BACKGROUND:Electroacupuncture (EA) is widely used for analgesia, but its central mechanisms remain unclear. We investigated whether EA alleviates neuropathic pain by suppressing metabotropic glutamate receptor 5 (mGluR5) signaling in the anterior cingulate cortex (ACC). METHODS:In naïve mice, we manipulated ACC pyramidal neurons using adeno-associated viral (AAV) vectors encoding calcium/calmodulin-dependent protein kinase II (CaMKII)-driven opsins-channelrhodopsin-2 (ChR2) or halorhodopsin (NpHR3.0)-followed by blue- or yellow-light stimulation to assess behavioral responses. In a chronic constriction injury (CCI) model, mice received EA and were evaluated for mechanical and thermal withdrawal thresholds. Western blotting (WB) and immunofluorescence (IF) quantified ACC mGluR5 expression. Then CaMKII-targeted adeno-associated viruses expressing chemogenetic receptors, such as hM3Dq or hM4Di, were injected into the ACC. Two weeks later, CCI was induced, and mice received either EA or intraperitoneal clozapine-N-oxide (CNO) while pain behaviors were monitored. Finally, proteomic profiling of ACC tissue compared CCI and EA groups. RESULTS:Optogenetic activation of ACC pyramidal neurons in naïve mice reduced both mechanical and thermal withdrawal thresholds, indicating a pronociceptive effect, whereas optogenetic inhibition increased thresholds. In CCI mice, EA significantly attenuated hypersensitivity and downregulated ACC mGluR5 protein levels by WB and IF. Chemogenetic inhibition of ACC pyramidal neurons similarly elevated thresholds in CCI mice, imitating EA. Notably, combining chemogenetic inhibition with EA produced no additional improvement, suggesting convergence on a common ACC mGluR5-dependent pathway. CONCLUSIONS:EA relieves neuropathic pain in mice, at least in part, by suppressing ACC pyramidal neuron activity via inhibition of mGluR5 signaling.

ABSTRACT Background and Aims: Tubeless microlaryngoscopic surgery provides an unobstructed operative field, but carbon dioxide accumulation remains a concern during apnoea. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) maintains oxygenation but has limited capacity for carbon dioxide clearance. This study compared THRIVE combined with jet ventilation with THRIVE alone during tubeless vocal fold polyp surgery. Methods: In this single-blind randomised controlled trial, 100 adults undergoing microlaryngoscopic vocal fold polyp surgery were allocated to THRIVE alone (Group T) or THRIVE combined with jet ventilation (Group M). The primary endpoint was the change in transcutaneous carbon dioxide partial pressure (ΔPtcCO 2 ) from the onset of apnoea to the end of surgery. Oxygenation, adverse events, conversion to tracheal intubation, and recovery characteristics were also assessed. Results: Compared with Group T, patients in Group M showed a markedly smaller ΔPtcCO 2 (−0.56 ± 2.74 vs 10.98 ± 5.41 ± 5.41 mmHg; P < 0.001) and a lower end-of-surgery PtcCO 2 (36.42 ± 2.13 vs 47.02 ± 6.16 mmHg; P < 0.001). Mild oxygen desaturation occurred more frequently in Group T than in Group M [7/50 (14%) vs 0/50 (0%); P = 0.019], whereas no patient in either group developed hypoxaemia or required tracheal intubation. Conclusion: Adding jet ventilation to THRIVE reduced intraoperative carbon dioxide accumulation during tubeless microlaryngoscopic vocal fold polyp surgery without increasing perioperative adverse events.

Background: Cerebral ischemia-reperfusion injury (CIRI) is a severe neurological condition where restoring neuronal mitochondrial function critically impacts prognosis. While electroacupuncture (EA) has demonstrated neuroprotective effects by improving mitochondrial function, the precise underlying mechanisms remain unclear. Emerging evidence suggests that astrocyte-to-neuron mitochondrial transfer, facilitated by mitochondrial Rho-GTPase 1 (Miro1), serves as a vital neuroprotective pathway. Therefore, this study investigates whether astrocytic Miro1 participates in the neuroprotective effects of EA against CIRI in mice by regulating the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 40 (TOM40) and adenosine triphosphate (ATP) levels in damaged neurons. Methods: 126 C57BL/6 mice were randomly allocated into seven experimental groups (n = 18 per group): Sham-operated (Sham), middle cerebral artery occlusion (MCAO) model, EA, sham electroacupuncture (SEA), EA combined with astrocyte-specific Miro1 knockdown (GFAP: glial fibrillary acidic protein, EA+AAV-GFAP-shMiro1), astrocyte-specific Miro1 over-expression (AAV-GFAP-hiMiro1), and adenoviral empty vector control (AAV-GFAP-control). The CIRI model was induced using MCAO. Prior to model induction, the EA group received pretreatment with EA at the Baihui (GV20) acupoint. The SEA group underwent identical procedures to the EA group except for electrical stimulation. For the EA+AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, and AAV-GFAP-control groups, mice received intracerebroventricular injections of AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, or AAV-GFAP-control, respectively, 48 hours prior to EA treatment, with other procedures matching the EA group. At 24 hours post-reperfusion, neurological deficit scores, cerebral infarct volume, and neuronal survival in the peri-infarct penumbra were assessed. Astrocytes and neurons from the peri-infarct penumbra were isolated to measure ATP levels and expression of the mitochondrial-specific protein TOM40 in neurons, as well as ATP levels, TOM40, and Miro1 protein expression in astrocytes. Results: Relative to the Sham group, the MCAO group displayed a significant increase in cerebral infarct volume and neurological deficit scores, accompanied by a marked reduction in neuronal viability, TOM40 expression, and ATP levels (p < 0.01). In contrast to the MCAO and SEA groups, the EA and AAV-GFAP-hiMiro1 groups demonstrated improved neurological scores, reduced infarct volume, enhanced neuronal viability, elevated neuronal ATP levels and TOM40 expression, as well as decreased astrocytic ATP and TOM40 levels, but significantly increased Miro1 expression in astrocytes (p < 0.01). When compared to the EA group, the EA+AAV-GFAP-shMiro1 group exhibited a reversal of all the aforementioned improvements (p < 0.01), while the AAV-GFAP-hiMiro1 group showed no significant changes (p > 0.05). Conclusions: EA exerts neuroprotective effects in MCAO mice by upregulating Miro1 protein expression in astrocytes and upregulating the mitochondrial marker TOM40 alongside ATP levels in neurons. Silencing Miro1 abolished the neuroprotective effects of EA and reduced neuronal TOM40 expression, while Miro1 overexpression increased this mitochondrial marker and mimicked EA-mediated neuroprotection. These findings identify Miro1 as a key effector of EA-induced neuroprotection, although the upstream signaling pathways linking EA to Miro1 upregulation require further investigation.

IntroductionPropofol-based sedation for gastroscopy is effective but may cause dose-dependent cardiorespiratory depression; therefore, optimizing adjunct strategies to reduce propofol exposure is clinically important.MethodsWe conducted a prospective, single-center, randomized, double-blind, dose-response trial to evaluate the propofol-sparing effect of remimazolam during procedural sedation for gastroscopy. A total of 150 ASA I-II adults aged 18–59 years were randomly assigned to receive remimazolam 0, 0.05, 0.1, 0.15, or 0.2 mg·kg−1, and propofol was titrated to achieve adequate sedation. The primary outcomes were the propofol effect-site EC50 and propofol requirement (mg·kg−1·min−1). Secondary outcomes included recovery profiles, post-anesthesia care unit (PACU) duration, and sedation-related adverse events.ResultsRemimazolam reduced the propofol EC50 in a dose-dependent manner, from 3.05 (95% CI, 2.88–3.21) μg·mL−1 at 0.05 mg·kg−1 to 1.47 (95% CI, 1.30–1.64) μg·mL−1 at 0.2 mg·kg−1, and decreased propofol requirement from 0.587 ± 0.193 mg·kg−1·min−1 in the control group to 0.414 ± 0.121 mg·kg−1·min−1 at 0.1 mg·kg−1 and 0.298 ± 0.088 mg·kg−1·min−1 at 0.2 mg·kg−1. Procedure duration and PACU duration did not differ significantly among groups, and the incidence of sedation-related adverse events was comparable.DiscussionAdjunctive remimazolam provided a dose-dependent propofol-sparing effect during gastroscopy sedation. Among the tested doses, 0.1 mg·kg−1 appeared to offer a favorable balance between reduced propofol requirement and recovery profile, supporting its clinical feasibility under the conditions studied.Clinical Trial RegistrationChinese Clinical Trial Registry, identifier ChiCTR2400094449.

Purpose:Respiratory management remains a major challenge during painless endoscopy in overweight or obese patients because of altered body fat distribution and reduced pulmonary reserve. This study evaluated whether ciprofol could reduce respiratory adverse events compared with propofol during painless gastroscopy in this population. Methods:In this single-center, prospective, single-blind randomized controlled trial, 106 overweight or obese patients undergoing painless gastroscopy were randomly assigned (1:1) to receive either propofol (2 mg/kg) or ciprofol (0.4 mg/kg) following intravenous alfentanil (5 μg/kg). The primary outcome was the overall incidence of respiratory adverse events from anesthesia induction to completion of endoscopy, including hypoxemia (SpO2 <90% for >15 s), respiratory depression (respiratory rate <8 breaths/min for >30 s), and apnea (absence of chest wall movement for >20 s). Results:A total of 106 patients completed the study (53 per group). The incidence of respiratory adverse events was significantly lower in the ciprofol group than in the propofol group (33.96% vs. 66.04%, P=0.001). The lowest intraoperative SpO2 was significantly higher in the ciprofol group (93.50% vs. 89.00%, P=0.044). Compared with ciprofol, propofol was associated with higher incidences of hypotension (22.64% vs. 7.55%, P=0.030) and injection pain (18.87% vs. 0%, P=0.001). No significant differences were observed in other adverse events, including nausea and vomiting. Conclusion:In overweight or obese patients undergoing painless gastroscopy, ciprofol at 0.4 mg/kg significantly reduced respiratory adverse events, improved oxygenation, and decreased injection pain compared with propofol. These findings suggest that ciprofol may be a preferable anesthetic option for painless endoscopy in this population. Clinical Trial Registration:ChiCTR2600117367.

Sepsis-associated encephalopathy (SAE) is a serious condition in which the immune system uncontrollably responds to infection, causing organ dysfunction. Neuroinflammation is one of the primary mechanisms underlying SAE. N6-methyladenosine (m6A) methylation is a common and reversible chemical modification of RNA molecules. Increasing evidence suggests that this modification plays a vital role in the inflammatory immune response. AlkB homolog 5 (ALKBH5) is an enzyme responsible for removing m6A modifications from RNA molecules and is known as a demethylase. However, the specific role of ALKBH5 in neuroinflammation remains unclear. To explore the role of ALKBH5 in neuroinflammation, researchers have used lipopolysaccharide (LPS) to induce inflammation in BV2 cells and mice. This study found that treatment of BV2 cells with LPS (1 μg/mL) significantly increased the total RNA m6A level and the ALKBH5 protein decreased significantly. Meanwhile, the NF-κB inflammatory signaling pathway was activated, leading to an obvious increase in IL-1β, IL-6, and TNF-α mRNA. The LPS-induced inflammatory response was alleviated when ALKBH5 was overexpressed in BV2 cells. This is due to a slower degradation rate of NFKBIA mRNA, an increase in NFKBIA protein levels, and inhibition of the NF-κB inflammatory signal pathway. When ALKBH5 was overexpressed in mice, as expected, there was an improvement in behavioral abnormalities induced by LPS. Compared to healthy volunteers, ALKBH5 mRNA levels were significantly decreased in peripheral blood mononuclear cells (PBMCs) from patients with sepsis and correlated with GCS and IL-6 levels. In summary, this study suggested that ALKBH5 is a potential therapeutic target for enhancing NFKBIA mRNA stability and alleviating neuroinflammation. Thus, ALKBH5 may provide new insights into the diagnosis and treatment of SAE.

Purpose:Laparoscopic hysterectomy(LH) is often associated with multimodal postoperative pain, which impedes patient recovery. This study aimed to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative acute visceral,incisional, and low back pain (LBP) and recovery in patients undergoing LH. Patients and Methods:Patients scheduled for elective LH at the First Affiliated Hospital of Wenzhou Medical University (February 2024-2025) were randomly divided (1:1 ratio) into a TEAS and control group. TEAS involved bilateral stimulation at Hegu-Neiguan, and Sanyinjiao-Zusanli 30 min before anesthesia induction and throughout surgery, while the control involved electrodes placed identically for sham stimulation. Pain intensity (visceral, incisional, and LBP) was evaluated using numerical rating scale on postoperative days (PODs) 0 (day of surgery), 1, and 2. Secondary outcomes comprised postoperative serum cytokine profiles, opioid consumption, rescue analgesia demands on POD 1, adverse events, and standardized recovery metrics. Results:The TEAS group (n=45) demonstrated superior pain control compared to the control group (n=48), with significantly lower visceral pain scores (POD 0-1), decreased LBP scores (POD 0-2), and reduced incidence of moderate-to-severe visceral pain (POD 0-2) and LBP (POD 0) (all P < 0.017). TEAS resulted in lower interleukin-6 levels, total sufentanil consumption, and rescue analgesia demands on POD 1(all P < 0.05). TEAS was associated with a shorter time to pelvic drain removal, decreased postoperative hospitalization, earlier ambulation, and lower incidence of postoperative nausea and vomiting (all P < 0.05). No significant improvement in incisional pain was observed with TEAS intervention. Conclusion:TEAS provided differential postoperative analgesia, effectively alleviating visceral and LBP but not incisional pain. This primary benefit, coupled with reduced inflammation, opioid use, and adverse events, facilitated recovery in LH patients. These findings support the incorporation of TEAS as an effective non-pharmacological adjuvant within multimodal analgesia and ERAS protocols.

Background: Ischemic stroke is a serious clinical condition that is challenging to cure; therefore, slowing down the depletion of ATP is crucial to enhancing the tolerance of ischemic tissue through preconditioning. Electroacupuncture (EA) preconditioning induces tolerance to cerebral ischemia; however, the underlying mechanism remains unclear. Objective: The P2×7 receptor (P2×7R) mediates the stimulation of microglial cells and is involved in the development of cerebral ischemia-reperfusion (I/R) damage. We hypothesized that the protective effect of EA preconditioning is associated with the downregulation of P2×7R expression. Methods: We performed EA at the ''Baihui'' and ''Fengfu'' for 30 min before establishing a rat model of cerebral I/R induced based on the middle cerebral artery occlusion model (MCAO). MCAO rats were administered a ventricular injection of 2 '(3′)-O-(4-benzoyl) adenosine triphosphate (BzATP), a P2×7R agonist, 30 min before EA. Neurologic scoring, infarction volume, and expression of cytokines, Bcl-2 and Bax, Iba1, P2×7R, p38, and phosphorylated p38 (p-p38) in ischemia penumbra were detected 24 h after cerebral I/R. Results: EA preconditioning ameliorated neurologic scoring, decreased infarction volume, and neuronal injury, and decreased cytokine release, while BzATP exacerbated cerebral I/R damage and inflammation events, unlike the favorable efficacy of EA. EA inhibited the expression of Iba-1, P2×7R, and p-p38/p38 in the ischemic penumbra, whereas BzATP reversed this effect. Conclusions: EA could induce cerebral tolerance to I/R damage by suppressing P2×7R expression and release of inflammatory factors.

Background:Acupuncture has pain-relief effects, but no data are available on transcutaneous electrical acupoint stimulation (TEAS) for pain relief during transurethral removal of ureteral stents. This study aimed to evaluate the efficacy of TEAS in reducing pain during cystoscopic ureteral stent extraction. Methods:This prospective, double-blinded, randomized controlled trial enrolled 122 patients scheduled for cystoscopic ureteral stent removal between June 2023 and March 2024. Participants were randomized into three groups: TEAS at Hegu (LI4) and Neiguan (PC6) (Group A, n=37), TEAS at Sanyinjiao (SP6) and Zusanli (ST36) (Group B, n=38), and sham TEAS (Group C, n=47). TEAS or sham TEAS were administered 30 minutes before the procedure. The primary endpoint was pain measured by visual analog scale (VAS) at stent removal (T2). Secondary endpoints included VAS at cystoscope insertion (T1) and 10 minutes post-procedure (T3), along with hemodynamic parameters. Results:Baseline characteristics were comparable (p > 0.05). Both TEAS groups showed significantly lower VAS scores during stent removal (T2: median 0.00 [IQR: 0.00-2.50] for Group A and median 0.00 [IQR0.00-2.50] for group B vs 0.00 [IQR: 2.00-5.00] for Group C; p = 0.027) and at 10 minutes post-procedure (T3: median 0.00 [IQR: 0.00-0.00] for Group A and median 0.00 [IQR0.00-1.00] for group B vs 0.00 [IQR: 0.00-2.00] for Group C; p = 0.012). Repeated measures ANOVA with gender and age group as covariates revealed a significant Time × Gender interaction (F = 7.044, p = 0.006), indicating different temporal patterns of pain reduction between males and females. However, no significant interaction was found involving the Age Group factor or the three-way interaction with the treatment groups. No significant hemodynamic differences were observed. One patient in Group C withdrew due to severe pain. Conclusion:TEAS effectively reduces procedural and post-procedural pain during cystoscopic ureteral stent extraction without affecting hemodynamic stability. Notably, the analgesic effect of TEAS demonstrated gender-specific temporal patterns (Time × Gender interaction, p = 0.006), being more pronounced in female patients, while remaining consistently effective across all age groups. These findings support TEAS as a valuable non-pharmacological analgesic adjunct in outpatient urological procedures, though further multicenter and heterogeneous population studies are warranted to validate its generalizability.

Cerebral ischemia-reperfusion injury (CIRI) involves innate immunity activation in astrocytes and the inflammatory response. The interferon-induced transmembrane protein 3 (IFITM3) is an immune protein whose role in CIRI remains largely unexplored. This study investigated the role of IFITM3 in CIRI in mice. Adeno-associated virus (AAV)-mediated delivery of siRNA was used to inhibit IFITM3 expression, assessing effects on astrocyte activation, inflammatory cytokine expression. Primary cultured astrocytes were exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to study IFITM3's role in vitro. Western blotting (WB) was employed to measure C-reactive protein (CRP) and IFITM3 levels, and enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokines. γ-Secretase activity, as well as Aβ40 and Aβ42 peptide levels, were measured to evaluate its activity. IFITM3 expression in astrocytes was significantly elevated following CIRI (p < 0.001), leading to increased γ-secretase activity and higher production of Aβ40 and Aβ42 peptides (p < 0.001). CRP levels were also upregulated in the context of IFITM3 expression (p < 0.01). Inhibiting IFITM3 expression via AAV-mediated delivery of siRNA significantly reduced astrocyte activation, inflammatory cytokine expression (p < 0.001 for IL-1β, IL-6, TNF-α, and IFN-γ), and improved neurobehavioral scores (p < 0.001). In vitro, IFITM3 inhibition significantly reduced the protein and mRNA levels of IFITM3, suppressed astrocyte activation, and decreased the expressions of inflammatory factors (p < 0.01). IFITM3 inhibition reduced the apoptosis of co-cultured neuronal cells (p < 0.01) and suppressed TLR4/NF-κB expression (p < 0.01), thereby attenuating the production of inflammatory factors. Inhibiting IFITM3 expression in astrocytes not only regulates γ-secretase activity but also mitigates neuroinflammation, thereby alleviating CIRI.

Mitochondria are important targets for preventing oxidative damage during the progression of sepsis-induced lung injury. Numerous studies have pointed out that maintaining the stabilization of Nrf-2, thereby activating its transcription, may combat pathological inflammation by sustaining the integrity of mitochondrial function. Our previous study found that protein interaction with C-kinase 1 (PICK1) deficiency disrupts the physiological anti-inflammatory mechanism by affecting Nrf-2 transcription. However, whether PICK1 participates in mitochondrial quality control regulation through Nrf-2 has not been explored, and the underlying interaction between PICK1 and Nrf-2 has not been fully elucidated. We found that PICK1 decreased mitochondria-derived ROS, upregulated MnSOD activity in endotoxin-induced acute lung injury mice, improved mitochondrial membrane potential, and restored the damaged structure of mitochondria in LPS-stimulated macrophages. Through in-depth studies, we demonstrated that PICK1 maintains the stability of Nrf-2 by preserving mitochondrial dynamic equilibrium, facilitating mitochondrial biogenesis, and participating in mitophagy by activating the PI3K/AKT/GSK-3β pathway. PICK1 also inhibits the β-TrCP-mediated ubiquitination of Nrf-2. Thus, PICK1 offers an unexplored alternative to current Nrf-2 activators by acting as a Nrf-2 activator that may have therapeutic value against septic inflammation. Our study demonstrated the protective effects of PICK1 overexpression in endotoxin-associated ALI. PICK1 overexpression and the subsequent PI3K/AKT/Nrf-2/HO-1 pathway-dependent and E3 ubiquitin ligase adapter β-TrCP-mediated mitochondrial quality control contribute to lung repair, which offers an unexplored alternative to current Nrf-2 activators by acting as a Nrf-2 activator that may have therapeutic value against septic inflammation.

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Background: Postoperative high-activity delirium (PDHA) manifests as a high alertness, restlessness, hallucinations, and delusions. Occurrence of PDHA represents an increased risk of poor prognosis for patients. Objective: To establish and validate a nomogram prediction model for high-activity delirium after non-cardiac surgery in a post- anesthesia care unit (PACU). Methods: This study retrospectively enrolled adult patients who underwent non-cardiac surgery and were observed in the PACU as training data. Patients were divided into PDHA (199 patients) and non-PDHA (396 patients) groups. Patients' general data, preoperative indicators, intraoperative conditions, and postoperative PACU conditions were collected. The risk factors for PDHA were identified using univariate and multivariate logistic regression analyses. A predictive column chart was created using R language. Adult patients who underwent non-cardiac surgery and entered the PACU for observation were randomly selected as the validation set data (198 cases) for model performance validation. Results: The incidence rate of adult PDHA in the PACU was 0.275%. Sex, age, smoking history, low preoperative albumin level, Society of Anesthesiologists (ASA) classification, anesthesia duration, and postoperative PACU pain score were independent risk factors for hyperactive delirium in PACU adults. In this study, an adult PACU PDHA nomogram prediction model was developed. The training dataset verified that the ROC curve (area under the curve) and 95% confidence interval (95% CI) were 0.936 (0.917-0.955). The ROC curve of the validation data row showed that the area under the curve and 95% CI were 0.926 (0.885-0.967). Conclusion: The nomogram predictive model for PACU adult high-activity delirium constructed in this study showed good predictive performance. This model could enable the visualization and graphical prediction of adult high-activity delirium occurrence after PACU, which has clinical value.

Dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, is often used to treat lactic acidosis and malignant tumors. Increasing studies have shown that DCA has neuroprotective effects. Here, we explored the role and mechanism of DCA in Sepsis associated encephalopathy (SAE). Single-cell analysis was used to determine the important role of PDK4 in SAE and identify the cell type. GO and GSEA analysis were used to determine the correlation between DCA and pyroptosis. Through LPS + ATP stimulation, a microglia pyroptosis model was established to observe the expression level of intracellular pyroptosis-related proteins under DCA intervention, and further detect the changes in intracellular ROS and JC-1. Additionally, a co-culture environment of microglia and neuron was simply constructed to evaluate the effect of DCA on activated microglia-mediated neuronal apoptosis. Finally, Novel object recognition test and the Morris water maze were used to explore the effect of DCA on cognitive function in mice from different groups after intervention. Based on the above experiments, this study concludes that DCA can improve the ratio of peripheral and central M1 macrophages, inhibit NLRP3-mediated pyroptosis through ROS and mitochondrial membrane potential (MMP). DCA can reduce neuron death caused by SAE and improve cognitive function in LPS mice. In SAE, DCA may be a potential candidate drug for the treatment of microglia-mediated neuroinflammation.

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture’s antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5‘-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture’s analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture’s facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture’s antinociceptive effect through the promotion of M2 macrophage/microglial polarization.

Background The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). Methods Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. Results The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups ( p < 0.05). Additionally, the two groups had significant differences in rScO 2 at each intraoperative time point and in the difference of rScO 2 from baseline at each intraoperative time point ( p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008–1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619–23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046–14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO 2 at T 1 >50.5 (OR, 0.832 [95% CI 0.736–0.941]; p = 0.003) was a protective factor for POD. Conclusion Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO 2 at T 1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.

BACKGROUND Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS In total, 441 patients were randomized; 405 patients (58.4 +/- 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 +/- 1.2) than in the sham sti-mulation group (1.7 +/- 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Abstract Background Recent studies report that transcutaneous electrical acupoint stimulation (TEAS), a non-invasive and non-pharmacological adjunctive for perioperative rehabilitation, may improve respiratory function and reduce the incidence of postoperative pulmonary complications in patients undergoing video-assisted thoracic surgery (VATS).We studied the hypothesis that TEAS may improve inflammatory reaction,Oxygenation and post operative pulmonary complications(PPCs) in patients undergoing VATS lobectomy. Methods Data from 130 patients undergoing VATS lobectomy were analysed.All patients were randomized to two groups (TEAS group and Control group),and were managed using the same anaesthetic protocol.TEAS were performed from 30min before induction and during the operation at 2/100 Hz over acupoints Lieque and Hegu on the both side.Veinal blood was drawn for blood routine examination to count quantity of Neutrophil, Platelet and Lymphocyte and then to calculate two inflammatory indicators PLR and NLR at 5 time points.Mixed venous and arterial blood was drawn for measurement of shunt-fraction and dead-space at 3 time points.PPCs(following the ARISCAT study) during postoperative hospitalization were recorded. Results Among 130 patients,respiratory infection and pleural effusion were the most common complications.PPCs were less detected in TEAS group than Control group (12.5% vs. 27.3%, OR 2.44 [95% CI, 0.285–0.010]. At T2(Two Lung Ventilation after intubation 5 min),dead-space,and shunt-fraction were no difference between two groups,with the prolonged operation,TEAS group showed obvious advantages after acupoint stimulation,lower dead-space and shunt-fraction were detected in TEAS group(P < 0.001).NLR was lower in TEAS group,the difference was significant at T4(end of One Lung Ventilation,P＜0.001) and T5(first day after operation,P＜0.001),while PLR in there was difference at T5(P = 0.015).Furthermore,binary logistic regression model was built to analyses the correlation between PLR,NLR with PPCs respectively.Result shows PLR and NLR were meaningful in predicting postoperative lung complications as a risk factor. Conclusions The effect of TEAS during VATS lobectomy reduces the incidence of the PPCs recorded,attenuates the systemic inflammatory response and improve intraoperative oxygenation.PLR and NLR could be used as a risk factor to predict PPCs.

Neuroinflammation and oxidative stress damage are involved in the pathogenesis of cerebral ischemia–reperfusion injury (CIRI). Ferroptosis emerged as a new player in the regulation of lipid peroxidation processes. This study aimed at exploring the potential involvement of ciprofol on ferroptosis-associated CIRI and subsequent neurological deficits in the mouse model of transient cerebral ischemia and reperfusion. Cerebral ischemia was built in male C57BL/6 J wild-type (WT) and Nrf2-knockout (Nrf2 KO) mice in the manner of middle cerebral artery occlusion (MCAO) followed by reperfusion. Ciprofol improved autonomic behavior, alleviated reactive oxygen species output and ferroptosis-induced neuronal death by nucleus transportation of NFE2 like BZIP transcription factor 2 (Nrf2) and the promotion of heme oxygenase 1 (Ho-1), solute carrier family 7 member 11 (SLC7A11/xCT), and glutathione peroxidase 4 (GPX4). Additionally, ciprofol improved neurological scores and reduced infarct volume, brain water content, and necrotic neurons. Cerebral blood flow in MCAO-treated mice was also improved. Furthermore, absence of Nrf2 abrogated the neuroprotective actions of ciprofol on antioxidant capacity and sensitized neurons to oxidative stress damage. In vitro, the primary-cultured cortical neurons from mice were pre-treated with oxygen–glucose deprivation/reperfusion (OGD/R), followed by ciprofol administration. Ciprofol effectively reversed OGD/R-induced ferroptosis and accelerated transcription of GPX4 and xCT. In conclusion, we investigated the ciprofol-induced inhibition effect of ferroptosis-sheltered neurons from lipid preoxidation in the pathogenesis of CIRI via Nrf2-xCT-GPX4 signaling pathway.

Background Postoperative cognitive dysfunction (POCD) is a significant neurological issue after surgery, linked to increased mortality, extended hospital stays, higher costs, and workforce dropout. However, effective prevention methods for POCD remain elusive. Objective This study aims to investigate the impact of transcutaneous electrical acupoint stimulation (TEAS) on the cognitive function of elderly patients after bronchoscopy. Design The research team conducted a double-blind, randomized, controlled clinical trial. Setting The study was conducted at a university hospital in Wenzhou, China. Participants The study involved 80 patients who underwent bronchoscopy between December 2019 and September 2020. Intervention The participants were randomly assigned to two groups, each with 40 participants: the intervention and control groups. The intervention group received Transcutaneous Electrical Acupoint Stimulation (TEAS) for 30 minutes before anesthesia, while the control group had electrodes applied but did not receive stimulation. Outcome Measures Seven neuropsychological tests were administered before the operation and one day afterwards. Participants were also assessed via telephone after 7 days and one-month post-operation. Results The TEAS group exhibited a significant reduction in the incidence of delayed neurocognitive recovery (DNR) compared to the control group on the 7th-day post-operation, although no such difference was observed at 1 day and 30 days post-operation. Conclusion TEAS demonstrated positive effects in preventing cognitive decline in elderly patients undergoing bronchoscopy.