Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

PURPOSE: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. METHODS: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. RESULTS: In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. CONCLUSION: DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Augmented reality technology shortens aneurysm surgery learning curve for residents.

OBJECTIVES: We aimed to prospectively investigate the benefit of using augmented reality (AR) for surgery residents learning aneurysm surgery. MATERIALS AND METHODS: Eight residents were included, and divided into an AR group and a control group (4 in each group). Both groups were asked to locate an aneurysm with a blue circle on the same screenshot after their viewing of surgery videos from both AR and non-AR tests. Only the AR group was allowed to inspect and manipulate an AR holographic representation of the aneurysm in AR tests. The actual location of the aneurysm was defined by a yellow circle by an attending physician after each test. Localization deviation was determined by the distance between the blue and yellow circle. RESULTS: Localization deviation was lower in the AR group than in the control group in the last 2 tests (AR Test 2: 2.7 ± 1.0 mm vs. 5.8 ± 4.1 mm, p = 0.01, non-AR Test 2: 2.1 ± 0.8 mm vs. 5.9 ± 5.8 mm, p < 0.001). The mean deviation was lower in non-AR Test 2 as compared to non-AR Test 1 in both groups (AR: p < 0.001, control: p = 0.391). The localization deviation of the AR group decreased from 8.1 ± 3.8 mm in Test 2 to 2.7 ± 1.0 mm in AR Test 2 (p < 0.001). CONCLUSION: AR technology provides an effective and interactive way for neurosurgery training, and shortens the learning curve for residents in aneurysm surgery.

Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study.

PURPOSE: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. METHODS: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. RESULTS: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant ( P =0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. CONCLUSION: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.

SAD score of intracranial aneurysms for rupture risk assessment based on high-resolution vessel wall imaging.

OBJECTIVE: We aimed to develop a comprehensive model that integrates the radiological, morphological, and clinical factors to assess rupture risk for intracranial aneurysms. METHODS: We prospectively enrolled patients with intracranial saccular aneurysms who underwent high-resolution vessel wall imaging (HR-VWI) preoperatively. Clinical characteristics, aneurysm features and aneurysm wall enhancement scale (AWES) were recorded. AWES was categorized into three grades (no/faint/strong enhancement) by comparing AWE to enhancement of the pituitary infundibulum or choroid plexus on HR-VWI. Univariate and multivariate logistic regression analyses were performed to determine risk factors associated with aneurysmal rupture. RESULTS: A total of 25 ruptured and 116 unruptured aneurysms were included. Multivariate logistic regression analysis revealed that non-ICA site (OR 6.25, 95% CI 1.35-28.30, P = 0.019), AWES (OR 5.99, 95% CI 2.51-14.29, P < 0.001) and daughter sac or lobulated shape (OR 6.22, 95% CI 1.68-23.16, P = 0.006) were independent factors associated with ruptured aneurysms. The "SAD" model was generated and named after the first letters of each of these factors. SAD scores of 0-4 predicted 0, 2%, 12%, 42% and 100% ruptured aneurysms, respectively. The area under the receiver operating characteristic curve for the SAD model was 0.8822. CONCLUSION: The SAD model aids in distinguishing aneurysm rupture status and in managing unruptured aneurysms. Larger cohort studies are needed to confirm its applicability in predicting the rupture risk of unruptured aneurysms.

Ticagrelor is related to nuisance bleeding after flow diversion of unruptured intracranial aneurysms.

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Protection of taraxasterol against acetaminophen-induced liver injury elucidated through network pharmacology and in vitro and in vivo experiments.

BACKGROUND: Drug-induced liver injury (DILI) is primarily caused by drugs or their metabolites. Acetaminophen (APAP) is an over-the-counter antipyretic analgesic that exhibits high hepatotoxicity when used for long-term or in overdoses. Taraxasterol is a five-ring triterpenoid compound extracted from traditional Chinese medicinal herb Taraxacum officinale. Our previous studies have demonstrated that taraxasterol exerts protective effects on alcoholic and immune liver injuries. However, the effect of taraxasterol on DILI remains unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of action of taraxasterol on APAP-induced liver injury using network pharmacology and in vitro and in vivo experiments. METHODS: Online databases of drug and disease targets were used to screen the targets of taraxasterol and DILI, and a protein-protein interaction network (PPI) was constructed. Core target genes were identified using the tool of Analyze of Cytoscape, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Oxidation, inflammation and apoptosis were evaluated to determine the effect of taraxasterol on APAP-stimulated liver damage in AML12 cells and mice. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the potential mechanisms of taraxasterol against DILI. RESULTS: Twenty-four intersection targets for taraxasterol and DILI were identified. Among them, 9 core targets were identified. GO and KEGG analysis showed that core targets are closely related to oxidative stress, apoptosis, and inflammatory response. The in vitro findings showed that taraxasterol alleviated mitochondrial damage in AML12 cells treated with APAP. The in vivo results revealed that taraxasterol alleviated pathological changes in the livers of mice treated with APAP and inhibited the activity of serum transaminases. Taraxasterol increased the activity of antioxidants, inhibited the production of peroxides, and reduced inflammatory response and apoptosis in vitro and in vivo. Taraxasterol promoted Nrf2 and HO-1 expression, suppressed JNK phosphorylation, and decreased the Bax/Bcl-2 ratio and caspase-3 expression in AML12 cells and mice. CONCLUSION: By integrating network pharmacology with in vitro and in vivo experiments, this study indicated that taraxasterol inhibits APAP-stimulated oxidative stress, inflammatory response and apoptosis in AML12 cells and mice by regulating the Nrf2/HO-1 pathway, JNK phosphorylation, and apoptosis-related protein expression. This study provides a new evidence for the use of taraxasterol as a hepatoprotective drug.

Thermal conductance between water and nm-thick WS2: extremely localized probing using nanosecond energy transport state-resolved Raman.

Liquid-solid interface energy transport has been a long-term research topic. Past research mostly focused on theoretical studies while there are only a handful of experimental reports because of the extreme challenges faced in measuring such interfaces. Here, by constructing nanosecond energy transport state-resolved Raman spectroscopy (nET-Raman), we characterize thermal conductance across a liquid-solid interface: water-WS2 nm film. In the studied system, one side of a nm-thick WS2 film is in contact with water and the other side is isolated. WS2 samples are irradiated with 532 nm wavelength lasers and their temperature evolution is monitored by tracking the Raman shift variation in the E2g mode at several laser powers. Steady and transient heating states are created using continuous wave and nanosecond pulsed lasers, respectively. We find that the thermal conductance between water and WS2 is in the range of 2.5-11.8 MW m-2 K-1 for three measured samples (22, 33, and 88 nm thick). This is in agreement with molecular dynamics simulation results and previous experimental work. The slight differences are attributed mostly to the solid-liquid interaction at the boundary and the surface energies of different solid materials. Our detailed analysis confirms that nET-Raman is very robust in characterizing such interface thermal conductance. It completely eliminates the need for laser power absorption and Raman temperature coefficients, and is insensitive to the large uncertainties in 2D material properties input.

Etomidate-remifentanil is more suitable for monitored anesthesia care during gastroscopy in older patients than propofol-remifentanil.

BACKGROUND: This prospective and randomized study was designed to compare safety, potential complications, and patient and examiner satisfaction of 2 anesthetic combinations - etomidate-remifentanil and propofol-remifentanil - in elderly patients undergoing diagnostic gastroscopy. MATERIAL AND METHODS: A group of 720 patients, aged 60-80 years, scheduled for diagnostic gastroscopy under sedation were prospectively randomized. After 0.4-0.6 µg kg⁻¹ of remifentanil was infused, etomidate or propofol was administered. Patients in the etomidate group received doses of etomidate at 0.1-0.15 mg kg⁻¹ followed by 4-6 mg. Patients in the propofol group received doses of propofol at 1-2 mg kg⁻¹ followed by 20-40 mg. Physiological indexes were evaluated for the 715 of 720 patients that completed the treatment. The onset time, duration time, and discharge time were recorded. Physicians, anesthetists, and patients were surveyed to assess their satisfaction. RESULTS: Systolic pressure and diastolic pressure decreased significantly after the procedure in the propofol group (P<0.001). The average heart rate was significantly lower in the propofol group (P<0.05). No periods of desaturation (SpO2 <95%) were observed in either group. The onset time was earlier in the etomidate group (P=0.00). All adverse events, with the exception of myoclonus, were greater in the propofol group, and physician and patient satisfaction in both groups was similar. CONCLUSIONS: Etomidate-remifentanil administration for sedation and analgesia during gastroscopy resulted in more stable hemodynamic responses and less adverse events in older patients.