Background:Non-intubated video-assisted thoracoscopic surgery (NIVATS) is increasingly used for selected non-small cell lung cancer (NSCLC) patients, but its long-term oncologic outcomes versus conventional VATS remain unclear. We therefore conducted this systematic review and meta-analysis to compare long-term oncologic outcomes between NIVATS and conventional intubated video-assisted thoracoscopic surgery (VATS). Methods:We searched major databases and trial registries through June 30, 2026 for comparative studies evaluating NIVATS or spontaneous ventilation VATS versus intubated or mechanical ventilation VATS in NSCLC. The primary outcomes were overall survival (OS) and disease-free survival or recurrence-free survival (DFS/RFS). Secondary oncologic outcomes included recurrence, R0 resection, total lymph node assessment, N1 and N2 lymph node assessment, and lymph node station or group assessment. Hazard ratios (HRs), risk ratios (RRs), and mean differences (MDs) with their 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool and the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was evaluated using the GRADE framework. Results:Seventeen comparative studies were included in the qualitative synthesis. NIVATS was associated with lower pooled hazards for OS compared with intubated VATS (HR 0.66, 95% CI 0.48-0.91; I2 = 0.0%; GRADE certainty: low) and lower pooled hazards for DFS/RFS (HR 0.66, 95% CI 0.50-0.87; I2 = 0.0%; GRADE certainty: low). These findings remained stable in sensitivity analyses. No significant difference was observed in total lymph nodes harvested or R0 resection rate. Recurrence showed a borderline lower risk after NIVATS, although follow-up definitions varied across studies. The randomized study was judged as having some concerns, and observational studies were generally moderate to high quality. Conclusions:In selected NSCLC patients, NIVATS does not appear to compromise long-term oncologic outcomes versus conventional intubated VATS. The observed survival advantage likely reflects selection bias and residual confounding, as NIVATS is often used in patients with favorable tumor features, operative suitability, or cardiopulmonary reserve. These findings support NIVATS as feasible under strict selection by experienced teams. Prospective multicenter studies with standardized protocols and long-term follow-up are needed to confirm its oncologic safety. Systematic review registration:crd.york.ac.uk/prospero/display_record.php?ID=CRD420261437783, identifier CRD420261437783.

Endotracheal tube (ETT) cuff compression can induce severe airway mucosal injury through ischemia-reperfusion mechanisms, wherein oxidative stress plays a critical pathogenic role. Despite its clinical significance, effective protective strategies remain limited. Here, we developed a hydrogen-releasing nanocoating for ETT cuffs to mitigate airway injury. The coating was fabricated by integrating palladium hydride (PdH) nanoparticles into a polydopamine (PDA) matrix, creating a stable, uniform layer capable of sustained hydrogen release. Characterization confirmed successful PdH incorporation through UV-vis spectroscopy and X-ray diffraction analysis. In in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell models using BEAS-2B human bronchial epithelial cells, the PDA-PdH coating (12.25 μg/mL) demonstrated selective scavenging of hydroxyl radicals and hydrogen peroxide while preserving beneficial superoxide species. The coating significantly reduced malondialdehyde and nitric oxide levels, enhanced superoxide dismutase activity, and protected mitochondrial integrity and cytoskeletal structure. Flow cytometry and TUNEL assays revealed marked reductions in intracellular reactive oxygen species and apoptosis rates. In in vivo evaluation using a rabbit tracheal intubation model with high cuff pressure (40 cmH2O) showed that PDA-PdH-coated ETTs effectively preserved tracheal mucosal integrity and attenuated inflammatory infiltration, as confirmed by histological examination and Western blot analysis of apoptosis-related proteins. Importantly, the coating exhibited acceptable short-term biocompatibility, with no observable cytotoxicity in vitro or gross histological organ damage within the 3-day observation window; however, comprehensive long-term biosafety evaluation remains to be conducted. These findings demonstrate that the PDA-PdH nanocoating represents a promising prophylactic strategy for preventing airway mucosal injury during endotracheal intubation.

Neuroinflammation underlies the pathogenesis of neurodegenerative diseases, CNS trauma, aging, and pain disorders, profoundly influencing disease progression and clinical outcomes. TREM2 is an innate immune transmembrane receptor predominantly expressed on microglia in the CNS, primarily for sensing tissue damage and coordinating immune remodeling. TREM2, by binding to its ligands and subsequently activating DAP12/10-mediated signaling pathways, coordinates microglial phagocytosis, metabolism, phenotype polarization, and inflammatory responses, thereby regulating neuroinflammation in various neurological diseases. Contrary to the conventional view of its neuroinflammatory suppression and neuroprotection, growing evidence has suggested that TREM2 exhibits dual functional roles that correlate with disease context and stage. This review provides a detailed overview of TREM2, including its structural features and relevant ligands, and elucidates the pathological mechanisms underlying TREM2-mediated regulation at both molecular and disease-specific levels—with particular focus on its effects on neuroinflammation through the modulation of microglial function. Finally, this review also discusses the current advances in TREM2-oriented therapeutic strategies and clinical translation, highlighting their potential applications for neuroinflammatory diseases. TREM2 acts as a central regulator of neuroinflammation by modulating microglial function, exhibiting context-dependent neuroprotective or pathological roles across neurological disorders. Current TREM2-targeted therapies show translational potential for neuroinflammatory diseases, while sTREM2 holds value as a clinical biomarker.

Ethnopharmacological relevance Xiaoyanlidan Tablet (XYLDT) is a Chinese patent medicine consisted of three traditional Chinese medicines (TCMs) including Andrographis Herba (AH), Linearstripe Rabdosia Herba (LRH) and Picrasmae Ramulus et Folium (PRF). In Chinese traditional medicine theory, XYLDT has the “heat-clearing, dampness-dispelling and gallbladder function promoting” properties, and was widely used in the clinic for decades to treat pain in the subcostal region or bitter taste in the mouth, which were induced by liver-gallbladder dampness-heat. Meanwhile, it was also used for the therapy of acute cholecystitis and cholangitis. Aim of the study To explore the mechanism of XYLDT in alleviating the alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury (CLI), and to find out which TCM consisted in XYLDT contributed the most to the therapeutic efficacy of XYLDT. Methods ANIT was orally given to mice to induce CLI in vivo. Each TCM in XYLDT alone, XYLDT-without one TCM or XYLDT was orally given to mice before or after ANIT administration. Serum biochemical indicators were measured by using commercial kits. Liver histopathology was observed. Clinical data analysis was used to predict molecules and signal pathways involved in the XYLDT-provided improvement on CLI, which was further verified by using RT-PCR and Western-blot assay. Results The alleviation of XYLDT on ANIT-induced CLI was proved by the data of serum biochemical indicators and liver histological observation. Results from clinical data analysis indicated that XYLDT improved CLI via improving mitochondrial function, oxidative phosphorylation, oxidative stress. XYLDT reduced the ROS level, MDA content, and increased GSH content. Meanwhile XYLDT improved the level of Nrf2 into the nucleus and mRNA expression of Nqo1, Gclc, Gclm. Andrographis Herba was proved to be the most crucial for the XYLDT-provided therapeutic efficacy on CLI. Moreover, andrographolide and neoandrographolide, two main active compounds in Andrographis Herba, had the apparent anti-inflammatory ability in LPS-stimulated RAW264.7 cells. Andrographolide also promoted nuclear translocation activation of Nrf2 in antioxidant response elements (ARE)-luciferin transfected L-02 cells. Conclusion XYLDT alleviated the ANIT-induced CLI via improving oxidative stress and activated Nrf2-related signaling pathways. Andrographis Herba was important for the XYLDT-provided alleviation on CLI.

INTRODUCTION:The association between remimazolam and emergence agitation (EA) remains unclear. This meta-analysis aimed to compare the relative risk of developing EA when using remimazolam vs. propofol in induction and maintenance of general anesthesia. METHOD:We searched PubMed, clinicaltrials.gov, Web of Science, Cochrane Library, and Embase databases to identify studies meeting the inclusion criteria. The primary outcome was the incidence of EA. Secondary outcomes included the incidence of postoperative delirium (POD) within 7 days after surgery, emergence time, extubation time, length of post-anesthesia care unit (PACU) stay, and adverse events. RESULTS:A total of 19 randomized controlled trials with 3031 patients were included in the meta-analysis. There was no statistically significant difference in the incidence of EA (RR = 0.82; 95 % confidence interval [CI], 0.41-1.65; p = 0.585) between remimazolam and propofol. Likewise, there were no significant intergroup differences in POD incidence, extubation time, emergence time, or length of PACU stay. Remimazolam exhibited superior hemodynamic stability, with a significantly reduced incidence of postinduction hypotension and intraoperative hypotension compared with propofol, while maintaining comparable safety profiles in terms of postoperative nausea and vomiting (PONV), intraoperative awareness, and hypoxemia. Subgroup analysis revealed that without routine postoperative antagonist administration, remimazolam was associated with prolonged extubation and length of PACU stay relative to propofol. In contrast, following antagonizing with flumazenil, the extubation and emergence times of the remimazolam group were shorter than those of the propofol group, while comparable PACU discharge time was maintained. CONCLUSION:The use of remimazolam for the induction and maintenance of general anesthesia does not lead to a higher occurrence of EA in adult patients undergoing surgery, relative to propofol. However, in patients with ASA III-IV, remimazolam may be linked to a greater risk of POD than propofol.

In the original publication [...].

BACKGROUND:To investigate the mechanisms underlying sevoflurane-induced POCD, C57BL/6 J mice and SH-SY5Y cells were treated with sevoflurane for model establishment. METHODS:After the treatment with sevoflurane, CCK-8, EdU and flow cytometry were employed to detect cell damage. The levels of N6-methyladenosine (m6A), METTL14 and DUSP6 were determined by qPCR and Western blot. The interaction between METTL14 and DUSP6 was analyzed using RIP-qPCR and Me-RIP methodologies. The cognitive function in mice were assessed by water maze test. RESULTS:After sevoflurane treatment, the cell viability, cell proliferation and METTL14 expression were markedly suppressed, while apoptosis was significantly enhanced. METTL14 overexpression elevated the levels of m6A and DUSP6, increased the binding level of METTL14 to DUSP6 mRNA, reducing damage to cells and cognitive dysfunction of mice. Knockdown of DUSP6 negated the beneficial effects observed with METTL14 overexpression. CONCLUSION:Sevoflurane induced POCD by regulating METTL14/DUSP6 through m6A methylation.

Ischemia-reperfusion injury (IRI) represents a major clinical challenge across various organ systems, with especially severe and often irreversible consequences in cardiac and cerebral tissues. Despite advances in understanding its pathophysiology, effective therapeutic strategies remain limited. MicroRNA-451 (miR-451), a highly conserved non-coding RNA located on human chromosome 17q11.2, has emerged as a critical regulator of key pathophysiological processes underlying IRI, including inflammation, immune cell function, oxidative stress, and programmed cell death. This review comprehensively examines the complex and sometimes paradoxical roles of miR-451 in cardiac and cerebral IRI. We explore miR-451’s potential as both a diagnostic biomarker and therapeutic target in IRI management, highlighting innovative approaches such as exosome-mediated miR-451 delivery. Finally, we address critical challenges in translating miR-451-based therapies to clinical practice and outline promising directions for future research. This comprehensive analysis provides a theoretical framework for developing novel miR-451-focused strategies for IRI detection and treatment, with significant implications for improving outcomes in ischemic disorders.

Introduction:The efficacy and safety of intranasal insulin (INI) for preventing postoperative delirium (POD) remain uncertain. Methods:We searched PubMed, Web of Science, Cochrane Library, Embase, and registers from inception to July 1, 2025, for randomized controlled trials (RCTs) enrolling adult surgical patients that compared INI with control (saline) investigating the efficacy of INI for POD prevention. The risk of bias was assessed using the revised Cochrane Risk of Bias tool (RoB 2), and the certainty of evidence was evaluated with the GRADE framework. Primary and secondary outcomes were POD incidence and a comprehensive set of secondary measures (including cognitive scores, hypoglycemia rates, pain scores, and inflammatory markers), respectively. Results:A meta-analysis of 7 randomized trials (n = 765) showed that INI significantly reduced the incidence of POD within 3 days postoperatively (RR = 0.35; 95% CI: 0.26-0.46; P < 0.001; I 2 = 0%) and improved cognitive recovery (MMSE mean difference = 0.99; 95% CI: 0.52-1.47; P < 0.001; I 2 = 1.7%). INI also reduced early postoperative interleukin-6 (IL-6) levels without affecting the incidence of hypoglycemia or pain scores. Conclusion:INI may protect perioperative cognitive function, reduce POD incidence within 3 days postoperatively, and alleviate postoperative inflammation without increasing hypoglycemia risk. However, larger-scale, randomized, multicenter trials are needed to confirm clinical efficacy and establish optimal protocols. Clinical trial registration:The protocol for this meta-analysis is available in PROSPERO (CRD42024614995).

Pyroptosis, a highly inflammatory programmed cell death pathway, drives pathogenesis in numerous diseases through gasdermin-mediated membrane pore formation and massive cytokine release. While conventional anti-inflammatory therapies show limited efficacy, hydrogen emerges as a novel therapeutic agent with unique pyroptosis-regulatory capabilities. This review establishes a comprehensive mechanistic framework demonstrating that hydrogen modulates pyroptosis through interconnected pathways including direct gasdermin redox modification, mitochondrial signaling integration, and inflammasome assembly disruption. Systematic analysis across diverse disease models-cardiac ischemia-reperfusion, neuroinflammation, metabolic dysfunction, and cancer-reveals hydrogen's remarkable context-dependent effects: cytoprotective in normal tissues while promoting therapeutic pyroptosis in malignant cells. Hydrogen's regulatory mechanisms exhibit striking tissue specificity and temporal complexity, with immediate antioxidant effects transitioning to sustained anti-inflammatory responses. Despite compelling preclinical evidence demonstrating efficacy in myocardial injury, neurodegeneration, and systemic inflammation, significant translational barriers remain including delivery optimization, dosimetric standardization, and biomarker development. This review critically evaluates hydrogen's transformative therapeutic potential while addressing realistic implementation challenges, providing a roadmap for advancing this innovative paradigm from bench to bedside.

Extracellular vesicles, which are predominantly classified into ectosomes and exosomes, are released by all cells under both physiological conditions and in response to acquired pathological states. Exosomes demonstrate multifaceted functions: they regulate cellular homeostasis through the elimination of redundant or detrimental intracellular components, function as mediators in intercellular signaling pathways, and serve as potential vectors for both diagnostic and therapeutic applications. Intestinal ischemia-reperfusion injury (IRI), a prevalent form of tissue and organ injury in surgical settings, has been extensively investigated. Emerging evidence indicates a crucial relationship between exosomes and intestinal IRI, specifically regarding how exosomes derived from either intestinal tissue or distant organs can modulate the pathophysiological progression of intestinal IRI. This review systematically evaluates the mechanistic roles of exosomes in intestinal IRI and their involvement in post-intestinal IRI multiple organ dysfunction, aiming to establish a theoretical foundation for therapeutic interventions and future research directions.

Introduction: Catheter ablation is a widely utilized treatment for symptomatic atrial fibrillation (AF), performed under general anesthesia (GA), deep sedation (DS), or conscious sedation (CS). However, the optimal anesthetic strategy remains controversial. Methods: We systematically searched PubMed, clinicaltrials.gov, Web of Science, Cochrane Library, and Embase databases for relevant studies. The primary outcome was defined as AF recurrence after catheter ablation, with secondary outcomes including procedural parameters (procedure time, ablation time, fluoroscopy time), acute procedural success rates, and complication rates. Mediation analysis was performed to explore electrophysiological mechanisms. Results: A total of 17 studies involving 12 484 patients demonstrated that GA or DS significantly reduced AF recurrence after ablation compared with CS [risk ratio (RR) 0.86, 95% confidence interval (CI), 0.82–0.91; very low certainty of evidence]. The reduction in AF recurrence with GA and DS was consistent across AF subtypes and long-term follow-up duration. While ablation time was slightly shorter with GA and DS, procedure time, fluoroscopy time, complications, and acute success rates were similar between groups. Mediation analysis further indicated that the benefit of GA is mediated by reduced pulmonary vein (PV) reconnection and dormant conduction. Conclusion: GA is recommended for radiofrequency ablation to improve long-term success, supported by its mechanistic benefits. While current evidence does not support DS as an equivalent alternative to GA for radiofrequency ablation, anesthetic strategy for cryoballoon ablation can be individualized.

Ischemia-reperfusion injury (IRI) is a common and clinically significant form of tissue damage encountered in medical practice. This pathological process has been thoroughly investigated across a variety of clinical settings, including, but not limited to, sepsis, organ transplantation, shock, myocardial infarction, cerebral ischemia, and stroke. Intestinal IRI, in particular, is increasingly recognized as a significant clinical entity due to marked changes in the gut microbiota and their metabolic products, often described as the body’s “second genome.” These changes in intestinal IRI lead to profound alterations in the gut microbiota and their metabolic outputs, impacting not only the pathology of intestinal IRI itself but also influencing the function of other organs through various mechanisms. Notable among these are brain, liver, and kidney injuries, with acute lung injury being especially significant. This review seeks to explore in depth the roles and mechanisms of the gut microbiota and their metabolic products in the progression of acute lung injury initiated by intestinal IRI, aiming to provide a theoretical basis and directions for future research into the treatment of related conditions.

The cuff of endotracheal tube (ETT) is an indispensable device for establishing an artificial airway, yet cuff-induced compression often causes damage to the airway mucosa. The mechanism of this damage involves mucosal compression ischemia and the oxidative stress injury following reperfusion. Currently, there is a lack of effective strategies to protect the mucosa. Hydrogen, as a natural antioxidant, has demonstrated significant potential in the prevention and treatment of oxidative stress injuries. This study aimed to determine the protective effects of hydrogen on compressed airway mucosa. We found that the damage to the airway mucosa caused by ETT cuff compression was associated with oxidative stress-induced pyroptosis of airway epithelial cells. Inhalation of hydrogen effectively reduced the levels of reactive oxygen species, significantly ameliorating changes in epithelial cell pyroptosis, and this protective effect is linked to the inhibition of the NLRP3-GSDMD pathway. Further cellular studies, involving knockdown and overexpression of NLRP3, clarified that hydrogen exerts its protective effects on the airway mucosa by inhibiting epithelial cell pyroptosis. Additionally, we observed that using hydrogen-rich saline to inflate the ETT cuff in patients under general anesthesia significantly reduced postoperative sore throat. This study confirms that hydrogen effectively enhances tolerance of airway mucosa to oxidative stress injuries, offering a potential preventive and therapeutic strategy for protecting the airway mucosa in patients undergoing endotracheal intubation.

Norepinephrine or phenylephrine administration to prevent and treat hypotension during spinal anesthesia for cesarean section has been a significant topic of discussion. This meta-analysis aimed to update existing evidence and provide further insights into neonatal and maternal outcomes associated with norepinephrine and phenylephrine. Review of randomized controlled trials (RCTs) was performed to assess the effectiveness of norepinephrine and phenylephrine in managing maternal hypotension during cesarean delivery under spinal anesthesia. Neonatal umbilical cord blood pH and maternal hypotension were the primary outcomes. Based on the analysis of 26 RCTs with 2984 participants, we found no significant difference between the norepinephrine and phenylephrine groups in umbilical artery pH in neonates (mean difference (MD) 0.00; 95% confidence interval (CI) -0.00 to 0.01, p = 0.20). Neonates Apgar scores did not differ between both groups. Norepinephrine was associated with lower incidences of bradycardia (risk ratio (RR) 0.44; 95% CI 0.37 to 0.51, p < 0.001) and reactive hypertension (RR 0.53; 95% CI 0.39 to 0.72, p < 0.001) in parturient women than phenylephrine. In neither group did umbilical cord blood levels of partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) levels of neonates differ significantly, nor did maternal hypotension, nausea or vomiting incidence during delivery. For maternal hypotension after spinal anesthesia, norepinephrine and phenylephrine did not significantly differ in neonatal acidemia. Despite similarities to phenylephrine in managing hypotension and maintaining maternal hemodynamic stability, norepinephrine is a promising alternative.

Background: The optimal endotracheal tube (ETT) cuff pressure remains contentious. In the traditional consideration that the level 30 cmH(2)O is considered safe, balancing the prevention of reflux aspiration against airway mucosal damage. Whether this pressure level can cause potential damage to the airway mucosa remains to be discussed. Methods: Airway mucosa damage and structural changes at 30 cmH(2)O were examined in patients under general anesthesia and in rabbit mechanical ventilation models. Prior to this, we also interviewed some anesthesiologists about the level of concern about ETT cuff pressure. Results: A total of 634 valid questionnaires suggested that anesthesiologists generally do not pay enough attention to ETT cuff pressure and the average established cuff pressure significantly exceeded 30 cmH(2)O. Airway mucosa images of 100 general anesthesia patients with different ventilation duration indicated that maintaining the pressure at 30 cmH(2)O did not cause significant damage to airway mucosa in a short period of time, while it still caused damage to airway mucosa in patients with long-term ventilation, with damage severity increasing with longer ventilation periods. This correlated strongly with postoperative sore throat (R-2 = 0.3884, p < 0.001). In rabbits, 4 h of ventilation at this pressure resulted in significant loss of ciliated epithelium and inflammation. Calculations suggested an effective dose (ED50) to prevent mucosal injury at a cuff pressure of 25.64 cmH(2)O (95% CI: 19.268-29.367 cmH(2)O). Conclusion: The currently established cuff pressure of 30 cmH(2)O is associated with airway mucosal damage in both clinical and animal models. Lowering the safety threshold of cuff pressure may be necessary to mitigate mucosal injury.

Trigeminal neuralgia (TN) is a complex orofacial neuropathic pain. The crippling condition's underlying mechanism is still not completely understood. The main cause of lightning-like pain in patients with TN may be chronic inflammation that causes nerve demyelination. Nano-silicon (Si) can safely and continuously produce hydrogen in the alkaline environment of the intestine to exert systemic anti-inflammatory effects. Hydrogen has a promising anti-neuroinflammatory impact. The study aimed to determine how intra-intestinal application of a hydrogen-producing Si-based agent affected the demyelination of the trigeminal ganglion in TN rats. We discovered that increased expression of the NLRP3 inflammasome and inflammatory cell infiltration occurred concurrently with demyelination of the trigeminal ganglion in TN rats. We could determine that the neural effect of the hydrogen-producing Si-based agent was connected to the inhibition of microglial pyroptosis by using transmission electron microscopy. The results demonstrated that the Si-based agent reduced the infiltration of inflammatory cells and the degree of neural demyelination. In a subsequent study, it was discovered that hydrogen produced by a Si-based agent regulates the pyroptosis of microglia may through the NLRP3-caspase-1-GSDMD pathway, preventing the development of chronic neuroinflammation and consequently lowering the incidence of nerve demyelination. This study offers a novel strategy for elucidating the pathogenesis of TN and developing potential therapeutic drugs.

Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage.