To compare the effects of different methods of administration of dexmedetomidine (Dex) on postoperative delirium (POD) and recovery in elderly male patients who underwent laparoscopic hernia repair. A total of 318 elderly male patients undergoing laparoscopic hernia repair under standardized general anesthesia from October 2023 to October 2024, who fell under the American Society of Anesthesiologists (ASA) grade I–Ⅲ and were aged 65 years or older, were selected for this study. They were divided into 3 groups according to a random number table: the intranasal administration group (DS group, 0.6 μg/kg intranasal Dex administered 10 min before the induction of anesthesia, on the evening of the operation, and in the following evening), intravenous dexmedetomidine infusion group (DV group, 0.6 μg/kg intravenous infusion administered 10 min before the induction of anesthesia, as well as the provision of an intravenous patient-controlled analgesia pump containing 1.2 μg/kg Dex), and the blank control group (DN group, intravenous infusion of an equivalent volume of normal saline 10 min before the induction of anesthesia, on the evening of the operation, and in the following evening). The primary outcome measure was the incidence of POD, which was assessed using the Confusion Assessment Method (CAM) [1] within 1–3 days after surgery. The secondary outcome measures included the Pittsburgh Sleep Quality Index (PSQI) [2], Athens Insomnia Scale (AIS) [3], Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) [4], Visual Analog Scale (VAS) [5], and Quality of Recovery-15 (QoR-15) [6] scores at 3 days after surgery. The occurrence of adverse reactions and the incidence of chronic pain 3 months after surgery were also recorded. Compared with the DN group, the DV and DS groups exhibited a lower incidence of POD on postoperative Day 1 (6.7
Postoperative ileus (POI) represents a frequent complication after posterior thoracolumbar fracture surgery. This study aimed to identify POI risk factors and construct predictive models enabling early identification and targeted intervention of vulnerable individuals. A literature review were conducted to quantify POI incidence and establish evidence-based predictors for variable selection. Subsequently, a retrospective cohort from the Second Affiliated Hospital of Wenzhou Medical University was used for model development and internal validation. Feature selection incorporated the least absolute shrinkage and selection operator (LASSO) regression with multivariate logistic regression, followed by predictive modeling using five distinct algorithms: logistic regression (LR), random forest (RFC), categorical boosting (CatBoost), extreme gradient boosting (XGB), and light gradient boosting machine (LGBM). Model interpretability was augmented through SHapley Additive exPlanations (SHAP) analysis. The literature review encompassed 20 eligible studies, determining a pooled POI incidence of 8.9
Background: With the increasing variety of pediatric diagnostic procedures, a growing number of children require sedation for diagnostic examinations. Appropriate sedation protocols guarantee the safety of children during sedation and improve its efficiency. Currently, there are significant differences in pediatric sedation practices across countries, regions, and medical institutions. Methods: The Pediatric Anesthesiology Group of the Chinese Society of Anesthesiology organized experts from multiple countries to develop the "Chinese Society of Pediatric Anesthesiology Guideline for Pediatric sedation (2025)" based on evidence-based medicine, considering the safety and efficacy, the preferences of children and parents, and drug accessibility. Results: The guideline provided 28 recommendations addressing 12 clinical issues related to pre-sedation assessment, safety measures for sedation personnel and facilities, sedation protocols, sedation monitoring, and post-sedation recovery. Conclusions: The guideline is planned to be disseminated globally through multiple channels, aiming to standardize the management of pediatric sedation and improve its safety and efficacy.
Objective:To investigate the analgesic effects of acupressure needle therapy combined with lumbar plexus block for anesthesia in elderly patients undergoing unilateral hip arthroplasty. Methods:A total of 147 older patients set to have elective hip surgery from February 2025 to September 2025 were randomly divided into three groups: the acupressure needle group (Group A), the lumbar plexus group (Group L), and the combined acupressure needle and lumbar plexus block group (Group AL), with 49 patients in each group. All patients underwent hip arthroplasty under general anesthesia with endotracheal intubation. We compared the intraoperative consumption of remifentanil and propofol among the three groups. Additionally, the incidence of cognitive dysfunction (assessed by the 3D-CAM) on postoperative within 48 hours, numerical rating scale (NRS) scores for pain at rest and during movement (hip lift at 45°) at 6, 12, 24, and 48 hours postoperatively, quality of recovery scores (QoR-40 and ADL scores), patient satisfaction, preoperative and postoperative levels of IL-1β/IL-6 and serum CRP, PACU NRS scores, total consumption of postoperative analgesic pumps, effective and total presses of the PCA button (at 12, 24, 36, and 48 hours after surgery), rescue analgesic use in the ward, and opioid-related adverse reactions (nausea and vomiting) were evaluated. Results:Using acupressure needle therapy along with a lumbar plexus block during general anesthesia led to less need for remifentanil and propofol during surgery, reduced the amount of pain relief needed afterward, decreased side effects from opioids like nausea and vomiting, lowered pain scores after surgery, and made patients more satisfied. Conclusion:This combined strategy provides an effective optimized multimodal analgesic option for elderly patients undergoing hip replacement and is particularly valuable in comprehensive management regimens aimed at reducing opioid exposure.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by impaired memory and cognitive decline. The early stages of AD in mice present with neuropathy in the hippocampus. Excessive mitochondrial fragmentation and dysfunction are critical pathological features of AD. Chloride intracellular channel 4 (CLIC4) is involved in neuronal apoptosis and regulates mitochondrial functions. Glial maturation factor β (GMFβ) inhibits mitochondrial DNA replication and energy metabolism, causes mitochondrial dysfunction, and regulates apoptosis. Dynamic related protein 1 (DRP1), a key protein in mitochondrial division, exhibits increased activity when its Ser616 site is phosphorylated. However, the role of CLIC4 in Aβ-induced cognitive impairment through the modulation of GMFβ and p-DRP1 (Ser616) to induce mitochondrial dysfunction remains unclear. This study examined the role of CLIC4 in Aβ-induced cognitive impairment in AD mice, focusing on its regulation of GMFβ and p-DRP1 (Ser616) and the subsequent effects on mitochondrial hyperfission and dysfunction. Our findings demonstrate that overexpression of CLIC4 in the mouse hippocampus or in HT22 cells resulted in pathological changes analogous to those observed following Aβ exposure. These changes include elevated levels of GMFβ and p-DRP1 (Ser616) proteins, mitochondrial fission, and increased intracellular ROS production. Conversely, CLIC4 knockdown mitigated Aβ-induced neuronal damage. These findings indicate that CLIC4 may be crucial in Aβ-induced hippocampal neurological damage in mice by regulating GMFβ and DRP1 phosphorylation.
Sepsis‑induced acute lung injury (S‑ALI) is a leading cause of respiratory failure and mortality in intensive care units, characterized by profound biological and clinical heterogeneity that explains the repeated failure of uniform anti‑inflammatory therapies. This variability underscores the urgent need for mechanism‑based patient stratification and precision medicine approaches. Pyroptosis, a regulated inflammatory cell death program driven by gasdermin‑mediated membrane pore formation, has emerged as a critical driver of alveolar‑capillary barrier disruption and cytokine amplification in S‑ALI. The activation of canonical and non‑canonical inflammasome pathways, together with molecular crosstalk within the integrated PANoptosome network, promotes context‑dependent pyroptotic responses across pulmonary endothelial, epithelial and immune cells. Notably, recent insights into lineage plasticity and transcriptional heterogeneity further elucidate the dynamic cellular orchestration of these pathways. Pyroptotic effectors, such as circulating gasdermin D fragments and mature IL‑1β/IL‑18, are detectable in patients with sepsis and acute respiratory distress syndrome, being associated with hyperinflammatory endotypes, disease severity and clinical trajectories. By integrating preclinical mechanistic insights with emerging human biomarker and trial data, the present review positions pyroptosis as a clinically actionable, stratification‑relevant target. The present review highlights current advances in pathway‑specific inhibitors and discusses their potential to enable biomarker‑guided, personalized interventions in critically ill patients.
Objective:To investigate the short-term efficacy and prognostic factors of severe to profound sudden sensorineural hearing loss(SSNHL) in pediatric patients. Methods:A retrospective analysis was conducted on the clinical data of 87 children with severe to profound SSNHL who were admitted to our department between January 2014 and December 2024. Hearing changes were evaluated 10 days after treatment initiation. Pearson's chi-square test was used to compare intergroup differences in categorical variables, including gender, affected side, vertigo, tinnitus, early combined use of batroxobin, degree of hearing loss, and upper respiratory tract infection. The Mann-Whitney U test was used to analyze intergroup differences in continuous variables, including age and duration of hearing loss. Univariate and multivariate logistic regression analyses assessed the short-term therapeutic efficacy and its influencing factors in severe and profound SSNHL. Grouped stacked bar charts and grouped box plots explored the relationship between significant influencing factors and therapeutic response rate. Results:Pearson's chi-square test and Mann-Whitney U test revealed that gender, age, duration of hearing loss, and early combined use of batroxobin were significantly associated with the therapeutic response rate of severe and profound SSNHL in children(P<0.05). No statistically significant differences in therapeutic response rate were observed among groups with affected side, tinnitus, vertigo, degree of hearing loss, or upper respiratory tract infection(P>0.05). Univariate logistic regression analysis indicated that age, gender, duration of hearing loss, and early combined use of batroxobin were influencing factors for the therapeutic efficacy of severe and profound SSNHL in children. Multivariate logistic regression analysis further demonstrated that duration of hearing loss was negatively correlated with the response rate, whereas female gender, older age, and early combined use of batroxobin were positively correlated with the response rate. Grouped stacked bar charts showed that the response rate was higher in females, and higher in patients with early batroxobin administration. Grouped box plots indicated that a shorter duration of hearing loss was associated with a more concentrated distribution of response rates, and older age was also correlated with a more concentrated distribution of response rates. Conclusion:Gender, age, early combined use of batroxobin, and duration of hearing loss are independent influencing factors for the short-term treatment of severe and profound SSNHL in children.
OBJECTIVE:To compare the effects of general anesthesia (GA) and regional anesthesia (RA) on postoperative anxiety and/or depression (PAD) in patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), and explore potential mediation by salivary cortisol (SC) or alpha-amylase (sAA). METHODS:This prospective, randomized trial compared GA versus RA in 82 patients undergoing ACL reconstruction. Primary outcomes were incidences of PAD, SC, sAA, and blood glucose levels. Secondary outcomes were knee swelling, skin temperature, postoperative opioid consumption, Numeric Rating Scale (NRS) pain scores, hospital stay, and hospitalization costs. Assessments were conducted at 1d preoperatively (T0), surgery day (T1), postoperative 2 h (T2), 1d (T3), 2d (T4), and 5d (T5). RESULTS:After adjusting for all confounding factors combined (anesthesia preference, preoperative NRS pain scores, and baseline HADS scores), the incidence of postoperative anxiety was significantly higher in the RA group than in the GA group at T3 ( P < 0.000), T4 ( P = 0.001), and T5 ( P = 0.001). In contrast, SC levels were significantly higher in the GA group than in the RA group at T2 ( P < 0.001), T3 ( P = 0.010), and T4 ( P = 0.012). Mediation analysis revealed a non-significant indirect effect of SC on the relationship between anesthesia technique and postoperative anxiety. No significant differences were observed in postoperative depression, sAA activity, or blood glucose levels between groups. CONCLUSIONS:GA exhibits lower postoperative anxiety in ACLR patients, whereas RA shows superior perioperative SC suppression. SC did not mediate the relationship between anesthesia technique and postoperative anxiety. These findings suggest GA may benefit anxiety-prone individuals, while RA appears advantageous for stress-sensitive cases.
IntroductionOxidative stress-mediated retinal pigment epithelial (RPE) cell injury is a key pathological feature of age-related macular degeneration (AMD). Ferroptosis—an iron-dependent form of regulated cell death driven by lipid peroxidation—has been increasingly identified as a critical executor of RPE degeneration and a key pathogenic mechanism in AMD. This study aimed to investigate the mechanism by which Salvianolic acid A (SalA) alleviates ferroptosis in RPE cells under sodium iodate (NaIO3)-induced damage.MethodsUsing in vitro (ARPE-19 cells) and in vivo (mice) NaIO3-induced injury models. We assessed cell viability, ferroptosis markers (iron, lipid peroxidation, glutathione), mitochondrial ultrastructure, and key protein expression via biochemical assays, flow cytometry, transmission electron microscopy, and Western blotting.ResultsSalA pretreatment effectively mitigated NaIO3-induced ferroptosis, reducing lipid peroxidation, iron overload, and mitochondrial damage. Mechanistically, SalA upregulated the key ferroptosis regulators SLC7A11 and GPX4. Critically, this protection was significantly attenuated by the SLC7A11 inhibitor erastin, confirming the essential role of this axis. In mice, SalA attenuated NaIO3-induced retinal structural damage and enhanced SLC7A11/GPX4 expression in retina tissues.ConclusionThis study identifies SalA as a potent inhibitor of ferroptosis in RPE cells, primarily through activation of the SLC7A11/GPX4 axis. These findings suggest that SalA may hold therapeutic potential for AMD and provide a preliminary pharmacological basis for further exploration in retinal degenerative diseases.
BACKGROUND:Intermittent hypoxia (IH), as a key pathogenic factor of obstructive sleep apnea syndrome (OSAS), can cause many diseases, such as increased inflammation and oxidative stress, diabetes, cardiovascular disease, and Alzheimer's disease (AD). The response of cells to hypoxia involves multiple levels of regulatory mechanisms, including transcriptional regulation of gene expression, regulation of mRNA stability, post-transcriptional regulation, and post-translational modification regulation. AIMS:The regulation of miRNA and alternative splicing (AS) in neuronal response to intermittent hypoxia deserve further study. MATERIALS & METHODS:By establishing a mouse model of intermittent hypoxia, we conducted functional studies on key miRNAs and splicing factor using methods such as miRNA sequencing, bioinformatics, and molecular biology. RESULTS:In the mouse hippocampus, intermittent hypoxia altered the expression of many miRNAs, with miR-448-3p and miR-1264-3p changing over the course of more than three time periods. Interestingly, the expression of Fam76b, the common target gene of these two miRNAs, also changed under intermittent hypoxia. Further studies showed that Fam76b may regulate the ratio of Nbr1 and Dph3 transcripts in response to hypoxia by affecting the localization of hnRNPA2B1 protein within cells. DISCUSSION:Research into intermittent hypoxia-induced disorders, including Alzheimer's disease and other neurodegenerative diseases, might benefit from a better understanding of the regulatory mechanisms of miRNA and alternative splicing in hypoxic response at the animal and cell levels. CONCLUSION:This study demonstrates that intermittent hypoxia alters the expression of miR-448-3p and miR-1264-3p, as well as the localization of the splicing factor hnRNPA2B1 in the cell nucleus. These findings enhance our understanding of the molecular mechanisms of neuronal responses to hypoxia and hold potential implications for treating hypoxia-related diseases like Alzheimer's disease.
BackgroundLumbar disc herniation (LDH) is also a degenerative disease of the spine, and age is an important factor affecting the prognosis of LDH patients. The aim of this study is to analyze the pain levels and physical function changes of LDH patients in different age groups before and after percutaneous transforaminal endoscopic discectomy (PTED) treatment, and to analyze the factors that affect postoperative clinical outcome indicators.MethodThis study included 100 LDH patients. Collect baseline characteristics of patients and compare the differences in pain levels, ODI scores, JOA scores, BBS scores, and SF-36 scores between LDH patients of different ages before and after PTED treatment. The generalized linear mixed model (GLMM) was used to analyze the impact of different factors on postoperative clinical outcomes, and the ROC curve was used to evaluate the predictive ability of age on postoperative indicator improvement.ResultThe research results indicate that after PTED treatment, the postoperative clinical outcomes of all patients have significantly improved, with the younger group showing the most significant improvement. In the young group, the amount of intraoperative bleeding, the length of operation, the length of postoperative bed rest, and the incidence rate of postoperative complications were the lowest. GLMM analysis showed that follow-up time, Pfirrmann grading, baseline NLR level, age, lumbar spondylolisthesis, affected intervertebral disc segment L5/S1, and the interaction between age and follow-up time were significant influencing factors for postoperative clinical outcomes. As the follow-up time prolongs, the influence of age on ODI and JOA gradually weakens. ROC curve analysis showed that age had the strongest predictive ability for the improvement of preoperative and postoperative ODI scores and JOA scores, with AUC values of 0.641 and 0.646, respectively.ConclusionThe clinical outcomes of PTED treatment in young patients showed the most significant improvement. With the extension of postoperative follow-up time, the influence of age on postoperative clinical outcomes gradually decreases. This study also provides valuable reference for exploring the factors that affect the therapeutic effect of PTED.
PurposeThis study compared the efficacy and acceptability of a ready-to-use intranasal dexmedetomidine spray (DS) versus traditional drops administered by syringe (DD) in pediatric patients undergoing elective surgery.Patients and MethodsEighty-six preschool children were enrolled in a prospective, randomized, controlled study. Children were randomly assigned to receive either DS or DD. For children weighing between 10.5 and 18.5 kg, a dexmedetomidine dosage of 30 μg (two sprays) was administered, while those weighing between 18.5 and 25.5 kg received 45 μg (three sprays). In the DD group, dexmedetomidine was administered at a dose of 2 μg/kg based on body weight. The primary outcome was the proportion of children achieving a Ramsay sedation scale (RSS) score of ≥3 within 30 min. Secondary outcomes included acceptance of intranasal medication, anxiety at parental separation and prior to induction, and compliance with induction.ResultsA total of 83 cases were analyzed. The proportion of children achieving an RSS score of ≥3 within 30 min was similar between the DS and DD groups (90.7% vs. 77.5%, respectively). However, the acceptance score was significantly better in the DS group (mean difference [95%]: −0.9 [−1.267 to −0.5325], P < 0.001). No significant differences were observed between the groups in terms of successful child-parent separation (88.4% vs. 85%) or satisfactory anxiolytic effect prior to induction (95.3% vs. 92.5%). Compliance with induction was comparable, with 53.5% in the DS group and 40.0% in the DD group demonstrating “optimal” compliance.ConclusionBoth intranasal spray and syringe drop methods were highly effective in providing sedation and anxiolysis, but the ready-to-use intranasal dexmedetomidine spray was more acceptable to children, offering a viable alternative to the syringe method.Clinical Trial RegistrationChiCTR.org.cn, identifier ChiCTR2400089374.
Evidence has continually accumulated to illustrate that sirtuin 1 (SIRT1) is a major factor in multiple animal models of neuropathic pain, encompassing those due to drug-induced peripheral nerves, diabetes-induced neuropathy, and chronic constriction injury. This investigation sought to examine if upregulating SIRT1 expression through the CDK5-Kalirin-7 signaling pathway can reduce pain in type 2 diabetic rats. A rat model simulating peripheral nerve injury as an imitation of type 2 diabetes was integrated into the investigation. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were utilized to evaluate pain-related behavior. Our findings revealed spinal SIRT1 expression is diminished in DNP (diabetic neuropathic pain) rats, and SRT1720 (SIRT1 agonist) can alleviate pain behavior. The expression of Kalirin-7 and P-NR2B was markedly increased, while the expression of t-NR2B had no statistical difference in DNP rats. The acetylation level of CDK5 in the DNP cohort was notably elevated, and after intrathecal injection of SRT1720, Ac-CDK5 in the SRT cohort was markedly diminished in contrast to the DNP cohort, and pain behavior was improved. Roscovitine (CDK5 antagonist) was validated to be significantly decreased in CDK5, p35, Kalirin-7, and p-NR2B protein on STZ 17, 21, and 28 days, and there was no difference in t-NR2B among all cohorts. Meanwhile, the thermal hyperalgesia and mechanical allodynia were markedly diminished in cohort Ros (the cohorts were administered Roscovitine). In vitro, the protein levels of CDK5 and p35 were elevated in BV2 cells, and the expression of Kalirin-7, PSD95, and p-NR2B was increased in co-cultured PC12 cells under high-glucose conditions. All of these in vitro effects were significantly attenuated following treatment with Roscovitine. These findings indicate that SIRT1 serves a crucial function in DNP advancement via CDK5-Kalirin-7 signaling pathway.
Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
PURPOSE:This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP). METHODS:The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394. RESULTS:The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats. CONCLUSION:Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.
Summary Introduction Data regarding the incidence of 12‐month postoperative cognitive decline following regional or general anaesthesia in older patients undergoing hip fracture surgery remain observational. Compared with general anaesthesia, we hypothesised that regional anaesthesia would decrease the incidence of 12‐month postoperative cognitive decline. Methods This is substudy of a multicentre randomised trial of regional anaesthesia with no sedation vs. general anaesthesia with 12‐month follow‐up, conducted in nine university hospitals in south‐eastern China. Patients aged ≥ 65 y with hip fractures requiring surgery were eligible for inclusion. The prespecified 1‐year primary outcome was the incidence of postoperative cognitive decline at 12 months post‐randomisation. Secondary outcomes included major or mild postoperative cognitive decline; changes in Mini‐Mental State Examination; newly developed dementia; affective status; and health‐related quality of life. Results We recruited 950 patients between October 2014 and September 2018 (n = 474 general and n = 476 regional), with the last participant interviewed in November 2019. A total of 293 patients (139 general vs. 154 regional) were included in the primary analysis of the 12‐month outcome. Median (IQR [range]) age of patients was 78 (71–82 [65–96]) y and 217 (74.1%) were female. The incidence of cognitive decline at 12 months was 29.7% vs. 25.4% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.2 (95%CI 0.7–2.1), p = 0.43, Bayes factor = 0.28). Major cognitive decline developed in 8.6% vs. 8.5% of patients allocated to general vs. regional anaesthesia, respectively (unadjusted OR 1.0 (95%CI 0.4–2.4)). Discussion The incidence of 12‐month postoperative cognitive decline was not significantly different in patients having general or regional anaesthesia for hip fracture surgery.
Lumbar spinal fusion (LSF) represents a primary surgical approach for treating degenerative lumbar diseases and spinal instability in elderly patients. However, the impact of ERAS protocols in elderly patients undergoing LSF remains unknown. This article aims to summarize the effectiveness and safety of ERAS protocols in elderly patients undergoing LSF, thereby providing evidence-based guidance for perioperative management of this population. A search was performed across multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, Preprint Platforms (MedRxiv), and Clinical Trial database, to identify eligible studies. Retrospective studies and randomized controlled trials that compared the clinical utility of ERAS with conventional pathways in elderly patients (≥ 65years) undergoing LSF were included. The retrieved literature underwent Meta-analysis R software. Trial sequential analyses were conducted for outcomes reported in at least five studies, using the Trial Sequential Analysis Software. The meta-analysis incorporated seventeen eligible studies. Compared with conventional perioperative care, ERAS protocols showed significant benefits across multiple outcomes: reduced length of stay(LOS) (mean difference: –2.29 days; 95
Streptococcus suis serotype 2 (SS2) is a prominent pathogen that impacts swine and presents a zoonotic threat to humans; it is a cause of bacterial meningitis, a severe condition linked to neurological impairment and elevated mortality rates. For SS2 to access the central nervous system, it must traverse the blood–brain barrier (BBB); however, the precise mechanisms underlying this process remain incompletely elucidated. In this study, we demonstrate that the RTX family exoprotein A (RfeA), which is secreted by SS2, can be internalized by human brain microvascular endothelial cells (hBMECs) via a caveolae/lipid raft-dependent pathway. RfeA subsequently induces pyroptosis through the NLRP3/Caspase-1 pathway, a process attributed to the increase in mitochondrial reactive oxygen species (mtROS). The interaction between the N-terminus of RfeA and voltage-dependent anion channel 1 (VDAC1) leads to mtROS production, which can be suppressed by a VDAC1 oligomerization inhibitor. RfeA-induced pyroptosis results in disruption of the BBB in both the hBMEC monolayer model and the mouse infection model, thereby promoting bacterial infection of the brain. These findings elucidate a novel mechanism by which SS2 induces pyroptosis to breach the BBB, suggesting a potential target for the prevention and treatment of SS2 infection.