Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice.

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing.

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

Social Determinants of Health and Surgical Desirability of Outcome Ranking in Older Veterans.

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement. Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR). Design, Setting, And Participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health Administration Corporate Data Warehouse, and the United States Veterans Eligibility Trends and Statistics file. Data were analyzed between September 2023 and February 2024. Exposure: Living in a highly deprived neighborhood (Area Deprivation Index >85), race and ethnicity used as a social construct, rurality, and care fragmentation (percentage of non-VA care days). Main Outcomes and Measures: DOOR is a composite, patient-centered ranking of 26 outcomes ranging from no complication (1, best) to 90-day mortality or near-death complications (6, worst). A series of proportional odds regressions was used to assess the impact of SDOH and care fragmentation adjusted for clinical risk factors, including presentation acuity (presenting with preoperative acute serious conditions and urgent or emergent surgical procedures). Results: The cohort had 93 644 patients (mean [SD] age, 72.3 [6.2] years; 91 443 [97.6%] male; 74 624 [79.7%] White). Veterans who identified as Black (adjusted odds ratio [aOR], 1.06; 95% CI, 1.02-1.10; P = .048) vs White and veterans with higher care fragmentation (per 20% increase in VA care days relative to all care days: aOR, 1.01; 95% CI, 1.01-1.02; P < .001) were associated with worse (higher) DOOR scores until adjusting for presentation acuity. Living in rural geographic areas was associated with better DOOR scores than living in urban areas (aOR, 0.93; 95% CI, 0.91-0.96; P < .001), and rurality was associated with lower presentation acuity (preoperative acute serious conditions: aOR, 0.88; 95% CI, 0.81-0.95; P = .001). Presentation acuity was higher in veterans identifying as Black, living in deprived neighborhoods, and with increased care fragmentation. Conclusions and Relevance: Veterans identifying as Black and veterans with greater proportions of non-VA care had worse surgical outcomes. VA programs should direct resources to reduce presentation acuity among Black veterans, incentivize veterans to receive care within the VA where possible, and better coordinate veterans' treatment and records between care sources.

Care Fragmentation, Social Determinants of Health, and Postoperative Mortality in Older Veterans.

INTRODUCTION: Veterans Affairs Surgical Quality Improvement Program (VASQIP) benchmarking algorithms helped the Veterans Health Administration (VHA) reduce postoperative mortality. Despite calls to consider social risk factors, these algorithms do not adjust for social determinants of health (SDoH) or account for services fragmented between the VHA and the private sector. This investigation examines how the addition of SDoH change model performance and quantifies associations between SDoH and 30-d postoperative mortality. METHODS: VASQIP (2013-2019) cohort study in patients ≥65 y old with 2-30-d inpatient stays. VASQIP was linked to other VHA and Medicare/Medicaid data. 30-d postoperative mortality was examined using multivariable logistic regression models, adjusting first for clinical variables, then adding SDoH. RESULTS: In adjusted analyses of 93,644 inpatient cases (97.7% male, 79.7% non-Hispanic White), higher proportions of non-veterans affairs care (adjusted odds ratio [aOR] = 1.02, 95% CI = 1.01-1.04) and living in highly deprived areas (aOR = 1.15, 95% CI = 1.02-1.29) were associated with increased postoperative mortality. Black race (aOR = 0.77, CI = 0.68-0.88) and rurality (aOR = 0.87, CI = 0.79-0.96) were associated with lower postoperative mortality. Adding SDoH to models with only clinical variables did not improve discrimination (c = 0.836 versus c = 0.835). CONCLUSIONS: Postoperative mortality is worse among Veterans receiving more health care outside the VA and living in highly deprived neighborhoods. However, adjusting for SDoH is unlikely to improve existing mortality-benchmarking models. Reduction efforts for postoperative mortality could focus on alleviating care fragmentation and designing care pathways that consider area deprivation. The adjusted survival advantage for rural and Black Veterans may be of interest to private sector hospitals as they attempt to alleviate enduring health-care disparities.

Social Determinants of Long-Term Opioid Use Following Total Knee Arthroplasty.

Total knee arthroplasty (TKA) risks persistent pain and long-term opioid use (LTO). The role of social determinants of health (SDoH) in LTO is not well established. We hypothesized that SDoH would be associated with postsurgical LTO after controlling for relevant demographic and clinical variables. This study utilized data from the Veterans Affairs Surgical Quality Improvement Program, VA Corporate Data Warehouse, and Centers for Medicare and Medicaid Services, including Veterans aged ≥ 65 who underwent elective TKA between 2013 and 2019 with no postsurgical complications or history of significant opioid use. LTO was defined as > 90 days of opioid use beginning within 90 days postsurgery. SDoH variables included the Area Deprivation Index, rurality, and housing instability in the last 12 months identified via medical record screener or International Classification of Diseases, Tenth Revision codes. Multivariable risk adjustment models controlled for demographic and clinical characteristics. Of the 9,064 Veterans, 97% were male, 84.2% white, mean age was 70.6 years, 46.3% rural, 11.2% living in highly deprived areas, and 0.9% with a history of homelessness/housing instability. Only 3.7% (n = 336) developed LTO following TKA. In a logistic regression model of only SDoH variables, housing instability (odds ratio [OR] = 2.38, 95% confidence interval [CI]: 1.09-5.22) and rurality conferred significant risk for LTO. After adjusting for demographic and clinical variables, LTO was only associated with increasing days of opioid supply in the year prior to surgery (OR = 1.52, 95% CI: 1.43-1.63 per 30 days) and the initial opioid fill (OR = 1.07; 95% CI: 1.06-1.08 per day). Our primary hypothesis was not supported; however, our findings do suggest that patients with housing instability may present unique challenges for postoperative pain management and be at higher risk for LTO.

Machine learning in nanozymes: from design to application.

Nanozymes, a distinctive class of nanomaterials endowed with enzyme-like activity and kinetics akin to enzyme-catalysed reactions, present several advantages over natural enzymes, including cost-effectiveness, heightened stability, and adjustable activity. However, the conventional trial-and-error methodology for developing novel nanozymes encounters growing challenges as research progresses. The advent of artificial intelligence (AI), particularly machine learning (ML), has ushered in innovative design approaches for researchers in this domain. This review delves into the burgeoning role of ML in nanozyme research, elucidating the advancements achieved through ML applications. The review explores successful instances of ML in nanozyme design and implementation, providing a comprehensive overview of the evolving landscape. A roadmap for ML-assisted nanozyme research is outlined, offering a universal guideline for research in this field. In the end, the review concludes with an analysis of challenges encountered and anticipates future directions for ML in nanozyme research. The synthesis of knowledge in this review aims to foster a cross-disciplinary study, propelling the revolutionary field forward.

Palliative Care Utilization and Hospital Transfers in Veterans Treated in Telecritical Care-Supported Intensive Care Units Versus Non-Telecritical Care Intensive Care Units.

Background: Although telecritical care (TCC) implementation is associated with reduced mortality and interhospital transfer rates, its impact on goal-concordant care delivery in critical illness is unknown. We hypothesized that implementation of TCC across the Veterans' Health Administration system resulted in increased palliative care consultation and goals of care evaluation, yielding reduced transfer rates. Methods: We included veterans admitted to intensive care units between 2008 and 2022. We compared palliative care consultation and transfer rates before and after TCC implementation with rates in facilities that never implemented TCC. We used generalized linear mixed multivariable models to assess the associations between TCC initiation, palliative care consultation, and transfer and subsequently used mediation analysis to evaluate potential causality in this relationship. Results: Overall, 1,020,901 veterans met inclusion criteria. Demographic characteristics of patients were largely comparable across groups, although TCC facilities served more rural veterans. Palliative care consultation rates increased substantially in both ever-TCC and never-TCC hospitals during the study period (2.3%-4.3%, and 1.6%-4.7%, p < 0.01). Admissions post-TCC implementation were associated with an increased likelihood of palliative care consultation (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01-1.15). TCC implementation was also associated with a reduction in transfer rates (OR 0.90, 95% CI 0.84-0.95). Mediation analysis did not demonstrate a causal relationship between TCC implementation, palliative care consultation, and reductions in interhospital transfer rate. Conclusions: TCC is associated with increased palliative care engagement, while TCC and palliative care engagement are both independently related to reduced transfers.

The activation impact of lactobacillus-derived extracellular vesicles on lipopolysaccharide-induced microglial cell.

Perioperative neurocognitive dysfunction (PND) emerges as a common postoperative complication among elderly patients. Currently, the mechanism of PND remains unclear, but there exists a tendency to believe that inflammation plays a significant role in PND. Alterations in the abundance of intestinal microbiota can increase the permeability of the intestinal mucosal barrier and incite extraintestinal inflammatory responses. Metabolites from these microbiota can be absorbed by the intestinal mucosa into the bloodstream, exerting influence upon the central nervous system (CNS). Lactobacillus (Lac), serving as an intestinal probiotic bacterium, possesses the capacity to modulate emotional behavior and cognitive functions. Extracellular vesicles (EVs) are recognized as novel therapeutic carriers for targeted delivery to regulate physiology and pathogenesis. While the mechanism governing the primary function of Lac-EVs in the CNS remains uncertain. Therefore, we established an in vitro neuroinflammation model to induce PND and then treated the mice with Lac-EVs to observe the effect of these EVs on neuroinflammation, particularly on microglial (MG) polarization. Our research unveils that Lac-EVs reduced inflammation induced by LPS in microglia and the activation of related proteins, including the mRNA expression of M1 labeled protein (iNOS). Moreover, the mRNA expression of M2-labeled protein (Arg1) increased. In addition, flow cytometry revealed that the ratio of M1/M2 microglia also changed significantly. Therefore, Lac-EVs promoted the differentiation of M2 microglia by inducing the preferential expression of specific markers related to M2 macrophages and inflammation. In terms of inflammatory cytokine expression, Lac-EVs decreased the secretion of proinflammatory cytokines (IL-1ß and IL-6) and increased IL-10 production after lipopolysaccharide (LPS) stimulation. Therefore, Lac-EVs induce the activation of M2 microglial cells without inducing cellular harm in vitro, and they demonstrate anti-inflammatory effects against lipopolysaccharide-induced neuroinflammation. This finding suggested that it is an effective anti-inflammatory strategy for alleviating inflammation-driven PNDs.

Association of preoperative neutrophil-lymphocyte ratios with the emergence delirium in pediatric patients after tonsillectomy and adenoidectomy: an observational prospective study.

PURPOSE: The study aimed to investigate potential risk factors for emergence delirium (ED) in pediatric patients after tonsillectomy and adenoidectomy (T&A). METHODS: This prospective, single-center observational study enrolled children aged 3-7 years who underwent T&A under general anesthesia. ED was assessed according to DSM-IV or V criteria. Receiver operating characteristic curve analysis was performed to evaluate the predicative and cut-off values of risk factors, including age, preoperative anxiety level, postoperative pain and neutrophil-lymphocyte ratio (NLR) for ED. Univariate and multivariate logistic regression analyses were performed to investigate risk factors for ED. RESULTS: 94 pediatric patients who underwent T&A were enrolled and 19 developed ED (an incidence of 25.3%). Receiver operating characteristic analysis indicated that preoperative NLR was a significant predictor of ED with a cut-off value of 0.8719 and an area under the curve (AUC) of 0.671 (95% confidence interval (CI) 0.546-0.796, P = 0.022). Preoperative NLR (< 0.8719) and postoperative pain were independent risk factors associated with ED (odds ratio: 0.168, 95% CI 0.033-0.858, P = 0.032; odds ratio: 7.298, 95% CI 1.563-34.083, P = 0.011) according to multivariate logistic regression analysis. CONCLUSIONS: Preoperative NLR level and postoperative pain were independent risk factors for ED in pediatric patients undergoing T&A.

Hydroxychloroquine use is associated with reduced mortality risk in older adults with rheumatoid arthritis.

BACKGROUND: There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). METHODS: In a retrospective cohort of Medicare beneficiaries aged ≥ 65 years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. RESULTS: The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63 years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78). CONCLUSION: HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats.

BACKGROUND: Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. METHODS: (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. RESULTS: The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. CONCLUSION: Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.

Home noninvasive ventilation use in patients hospitalized with COPD.

INTRODUCTION: The study objective was to estimate the prevalence of chronic hypercapnic respiratory failure (CHRF) and home noninvasive ventilation (NIV) use in a high-risk population, individuals with a history of at least one COPD-related hospitalizations. METHODS: We retrospectively analyzed electronic medical record data of patients with at least one COPD-related hospitalization between October 1, 2011, and September 30, 2017, to the Iowa City VA Medical Center. We excluded individuals with no obstructive ventilatory defect. RESULTS: Of 186 patients, the overall prevalence of compensated hypercapnic respiratory failure (CompHRF), defined as PaCO2  > 45 mmHg with a pH = 7.35-7.45, was 52.7%, while the overall prevalence of home NIV was 4.3%. The prevalence of CompHRF was 43.6% and home NIV was 1.8% in those with one COPD-related hospitalization. Among those with ≥4 COPD-related hospitalizations, the prevalence of CompHRF was 77.8% (14 of 18), and home NIV was 11.1% (2 of 18). CONCLUSION: Approximately half of individuals with at least one COPD-related hospitalization have CompHRF, but only 8.2% of those use home NIV. Future studies should estimate CHRF rates and the degree of underutilization of home NIV in larger multicenter samples.

The impact of COVID-19 lockdown on the quality of life of Chinese football referees: the chain mediating role of occupational stress and job burnout.

BACKGROUND: COVID-19 lockdown measures have had a great negative impact on the development of sports competition in China, as well as on the quality of life of football referees. This study aims to explore the impact of lockdown measures implemented in response to the COVID-19 pandemic on the quality of life of football referees in China and its mechanism of action. METHODS: The Impact of Event Scale-Revised (IES-R), the Effort-Reward Imbalance Scale (ERI), the Maslach Burnout Inventory General Survey (MBI-GS), and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). The scale was used from August to September 2022. Using an online questionnaire, 350 questionnaires were sent out and 338 were returned, for a return rate of 96.57%. Invalid questionnaires were excluded, and 307 football referees with referee grades in 29 provinces registered with the CFA were surveyed. SPSS 24.0 and Mplus 8.0 were used for data analysis and structural equation model testing in this study. RESULTS: The results showed that the COVID-19 lockdown had no significant impact on the quality of life of Chinese football referees. However, the COVID-19 lockdown can affect the quality of life of Chinese football referees through occupational stress or job burnout. Occupational stress and job burnout also play a chain intermediary role between the COVID-19 lockdown and the quality of life of Chinese football referees. In addition, this study further explores the quality of life by dividing it into four dimensions (physical, social, psychological, and environmental). The results show that all four dimensions satisfy the chain mediation model. CONCLUSIONS: Therefore, the quality of life of Chinese football referees can be improved by reducing their occupational stress and job burnout during the COVID-19 lockdown.

Association of rural living with COPD-related hospitalizations and deaths in US veterans.

It is unclear whether the high burden of COPD in rural areas is related to worse outcomes in patients with COPD or is because the prevalence of COPD is higher in rural areas. We assessed the association of rural living with acute exacerbations of COPD (AECOPDs)-related hospitalization and mortality. We retrospectively analyzed Veterans Affairs (VA) and Medicare data of a nationwide cohort of veterans with COPD aged ≥ 65 years with COPD diagnosis between 2011 and 2014 that had follow-up data until 2017. Patients were categorized based on residential location into urban, rural, and isolated rural. We used generalized linear and Cox proportional hazards models to assess the association of residential location with AECOPD-related hospitalizations and long-term mortality. Of 152,065 patients, 80,162 (52.7%) experienced at least one AECOPD-related hospitalization. After adjusting for demographics and comorbidities, rural living was associated with fewer hospitalizations (relative risk-RR = 0.90; 95% CI: 0.89-0.91; P < 0.001) but isolated rural living was not associated with hospitalizations. Only after accounting for travel time to the closest VA medical center, neighborhood disadvantage, and air quality, isolated rural living was associated with more AECOPD-related hospitalizations (RR = 1.07; 95% CI: 1.05-1.09; P < 0.001). Mortality did not vary between rural and urban living patients. Our findings suggest that other aspects than hospital care may be responsible for the excess of hospitalizations in isolated rural patients like poor access to appropriate outpatient care.

Maresin1 ameliorates postoperative cognitive dysfunction in aged rats by potentially regulating the NF-κB pathway to inhibit astrocyte activation.

Postoperative cognitive dysfunction (POCD) is one of the most serious postoperative complications in the elderly population. Perioperative central neuroinflammation is considered to be an important pathological mechanism of POCD, with the activation of astrocytes playing a key role in central neuroinflammation. Maresin1 (MaR1) is a specific pro-resolving mediator synthesized by macrophages in the resolution stage of inflammation, and provides unique anti-inflammatory and pro-resolution effects by limiting excessive neuroinflammation and promoting postoperative recovery. However, the question remains whether MaR1 can have a positive effect on POCD. The objective of this study was to investigate the protective effect of MaR1 on POCD cognitive function in aged rats after splenectomy. Morris water maze test and IntelliCage test showed that splenectomy could cause transient cognitive dysfunction in aged rats; however, the cognitive impairment of rats was significantly mitigated when MaR1 pretreatment was administered. MaR1 significantly alleviated the fluorescence intensity and protein expression of glial fibrillary acidic protein and central nervous system specific protein in the cornu ammonis 1 region of the hippocampus. Simultaneously, the morphology of astrocytes was also severely altered. Further experiments showed that MaR1 inhibited the mRNA and protein expression of several key proinflammatory cytokines-interleukin-1ß, interleukin-6, and tumor necrosis factor-α in the hippocampus of aged rats following splenectomy. The molecular mechanism underlying this process was explored by evaluating expression of components of the nuclear factor κB (NF-κB) signaling pathway. MaR1 substantially inhibited the mRNA and protein expression of NF-κB p65 and κB inhibitor kinase ß. Collectively, these results suggest that MaR1 ameliorated splenectomy-induced transient cognitive impairment in elderly rats, and this neuroprotective mechanism may occur through regulating the NF-κB pathway to inhibit astrocyte activation.

Neuroprotective effects of different doses of Maresin1 pretreatment in aged rats after anesthesia/surgery.

OBJECTIVE: The study is to investigate the neuroprotective effect of different doses of Maresin1 pretreatment in aged rats after anesthesia/surgery and the related mechanisms. METHODS: Aged male rats were randomly divided into a control group, an anesthesia/surgery group, and low, medium, and high-dose Maresin1 pretreatment groups, and the hippocampus was taken for study. The Morris water maze was performed to detect the cognitive ability of rats. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and central nervous system-specific protein (S100ß). The ultrastructure of astrocytes was observed by a transmission electron microscope. Quantitative real-time PCR was used to detect the relative expression of IL-1ß, IL-6, and TNF-α mRNA. RESULTS: Compared with the control group, the cognition of rats in the anesthesia/surgery group was significantly reduced. The expression of astrocyte markers (GFAP and S100ß) in the hippocampus of rats in the anesthesia/surgery group was increased. The levels of hippocampal inflammatory cytokines (TNF-α, IL-1ß, and IL-6) were also higher in the anesthesia/surgery group than in the control group. After pretreatment with different doses of Maresin1, the cognitive impairment of rats was alleviated to varying degrees. Maresin1 pretreatment decreased the expression of astrocyte markers and inflammatory factors in the hippocampus of rats after anesthesia/surgery, and improve the microstructures of activated astrocytes, especially in the medium-dose group. CONCLUSION: Pretreatment with Maresin1 (especially at medium-dose) showed neuroprotective effects in aged rats after anesthesia/surgery, which may be related to the inhibition of astrocyte activation.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Application of exosomal miRNA mediated macrophage polarization in colorectal cancer: Current progress and challenges.

Colorectal cancer (CRC) is a major global health problem with high morbidity and mortality rates. Surgical resection is the main treatment for early-stage CRC, but detecting it early is challenging. Therefore, effective therapeutic targets for advanced patients are still lacking. Exosomes, tiny vesicles in body fluids, play a crucial role in tumor metastasis, immune regulation, and drug resistance. Interestingly, they can even serve as a biomarker for cancer diagnosis and prognosis. Studies have shown that exosomes can carry miRNA, mediate the polarization of M1/M2 macrophages, promote the proliferation and metastasis of cancer cells, and affect the prognosis of CRC. Since the gastrointestinal tract has many macrophages, understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial. This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.