Expression of microRNA induced by postoperative delirium-like behavior is associated with long-term default mode network disruption: Sequencing and a secondary analysis of resting-state fMRI data.

AIMS: Resting state functional magnetic resonance imaging (rs-fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied. METHODS: Delirium-like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium-like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes. RESULTS: POD-like behavior caused significant changes of miR-34b-5p, miR-328-5p, and miR-3505 in miRNA level and Nos1, Tubb3, and Gys1 in the gene level. The FC in left and right hippocampus (L-Hip and R-Hip) and right auditory cortex (R-AC) was found significantly changed. Significant correlations were found in FCL-Hip/R-AC and FCR-Hip/R-AC for miR-34b-5p and miR-3505, as well as Nos1 and Tubb3. For miR-328-5p, no significant correlations were found. CONCLUSION: Our study demonstrates that POD-like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long-term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs-fMRI data analysis, as well as providing potential targets for postoperative delirium treatment.

Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Enhancing Stability of SAPO-37 Molecular Sieve through Aluminum Phosphate Utilization: Synthesis, Stability Mechanism, and Catalytic Performance.

SAPO-37 molecular sieve, characterized by its three-dimensional 12-membered-ring FAU structure, has drawn wide attention due to its unique properties and catalytic potential. However, its susceptibility to framework collapse under low-temperature and humid conditions hinders practical applications, affecting both the reaction performance and sample storage. To tackle this, we utilized aluminum phosphate as a precursor for synthesizing SAPO-37, aiming to modify Si incorporation mechanisms and improve P and Al environments. Solid NMR spectroscopy combined with other techniques proves that the resulting SAPO-37-AP has enriched silicon islands, leading to reduced water adsorption, more reversible structural change, and significantly enhanced stability after low-temperature vapor treatment compared to conventional SAPO-37. Remarkably, SAPO-37-AP, after water vapor treatment, still exhibits superior performance in the liquid-phase Beckmann rearrangement reaction. This approach enhances stability, reduces templating agent amounts, and improves the solid product yield, offering promising practical applications.

A modified low-priming cardiopulmonary bypass system in patients undergoing cardiac surgery with medium risk of transfusion: A randomized controlled trial.

Objectives: The FUWAI-SAVE system is a modified low-priming cardiopulmonary bypass (CPB) system. The study aimed to explore whether the FUWAI-SAVE system can reduce the perioperative blood transfusion and its impact on other postoperative complications during cardiac surgery. Metohds: This study was a single-center, single-blind, randomized controlled trial, registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2100050488). Adult patients undergoing cardiac surgery with CPB and intermediate risk for transfusion risk stratification were randomly assigned to an intervention group (FUWAI-SAVE group) or a control group (conventional group). The primary endpoint of the study was the peri-CPB red blood cell transfusion (RBC) rate. The secondary endpoints included the transfusion rate of other blood products, the amount of blood products transfused, the incidence of major complications, in-hospital mortality, and others. Results: 360 patients were randomized from December 9, 2021, to January 30, 2023. The rate of the primary endpoint was significantly lower in the FUWAI-SAVE group compared to the control group [ OR (95%CI): 0.649 (0.424-0.994)]. Meanwhile, the amount of RBC transfusion during the peri-CPB period was significantly lower in the FUWAI-SAVE group compared to the control group, with a mean difference of -0.626 (-1.176 to -0.076) units. The occurrence rate of major complications did not differ significantly between the two groups. Conclusions: Among adult patients undergoing cardiac surgery with CPB, the application of the FUWAI-SAVE system significantly reduced RBC transfusion rate and amount. The FUWAI-SAVE system can be considered an important component of comprehensive blood management strategies in cardiac surgery.

Impact of neuromuscular block on myocardial injury after non-cardiac surgery (MINS) incidence in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection: a randomized controlled study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. METHODS: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. RESULTS: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg-1·h-1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), µg·kg-1·min-1, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant. CONCLUSIONS: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).

Enhancing anti-angiogenic immunotherapy for melanoma through injectable metal-organic framework hydrogel co-delivery of combretastatin A4 and poly(I:C).

The interplay between vascularization and macrophage-induced immune suppression plays a crucial role in melanoma treatment. In this study, we propose a novel combination approach to combat melanoma by simultaneously inhibiting tumor vascularization and enhancing macrophage-mediated anti-tumor responses. We investigate the potential of combining combretastatin A4 (CA4), a vascular-disrupting agent, with poly(I:C) (PIC), an immunostimulatory adjuvant. This combination approach effectively suppresses melanoma cell proliferation, disrupts vascularization, and promotes macrophage polarization towards the M1 phenotype for melanoma suppression. To facilitate efficient co-delivery of CA4 and PIC for enhanced anti-angiogenic immunotherapy, we develop an injectable metal-organic framework hydrogel using Zeolitic Imidazolate Framework-8 (ZIF-8) and hyaluronic acid (HA) (ZIF-8/HA). Our findings demonstrate that ZIF-8 enables efficient loading of CA4 and enhances the stability of PIC against RNAase degradation in vitro. Furthermore, the developed co-delivery hydrogel system, PIC/CA4@ZIF-8/HA, exhibits improved rheological properties, good injectability and prolonged drug retention. Importantly, in vivo experiments demonstrate that the PIC/CA4@ZIF-8/HA formulation significantly reduces the dosage and administration frequency while achieving a more pronounced therapeutic effect. It effectively inhibits melanoma growth by suppressing angiogenesis, destroying blood vessels, promoting M1 macrophage infiltration, and demonstrating excellent biocompatibility. In conclusion, our study advances anti-angiogenic immunotherapy for melanoma through the potent combination of PIC/CA4, particularly when administered using the PIC/CA4@ZIF-8/HA formulation. These findings provide a new perspective on clinical anti-angiogenic immunotherapy for melanoma, emphasizing the importance of targeting tumor vascularization and macrophage-mediated immune suppression simultaneously.

An in-depth analysis of postoperative insomnia in elderly patients and its implications on rehabilitation.

OBJECTIVES: (1) Assess the prevalence of postoperative insomnia; (2) identify the risk factors for postoperative insomnia before exposure to surgery; (3) explore the impact of postoperative insomnia on rehabilitation. METHODS: A study was conducted with 132 participants aged ≥ 65 undergoing spine interbody fusion. We collected the basic demographic data, Numeric Rating Scales (NRS), Pittsburgh Sleep Quality Index (PSQI), Geriatric Depression Scale (GDS), and Beck Anxiety Inventory (BAI). We measured Quality of Recovery 40 (QoR-40), GDS, BAI, NRS, and PSQI on the first and third nights post-surgery, followed by QoR-40 and NRS assessments two weeks after surgery. RESULTS: The cases of postoperative insomnia on the first and third nights and after two weeks were 81 (61.36%), 72 (54.55%), and 64 (48.48%), respectively, and the type of insomnia was not significantly different (P = 0.138). Sleep efficiency on the first night was 49.96% ± 23.51. On the first night of postoperative insomnia, 54 (66.67%) cases were depression or anxiety, and the PSQI was higher in this group than in the group without anxiety or depression (P < 0.001). PSQI, GDS, and the time of surgery were related factors for postoperative insomnia (PPSQI < 0.001, PGDS = 0.008, and PTime = 0.040). Postoperative rehabilitation showed differences between the insomnia and non-insomnia groups (P < 0.001). CONCLUSIONS: The prevalence of postoperative insomnia in the elderly was high, and postoperative insomnia had a significant correlation with postoperative rehabilitation. Interventions that target risk factors may reduce the prevalence of postoperative insomnia and warrant further research. CLINICAL TRIAL REGISTRATION: Multivariate analysis of postoperative insomnia in elderly patients with spinal surgery and its correlation with postoperative rehabilitation ( https://www.chictr.org.cn/bin/project/edit?pid=170201 ; #ChiCTR2200059827).

FAT1 inhibits the proliferation of DLBCL cells via increasing the m6A modification of YAP1 mRNA.

Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3'UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3'UTR m6A modification by decreasing the activity of the TGFß-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3'UTR via the TGFß-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.

Decitabine suppresses MDSC-induced immunosuppression through dual functional mechanism and inhibits melanoma metastasis.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in promoting melanoma metastasis. Reprogramming MDSCs into mature M1 macrophages has emerged as a strategy to inhibit metastasis. Decitabine (Dec) is known to eradicate MDSCs and suppress tumor growth. In this study, we provide evidence that Dec not only reduces the MDSC population by inducing apoptosis, arresting cell cycle, and impairing recruitment, but also suppresses their immunosuppressive function by downregulating related genes and facilitating differentiation into M1 macrophages. Transcriptomic analysis of Dec-treated MDSCs revealed a marked downregulation of immunosuppressive genes including S100a9, S100a8, Vegf, Cxcr2, and Nos2. Meanwhile, M1 macrophage-associated genes involved in immune activation were upregulated, such as Ddx58, Isg15, Tap1, Ccl5, Cxcl9, and Cxcl10. Further bioinformatic analysis indicated that Dec promotes MDSC-to-M1 macrophage differentiation and activates innate immune pathways including NOD-like signaling to enhance anti-tumor immunity. Time-course studies implied that Dec upregulates myeloid transcription factor Irf7 to initiate MDSC differentiation and orchestrate the anti-tumor immune response. Collectively, our study unveils a novel dual-functional mechanism of Dec as both a cytotoxic agent reducing MDSCs and an inducer of their differentiation into M1 macrophages, thereby alleviating immunosuppression. This highlights Dec's potential for clinical melanoma metastasis suppression.

Risk factors for postoperative pulmonary complications in elderly patients undergoing video-assisted thoracoscopic surgery lobectomy under general anesthesia: a retrospective study.

BACKGROUND: The objective of this study is to identify and evaluate the risk factors associated with the development of postoperative pulmonary complications (PPCs) in elderly patients undergoing video-assisted thoracoscopic surgery lobectomy under general anesthesia. METHODS: The retrospective study consecutively included elderly patients (≥ 70 years old) who underwent thoracoscopic lobectomy at Xuanwu Hospital of Capital Medical University from January 1, 2018 to August 31, 2023. The demographic characteristics, the preoperative, intraoperative and postoperative parameters were collected and analyzed using multivariate logistic regression to identify the prediction of risk factors for PPCs. RESULTS: 322 patients were included for analysis, and 115 patients (35.7%) developed PPCs. Multifactorial regression analysis showed that ASA ≥ III (P = 0.006, 95% CI: 1.230 ∼ 3.532), duration of one-lung ventilation (P = 0.033, 95% CI: 1.069 ∼ 4.867), smoking (P = 0.027, 95% CI: 1.072 ∼ 3.194) and COPD (P = 0.015, 95% CI: 1.332 ∼ 13.716) are independent risk factors for PPCs after thoracoscopic lobectomy in elderly patients. CONCLUSION: Risk factors for PPCs are ASA ≥ III, duration of one-lung ventilation, smoking and COPD in elderly patients over 70 years old undergoing thoracoscopic lobectomy. It is necessary to pay special attention to these patients to help optimize the allocation of resources and enhance preventive efforts.

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis.

BACKGROUND: In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS: The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS: The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION: Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.

Index of consciousness monitoring during general anesthesia may effectively enhance rehabilitation in elderly patients undergoing laparoscopic urological surgery: a randomized controlled clinical trial.

BACKGROUND: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia. METHODS: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group or the control group (BIS monitoring). All patients underwent blood gas analysis at T1 (before anesthesia induction) and T2 (the end of operation). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered to all patients at T0 (1 day before surgery) and T4 (7 days after surgery). Serum concentrations of C-reactive protein (CRP) and glial fibrillary acid protein (GFAP) were assessed at T1, T2, and T3 (24 h after surgery). Postoperative complications and the duration of hospitalization were subjected to comparative evaluation. RESULTS: The incidence of postoperative cognitive dysfunction (POCD) was notably lower in the IoC group (10%) than in the control group (31.7%) (P = 0.003). Postoperative serum CRP and GFAP concentrations exhibited significant differences at time points T2 (CRP: P = 0.000; GFAP: P = 0.000) and T3 (CRP: P = 0.003; GFAP: P = 0.008). Postoperative blood glucose levels (P = 0.000) and the overall rate of complications (P = 0.037) were significantly lower in Group IoC than in Group control. CONCLUSION: The employment of IoC monitoring for the management of elderly surgical patients can accelerate postoperative convalescence by mitigating intraoperative stress and reducing peripheral and central inflammatory injury. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900025241 (17/08/2019).

Risk factors for postoperative acute ischemic stroke in advanced-aged patients with previous stroke undergoing noncardiac surgery: a retrospective cohort study.

BACKGROUND: The current study aimed to investigate the incidence and risk factors for postoperative acute ischemic stroke (PAIS) in advanced-aged patients (≥ 75 years) with previous ischemic stroke undergoing noncardiac surgery. METHODS: In this single-center retrospective cohort study, all advanced-aged patients underwent noncardiac surgery from 1 January, 2019, to 30 April, 2022. Data were extracted from hospital electronic medical records. Multivariable logistic regression analysis was performed to determine predictors of PAIS. Multivariable linear or logistic regression analysis was performed to determine predictors of outcomes due to PAIS. RESULTS: Twenty-four patients (6.0%) of the 400 patients developed PAIS. Carotid endarterectomy (CEA), length of surgery and preoperative Modified Rankin scale (mRS) ≥ 3 were significant predictors of PAIS. CEA was associated with increased risk of PAIS (OR 4.14; 95%CI, 1.43-11.99). Each additional minute in length of surgery had slightly increased the risk of PAIS (OR, 1.01; 95%CI, 1.00-1.01). Compared with reference (mRS < 3), mRS ≥ 3 increased odds of PAIS (OR, 4.09;95%CI, 1.12-14.93). Surgery type and length of surgery were found to be significant predictors of in-hospital expense (P < 0.001) and hospital stays (P < 0.05). CONCLUSIONS: CEA, length of surgery and preoperative mRS ≥ 3 may increase the development of PAIS in advanced-aged patients (≥ 75 years) with previous stroke undergoing noncardiac surgery. PAIS increased in-hospital mortality and prolonged hospital stay.

Cerebrospinal fluid biomarkers of neuroinflammation and postoperative neurocognitive disorders in patients undergoing orthopaedic surgery: protocol for a systematic review and meta-analysis.

INTRODUCTION: Postoperative neurocognitive disorders (PNDs) are characterised by gradual cognitive decline or change occurring after anaesthesia and surgery, and they are common in patients undergoing orthopaedic surgery. The onset of PNDs has been associated with dementia or other types of neurocognitive disorders in later life. Moreover, cerebrospinal fluid (CSF) biomarkers of neuroinflammation, including amyloid beta-40 peptide, amyloid beta-42 peptide, total tau protein, phosphorylated tau protein and neurofilament light chain, have been reported to be crucial in several high-quality clinical studies on PNDs. However, the role of these biomarkers in the onset of PNDs remains controversial. Therefore, this study aims to determine the association between CSF biomarkers of neuroinflammation and the onset of PNDs in patients undergoing orthopaedic surgery, which will provide novel insights for investigating PNDs and other types of dementia. METHODS AND ANALYSIS: This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviewd and Meta-Analyses 2020 statement. Moreover, we will search MEDLINE (via OVID), EMBASE and the Cochrane Library without any language and date restrictions. Observational studies will be included. Two reviewers will independently perform the entire procedure, and disagreements will be settled by discussion between them and consultation with a third reviewer. Standardised electronic forms will be generated to extract data. The risk of bias in the individual studies will be evaluated using the Newcastle-Ottawa scale. All statistical analyses will be performed using the RevMan software or the Stata software. ETHICS AND DISSEMINATION: This study will include peer-reviewed published articles; thus, no ethical issues will be involved. Further, the final manuscript will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022380180.

General anesthesia combined with bilateral 2-level erector spinae plane block may accelerate postoperative gastrointestinal function recovery and rehabilitation process in patients undergoing posterior lumbar surgery: A randomized controlled trial.

BACKGROUND: This randomized controlled trial explored whether bilateral 2-level erector spinae plane block could accelerate postoperative gastrointestinal function and rehabilitation in patients undergoing posterior lumbar surgery. METHODS: A total of 80 adult patients undergoing posterior lumbar surgery between March 2021 and August 2021 were randomized to either ultrasound-guided bilateral 2-level erector spinae plane block (group E) or not (group C). General anesthesia was routinely performed. The primary outcome was the time of the first flatus after surgery. We also recorded the first food and liquid intake, first off-bed activity, days of hospital stay, and postoperative complications. Postoperative visual analog scale score and opioid consumption were also recorded. A venous blood sample was taken to measure the serum concentration of lipopolysaccharides, c-reactive protein, tumor necrosis factor-alpha, interleukin-6, and blood glucose before induction of anesthesia, immediately after, and 24 and 48 hours after surgery. RESULTS: Seventy-seven patients, 39 in group C and 38 in group E, finished the trial. Patients in group E had a significantly shorter time to first flatus (16.2 ± 3.2 vs 19.7 ± 3.0 hours, P < .05), earlier liquid intake (1.7 ± 0.2 vs 1.9 ± 0.3 hours, P < .05), earlier food intake (1.9 ± 0.2 vs 2.1 ± 0.3 hours, P < .05), and first off-bed activity (27.9 ± 3.2 vs 31.4 ± 3.3 h, P < .05). Patients in group E had shorter postoperative hospital stay (4.6 [4.2-5.5] d vs 5.4 [4.5-6.3], P < .05). We found that patients in group E had less pain and total sufentanil consumption (129 [120-133] vs 138 [132-147] µg, P < .05) within 24 hours after surgery. At 24 hours after surgery, the serum concentrations of lipopolysaccharides, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in group E were significantly decreased compared to group C (P < .05). CONCLUSION: Bilateral 2-level erector spinae plane block can accelerate gastrointestinal function recovery and shorten the length of hospital stay in patients undergoing open posterior lumbar surgery. The potential mechanism may attribute to the opioids-sparing effects and anti-stress-related anti-inflammatory effects of bilateral 2-level erector spinae plane block.

Ground Movement in the Hanging Wall of Underground Iron Mines with Steeply Dipping Discontinuities: A Case Study.

To ensure the safety of underground mining activities and effectively protect the surface production facilities and houses of the nearby residents, the ground movement caused by the sublevel caving method needs to be studied. In this work, the failure behaviors of the surface and drift of the surrounding rock were investigated based on the results of in situ failure investigations, monitoring data, and engineering geological conditions. The results were then combined with theoretical analysis to reveal the mechanism responsible for the movement of the hanging wall. Driven by the in situ horizontal ground stress, horizontal displacement plays an imperative role in both the movement of the ground surface and underground drifts. Accelerated movement is found to occur in the ground surface which coincides with the occurrence of drift failure. Failure occurs in the deep rock masses and then gradually propagates to the surface. The steeply dipping discontinuities are the main reason for the unique ground movement mechanism in the hanging wall. As steeply dipping joints cut through the rock mass, the rock surrounding the hanging wall can be modeled as cantilever beams subjected to in situ horizontal ground stress and lateral stress due to caved rock. This model can be used to obtain a modified formula for toppling failure. Also, a mechanism of fault slipping was proposed, and the condition required for fault slipping was obtained. Based on the failure mechanism of steeply dipping discontinuities, the ground movement mechanism was proposed considering the horizontal in situ ground stress and caved rock mass: slippage of fault F3, slippage of fault F4, and toppling of rock columns. Based on the unique ground movement mechanism, the goaf surrounding rock mass could be divided into six zones: a caved zone, a failure zone, a toppling-slipping zone, a toppling-deformation zone, a fault-slipping zone, and a movement-deformation zone.

Immunologically active ferumoxytol-poly(I : C) nanomaterials inhibit metastatic melanoma by regulating myeloid-derived suppressor cell differentiation.

Nanomaterials have been identified as a potential therapeutic option for targeting myeloid-derived suppressor cells (MDSCs), which are known to play a crucial role in tumor metastasis and treatment resistance. Here, we report a unique immunologically active nanomaterial composed of ferumoxytol and poly(I : C) (FP-NPs) and investigate its immunoregulatory activities on MDSCs in metastatic melanoma. In vivo assays demonstrated that FP-NPs had the ability to significantly impede the progression of metastatic melanoma and decrease the MDSC population in the lungs, spleen, and bone marrow of mice. Both in vivo and in vitro experiments revealed that FP-NPs reduced the number of granulocytic MDSCs and promoted the differentiation of monocytic MDSCs into anti-tumor M1 macrophages. Transcriptome sequencing indicated that FP-NPs significantly altered the expression of several genes involved in immunity. Analysis of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and quantitative real-time PCR revealed that FP-NPs significantly increased the expression of the myeloid cell differentiation-related gene interferon regulatory factor 7 and activated interferon beta-related signaling pathways, which stimulated the differentiation of MDSCs into M1 macrophages. These findings suggest that FP-NPs, a unique nanomaterial with immunological properties, can induce MDSCs to differentiate into M1 macrophages, potentially offering new treatment prospects for metastatic melanoma in the future.