Systematic analysis based on bioinformatics and experimental validation identifies Alox5 as a novel therapeutic target of quercetin for sepsis.

PURPOSE: This study investigated the molecular mechanism of quercetin in the treatment of sepsis using network pharmacological prediction and experimentation. METHODS: Hub genes were identified by intersecting the differentially expressed genes (DEGs) of the GSE131761 and GSE9960 databases with genes from the hub modules of Weighted Gene Co-Expression Network Analysis (WGCNA), targets of quercetin, and ferroptosis. Subsequently, in order to determine the functional characteristics and molecular link of hub gene obtained above, we redetermined the hub-DEGs in GSE131761 according to high or low hub gene expression. Afterward, the main pathways of enrichment analysis were validated using these hub-DEGs. Finally, an experiment was conducted to validate the findings. RESULTS: By intersecting 1415 DEGs in GSE131761, 543 DEGs in GSE9960, 5784 key modular genes, 470 ferroptosis-related genes, and 154 quercetin-related genes, we obtained one quercetin-related gene, Alox5. Subsequently, 340 hub-DEGs were further validated according to high or low Alox5 expression. The results of the enrichment analysis revealed that hub-DEGs were mainly associated with inflammation and the immune response. Immune infiltration analysis showed that higher expression of Alox5 was related to macrophage infiltration and could be a predictor of diagnosis in patients with sepsis. The expression pattern of Alox5 was then depicted and the upregulation of Alox5 in the vital organs of septic mice was further demonstrated. In vitro and in vivo experiments showed that upregulation of Alox5 and inflammation-related cytokines induced by sepsis could be inhibited by quercetin (p < 0.05). CONCLUSIONS: Alox5 may be involved in the occurrence and development of multi-organ functional disturbances in sepsis and is a reliable target of quercetin against sepsis.

Mendelian randomization analysis reveals causal association of anthropometric measures on sepsis risk and mortality.

The objective of this study was to explore the potential causalities of fat mass, nonfat mass and height (henceforth, 'anthropometric measures') with sepsis risk and mortality. We conducted the Mendelian randomization (MR) investigation using genome-wide association study (GWAS) summary statistics of anthropometric measures, sepsis, and sepsis mortality. The GWAS summary data from the UK Biobank was used. Firstly, MR analysis was performed to estimate the causal effect of anthropometric measures on the risk of sepsis. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach, together with weighted median-based method. Cochrane's Q test and MR-Egger intercept test were performed to assess heterogeneity and pleiotropy, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted weight-related measures were suggestively linked to an increased risk of sepsis. However, height displayed no causal association with sepsis risk and mortality. Furthermore, weight-related measures also displayed significant MR association with the sepsis mortality, except body nonfat mass and right leg nonfat mass. However, MVMR analysis indicated the observed effects for weight-related measures in the univariable MR analyses are more likely a bias caused by the interrelationship between anthropometric measures. According to the MR-Egger intercept assessment, our MR examination was not influenced by horizontal pleiotropy (all p>0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. In conclusion, these findings provided vital new knowledge on the role of anthropometric-related measures in the sepsis etiology.

Particulate matter 2.5 accelerates aging: Exploring cellular senescence and age-related diseases.

Exposure to Particulate matter 2.5 (PM2.5) accelerates aging, causing declines in tissue and organ function, and leading to diseases such as cardiovascular, neurodegenerative, and musculoskeletal disorders. PM2.5 is a major environmental pollutant and an exogenous pathogen in air pollution that is now recognized as an accelerator of human aging and a predisposing factor for several age-related diseases. In this paper, we seek to elucidate the mechanisms by which PM2.5 induces cellular senescence, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction, and age-related diseases. Our goal is to increase awareness among researchers within the field of the toxicity of environmental pollutants and to advocate for personal and public health initiatives to curb their production and enhance population protection. Through these endeavors, we aim to promote longevity and health in older adults.

[Research progress on the molecular mechanism of endoplasmic reticulum stress-mediated macrophage polarization].

The endoplasmic reticulum (ER) is an essential organelle that maintains intracellular Ca2+ homeostasis, folds newly synthesized secreted and membrane proteins, and facilitates post-translational protein modifications. Misfolding and aggregation of unfolded proteins within the ER lumen can activate endoplasmic reticulum stress (ERS), which in turn activates three different downstream signaling pathways: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α(IRE-1α), and activating transcription factor 6 (ATF6). These pathways affect cell survival, differentiation, and phenotype transition. Recent studies have shown a close interaction between the downstream signaling cascade of ERS and the signaling pathways that induce macrophage polarization towards pro-inflammatory M1 type (IFN-γ and LPS) and anti-inflammatory M2 type (IL-4 and IL-10). However, the specific molecular mechanisms underlying these interactions are complex and intriate. The article summarizes the primary mechanisms by which ERS mediates macrophage polarization, focusing on discussing the molecular mechanisms by which three different downstream signals of ERS affect macrophage polarization.

Quercetin protects against sepsis-associated encephalopathy by inhibiting microglia-neuron crosstalk via the CXCL2/CXCR2 signaling pathway.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common brain lesion associated with severe sepsis, for which ferroptosis is a key driving factor. Thus, suppressing ferroptosis may be an effective strategy for treating SAE. Quercetin (QUE) is a natural flavonoid with antioxidant and anti-inflammatory properties. However, its role on ferroptosis in SAE remains unclear. PURPOSE: This study aimed to investigate the mechanism underlying the therapeutic effect of QUE on cecal ligation perforation (CLP)-induced SAE. METHODS: In vivo and in vitro SAE models were established using CLP and lipopolysaccharide (LPS), respectively. Both models underwent pre-treatment with QUE. RESULTS: QUE attenuated CLP-induced symptoms, including temperature changes, neurological severity scores, learning and memory dysfunction, inflammatory cytokine release, and microglia activation in SAE mice, and inhibited LPS-induced microglia recruitment and chemotaxis. Bioinformatics analysis revealed that the C-X-C motif chemokine ligand 2 (CXCL2)/C-X-C motif chemokine receptor 2 (CXCR2) axis may play a key role in QUE-mediated protection against SAE. Moreover, QUE significantly inhibited LPS-induced CXCL2 up-regulation and protein secretion from microglia. Recombinant mouse-derived CXCL2 (rmCXCL2) promoted inflammatory cytokine secretion, NF-κB/NLRP3 signaling activation, and microglia recruitment and chemotaxis. Furthermore, rmCXCL2 induced ferroptosis in mouse hippocampal neurons, as evidenced by elevated malondialdehyde levels, decreased glutathione levels, excessive iron uptake, and altered ferroptosis-related protein expression. The CXCR2 antagonist SB225002 effectively reversed the effects of rmCXCL2. Importantly, in vivo experiments further demonstrated that the therapeutic effect of QUE on SAE was inhibited by rmCXCL2. CONCLUSION: This study demonstrates that CXCL2 secreted by activated microglia mediates microglia self-activation and induces hippocampal neuronal ferroptosis via CXCR2 and that QUE exerts neuroprotective effects on SAE by blocking interactions between microglia and neurons via CXCL2/CXCR2 pathway inhibition.

The Association of Cerebral Oxygen Desaturation with Postoperative Cognitive Dysfunction in Older Patients: A Review.

Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.

Role of serum neuron-specific enolase levels in the early diagnosis and prognosis of sepsis-associated encephalopathy: a systematic review and meta-analysis.

Background: Sepsis-associated encephalopathy (SAE) is one of the most ubiquitous complications of sepsis and is characterized by cognitive impairment, poor prognosis, and a lack of uniform clinical diagnostic criteria. Therefore, this study investigated the early diagnostic and prognostic value of serum neuron-specific enolase (NSE) in SAE. Methods: This systematic review and meta-analysis systematically searched for clinical trials with serum NSE information in patients with sepsis in the PubMed, Web of Science, Embase, and Cochrane databases from their inception to April 10, 2023. Included studies were assessed for quality and risk of bias using The Quality Assessment of Diagnostic Accuracy-2 tool. The meta-analysis of the included studies was performed using Stata 17.0 and Review Manager version 5.4. Findings: Eleven studies were included in this meta-analysis involving 1259 serum samples from 947 patients with sepsis. Our results showed that the serum NSE levels of patients with SAE were higher than those of the non-encephalopathy sepsis group (mean deviation, MD,12.39[95% CI 8.27-16.50, Z = 5.9, p < 0.00001]), and the serum NSE levels of patients with sepsis who died were higher than those of survivors (MD,4.17[95% CI 2.66-5.68, Z = 5.41, p < 0.00001]). Conclusion: Elevated serum NSE levels in patients with sepsis are associated with the early diagnosis of SAE and mortality; therefore, serum NSE probably is a valid biomarker for the early diagnosis and prognosis of patients with SAE. Systematic review registration: This study was registered in PROSPERO, CRD42023433111.

Risk factors and related miRNA phenotypes of chronic pain after thoracoscopic surgery in lung adenocarcinoma patients.

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.

Latest advances and clinical application prospects of resveratrol therapy for neurocognitive disorders.

Neurocognitive disorders, such as Alzheimer's disease, vascular dementia, and postoperative cognitive dysfunction, are non-psychiatric brain syndromes in which a significant decline in cognitive function causes great trauma to the mental status of the patient. The lack of effective treatments for neurocognitive disorders imposes a considerable burden on society, including a substantial economic impact. Over the past few decades, the identification of resveratrol, a natural plant compound, has provided researchers with an opportunity to formulate novel strategies for the treatment of neurocognitive disorders. This is because resveratrol effectively protects the brain of those with neurocognitive disorders by targeting some mechanisms such as inflammation and oxidative stress. This article reviews the status of recent research investigating the use of resveratrol for the treatment of different neurocognitive disorders. By examining the possible mechanisms of action of resveratrol and the shared mechanisms of different neurocognitive disorders, treatments for neurocognitive disorders may be further clarified.

The effect of multimodal care based on Peplau's interpersonal relationship theory on postoperative recovery in lung cancer surgery: a retrospective analysis.

BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.

Spinal cord injury: Olfactory ensheathing cell-based therapeutic strategies.

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.

Effect of esketamine pretreatment on acute sepsis-associated encephalopathy.

PURPOSE: Esketamine, the S(+) enantiomer of ketamine, exhibits good anesthetic efficacy and controllability; however, its potential clinical applications, particularly in sepsis-associated encephalopathy (SAE), remain underexplored. SAE involves the development of diffuse brain dysfunction after sepsis, leading to markedly increased sepsis-related disability and mortality. In this study, we investigated the effects of esketamine pretreatment on acute SAE. METHODS: Mice were randomly divided into four groups: control (C, n = 22), acute SAE (L, n = 22), esketamine pretreatment + acute SAE (EL, n = 22), and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) + esketamine pretreatment + acute SAE (N + EL, n = 22). Acute SAE was established using intraperitoneal (i.p.) injection of lipopolysaccharide (LPS; 10 mg/kg), while controls received equal amounts of saline. The EL group received daily i.p. injections of esketamine (10 mg/kg) for 5 consecutive days, followed by LPS on day 6. The N + EL group received i.p. injections of ML385 (30 mg/kg) 1 h before esketamine pretreatment. The remainder of treatment followed the same protocol as the EL group. Behavioral tests were performed 24 h post-LPS injection, and whole blood and brain tissues were collected for further analysis. RESULTS: Esketamine improved sepsis symptoms, 7-day survival, and spatial cognitive impairment, without altering locomotor activity. Moreover, esketamine reversed the LPS-induced increase in serum S100 calcium-binding protein ß and neuron-specific enolase levels and reduced hippocampal neuroinflammation, oxidative stress, and neuronal apoptosis in the EL group. However, these neuroprotective effects of esketamine were reversed by ML385. CONCLUSION: The results of our study suggest that esketamine pretreatment mitigates acute SAE, highlighting the involvement of the Nrf2/heme oxygenase-1 pathway in mediating its neuroprotective effects.

Effects of xenon anesthesia on postoperative neurocognitive disorders: a systematic review and meta-analysis.

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.

Plasma D-dimer levels are a biomarker for in-hospital complications and long-term mortality in patients with traumatic brain injury.

Introduction: Traumatic brain injury (TBI) is a major health concern worldwide. D-dimer levels, commonly used in the diagnosis and treatment of neurological diseases, may be associated with adverse events in patients with TBI. However, the relationship between D-dimer levels, TBI-related in-hospital complications, and long-term mortality in patients with TBI has not been investigated. Here, examined whether elevated D-dimer levels facilitate the prediction of in-hospital complications and mortality in patients with TBI. Methods: Overall, 1,338 patients with TBI admitted to our institute between January 2016 and June 2022 were retrospectively examined. D-dimer levels were assessed within 24 h of admission, and propensity score matching was used to adjust for baseline characteristics. Results: Among the in-hospital complications, high D-dimer levels were associated with electrolyte metabolism disorders, pulmonary infections, and intensive care unit admission (p < 0.05). Compared with patients with low (0.00-1.54 mg/L) D-dimer levels, the odds of long-term mortality were significantly higher in all other patients, including those with D-dimer levels between 1.55 mg/L and 6.35 mg/L (adjusted hazard ratio [aHR] 1.655, 95% CI 0.9632.843), 6.36 mg/L and 19.99 mg/L (aHR 2.38, 95% CI 1.416-4.000), and >20 mg/L (aHR 3.635, 95% CI 2.195-6.018; p < 0.001). D-dimer levels were positively correlated with the risk of death when the D-dimer level reached 6.82 mg/L. Conclusion: Overall, elevated D-dimer levels at admission were associated with adverse outcomes and may predict poor prognosis in patients with TBI. Our findings will aid in the acute diagnosis, classification, and management of TBI.

Development of nomograms for predicting the survival of intestinal-type gastric adenocarcinoma patients after surgery.

Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation.

Mitophagy-related genes could facilitate the development of septic shock during immune infiltration.

Septic shock often occurs following critically low blood pressure in patients with sepsis, and is accompanied by a high death rate. Although mitophagy is associated with infection and immune responses, its role in septic shock remains unknown. This study screened effective mitophagy-related genes (MRGs) for medical practice and depicted immune infiltration situations in patients with septic shock. Gene expression profiles of GSE131761 from the Gene Expression Omnibus database were compiled for differential analysis, weighted gene co-expression network analysis, and immune infiltration analysis, while other GSE series were used as validation datasets. A series of validation methods were used to verify the robustness of hub genes, while a nomogram and prognosis model were established for medical practice. Six genes were screened via combinations of differentially expressed genes, weighted gene co-expression network analysis, and MRGs. From this, 3 hub genes (MAP1LC3B, ULK1, and CDC37) were chosen for subsequent analysis based on different validation methods. Gene set enrichment analysis showed that leukocyte trans-endothelial migration and the p53 signaling pathway were abnormally activated during septic shock. Immune infiltration analysis indicated that the imbalance of neutrophils and CD4 naive T cells was significantly correlated with septic shock progression. A nomogram was generated based on MAP1LC3B, ULK1, and CDC37, as well as age. The stability of our model was confirmed using a calibration plot. Importantly, patients with septic shock with the 3 highly expressed hub genes displayed worse prognosis than did patients without septic shock. MAP1LC3B, ULK1, and CDC37 are considered hub MRGs in the development of septic shock and could represent promising diagnostic and prognostic biomarkers in blood tissue. The validated hub genes and immune infiltration pattern expand our knowledge on MRG functional mechanisms, which provides guidance and direction for the development of septic shock diagnostic and therapeutic markers.

Copper metabolism-related Genes in entorhinal cortex for Alzheimer's disease.

The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the formation of amyloid plaques. However, their role has been controversial. The aim of this study was to explore the role of Cu in AD. We applied the "R" software for our differential analysis. Differentially expressed genes were screened using the limma package. Copper metabolism-related genes and the intersection set of differential genes with GSE5281 were searched; functional annotation was performed. The protein-protein interaction network was constructed using several modules to analyse the most significant hub genes. The hub genes were then qualified, and a database was used to screen for small-molecule AD drugs. We identified 87 DEGs. gene ontology analysis focused on homeostatic processes, response to toxic substances, positive regulation of transport, and secretion. The enriched molecular functions are mainly related to copper ion binding, molecular function regulators, protein-containing complex binding, identical protein binding and signalling receptor binding. The KEGG database is mainly involved in central carbon metabolism in various cancers, Parkinson's disease and melanoma. We identified five hub genes, FGF2, B2M, PTPRC, CD44 and SPP1, and identified the corresponding small molecule drugs. Our study identified key genes possibly related to energy metabolism in the pathological mechanism of AD and explored potential targets for AD treatment by establishing interaction networks.

A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation.

Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord's poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair in vitro and in vivo, effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.

Fever burden within 24 h after hematoma evacuation predicts early neurological deterioration in patients with intracerebral hemorrhage: a retrospective analysis.

Background: Early neurological deterioration after hematoma evacuation is closely associated with a poor prognosis in patients with intracerebral hemorrhage. However, the relationship between body temperature after hematoma evacuation and early neurological deterioration remains unclear. Therefore, this study aims to explore the possible relationship between body temperature and early neurological deterioration in patients with intracerebral hemorrhage after hematoma evacuation. Methods: We retrospectively collected data from patients with cerebral hemorrhage at our institute between January 2017 and April 2022. The Student's t-test, Mann-Whitney U-test, and χ2 Test and Fisher's exact test were used to analyze the clinical baseline data. A univariate logistic regression model was used to evaluate the association between the body temperature indices and early neurological deterioration. The predictive power was assessed using the area under the Receiver Operating Characteristic (ROC) curve. The secondary outcome was a poor functional outcome. Results: Among 2,726 patients with intracerebral hemorrhage, 308 who underwent hematoma evacuation were included in the present analysis. A total of 82 patients (22.6%) developed early neurological deterioration. Univariate analysis showed that sex (p = 0.041); body temperature at 6 h (p = 0.005), 12 h (p = 0.01), and 24 h (p = 0.008) after surgery; duration of fever (p = 0.008); and fever burden (p < 0.001) were associated with early neurological deterioration. Multivariate logistic regression showed that fever burden was independently associated with early neurological deterioration (OR = 1.055 per °C × hour, 95%CI 1.008-1.103, p = 0.020). ROC showed that fever burden (AUC = 0.590; 95%CI: 0.514-0.666) could predict the occurrence of early neurological deterioration. Conclusion: Fever burden is associated with early neurological deterioration in intracerebral hemorrhage patients undergoing hematoma evacuation. Our findings add to previous evidence on the relationship between the fever burden and the occurrence of early neurological deterioration in patients with intracerebral hemorrhage. Future studies with larger sample sizes are required to confirm these findings.