Fever of unknown origin associated with immune checkpoint inhibitors.

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO.

BMSCs attenuate radiation-induced brain injury induced hippocampal neuronal apoptosis through a PI3K/Akt/Bax/Bcl-2 signaling pathway.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs) -based therapies represent a promising treatment for neurological disorders. However, therapeutic effects and mechanisms of BMSCs transplantation for radiation-induced brain injury (RIBI) have not been fully disclosed. In this article, we explored the functions of BMSCs transplantation on RIBI and investigated the protective effects of BMSCS on hippocampal neurons in RIBI as well as the related molecular mechanisms. MATERIALS AND METHODS: 6-8 weeks-old rats were used to build a RIBI model. Rats in BMSC group were treated with a 3 × 106 BMSCs injection through the tail vein on the 1st day and 8th day after irradiation; rats in both control and RIBI groups were injected with an equivalent volume of physiological saline for comparisons. The Morris water maze was applied to detect the variations in cognitive function after RIBI. MRS was performed to test changes in NAA/Cr, indicating neuronal apoptosis after RIBI. TUNEL was conducted to detect apoptosis of rat hippocampal neurons, and HE staining was carried out to show pathological variations in the hippocampal region of rats. Protein levels of PI3K, P-PI3K, AKT, P-AKT, Bcl-2, and Bax proteins of rats in the hippocampal area were all determined by Western blot. RESULTS: Cognitive function was reduced and hippocampal neurons underwent apoptosis in the rats of the RIBI group, and cognitive abilities, histopathological alterations, and apoptosis of hippocampal neurons were significantly improved after BMSCs treatment; the expression of PI3K, P-PI3K, AKT, P-AKT, and Bcl-2 proteins, in the hippocampal region of the rat, was up-regulated, and Bax proteins were down-regulated. CONCLUSIONS: BMCSs can inhibit hippocampal neuronal apoptosis in RIBI, and the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax by the PI3K/AKT signaling pathway.

Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit?

BACKGROUND: Angioplasty and/or stenting is a rescue therapy for mechanical thrombectomy (MT) in acute intracranial large vessel occlusion. This study was undertaken to determine whether rescue angioplasty and/or stenting improves the outcome after MT and to investigate whether outcomes differ by subgroup of rescue indication. METHODS: We performed propensity score matching (PSM) with data from a prospective multicenter registry of patients with acute large vessel occlusion receiving endovascular treatment. Patients were divided into the MT alone group and the MT with rescue therapy group. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. PSM was also performed in the failed MT (modified Thrombolysis In Cerebral Infarction (mTICI) 0-2a) and the residual severe stenosis (mTICI 2b-3) subgroups, respectively. RESULTS: 326 patients of mean±SD age 62.7±12.0 years (90 women, 27.6%) were matched from 1274 patients. In the matched cohort, functional independence at 90 days was higher in the rescue therapy group than in the MT alone group (44.2% vs 29.5%; OR 1.90, 95% CI 1.18 to 3.06, P=0.008). In the failed MT subgroup with 66 matched pairs, more patients had functional independence in the rescue therapy group than in the MT alone group (39.0% vs 17.0%; OR 3.12, 95% CI 1.29 to 7.59, P=0.01). In the residual stenosis subgroup with 63 matched pairs, functional independence rates were similar in the rescue therapy and the MT alone groups (51.6% vs 55.7%; OR 0.85, 95% CI 0.42 to 1.72, P=0.65). CONCLUSION: Rescue angioplasty and/or stenting could improve the clinical outcome in patients with acute large vessel occlusion with failed MT, while no benefit was seen in those with residual severe stenosis but substantial reperfusion.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Manganese-enhanced magnetic resonance assessment of changes in hippocampal neural function after the treatment of radiation-induced brain injury with bone marrow mesenchymal stem cells.

The role of bone marrow mesenchymal stem cells (BMSCs) in treating radiation-induced brain injury (RIBI) is not completely understood, and assessment methods to directly characterize neurological function are lacking. In this study, we aimed to evaluate the effects of BMSCs treatment on changes in hippocampal neural function in Sprague-Dawley(SD) rats with RIBI, and to evaluate the therapeutic effect of BMSCs by manganese-enhanced magnetic resonance imaging (MEMRI). First, we assessed cognitive function after RIBI treatment with BMSCs using the Morris water maze. Next, we used MEMRI at two time points to observe the treatment effect and explore the correlation between MEMRI and cognitive function. Finally, we evaluated the expression of specific hippocampal neurofunctional proteins, the ultrastructure of hippocampal nerves, and the histological changes in the hippocampus. After BMSCs treatment of RIBI, cognitive dysfunction improved significantly, the expression of hippocampal neurofunctional proteins was increased, the integrity of the hippocampal neural structure was protected, and nerve cell survival was enhanced. The improvement in neurological function was successfully detected by MEMRI, and MEMRI was highly correlated with cognitive function and histological changes. These results suggest that BMSCs treatment of RIBI is an optional modality, and MEMRI can be used for treatment evaluation.

Cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarct in China.

BACKGROUND: Endovascular therapy administered within 24 hours has been shown to improve outcomes for patients with acute ischemic stroke with large infarction, but the data on its cost-effectiveness are limited. OBJECTIVE: To evaluate the cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarction in China, the largest low- and middle-income country. METHODS: A short-term decision tree model and a long-term Markov model were used to analyze the cost-effectiveness of endovascular therapy for patients with acute ischemic stroke with large infarction. Outcomes, transition probability, and cost data were obtained from a recent clinical trial and published literature. The benefit of endovascular therapy was assessed by the cost per quality-adjusted life-years (QALYs) gained in the short and long term. Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: Compared with medical management alone, endovascular therapy for acute ischemic stroke with large infarction was found to be cost-effective from the fourth year onward and during a lifetime. In the long term, endovascular therapy yielded a lifetime gain of 1.33 QALYs at an additional cost of ¥73 900 (US$ 11 400), resulting in an incremental cost of ¥55 500 (US$ 8530) per QALY gained. Probabilistic sensitivity analysis showed that endovascular therapy was cost-effective in 99.5% of the simulation runs at a willingness-to-pay threshold of ¥243 000 (3 × gross domestic product per capita of China in 2021) per QALY gained. CONCLUSIONS: Endovascular therapy for acute ischemic stroke with large infarction could be cost-effective in China.

Intravascular ultrasound characteristics of different types of stenosis in idiopathic intracranial hypertension with venous sinus stenosis.

BACKGROUND: In this study, we analyzed the characteristics of different stenosis types in idiopathic intracranial hypertension (IIH) patients with venous sinus stenosis (VSS) using intravascular ultrasound (IVUS). METHODS: We retrospectively reviewed data from patients who underwent IVUS evaluation during venography or stenting procedures between January 2014 and February 2022. RESULTS: Among the 80 patients with intrinsic lesions, 47 cases were identified, including 41 single lesions and 6 multiple lesions. Single lesions consisted of 36 cases of AG, 3 cases of brain herniation, and 2 cases of septation. Multiple intrinsic lesions were found in 6 patients, with AG observed in the transverse sinus and sigmoid sinus. IVUS features varied depending on the anatomical variations of intrinsic stenosis. Additionally, among the 33 cases of extrinsic stenosis, two types were observed: unilateral compression (22 cases) and bilateral compression (11 cases), primarily affecting the transverse sinus. CONCLUSION: IVUS effectively differentiated intrinsic and extrinsic types of stenosis and identified intraluminal and mural components of intrinsic stenosis.

Enhancement of Energy Storage Performance of PMMA/PVDF Composites by Changing the Crystalline Phase through Heat Treatment.

In today's contemporary civilization, there is a growing need for clean energy focused on preserving the environment; thus, dielectric capacitors are crucial equipment in energy conversion. On the other hand, the energy storage performance of commercial BOPP (Biaxially Oriented Polypropylene) dielectric capacitors is relatively poor; hence, enhancing their performance has drawn the attention of an increasing number of researchers. This study used heat treatment to boost the performance of the composite made from PMAA and PVDF, combined in various ratios with good compatibility. The impacts of varying percentages of PMMA-doped PMMA/PVDF mixes and heat treatment at varying temperatures were systematically explored for their influence on the attributes of the blends. After some time, the blended composite's breakdown strength improves from 389 kV/mm to 729.42 kV/mm at a processing temperature of 120 °C. Consequently, the energy storage density is 21.12 J/cm3, and the discharge efficiency is 64.8%. The performance has been significantly enhanced compared to PVDF in its purest state. This work offers a helpful technique for designing polymers that perform well as energy storage materials.

First pass effect of mechanical thrombectomy for acute vertebrobasilar artery occlusion: data from the ANGEL-ACT registry.

BACKGROUND: To explore the incidence, predictors, and association of first pass effect (FPE) on clinical outcomes of mechanical thrombectomy (MT) for acute vertebrobasilar artery occlusion (VBAO) in the Asian population. METHODS: We selected patients from the ANGEL-ACT registry. We defined FPE as complete recanalization after one MT attempt without rescue treatment, multiple pass effect (MPE) as complete recanalization after >1 MT attempt or after one MT attempt with rescue treatment, and incomplete recanalization (ICR) as a modified Thrombolysis in Cerebral Ischemia score of 2b, independent of the number of MT attempts. We conducted multivariable logistic analyses to identify the independent predictors of FPE and to compare the outcomes, including favorable outcome, mortality within 90 days, and intracranial hemorrhage (ICH) among the FPE, MPE, and ICR groups. RESULTS: Two hundred and seventy-nine patients, 68 with FPE (24.4%), 114 with MPE (40.9%), and 83 with ICR (29.7%), were included. Underlying intracranial atherosclerosis disease (ICAD) (adjusted OR (aOR) 0.16, 95% CI 0.08 to 0.34, P<0.001) was independently associated with a low chance of FPE. Furthermore, FPE was associated with a favorable outcome compared with MPE and ICR (MPE vs FPE, aOR 0.49, 95% CI 0.25 to 0.97, P=0.040; ICR vs FPE, aOR 0.38, 95% CI 0.18 to 0.81, P=0.012), and decreased mortality (MPE vs FPE, aOR 2.57, 95% CI 1.04 to 6.36, P=0.041) compared with MPE but similar mortality to ICR (P=0.374). No difference was found for ICH among the three groups (P>0.05). CONCLUSIONS: FPE occurred in 24.4% of patients with VBAO in our cohort, which was associated with improved clinical outcomes compared with MPE and ICR. VBAO with underlying ICAD was less likely to achieve FPE. TRIAL REGISTRATION NUMBER: NCT03370939.

HNF4G stimulates the development of pancreatic cancer by promoting IGF2BP2 transcription.

OBJECTIVE: Pancreatic cancer is a devastating and lethal malignancy. Our study investigated the effective mechanism of HNF4G on pancreatic cancer cell functions through the IGF2BP2 transcription. METHODS: HNF4G and IGF2BP2 expressions in pancreatic cancer were examined. The relationship between HNF4G expression and pancreatic cancer patients' clinicopathological characteristics was evaluated. After interfering with HNF4G expression in pancreatic cancer cells, the cell proliferative, migratory, and invasive capabilities were evaluated. Also, the expression of proliferation-related gene PCNA and migration and invasion-related gene MMP2 was determined. The binding relation between HNF4G and HNF4G promoter was forecasted and testified. A tumorigenesis assay in nude mice was performed to detect the HNF4G interference's effect on the subcutaneous tumorigenic capacity of pancreatic cancer cells. RESULTS: HNF4G and IGF2BP2 expressions were up-regulated in pancreatic cancer. Specifically, interfering with HNF4G inhibited PANC-1 cell proliferative, invasive and migratory behaviors, and decreased PCNA and MMP2 expression. Mechanistically, HNF4G as a transcription factor could specifically bind to IGF2BP2 and promote its expression. Rescue assay findings showed that IGF2BP2 overexpression could reverse the inhibiting effect of HNF4G interference on pancreatic cancer cells. For the in vivo finding, interfering HNF4G expression retarded the subcutaneous tumorigenic ability of pancreatic cancer cells. CONCLUSION: We summarize that HNF4G as a transcription factor regulates IGF2BP2 expression to promote pancreatic cancer cell proliferation and migration capacities.

Futile reperfusion of endovascular treatment for acute anterior circulation large vessel occlusion in the ANGEL-ACT registry.

BACKGROUND: Some patients with large vessel occlusion (LVO) still cannot achieve functional independence despite successful reperfusion after endovascular treatment (EVT), named futile reperfusion. We aimed to explore the incidence and predictors of futile reperfusion of EVT for anterior circulation LVO in the Chinese population based on a nationwide prospective multicenter registry. METHODS: We selected patients from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) registry. Successful reperfusion was defined as modified Treatment In Cerebral Ischemia (mTICI) 2b-3 after EVT, and functional independence was defined as 90-day modified Rankin Scale (mRS) 0-2. A multivariable regression model was performed to identify the independent predictors of futile reperfusion in anterior circulation LVO patients. RESULTS: A total of 1158 anterior circulation LVO patients were included in our study. 600 of the 1158 patients (51.8%) suffered futile reperfusion. Age ≥69 (adjusted OR (aOR) 1.69, 95% CI 1.21 to 2.35, P=0.002), baseline National Institutes of Health Stroke Scale (NIHSS) ≥14 (aOR 2.36, 95% CI 1.71 to 3.27, P<0.001), baseline serum glucose ≥6.5 mmol/L (aOR 1.73, 95% CI 1.27 to 2.36, P=0.001), drip and ship (aOR 1.56, 95% CI 1.11 to 2.18, P=0.011), and general anesthesia (aOR 2.28, 95% CI 1.66 to 3.14, P<0.001) were associated with a high risk of futile reperfusion in the anterior LVO patients after EVT, whereas baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥8 (aOR 0.65, 95% CI 0.47 to 0.91, P=0.011) and complete reperfusion (aOR 0.62, 95% CI 0.43 to 0.89, P=0.010) were associated with a low risk of futile reperfusion in the anterior LVO patients after EVT. CONCLUSIONS: In the ANGEL-ACT registry, 51.8% of anterior circulation LVO patients suffered futile reperfusion after EVT. Age ≥69 years, baseline NIHSS ≥14, baseline serum glucose ≥6.5 mmol/L, drip and ship, general anesthesia, baseline ASPECTS <8, and incomplete reperfusion were the independent predictors of futile reperfusion.

Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry.

BACKGROUND: Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT). OBJECTIVE: To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). METHODS: Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score. RESULTS: Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12-36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001). CONCLUSIONS: In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting. TRIAL REGISTRATION NUMBER: NCT03370939.

Association of post-intervention pressure gradient with symptom-free at 6 months in idiopathic intracranial hypertension with venous sinus stenosis treated by stenting.

OBJECTIVE: This study aimed to identify the key factors that might affect the clinical outcome of patients with idiopathic intracranial hypertension (IIH) and Venous sinus stenting (VSS). METHODS: We performed an analysis of a prospectively collected database of patients with IIH and VSS who underwent stenting. The trans-stenotic pressure gradient was measured before and after intervention. In additional, patients' baseline characteristics, procedure details and clinical outcomes at 6-month follow-up (including changes in headache, visual impairment, papilledema, etc.) were recorded. The effects of post-intervention pressure gradient on symptom-free at 6 months were explored using logistic regression analysis, generalized additive model and receiver operator characteristic (ROC) curve. RESULTS: Of 101 patients included in this study, the median pressure gradient across stenosis decreased from 19 mmHg before intervention to 2 mmHg after intervention. At 6 months, symptom-free was observed in 58 cases (57.4%). Multivariable logistic analysis and generalized additive model showed that post-intervention pressure gradient (increased by 1 mmHg) was independently and linearly correlated with symptom-free (OR = 0.79, 95% CI = 0.67-0.94). Moreover, the post-intervention pressure gradient revealed moderate discrimination with an area under ROC curve of 0.68 (95% CI = 0.57-0.78). Similar associations were observed for the disappearance of headache and papilledema, but not for the visual recovery. CONCLUSION: The post-intervention pressure gradient may be a valid and reliable predictor of 6-month clinical outcome in patients with IIH and VSS treated by stenting. Nevertheless, external validation with blinded outcome is still needed to confirm its performance before clinical application.

Comparison of microcatheter and pressure wire for venous sinus manometric evaluation of patients with idiopathic intracranial hypertension.

BACKGROUND: Venous sinus manometry performed by microcatheter to assess candidacy for venous sinus stenting in patients with idiopathic cranial pressure (IIH) can be tiring, time-consuming and unreliable. Pressure wire is widely used to measure coronary pressure and evaluate coronary stenosis severity, but venous sinus manometry using the pressure guide wire has only been reported in one case, and few studies have examined the accuracy of this approach. OBJECTIVE: To compare venous manometry performed by microcatheter with by pressure wire under awake setting in patients with IIH. METHODS: The manometry results of 30 patients with IIH were recorded by Rebar-27 microcatheter and a pressure wire under awake setting. The mean venous pressures (MVPs) and trans-stenosis pressure gradients were obtained and compared between microcatheter and pressure wire. Paired t-test) were used to evaluate the data between the two groups. RESULTS: MVPs in superior sagittal sinus (SSS) and torcula were slightly higher with microcatheter, though without statistically significant differences (p > 0.05). MVPs in transverse sinus (TS) and sigmoid sinus (SS) were significantly higher with microcatheter (p < 0.05). Trans-stenotic pressure gradient with microcatheter was significantly higher than with pressure wire (p＜0.001). CONCLUSIONS: Intracranial venous pressure measured with the microcatheter and pressure wire showed a moderate difference. Compared with the traditional microcatheter method，the pressure wire is safe, fast and effective method to identify the patient needing intervention.

Predicting the Rapid Improvement of Papilledema After Stenting in Idiopathic Intracranial Hypertension.

PURPOSE: This study aimed to identify predictors of rapid improvement of papilledema after stenting and develop a simple preintervention scale. METHODS: A prospective cohort of idiopathic intracranial hypertension (IIH) with venous sinus stenosis (VSS) treated with stenting in a tertiary hospital from January 2014 to December 2019 was reviewed. We categorized papilledema improvement into favorable (grades 0-1) and unfavorable (grades 2-5). We employed logistic regression analysis to find the predictive factors and develop the predictive scale. We then estimated the performance of the scale using the ROC curve and Hosmer-Lemeshow test. RESULTS: There were 110 patients who underwent venous sinus stenting, with a mean age of 37.1 years and a predominance of females (77.3%). A total of 85 patients had a favorable outcome following stenting, while 25 patients had an unfavorable outcome. The results of the multivariate analysis indicate that lower preoperative pressure gradients (odds ratio, OR: 4.01; 95% confidence interval, CI: 1.27-12.68), stenosis rates (OR: 4.16; 95% CI: 1.11-15.56), and preoperative papilledema grades (OR: 2.92; 95% CI: 1.44-5.91) were independently associated with rapid improvement of papilledema following stenting treatment. The 3­item scale exhibited good discrimination with an area under the curve (AOC) of 0.81 (95% CI 0.72-0.89, p < 0.001), as well as acceptable calibration determined by the Hosmer-Lemeshow test (P = 0.42). The optimal cut-off value of the scale (range 0-6 points) was ≥ 4 points, with a sensitivity of 72%, specificity of 73%, and accuracy of 78%. CONCLUSION: The presence of lower preoperative pressure gradients, stenosis severity, and preoperative status of papilledema were identified as positive predictors of rapid improvement of the papilledema following stenting in IIH patients. The 3­item scale provides a promising preintervention predictive model for predicting rapid response following stenting treatment in IIH patients with VSS.

Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury.

CDGSH iron sulfur domain 2 can inhibit ferroptosis, which has been associated with cerebral ischemia/reperfusion, in individuals with head and neck cancer. Therefore, CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury. To validate this hypothesis in the present study, we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro, respectively. We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells. When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately, mouse neurological dysfunction was greatly improved; the cerebral infarct volume was reduced; the survival rate of HT22 cells was increased; HT22 cell injury was alleviated; the expression of ferroptosis-related glutathione peroxidase 4, cystine-glutamate antiporter, and glutathione was increased; the levels of malondialdehyde, iron ions, and the expression of transferrin receptor 1 were decreased; and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased. Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway. Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury, thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.

Estimation of venous sinus pressure drop in patients with idiopathic intracranial hypertension using 4D-flow MRI.

OBJECTIVE: We aimed to explore a non-invasive estimate of pressure drop in patients who undergo venous sinus stenting to treat idiopathic intracranial hypertension (IIH). METHODS: This prospective study included 28 IIH patients scheduled for venous stenting. 4D-flow MRI was acquired 24-48 h before venous manometry. Manometry-obtained pressure drop (Mp) was dichotomized into low (Lp: 0-8 mmHg) and high (Hp: 8-30 mmHg) groups. Hemodynamic indices were compared between Lp and Hp. Trans-stenotic pressure drop was estimated by work-energy equation, simplified Bernoulli equation, vorticity magnitude, and velocity difference between inlet and outlet and was compared with Mp. Measurement agreement, correlation, and accuracy were evaluated using the κ coefficient, Pearson's r, and confusion matrix-derived accuracy. RESULTS: Among 28 patients (mean age 38.8 ± 12.7), 19 (67.9%) were female. Work-energy equation-estimated pressure drop (WEp) had strong correlation (r = 0.91, 95% confidence interval [CI]: 0.81-0.96, p < 0.001) and high agreement (intraclass correlation coefficient = 0.90, 95% CI: 0.78-0.95, p < 0.001) with Mp. WEp classified Lp and Hp with an accuracy of 0.96. The κ value between WEp and Mp was 0.92 (95% CI: 0.78-1.00). In the work-energy equation, the viscosity energy term (Ve) had the largest weights, and the ratio of Ve to the summation of the three energy terms was 0.93 ± 0.07. Ve had strong correlation with mVort (r = 0.93, 95% CI: 0.85-0.97, p < 0.001), and mean vorticity magnitude was significantly elevated in Hp compared to that in Lp (259.8 vs. 174.9 mL/s, p < 0.001). CONCLUSION: Trans-stenotic pressure drop in IIH can be estimated using the work-energy equation with favorable accuracy. KEY POINTS: • Trans-stenotic pressure drop in patients with idiopathic intracranial hypertension can be estimated accurately with the work-energy equation using the 4D-flow MRI full velocity field. • Compared with traditional venous sinus manometry, the 4D-flow MRI-derived pressure drop is totally non-invasive and cost-saving. • 4D-flow MRI may help neurointerventionalist to select IIH patients suitable for venous sinus stenting.

Stenting versus medical treatment for idiopathic intracranial hypertension: a matched-control study.

BACKGROUND: This prospective cohort study compared the outcomes of stenting and medical treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS). METHODS: In this single-center cohort study, patients with IIH and VSS were evaluated between January 2014 and December 2019 with follow-up periods of 1, 3, and 6 months. The patients received either stenting or medical treatment. The two groups underwent 1:1 matching using propensity score analysis, and the clinical outcomes were compared. RESULTS: Following 1:1 matching, 36 patients who underwent stenting and 36 who underwent medical treatment were matched. The median improvements in the papilledema Frisén grade were greater in the stenting group at 1 month (-2 vs 0), 3 months (-3 vs -1), and 6 months (-3 vs -1) than in the medical treatment group. Patients who received stenting treatment had a significantly higher prevalence of complete resolution of their respective symptoms (headache, tinnitus, or visual disturbances) at 3 months (58.3% vs 13.9%, OR 8.68, 95% CI 2.74 to 27.52) and 6 months (80.6% vs 22.2%, OR 14.50, 95% CI 4.64 to 45.32) than those receiving medical treatment. CONCLUSIONS: This matched-control study shows that stenting has a greater efficacy rate and rapid resolution of papilledema and its respective symptoms compared with medical treatment.

Construction of novel coumarin-carbazole-based fluorescent probe for tracking of endogenous and exogenous H2S in vivo with yellow-emission and large Stokes shift.

Recent medical studies have confirmed that endogenous H2S serves as the third gas-messenger besides nitric oxide (NO) and carbon monoxide (CO), which is produced by enzyme-catalyzed metabolism of cysteine and takes part in multiple physiological processes. The abnormal levels induced by H2S overproduction in mammals can destroy tissues and organ systems, which lead to certain serious diseases, such as neurodegenerative diseases, cardiovascular diseases, and various cancers. In this work, we developed a novel coumarin-carbazole fluorescent probe COZ-DNB with yellow emission and a large Stokes shift for H2S detection. In probe COZ-DNB, the newly dye COZ-OH as a luminophore and the 2,4-dinitrophenyl ether moiety was chosen as a trigger group for H2S. Probe COZ-DNB itself displayed nearly non-fluorescent. However, COZ-DNB gave the remarkable fluorescence with an 83-fold enhancement in the yellow region after interaction with H2S. The sensing mechanism of COZ-DNB toward H2S was checked by means of UHPLC, HRMS and DFT/TD-DFT calculations. What's more, probe COZ-DNB also exhibited fast response (2.0 min), high sensitivity (65.0 nM), a large Stokes shift (161.0 nm), high stability and excellent selectivity. Furthermore, COZ-DNB was applied for imaging of exogenous and endogenous H2S in living HeLa cells and zebrafish with satisfactory performances. We anticipate COZ-DNB would be served as a potential tool for investigating the biological functions of H2S in pathological processes.

A fast-responsive fluorescent probe based on a styrylcoumarin dye for visualizing hydrogen sulfide in living MCF-7 cells and zebrafish.

As a vital antioxidant molecule, H2S can make an important contribution to regulating blood vessels and inhibiting apoptosis when present at an appropriate concentration. Higher levels of H2S can interfere with the physiological responses of the respiratory system and central nervous system carried out by mammalian cells. This is associated with many illnesses, such as diabetes, mental decline, cardiovascular diseases, and cancer. Therefore, the accurate measurement of H2S in organisms and the environment is of great significance for in-depth studies of the pathogenesis of related diseases. In this contribution, a new coumarin-carbazole-based fluorescent probe, COZ-DNBS, showing a rapid response and large Stokes shift was rationally devised and applied to effectively sense H2S in vivo and in vitro. Upon using the probe COZ-DNBS, the established fluorescent platform could detect H2S with excellent selectivity, showing 62-fold fluorescence enhancement, a fast-response time (<1 min), high sensitivity (38.6 nM), a large Stokes shift (173 nm), and bright-yellow emission. Importantly, the probe COZ-DNBS works well for monitoring levels of H2S in realistic samples, living MCF-7 cells, and zebrafish, showing that COZ-DNBS is a promising signaling tool for H2S detection in biosystems.