely used in stroke treatment. However, the exact molecular mechanisms behind its neuroprotective effects during recovery remain unclear. AIM OF THE STUDY:This research aims to evaluate DI's therapeutic potential in promoting functional recovery following cerebral ischemia/reperfusion (CI/R) injury and to uncover the molecular basis of its neuroprotective effects. METHODS:A rat MCAO/R model was established and treated with varying doses (low, medium, high) of DI through tail vein injection over 14 days. Treatment outcomes were assessed via Longa neurological scoring, thermal nociception tests, TTC staining, and histological analysis. Mechanistic studies were conducted using immunohistochemistry, immunofluorescence, and western blotting techniques. RESULTS:Research outcomes showed that DI intervention significantly enhanced neurological performance and thermal sensitivity in CI/R rats, particularly at the 1.0 mL/kg dosage. Histopathological analysis verified DI's capacity to mitigate tissue injury, preserve neuronal integrity, and restore microvascular structure in ischemic cortical regions. Molecular profiling demonstrated that DI boosted angiogenesis via elevated VEGF-A and PDGF-B expression, along with increased CD34+ endothelial progenitor cells and BrdU+/vWF+ newborn endothelial cells. DI treatment also elevated populations of Sox2+/Nestin+ neural progenitors and DCX+/NeuN+ newborn neurons while enhancing tight junction protein ZO-1 expression and ERK1/2 phosphorylation. Furthermore, intraperitoneal co-administration of sunitinib (a specific receptor tyrosine kinase inhibitor) abolished the therapeutic effects of DI, confirming the essential role of receptor tyrosine kinase pathways. CONCLUSIONS:This work reveals that DI administration provides neuroprotection and enhances functional recovery following CI/R injury, with its mechanism of action linked to the promotion of neurovascular regeneration.

Manipulation of the gut microbiota using oral microecological preparations has shown great promise in treating various inflammatory disorders. However, delivering these preparations while maintaining their disease-site specificity, stability, and therapeutic efficacy is highly challenging due to the dynamic changes associated with pathological microenvironments in the gastrointestinal tract. Herein, a superior armored probiotic with an inflammation-targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease (IBD). The coating strategy exhibits suitability for diverse probiotic strains and has negligible influence on bacterial viability. This study demonstrates that these armored probiotics have ultraresistance to extreme intraluminal conditions and stable mucoadhesive capacity. Notably, the HA-functionalized nanoarmor equips the probiotics with inflamed-site targetability through multiple interactions, thus enhancing their efficacy in IBD therapy. Moreover, timely "awakening" of ingested probiotics through the responsive transferrin-directed degradation of the nanoarmor at the site of inflammation is highly beneficial for bacterial therapy, which requires the bacterial cells to be fully functional. Given its easy preparation and favorable biocompatibility, the developed single-cell coating approach provides an effective strategy for the advanced delivery of probiotics for biomedical applications at the cellular level.

Theranostic prodrugs that enable real-time, non-invasive monitoring of drug release and biodistribution are highly desirable for optimizing therapeutic efficacy and guiding personalized medication. Herein, we report a colon-targeted theranostic prodrug system (P1) for the simultaneous delivery and tracking of 5-aminosalicylic acid (5-ASA) in the treatment of ulcerative colitis (UC). P1 comprises a fluorescent 7-amino-4-methylcoumarin (7-AMC) reporter covalently linked to 5-ASA via an azo bond, which quenches the fluorescence of 7-AMC until P1 is activated by azoreductases in the colonic microenvironment. This selective activation triggers the release of 5-ASA and the revival of 7-AMC fluorescence, enabling real-time monitoring of drug delivery. To improve the solubility and targeted delivery of P1, it was encapsulated within polymeric micelles (PM) that selectively adhere to the positively charged, inflamed colonic tissues. In vitro studies confirmed the stability, biocompatibility, and selective activation of P1 under simulated colonic conditions. Notably, in a mouse model of UC, the P1-loaded PM achieved targeted delivery of 5-ASA to the inflamed colon, resulting in effective attenuation of colitis symptoms. Importantly, the in situ activation of P1 allowed for the real-time, non-invasive visualization of drug release and biodistribution, providing valuable insights for treatment optimization. This theranostic prodrug approach offers a promising strategy for the simultaneous therapy and tracking of 5-ASA delivery in UC treatment, with the potential to facilitate personalized medication and improve therapeutic outcomes.

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Abstract Background Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. Methods A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. Results In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. Conclusions The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. Trial registration Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 mu g mL(-1) CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPR/Cas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPR/Cas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPR/Cas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPR/Cas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules, or invading microorganisms to lysosomes for degradation[1]. Sequestosome 1 （p62/SQSTM1） was the first protein shown to bind target-associated ubiquitin （Ub） and LC3 conjugated to the phagophore membrane, thus, acting as an important autophagy receptor for ubiquitinated targets[2].

Purpose: Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions. However, the treatment efficacy and potential causal links of RA in SIC are still elusive. Methods: By virtue of the STITCH database, we identified the targets of RA. Differentially expressed genes in SIC were acquired from the GEO database. The PPI network of intersected targets was established. GO and KEGG pathway enrichment analysis was completed. Hub genes were analyzed by cytoHubba plug-in. In the process of experimental validation, a mouse sepsis model was established by lipopolysaccharide (LPS), and the treated mice were intraperitoneally injected with RA or Dexamethasone (DEX) 60 min prior to LPS injections. Survival conditions, cardiac functions and antioxidant levels of the mice were assessed. Cardiac inflammation and injury were detected by HE and TUNEL. The levels of key genes and signal pathway expression were analyzed by RT-PCR and Western blot. Results: PPARA, ITGAM, VCAM-1, IGF-1 and IL-6 were identified as key therapeutic targets of RA by network pharmacology. PI3K-Akt signaling pathway is the main regulatory pathway of RA. In vivo researches unraveled that RA can improve the survival rate and cardiac function of LPS-treated mice, inhibit inflammatory factors and myocardial injury, and regulate the expression of key therapeutic targets and key pathways, which is PI3K-Akt signaling pathway. Conclusion: Network pharmacological method offers a predicative strategy to explore the treatment efficacy and causal links of RA in endotoxemic myocarditis. Through experimental verification, we discover that RA can reduce lipopolysaccharide-induced cardiac dysfunction by regulating the PI3K-Akt signaling pathway and key genes.

Introduction. The global incidence of brain tumors, the most common of which is lower grade glioma (LGG), remains high. Pleckstrin homology domain-containing family A member 4 (PLEKHA4) has been reported to be related to tumor invasion and growth. However, its role and correlation with immunity in LGG remain elusive. Methods. We evaluated the expression pattern, prognostic value, biological functions, and immune effects of PLEKHA4 in LGG. We also analyzed the association between PLEKHA4 levels in different tumors, patient prognosis, and its role in tumor immunity. Depending on the type of research data, we used statistical methods such as Student’s t-tests, Mann–Whitney U tests one-way ANOVA tests Kruskal–Wallis tests Pearson’s or Spearman’s correlation analysis Chi-square and Fisher’s exact tests in this paper. Results and Conclusions. The results revealed that PLEKHA4 levels were markedly elevated in most tumors (such as LGG). High PLEKHA4 levels are associated with poor overall survival (OS), progression-free interval (PFI) rates, and disease-specific survival (DSS) in LGG patients. Cox regression analysis and nomograms showed that PLEKHA4 levels are independent prognostic factors for LGG patients. According to functional enrichment analysis, PLEKHA4 levels in LGG are associated with immune infiltration and immunotherapy. In conclusion, PLEKHA4 is a potential prognostic marker and immunotherapy target for LGG.