Background: Dezocine has been used for postoperative analgesia. However, its combination with sufentanil on postoperative recovery quality remains poorly understood. Methods: The Ease Go multicenter randomized controlled trial recruited 210 patients undergoing laparoscopic thoracic surgery from eight tertiary academic medical centers. The dezocine–sufentanil group received dezocine 1.0 mg/kg combined with sufentanil 2.0 μg/kg, while the sufentanil monotherapy group received sufentanil 3.0 μg/kg via a patient-controlled intravenous analgesia (PCIA) pump. The primary outcome was the quality of recovery (QoR-15) at 24 hours after PCIA pump initiation. The secondary outcomes included qualified recovery quality, patient global impression of change, the effective number of analgesic pump compressions, postoperative pain scores, as well as the use of rescue analgesics within 48 hours after PCIA pump initiation. Results: The mean QoR-15 scores at 24 and 48 hours after PCIA pump initiation in the dezocine–sufentanil vs. sufentanil group were 111.16 vs. 108.12 ( P = 0.321) and 121.96 vs. 120.14 ( P = 0.501), respectively. A higher proportion of qualified recovery quality was observed in the dezocine–sufentanil group (71.72% vs. 57.00%, P = 0.030 at 24 hours; 78.79% vs. 63.00%, P = 0.014 at 48 hours). The pain score was significantly lower in the dezocine–sufentanil group compared to the sufentanil group at 2, 4, 6, and 12 hours after PCIA pump initiation (all P < 0.05). The effective number of analgesic pump compressions (6.54 vs. 11.85, P = 0.001) and the proportion of patients requiring rescue medication (18.18% vs. 32.00%, P = 0.025) within 48 hours after pump initiation were both lower in the dezocine–sufentanil group. Conclusions: The QoR-15 score after laparoscopic thoracic surgery was not improved by the combined analgesia with dezocine and sufentanil. Nevertheless, the combined analgesia provided a higher qualified recovery quality rate and fewer analgesic requirements than sufentanil analgesia.

Polycystic kidney disease (PKD), the most common inherited kidney disorder, is characterized by progressive cyst growth and eventual organ failure. Although aberrant innate immune activation is a recognized contributor to PKD progression, the underlying molecular mechanisms remain incompletely defined. Here, we showed that Pkd1 deletion increased TLR2 and MyD88 mRNA expression in renal epithelial cells, indicating enhanced innate immune priming. In vivo, administration of Pam3CSK4 (PAM), a synthetic TLR2 agonist, preferentially amplified pro-inflammatory and pro-fibrotic responses in Pkd1RC/RC mice compared with wild-type controls, despite inducing similar signaling responses in vitro. Acute PAM treatment for one week rapidly enhanced NF-κB activation in cyst-lining epithelial cells, increased renal inflammation and cell proliferation, and was associated with activation of mTOR signaling and upregulation of c-Myc and Wnt proteins. Sustained PAM treatment further accelerated cyst expansion and renal fibrosis in PKD mice. Importantly, the endogenous TLR2 ligands decorin and biglycan were markedly elevated in human PKD kidneys, supporting the translational relevance of enhanced TLR2 signaling in disease progression. Together, these findings suggest that TLR2 signaling is an important contributor to PKD progression and a potential therapeutic target.

This study aims to investigate the effects of acupuncture anesthesia combined with erector spinae plane block (ESPB) on postoperative pain, nausea severity, and stress responses in patients undergoing thoracoscopic lung lobectomy, providing evidence for optimizing anesthesia protocols. Forty patients who underwent elective unilateral thoracoscopic lung lobectomy at the First Affiliated Hospital of Nanchang University (American Society of Anesthesiologists I-II) during the study period were retrospectively identified. According to the perioperative analgesic strategy recorded in the clinical database, patients were categorized into the ESPB-only group (E group) and the acupuncture combined with ESPB group (A + E group). The E group underwent ESPB at the T5 transverse process level (0.5% ropivacaine), while the A + E group received ESPB combined with electroacupuncture at bilateral Hegu, Houxi, Zhigou, and Neiguan acupoints (sparse-dense wave 2/100 Hz) until the end of surgery. The following parameters were recorded for both groups: intraoperative remifentanil dosage, visual analog scale scores at 4, 8, 12, 24, and 48 hours postoperatively, nausea numerical rating scale scores, patient-controlled analgesia button presses, sufentanil dosage, plasma neutrophil concentration before and 24 hours after surgery, and postoperative hospital stay. In the A + E group, visual analog scale scores and numerical rating scale scores at rest and during coughing at all postoperative time points were significantly lower than those in the E group (P < .05); The A + E group had fewer patient-controlled analgesia presses, lower postoperative sufentanil dosage, and lower intraoperative remifentanil dosage than the E group (P < .05); the A + E group had a lower increase in plasma neutrophil concentration at 24 hours postoperatively than the E group (P < .05); and the A + E group had a shorter postoperative hospital stay than the E group (P < .05). Acupuncture anesthesia combined with erector spinae plane block effectively reduces postoperative pain and nausea in patients undergoing thoracoscopic lung lobectomy, reduces opioid consumption, inhibits postoperative stress responses, and promotes postoperative recovery.

Background:The optimal analgesia regimen for patients undergoing laparoscopic gastrectomy is still unclear. This study evaluated the efficacy of ultrasound-guided rectus sheath block (RSB) with liposomal bupivacaine in providing sustained and effective analgesia to enhance recovery after laparoscopic gastrectomy. Methods:The study population comprised 102 individuals who underwent randomization to receive a rectus sheath block with one of the following: Ropivacaine-Dexamethasone (RD group), Liposomal Bupivacaine (LB group), or Liposomal Bupivacaine-Dexamethasone (LBD group). The primary efficacy measure was defined as total opioid consumption (within 72 hour postoperative), converted to morphine milligram equivalents (MME). Secondary outcomes included pain scores at rest and during movement (within 72 hours postoperatively), QoR-15-based recovery quality, perioperative satisfaction, inflammatory biomarker levels (preoperative, 24h and 72h postoperatively), PACU/hospital stay duration, and adverse events. Results:The RD group had significantly higher total opioid consumption compared with the LB group and the LBD group. The LB group and the LBD group had significantly lower pain scores at rest and on movement at 12 h, 24 h, and 48 h after surgery, when compared with the RD group. The LB group and the LBD group had lower concentrations of Interleukin-1β (IL-1β) and interleukin-6 (IL-6) at 24 h compared with the RD group. In addition to reporting significantly better QoR-15 scores in the initial 48 hours, patients receiving liposomal bupivacaine (with or without dexamethasone) also experienced lower rates of PONV compared to the ropivacaine-dexamethasone cohort. Furthermore, there were no statistically significant differences between the three groups regarding length of post-anesthesia care unit stay, perioperative satisfaction, and length of hospital stay. There were no statistical differences between the LB group and the LBD group in all data. And the addition of dexamethasone to LBD provided no additional benefit over liposomal bupivacaine alone LB. Conclusion:In conclusion, ultrasound-guided rectus sheath block with liposomal bupivacaine provided superior analgesia and reduced opioid consumption for up to 48 hours compared with a ropivacaine-dexamethasone regimen in patients undergoing laparoscopic gastrectomy. However, the addition of perineural dexamethasone to liposomal bupivacaine did not confer further analgesic benefit. Trial Registration:www.chictr.org.cn: Identifier: ChiCTR2500098338.

Background Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent a major and growing public health burden. Neuroinflammation is a critical driver of pathology in these disorders, and the ubiquitin-proteasome system (UPS) has emerged as a central regulator of inflammatory signaling within the nervous system. This review systematically examines the molecular interplay between the UPS and neuroinflammation in the progression of AD and PD. Main body We synthesize the core advances of the past decade in targeting the UPS to modulate neuroinflammation for therapeutic intervention. The UPS, primarily through the specific actions of E3 ubiquitin ligases and deubiquitinating enzymes, exerts precise control over key neuroinflammatory pathways, including NF-κB and the NLRP3 inflammasome, thereby critically shaping the functional states of microglia and astrocytes. In AD, UPS-targeted strategies have evolved beyond the clearance of Aβ and tau to include the reprogramming of microglial phenotype via nodes such as A20 and C/EBPβ. In PD, therapeutic focus has centered on augmenting PINK1/Parkin-dependent mitophagy and on suppressing specific pro-inflammatory factors like Peli1 and USP9X to disrupt pathogenic neuroinflammatory circuits. Conclusions This review provides a focused update on the mechanisms linking UPS dysfunction to neuroinflammation in AD and PD. It highlights the translational potential of targeting specific UPS components to modulate glial cell activation, with particular emphasis on the NF-κB and NLRP3 inflammasome axes as key regulatory hubs for future therapeutic development.

Perioperative neurocognitive disorders (PND) are prevalent neurological complications that may delay postoperative recovery in elderly patients, but effective preventive and therapeutic targets remain lacking. Protein S-palmitoylation is essential for normal neuronal function and synaptic plasticity, but its detailed role in PND development remains largely undefined. Here, we established a PND model in aged mice using partial hepatectomy under isoflurane anesthesia. We found that anesthesia and surgery markedly reduced S-palmitoylation of synaptosome-associated protein 25 (SNAP25) at four conserved cysteine residues (Cys85/Cys88/Cys90/Cys92) in the hippocampal neurons. Depalmitoylation impaired SNAP25 localization to the mitochondrial outer membrane and reduced its stability, causing defective mitophagy in hippocampal neurons. Mechanistically, palmitoyltransferase 17 (ZDHHC17) was identified as a major palmitoyl acyltransferase responsible for SNAP25 palmitoylation, and hippocampal ZDHHC17 expression was downregulated after anesthesia and surgery. ZDHHC17 interacted physically with SNAP25 and mediated the palmitoylation of SNAP25. Neuron-specific overexpression of ZDHHC17 restored SNAP25 palmitoylation, mitochondrial membrane localization and protein stability, and promoted neuronal mitophagy, ultimately improving hippocampal synaptic plasticity and cognitive function. Consistently, SNAP25 overexpression enhanced mitophagy and ameliorated cognitive impairments, whereas pharmacological inhibition of mitophagy with Mdivi-1 attenuated these neuroprotective effects. Collectively, our findings uncover a novel ZDHHC17-SNAP25 palmitoylation axis that can preserve hippocampal mitophagy and synaptic integrity, offering a promising therapeutic target for PND prevention and treatment.

Background:Liposomal bupivacaine may provide prolonged postoperative analgesia, but its efficacy in median sternotomy remains underexplored. This study evaluated whether liposomal bupivacaine for superficial parasternal intercostal plane (SPIP) block improves postoperative analgesia and reduces surgical stress in patients undergoing median sternotomy. Methods:In this prospective, randomized, double-blind controlled trial, 44 patients undergoing elective median sternotomy under cardiopulmonary bypass were randomized to receive SPIP block with either liposomal bupivacaine or ropivacaine. Primary outcomes were visual analog scale (VAS) pain scores within 72 h postoperatively and serum levels of stress markers, including angiotensin II (Ang-II) and interleukin-6 (IL-6). Secondary outcomes included patient-controlled intravenous analgesia boluses, postoperative nausea and vomiting, extubation time, intensive care unit stay, Quality of Recovery-15 (QoR-15) scores, and complications. Results:Compared with the ropivacaine group, the liposomal bupivacaine group showed significantly lower VAS pain scores from 18 to 72 h postoperatively (P < 0.05). Although Ang-II and IL-6 levels increased postoperatively in both groups, concentrations were significantly lower in the liposomal bupivacaine group (P < 0.01). Patients receiving liposomal bupivacaine required fewer analgesic boluses, had shorter intensive care unit stays, faster postoperative recovery, lower incidence of postoperative nausea and vomiting, and significantly improved QoR-15 scores (all P < 0.05). No significant differences were observed in extubation time, hospital stay, or hospitalization costs. No block-related complications were observed. Conclusion:Liposomal bupivacaine for SPIP block improved analgesia up to 72 hours after surgery, may attenuate the surgical stress response, and could promote early recovery in patients undergoing median sternotomy under cardiopulmonary bypass. Trial Registration:Chinese Clinical Trial Registry (ChiCTR2400091199).

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited effective treatments and significant challenges in early diagnosis. Identifying reliable biomarkers is crucial for improving diagnostic accuracy and patient outcomes. MATERIAL AND METHODS We analyzed TRIM family gene expression in IPF patients and healthy controls using GSE93606, GSE33566, and GSE38958 datasets. Consensus clustering and WGCNA identified IPF subtypes and hub genes. Machine learning models (RF, GLM, SVM, XGB) were built to identify key disease genes. A nomogram for clinical prediction was developed and validated. Peripheral blood samples from IPF patients and healthy controls were used to validate gene expression via qPCR. RESULTS TRIM family genes were significantly differentially expressed between IPF patients and healthy controls. Two distinct IPF subtypes (C1 and C2) were identified, each exhibiting unique biological functions and signaling pathways. The RF model outperformed other machine learning models, identifying TNIK, NCL, ROPN1L, MTR, and HNRNPH1 as key disease-characteristic genes. The nomogram demonstrated good predictive accuracy (AUC: 0.741, 95% CI: 0.556-0.897). qPCR validation confirmed increased expression of 4 genes in IPF patients, except for ROPN1L, which showed decreased expression. CONCLUSIONS This study identifies and validates TRIM family genes as potential biomarkers for IPF diagnosis using clinical samples. The findings support the integration of these biomarkers into diagnostic workflows, potentially enhancing early diagnosis and personalized treatment strategies for IPF patients. Further research is needed to explore the prognostic value and underlying mechanisms of these genes.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder that is characterized by the disruption of lung architecture and respiratory failure. Notwithstanding the advent of novel therapeutic agents such as pirfenidone and nintedanib, there remains a pressing need for the development of innovative diagnostic and therapeutic strategies. Next-generation sequencing allows for the analysis of gene expression and the discovery of biomarkers. The objective of our study was to identify IPF-specific gene signatures, construct a diagnostic nomogram, and explore the role of the extracellular matrix (ECM) and epithelial-to-mesenchymal transition (EMT) in IPF pathogenesis. Utilizing data from the Gene Expression Omnibus (GEO) database, we identified differentially expressed genes (DEGs), performed weighted correlation network analysis (WGCNA), and constructed a nomogram. The present study has identified a group of key genes that are associated with IPF. The identified genes include GREM1, ITLN2, MAP3K15, RGS9BP, and SLCO1A2. The results of the immunohistochemical analysis indicated a significant correlation between these central genes and immune cell infiltration. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that these genes play a critical role in the pathogenesis of IPF. To validate the diagnostic potential of these core genes, we performed confirmatory analyses in independent Gene Expression Omnibus (GEO) datasets. We observed a significant upregulation of GREM1 expression in IPF animal and cellular models. These findings provide new insights into the molecular mechanisms of IPF and suggest potential targets for future diagnostic and therapeutic strategies.

Organ fibrosis, a common consequence of chronic tissue injury, presents a significant health challenge. Recent research has revealed the regulatory role of N6-methyladenosine (m6A) RNA modification in fibrosis of various organs, including the lung, liver, kidney, and heart. In this comprehensive review, we summarize the latest findings on the mechanisms and functions of m6A modification in organ fibrosis. By highlighting the potential of m6A modification as a therapeutic target, our goal is to encourage further research in this emerging field and support advancements in the clinical treatment of organ fibrosis.

Purpose:This study aimed to compare the effects of ciprofol and propofol on motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) in elderly patients undergoing spinal surgery. Patients and Methods:This trial enrolled 60 elderly patients scheduled for elective spinal surgery with intraoperative neurophysiological monitoring (IONM) and assigned them to Group C (receiving ciprofol) or Group P (receiving propofol) using random allocation. Primary outcome measures focused on MEPs and SEPs amplitudes of lower extremities at T6. The secondary outcomes encompassed neurophysiological measures (MEPs and SEPs latencies at T6, as well as their amplitudes and latencies at T5), hemodynamic parameters of heart rate (HR), mean arterial pressure (MAP), and bispectral index (BIS) values at T1-T6, along with the incidence of hypotension, bradycardia, requirements for vasoactive medications. Results:Neurophysiological recordings at T6 showed significantly higher amplitudes in Group C across all measured parameters during inter-group comparison. For MEPs, Group C demonstrated greater amplitudes in lower extremities (1378 μV, IQR 1256-1605 vs 1121 μV, IQR 1077-1307; P<0.001). Similarly, SEPs were significantly elevated in Group C for lower extremities (1.34 μV, IQR 0.9-1.63 vs 1.11 μV, IQR 0.82-1.16; P=0.013). However, no inter-group differences existed in MEPs or SEPs latency. From T3 to T6, Group C exhibited higher MAP values than in Group P(all P<0.05); and no intergroup difference in BIS values was observed at T5-T6 (T5: 47.4 ± 4.0 vs 49.1 ± 4.7, P = 0.145; T6: 46.4 ± 3.5 vs 46.2 ± 4.0, P=0.892). Group C had a reduced need for vasoactive medications (13% vs 50%, P = 0.002), less hypotension incidence (17% vs 40%, P= 0.045). Conclusion:Ciprofol outperforms propofol in hemodynamic stability for the elderly undergoing spinal surgery, with less suppression of the amplitudes of MEPs and SEPs, and no prolongation of latency, thereby potentially improving the quality of IONM. Trial Registration Clinicaltrialsgov Identifier:ChiCTR2400091429.

Acute kidney injury (AKI) is a prevalent and serious clinical disease with a high incidence rate and significant health burden. The limited understanding of the complex pathological mechanisms has hindered the development of efficacious therapeutics. Tripartite motif containing 65 (TRIM65) has recently been identified as a key regulator of acute inflammation. However, its role in AKI remains unclear. The present study observed that TRIM65 expression was upregulated in AKI. Moreover, the knockout of the Trim65 gene in mice exhibited a substantial protective impact against rhabdomyolysis, ischemia-reperfusion (I/R), and cisplatin-induced AKI. Mechanistically, TRIM65 directly binds and mediates K48/K63-linked polyubiquitination modifications of voltage-dependent anion channel 1 (VDAC1) at its K161 and K200 amino acid sites. TRIM65 plays a role in maintaining the stability of VDAC1 and preventing its degradation by the autophagy pathway. TRIM65 deficiency attenuates mitochondrial dysfunction in renal tubular epithelial cells during AKI. Conversely, the overexpression of VDAC1 in renal tissues has been demonstrated to negate the protective effect of TRIM65 deficiency on AKI. These findings suggest that TRIM65 may play a role regulating of AKI through the targeting of VDAC1-dependent mitochondrial function, offering potential avenues for the development of new drug targets and strategies for the treatment of AKI.

Background:The optimal analgesic regimen after video-assisted thoracoscopic surgery (VATS) is unclear. We aimed to examine whether ultrasound-guided serratus anterior plane block (SAPB) with liposomal bupivacaine could provide continuous and effective analgesic effects for lung cancer patients undergoing VATS. Methods:A total of 64 patients were randomly allocated to receive either the liposomal bupivacaine (LB group) or the ropivacaine (RO group). The primary outcome was pain score at rest and on movement in the first three days after surgery. The secondary outcomes included intraoperative remifentanil consumption, perioperative consumption of sufentanil and flurbiprofen axetil, time to extubation, time to first bowel movement, time to first flatus, incidence of postoperative nausea and vomiting (PONV), length of intensive care unit (ICU) stay, length of hospital stay, hospitalization costs, and early recovery quality as assessed by QoR-15 score. Results:The LB group had significantly lower pain scores at rest and on movement at 12h, 24h, 36h, 48h, and 72h after surgery, and lower pain scores on movement at 8h after surgery, when compared with the RO group. Perioperative sufentanil consumption and postoperative flurbiprofen axetil consumption were significantly reduced in the LB group than in the RO group. In addition, compared with the RO group, the LB group had earlier first flatus, mobilization, and urinary catheter removal, shorter ICU stay, lower incidence of PONV, and lower hospitalization costs. The QoR-15 scores in the first three days after surgery were significantly higher in the LB group than in the RO group. There were no statistically significant differences between the two groups regarding time to extubation, intraoperative remifentanil consumption, and length of hospital stay. Conclusion:Ultrasound-guided SAPB with liposomal bupivacaine was effective in relieving postoperative pain for three days after surgery in patients undergoing VATS.

Alzheimer's disease (AD) is a gradual neurodegenerative ailment that lacks any disease-modifying intervention. Our objective was to pinpoint pharmacological targets with a focus on amyloid beta (Aβ) and tau to treat and prevent AD in the European population. A proteome-wide Mendelian randomization (MR) analysis was carried out to estimate the associations between proteins and cerebrospinal fluid (CSF) Aβ-42 and phosphorylated Tau (p-Tau). We utilized colocalization and MR analysis to investigate whether the identified proteins were associated with the risk of AD. Additionally, we expanded our investigation to include non-AD phenotypes by conducting a phenome-wide MR analysis of 1646 disease traits based on the FinnGen and UK Biobank databases to explore potential side effects. We identified 11 proteins that were genetically associated with both CSF Aβ-42 and p-Tau levels. The genetically predicted levels of three proteins, GAL3ST2, POLR1C, and BIN1, were found to be associated with an increased risk of AD with high colocalization. In the phenome-wide MR analysis, two out of the three biomarkers were associated with at least one disease, except for GAL3ST2, which was not associated with any disease under the threshold of FDR <0.1. POLR1C was found to be associated with the most disease traits, and all disease associations with genetically inhibited BIN1 were protective. The proteome-wide MR investigation revealed 11 proteins that were associated with the level of CSF Aβ-42 and p-Tau. Among them, GAL3ST2, POLR1C, and BIN1 were identified as potential therapeutic targets for AD and warrant further investigation.

Perioperative neurocognitive disorders (PND) are postoperative or anesthesia-related complications of the central nervous system, characterized by intelligence decline, memory loss, attention deficit, impaired decision-making skills, reduced language comprehension performance, and psychological disorders. This study aims to investigate the impact of a subanesthetic dose of esketamine on PND in aged mice by regulating the microglia toll-like receptor 4 (TLR4)/nuclear factor κ B (NF- κ B) pathway. An exploratory laparotomy model was established in 18-month-old C57BL/6 mice post-anesthesia. Behavioral evaluations such as open field tests and Morris water maze tests for autonomous activity and spatial learning and memory ability. Different esketamine doses were administered to aged mice, followed by behavioral assessment for autonomous activity and learning/memory abilities. Nucleic acid extraction employed magnetic nanoparticles, while qRT-PCR measured mRNA levels of tumor necrosis factor- α , interleukin-6, and interleukin-1 β . Western Blot detected the Iba-1 and TLR4 protein expression and phosphorylation status of the P65 protein. Immunofluorescence determined the fluorescence intensity of Iba-1 and P-NF- κ Bp65. MTT assay evaluated cell viability. As a result, we demonstrated that a subanesthetic dose of esketamine effectively inhibited microglia activation and TLR4/NF- κ B signaling pathway both in vivo and in vitro , resulting in decreased levels of inflammatory factors and improved neuroinflammatory responses, ultimately alleviating postoperative neurocognitive dysfunction. Notably, our findings revealed that laparotomy exploratory surgery-induced cognitive dysfunction, which can be improved by esketamine’s neuroprotective effects. Furthermore, our study also highlighted the protective effect of esketamine against lipopolysaccharide-induced inflammatory response in BV2 cells by inhibiting the TLR4/NF- κ B signaling pathway.

Acute lung injury (ALI) is characterized by acute respiratory failure with tachypnea and widespread alveolar infiltrates, badly affecting patients’ health. Desflurane (Des) is effective against lung injury. However, its mechanism in ALI remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) to construct an ALI cell model. Cell apoptosis was evaluated using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of inflammatory cytokines. Interactions among let-7b-5p, homeobox A9 (HOXA9), and suppressor of cytokine signaling 2 (SOCS2) were verified using Dual luciferase activity, chromatin immunoprecipitation (ChIP), and RNA pull-down analysis. All experimental data of this study were derived from three repeated experiments. Des treatment improved LPS-induced cell viability, reduced inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)) levels, decreased cell apoptosis, down-regulated the pro-apoptotic proteins (Bcl-2-associated X protein (Bax) and cleaved caspase 3) expression, and up-regulated the anti-apoptotic protein B-cell-lymphoma-2 (Bcl-2) expression in LPS-induced BEAS-2B cells. Des treatment down-regulated let-7b-5p expression in LPS-induced BEAS-2B cells. Moreover, let-7b-5p inhibition improved LPS-induced cell injury. let-7b-5p overexpression weakened the protective effects of Des. Mechanically, let-7b-5p could negatively modulate HOXA9 expression. Furthermore, HOXA9 inhibited the NF-κB signaling by enhancing SOCS2 transcription. HOXA9 overexpression weakened the promotion of let-7b-5p mimics in LPS-induced cell injury. Des alleviated LPS-induced ALI via regulating let-7b-5p/ HOXA9/NF-κB axis.

Background: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. Methods: The DNP rat model was established through a high -fat -glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal -regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick -end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. Results: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL -induced spinal nerve injury and inhibit mitophagy. Conclusion: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL -induced neurotoxicity.

Most patients undergoing the Nuss procedure reported moderate to severe pain after surgery. This study aimed to investigate the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) combined with transversus thoracic muscle plane (TTMP) block for relieving acute pain in patients undergoing the Nuss procedure. The enrolled patients in our study were allocated to either receive combined nerve blocks with ropivacaine (NB group) or saline (CON group). The primary outcome of this study was postoperative pain at 2, 4, 8, 16, 24, 36, and 48 h during rest and movement (coughing). Secondary outcomes included intraoperative dosage of remifentanil, the time to extubation and the length of stay in the post-anesthesia care unit (PACU), the total acetaminophen and codeine tablet consumption, time to first bowel movement, time to first flatus, opioid-related adverse events, and the length of hospital stay. Patients in the NB group had significantly lower Numerical Rating Scale (NRS) pain scores compared with the CON group. The NB group required significantly less postoperative acetaminophen consumption and lower dosages of perioperative sufentanyl and remifentanil compared with the CON group. The length of stay in the PACU and time to extubation were significantly increased in the CON group compared with the NE group. Time to first bowel movement and time to first flatus were earlier in the NB group. But there were no significant differences between the groups in terms of the length of hospital stay and codeine tablet consumption. Ultrasound-guided SAPB and TTMP blocks in patients undergoing the Nuss procedure could provide effective analgesia. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038506).

Abstract Background Open cardiac surgical patients may experience severe acute poststernotomy pain. The ultrasound-guided Pecto-intercostal Fascial Block (PIFB) can cover anterior branches of intercostal nerves from T2 to T6. The aim of this study was to investigate the effect of bilateral PIFB in patients undergoing open cardiac surgery. Methods A group of 108 patients were randomly allocated to either receive bilateral PIFB (PIFB group) or no nerve block (SALI group). The primary endpoint was postoperative pain. The secondary outcome measures included intraoperative and postoperative sufentanil and parecoxib consumption, time to extubation, time to first feces, length of stay in the ICU and the length of hospital stay. Insulin, glucose, insulin resistance and interleukin (IL)-6 at 1, 2, 3 days after surgery were mearsured. The homeostasis model assessment (HOMA-IR) was used to measure perioperative insulin resistance. Results The PIFB group reported significantly less sufentanil and parecoxib consumption than the SALI group. Compared to the PIFB group, the SALI group had higher Numerical Rating Scale (NRS) pain scores at 24 h after operation both at rest and during coughing. The time to extubation, length of stay in the ICU and length of hospital stay were significantly decreased in the PIFB group compared with the SALI group. The PIFB group had a lower insulin, glucose, IL-6, HOMA-IR level than the SALI group 3 days after surgery. Conclusion Bilateral PIFB provides effective analgesia and accelerates recovery in patients undergoing open cardiac surgery. Trial registration This study was registered in the Chinese Clinical Trial Registry ( ChiCTR 2000030609 ) on 08/03/2020.

The optimal analgesia regimen after open cardiac surgery is unclear. The aim of this study was to investigate the beneficial effects of continuous transversus thoracis muscle plane (TTMP) blocks initiated before surgery on open cardiac surgery outcomes. A group of 110 patients were randomly allocated to either receive bilateral continuous TTMP blocks (TTP group) or no nerve block (SAL group). The primary endpoint was post-operative pain at 4, 8, 16, 24, 48 and 72 h after extubation at rest and exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen axetil administration), time to extubation, incidence of reintubation, length of stay in the ICU, incidence of post-operative nausea and vomiting (PONV), time until return of bowel function, time to mobilization, urinary catheter removal and length of hospital stay. The length of stay in the ICU and length of hospital stay were significantly longer in the SAL group than in the TTP group. NRS scores at rest and exercise were significantly lower in the TTP group than in the SAL group at all time points. The TTP group required significantly less intraoperative and post-operative sufentanil and post-operative dynastat consumption than the SAL group. Time to extubation, time to first flatus, time until mobilization and time until urinary catheter removal were significantly earlier in the TTP group than in the SAL group. The incidence of PONV was significantly lower in the TTP group. Bilateral continuous TTMP blocks provide effective analgesia and accelerate recovery in patients undergoing open heart valve replacement surgery.