High-resolution magnetic resonance vessel wall imaging provides new insights into Moyamoya disease.

Moyamoya disease (MMD) is a rare condition that affects the blood vessels of the central nervous system. This cerebrovascular disease is characterized by progressive narrowing and blockage of the internal carotid, middle cerebral, and anterior cerebral arteries, which results in the formation of a compensatory fragile vascular network. Currently, digital subtraction angiography (DSA) is considered the gold standard in diagnosing MMD. However, this diagnostic technique is invasive and may not be suitable for all patients. Hence, non-invasive imaging methods such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are often used. However, these methods may have less reliable diagnostic results. Therefore, High-Resolution Magnetic Resonance Vessel Wall Imaging (HR-VWI) has emerged as the most accurate method for observing and analyzing arterial wall structure. It enhances the resolution of arterial walls and enables quantitative and qualitative analysis of plaque, facilitating the identification of atherosclerotic lesions, vascular entrapment, myofibrillar dysplasia, moyamoya vasculopathy, and other related conditions. Consequently, HR-VWI provides a new and more reliable evaluation criterion for diagnosing vascular lesions in patients with Moyamoya disease.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention.

Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post-translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2-mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ-resistant cells, and is mainly concentrated in histone H3K9. Combined multi-omics analysis, including CUT&Tag, SLAM-seq, and RNA-seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2 transcription to promote its expression. LUC7L2 mediates intron 7 retention of MLH1 to reduce MLH1 expression, and thereby inhibit mismatch repair (MMR), ultimately leading to GBM TMZ resistance. Of note, it is identified that a clinical anti-epileptic drug, stiripentol, which can cross the blood-brain barrier and inhibit lactate dehydrogenase A/B (LDHA/B) activity, acts as a lactylation inhibitor and renders GBM cells more sensitive to TMZ in vitro and in vivo. These findings not only shed light on the mechanism of lactylation in GBM TMZ resistance but also provide a potential combined therapeutic strategy for clinical GBM treatment.

Effect of ferroptosis on chronic cerebral hypoperfusion in vascular dementia.

Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease and is caused by impaired nerve cell function resulting from cerebrovascular disease and vascular risk factors. Chronic cerebral hypoperfusion (CCH) is a common pathological and physiological state that may result from cerebral ischemia and hypoxia, causing widespread diffuse lesions in the brain parenchyma which leads to progressive nerve damage. Transferrin (TF) and transferrin receptor 1 (TfR1), two proteins involved in iron uptake, were upregulated by CCH, whereas ferroprotein (FPN), a protein involved in iron efflux, was downregulated. This process may involve various mechanisms including tau and iron regulatory proteins (IRP). CCH can also exacerbate lipid peroxidation caused by an iron imbalance by inhibiting glutathione peroxidase 4 (Gpx4) synthesis and some Gpx4 independent pathways through cystine/glutamate transporters (system Xc-), ultimately leading to ferroptosis in nerve cells and accelerating the progression of VaD.

IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2.

The prognosis of glioblastoma (GBM) patients is poor, and temozolomide (TMZ) resistance has become an important obstacle to its treatment effect. A growing number of researches have revealed the special characteristics of iron metabolism in GBM chemosensitivity. Iron regulatory protein 1 (IRP1) is an important protein for maintaining intracellular iron homeostasis. IRP1 has been indicated to have additional vital roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we unprecedentedly demonstrated that amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growth in vivo via inhibiting NFKB2 in the noncanonical NF-κB signaling pathway. In addition, we identified that NFKB2 affected TMZ sensitivity of GBM by modulating the expression of LCN2 and FPN1. Taken together, this study established a role for the IRP1/NFKB2 pathway in regulating LCN2/FPN1 signaling axis among the progression of TMZ resistance, suggesting a potential innovative GBM therapeutic strategy.

Risk factors and outcomes of intraoperative hypothermia in neonatal and infant patients undergoing general anesthesia and surgery.

Objective: The incidence of intraoperative hypothermia remains high in pediatric patients during anesthesia and surgery even though core body temperature monitoring and warming systems have been greatly improved in recent years. We analyzed the risk factors and outcomes of intraoperative hypothermia in neonates and infants undergoing general anesthesia and surgery. Methods: The data on the incidence of intraoperative hypothermia, other clinical characteristics, and outcomes from electronic records of 1,091 patients (501 neonates and 590 infants between 28 days and 1 year old), who received general anesthesia and surgery, were harvested and analyzed. Intraoperative hypothermia was defined as a core temperature below 36°C during surgery. Results: The incidence of intraoperative hypothermia in neonates was 82.83%, which was extremely higher than in infants (38.31%, p < 0.001)-the same as the lowest body temperature (35.05 ± 0.69°C vs. 35.40 ± 0.68°C, p < 0.001) and the hypothermia duration (86.6 ± 44.5 min vs. 75.0 ± 52.4 min, p < 0.001). Intraoperative hypothermia was associated with prolonged PACU, ICU, hospital stay, postoperative bleeding, and transfusion in either age group. Intraoperative hypothermia in infants was also related to prolonged postoperative extubation time and surgical site infection. After univariate and multivariate analyses, the age (OR = 0.902, p < 0.001), weight (OR = 0.480, p = 0.013), prematurity (OR = 2.793, p = 0.036), surgery time of more than 60 min (OR = 3.743, p < 0.001), prewarming (OR = 0.081, p < 0.001), received >20 mL/kg fluid (OR = 2.938, p = 0.004), and emergency surgery (OR = 2.142, p = 0.019) were associated with hypothermia in neonates. Similar to neonates, age (OR = 0.991, p < 0.001), weight (OR = 0.783, p = 0.019), surgery time >60 min (OR = 2.140, p = 0.017), pre-warming (OR = 0.017, p < 0.001), and receive >20 mL/kg fluid (OR = 3.074, p = 0.001) were relevant factors to intraoperative hypothermia in infants along with the ASA grade (OR = 4.135, p < 0.001). Conclusion: The incidence of intraoperative hypothermia was still high, especially in neonates, with a few detrimental complications. Neonates and infants each have their different risk factors associated with intraoperative hypothermia, but younger age, lower weight, longer surgery time, received more fluid, and no prewarming management were the common risk factors.

Research progress of endogenous hematoma absorption after intracerebral hemorrhage.

Non-traumatic intraparenchymal brain hemorrhage is referred to as intracerebral hemorrhage (ICH). Although ICH is associated with a high rate of disability and case fatality, active intervention can significantly lower the rate of severe disability. Studies have shown that the speed of hematoma clearance after ICH determines the patient's prognosis. Following ICH, depending on the hematoma volume and mass effect, either surgical- or medication-only conservative treatment is chosen. The goal of promoting endogenous hematoma absorption is more relevant because surgery is only appropriate for a small percentage of patients, and open surgery can cause additional trauma to patients. The primary method of removing hematoma after ICH in the future will involve understanding how to produce and manage macrophage/microglial endogenous phagocytic hematomas. Therefore, it is necessary to elucidate the regulatory mechanisms and key targets for clinical purposes.

Intraoperative hypothermia in the neonate population: risk factors, outcomes, and typical patterns.

The risk factors, outcomes, and typical patterns of intraoperative hypothermia were studied in neonates to better guide the application of insulation measures in the operating room. This retrospective study enrolled 401 neonates undergoing surgery under general anaesthesia with tracheal intubation, including abdominal surgery, thoracic surgery, brain surgery, and others. The study collected basic characteristics, such as age, sex, weight, birth weight, gestational week, primary diagnosis and American Society of Anaesthesiologists (ASA) grade. Perioperative data included preoperative body temperature, length of hospital stay, length of intensive care unit (ICU) stay, intubation time, postoperative bleeding, postoperative pneumonia, postoperative death, and total cost of hospitalization. Intraoperative data included surgical procedures, anaesthesia duration, operation duration, blood transfusion, fluid or albumin infusion, and application of vasoactive drugs. The incidence of intraoperative hypothermia (< 36 °C) was 81.05%. Compared to normothermic patients, gestational week (OR 0.717; 95% CI 0.577-0.890; P = 0.003), preoperative temperature (OR 0.228; 95% CI 0.091-0.571; P = 0.002), duration of anaesthesia (OR 1.052; 95% CI 1.027-1.077; P < 0.001), and type of surgery (OR 2.725; 95% CI 1.292-5.747; P = 0.008) were associated with the risk of intraoperative hypothermia. Patients with hypothermia had longer length of ICU stay (P = 0.001), longer length of hospital stay (P < 0.001), and higher hospital costs (P < 0.001). But there were no association between clinical outcomes and intraoperative hypothermia in the multivariable regression adjusted analysis. The lowest point of intraoperative body temperature was approximately 1 h 30 min. Then, the body temperature of patients successively entered a short plateau phase and a period of slow ascent. The greatest decrease in body temperatures occurred in preterm babies and neonates with preoperative hypothermia. The lowest core temperatures that occurred in neonates with preoperative hypothermia was lower than 35 °C. This study shows that there is a high incidence of intraoperative hypothermia in the neonate population. The intraoperative body temperature of neonates dropped to the lowest point in 1-1.5 h. The greatest decrease in core temperatures occurred in preterm babies and neonates with lower preoperative temperature.

Study of risk factors for intraoperative hypothermia during pediatric burn surgery.

Background: Intraoperative hypothermia (core temperature <36.0°C) is common during the perioperative period and can result in adverse consequences, especially in children. We aimed to determine the incidence of intraoperative hypothermia and its risk factors in pediatric patients during burn surgery. Methods: In the present study we enrolled 197 pediatric patients with burn injury undergoing surgical debridement and skin grafting. Factors, such as total burn surface area (TBSA), were collected and analyzed to identify the potential risk factors for intraoperative hypothermia. Results: The incidence of intraoperative hypothermia among all patients was 17.8%. Compared with patients with normothermia, children with hypothermia were associated with larger TBSA (25% vs 15%, p<0.001) and with less intraoperative active warming (34.28% vs 54.93%, p<0.05). In addition, compared with patients with moderate-degree burn, patients with severe and extremely severe burn were associated with much higher risk of intraoperative hypothermia [severe: odds ratio (OR)=3.805, 95% confidence interval (CI)=1.396-10.368, p=0.009; extremely severe: OR=6.933, 95% CI=2.604-18.462, p<0.001]. TBSA was the only independent risk factor that emerged as being strongly associated with intraoperative hypothermia (OR=1.068, p=0.001) and could be used to predict the occurrence of hypothermia when combined with other factors. TBSA for predicting intraoperative hypothermia by receiver operating characteristic (ROC) curve analysis showed a good predictive ability with an area under the ROC curve of 0.758. Conclusion: TBSA is an important risk factor for intraoperative hypothermia in pediatric patients with burn.

Sulforaphane prevents PC12 cells from oxidative damage via the Nrf2 pathway.

The aim of this study was to investigate the protective effect of sulforaphane (SFN) on 1­methyl­4­phenyl pyridine ion (MPP+)­induced cytotoxicity and to investigate its possible mechanisms. METHODS: PC12 cell toxicity induced by MPP+ served as a cell model of Parkinson's diseases. The cell culture + experiments were divided into four groups based on the different treatments, namely, vehicle control, SFN, MPP+ and SFN pretreatment plus MPP+. Cell viability and apoptosis were examined by MTT assay and flow cytometry, respectively. Expressions of nuclear factor erythroid 2­related factor 2 (Nrf2), heme oxygenase 1 (HO­1) and nicotinamide quinone oxidoreductase 1 (NQO1) were detected using western blotting. RESULTS: MPP+ reduced the survival rate of PC12 cells in a dose­ and time­dependent manner. After 24­h treatment with 500 µmol/l MPP+, the survival rate of PC12 cells decreased to 58.2±0.03% of that in the control groups. Under the same conditions MPP+ resulted in significant apoptosis of PC12 cells (apoptosis rate: 30.4±0.6%). However, SFN pretreatment significantly attenuated the cell damage induced by MPP+. Furthermore, it was demonstrated that SFN reversed the reduction of Nrf2, HO­1 and NQO1 expression induced by MPP+. CONCLUSION: SFN may protect PC12 cells from MPP+­induced damage via activating the Nrf2­ARE (antioxidant responsive element) pathway.