Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms.

BACKGROUND: Stroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood-brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment. RESULTS: Synaptic dysfunction occurs in various ways after stroke and includes the following: damage to neuronal structures, accumulation of pathologic proteins in the cell body, decreased fluidity and release of synaptic vesicles, disruption of mitochondrial transport in synapses, activation of synaptic phagocytosis by microglia/macrophages and astrocytes, and a reduction in synapse formation. CONCLUSIONS: This review summarizes the cellular and molecular mechanisms related to synapses and the protective effects of drugs or compounds and rehabilitation therapy on synapses in stroke according to recent research. Such an exploration will help to elucidate the relationship between stroke and synaptic damage and provide new insights into protecting synapses and restoring neurologic function.

Moyamoya syndrome may result from psoriasis: Four case reports.

BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

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.

Normobaric hyperoxia alleviates complement C3-mediated synaptic pruning and brain injury after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH-mediated brain damage, but the underlying mechanism still remains elusive. AIMS: In the present study, we investigated the effects of complement C3 on NBO-treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH-mediated brain injury. RESULTS: Hemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic-induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia-mediated synaptic pruning. CONCLUSIONS: Our results revealed that NBO exerts its neuroprotective effects by reducing C3-mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH.

Clinical Efficacy of Two Different Surgical Methods in the Treatment of Type IB Triangular Fibrocartilage Complex Injury.

Objective: This study aims to compare the clinical efficacy of two surgical methods, miniaturized anchor nail repair and transosseous tunnel repair, in treating type IB triangular fibrocartilage complex (TFCC) injuries, highlighting the importance of this comparison in optimizing surgical approaches. Methods: We retrospectively analyzed 91 patients with type IB TFCC injuries, treated from June 2020 to January 2022. Group A (43 patients) underwent miniaturized anchor nail repair, and Group B (48 patients) underwent transosseous tunnel repair, both under wrist arthroscopy. Follow-up for 12 months post-surgery included assessments of efficacy, Mayo wrist function score, range of motion, VAS score for ulnar wrist pain, grip strength, DASH score, PRWE, and postoperative complications, along with flow cytometry and lymphocyte immune subset assays. Results: Both groups showed significant improvements in wrist function, grip strength, and range of motion post-surgery, with reduced pain and disability scores. No significant differences in outcomes were observed between the groups. Conclusion: Both miniaturized anchor nail and transosseous tunnel repairs under wrist arthroscopy are effective in improving wrist function and alleviating symptoms in type IB TFCC injuries, with comparable clinical efficacy. These findings could significantly influence surgical practices and future research in TFCC injury management.

Development of a novel hybrid antimicrobial peptide for enhancing antimicrobial spectrum and potency against food-borne pathogens.

AIMS: To address the increasingly serious challenge of the transmission of foodbrone pathogens in the food chain. METHODS AND RESULTS: In this study, we employed rational design strategies, including truncation, amino acid substitution, and heterozygosity, to generate seven engineered peptides with α-helical structure, cationic property, and amphipathic characteristics based on the original Abhisin template. Among them, as the hybird antimicrobial peptide (AMP), AM exhibits exceptional stability, minimal toxicity, as well as broad-spectrum and potent antimicrobial activity against foodborne pathogens. Besides, it was observed that the electrostatic incorporation demonstrates by AM results in its primary targeting and disruption of the cell wall and membrane of Escherichia coli O157: H7 (EHEC) and methicillin-resistant Staphylococcus aureus (MRSA), resulting in membrane perforation and enhanced permeability. Additionally, AM effectively counteracts the deleterious effects of lipopolysaccharide, eradicating biofilms and ultimately inducing the demise of both food spoilage and pathogenic microorganisms. CONCLUSIONS: The findings highlight the significant potential of AM as a highly promising candidate for a novel food preservative and its great importance in the design and optimization of AMP-related agents.

Activation and Transformation of Methane on Boron-Doped Cobalt Oxide Cluster Cations CoBO2.

The cleavage of inert C-H bonds in methane at room temperature and the subsequent conversion into value-added products are quite challenging. Herein, the reactivity of boron-doped cobalt oxide cluster cations CoBO2+ toward methane under thermal collision conditions was studied by mass spectrometry experiments and quantum-chemical calculations. In this reaction, one H atom and the CH3 unit of methane were transformed separately to generate the product metaboric acid (HBO2) and one CoCH3+ ion, respectively. Theoretical calculations strongly suggest that a catalytic cycle can be completed by the recovery of CoBO2+ through the reaction of CoCH3+ with sodium perborate (NaBO3), and this reaction generates sodium methoxide (CH3ONa) as the other value-added product. This study shows that boron-doped cobalt oxide species are highly reactive to facilitate thermal methane transformation and may open a way to develop more effective approaches for methane (CH4) activation and conversion under mild conditions.

Mechanisms and therapeutic targets of mitophagy after intracerebral hemorrhage.

Mitochondria are dynamic organelles responsible for cellular energy production. In addition to regulating energy homeostasis, mitochondria are responsible for calcium homeostasis, clearance of damaged organelles, signaling, and cell survival in the context of injury and pathology. In stroke, the mechanisms underlying brain injury secondary to intracerebral hemorrhage are complex and involve cellular hypoxia, oxidative stress, inflammatory responses, and apoptosis. Recent studies have shown that mitochondrial damage and autophagy are essential for neuronal metabolism and functional recovery after intracerebral hemorrhage, and are closely related to inflammatory responses, oxidative stress, apoptosis, and other pathological processes. Because hypoxia and inflammatory responses can cause secondary damage after intracerebral hemorrhage, the restoration of mitochondrial function and timely clearance of damaged mitochondria have neuroprotective effects. Based on studies on mitochondrial autophagy (mitophagy), cellular inflammation, apoptosis, ferroptosis, the BNIP3 autophagy gene, pharmacological and other regulatory approaches, and normobaric oxygen (NBO) therapy, this article further explores the neuroprotective role of mitophagy after intracerebral hemorrhage.

Normobaric hyperoxia therapy in acute ischemic stroke: A literature review.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke. Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed. Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO. Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety.

Deeply analyzing dynamic fermentation of highland barley vinegar: Main physicochemical factors, key flavors, and dominate microorganisms.

Highland barley vinegar, as a solid-state fermentation-type vinegar emerged recently, is well-known in Qinghai-Tibet plateau area of China. This work aimed to explore the main physicochemical factors, key flavor volatile compounds, and dominate microorganisms of highland barley vinegar during fermentation. The results showed that the decrease trend of reducing sugar, pH and the increase trend of amino acid nitrogen were associated with the metabolism of dominate bacteria, especially Lactobacillus and Acetobacter. Totally, 35 volatile compounds mainly including 20 esters, 10 alcohols, 2 aldehydes, 1 ketone and 2 pyrazines and 7 organic acids were identified. Especially, isoamyl acetate, acetyl methyl carbinol, ethyl caprylate, 1,2-propanediol, 3-methyl-1-butanol and ethyl isovalerate with high odor activity values were confirmed as key aroma compounds. Meanwhile, the relative average abundance of bacteria at genus level decreased significantly as fermentation time goes on. Among these microbes, Lactobacillus were the dominate bacteria at alcohol fermentation stage, Lactobacillus and Acetobacter were dominate at acetic acid fermentation stage. Furthermore, the correlations between dominate bacteria and the key volatile compounds were revealed, which highlighted Lactobacillus and Acetobacter were significantly correlated with key volatile compounds (|r| > 0.5, P < 0.01). The fundings of this study provide insights into the flavor and assist to improve the production quality of highland barley vinegar.

Effect of microbial communities on flavor profile of Hakka rice wine throughout production.

Hakka rice wine is produced from grains by co-fermentation with abundant microbes in an open fermentation environment. Indigenous microbiota and enzymes convert the nutrients in grains into flavor compounds through enzymatic biochemical reactions and microbial metabolism. High-throughput sequencing technology revealed that non-Saccharomyces yeasts dominated the traditional fermentation process, with genera such as Kodamaea ohmeri, Candida orthopsilosis, and Trichosporon asteroides forming a dynamic community that highly correlated with the evolution of 80 volatile compounds in Hakka rice wine. Among the 104 volatile compounds detected by GC-MS, 22 aroma-active compounds with relative odor activity values (ROAV) > 1 were quantified, 11 of which made significant contributions (P < 0.05) to the overall aroma and were responsible for the sweet, grainy, and herbal aromas of Hakka rice wine.

Application of Artificial Dermis Combined With a Medial Flap From the Second Toe to Repair Degloving Injury of the Fingertip.

There is no standard technique for repairing degloving injuries of the fingertip. Nail bed flap transplantation is a common surgical technique to address this injury, but this procedure inevitably damages the donor site in the toe. This article describes a surgical technique that can restore the appearance of the injured fingernail and preserve the length and function of the injured finger without damaging the toenail.

Design of a mid-field wireless power transmission system for deep-tissue implants.

BACKGROUND: Implantable medical devices are being valued as one of the developments of wireless biomedical technology. OBJECTIVE: This paper presents a mid-field wireless power transmission (WPT) system, which is designed for implantable applications and operates at the 2.40-2.48 GHz band of Industrial, Scientific, and Medical (ISM). METHODS: A new compact transmitter structure is proposed, and a small 4-C planar ring antenna is designed as the receiving element. A measurement setup is fulfilled on porcine tissues to verify the power transmission system. RESULTS: The experimental results show that the operating bandwidth is 2.2-2.62 GHz and the transmission coefficient can reach -26.32 dB at a distance of 50 mm. The effects of tissue differences, placement depth, and different transmission distances were also measured. The displacement and deflection tolerances between the transmitter and the implant receiver also have good performance. In the safety standard of specific absorption rate, for the 1 W output power from the mid-field transmitter, the receiving power of the implantable antenna at the mid-field distance can reach 79.6 mW. CONCLUSION: With measurements of different implantation and transmission distance on pork, the mid-field power transmission efficiency is proven and shows the high performance of the system.

Association of plasma MMP-2 levels and prognosis of patients with intracerebral hemorrhage: a prospective cohort study.

Objective: The role of MMP-2 in patients with ICH is controversial and the impact of plasma MMP-2 level on clinical outcome is still unclear. Materials and methods: In this study, the peripheral venous blood was acquired from 93 patients with ICH and 88 healthy controls within 24 h of hospitalization and at enrollment. We retrospectively investigated plasma MMP-2 levels of patients and healthy controls. The edema volume, the NIHSS score, the GCS score, and mRS were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma MMP-2 levels with clinical outcomes. In addition, the plasma MMP-14 levels and complement C4 level were tested to explore the relationship with plasma MMP-2 level. Results: There was a significant reduction of plasma MMP-2 levels in ICH patients than that in healthy controls (38.02 ± 1.71 vs. 54.03 ± 2.15, p < 0.0001), and MMP-2 is negatively correlated with the edema volume (r = -0.2187, p < 0.05), NIHSS score (r = -0.2194, p < 0.05), blood leucocyte count (r = -0.2549, p = 0.012), and complement C4 level (r = -0.2723, p = 0.005). There is positive correlation between MMP-2 level and GCS score (r = 0.2451, p = 0.01) and MMP-14 level (r = 0.7013, p = 0.005). The multivariate analysis revealed that reduced plasma MMP-2 level is associated with elevated edema volume (OR = 0.2604, 95% CI [0.07 to 0.84], p = 0.02). Conclusion: The plasma MMP-2 level in patients with ICH is significantly lower than that of healthy controls, and plasma MMP-2 level may be a prognostic factor. Plasma MMP-2 levels are correlated with the clinical outcomes of patients and negatively correlated with blood leucocyte count and complement C4 level in patients with ICH.

Rational Design and Antimicrobial Potency Assessment of Abaecin Analogues.

The widespread and escalating emergence of multidrug resistance is now recognized as one of the most severe global threats to human health. To address the urgent issue of drug-resistant bacteria and the limitation of effective clinical treatments, antimicrobial peptides (AMPs) have been developed as promising substituents of conventional antibiotics. In this study, rational design strategies were employed to acquire seven cationic and α-helical engineered peptides based on the original template of Abaecin. After investigation, we found that AC7 (LLRRWKKLFKKIIRWPRPLPNPGH) demonstrated potent and broad-spectrum antimicrobial activity. Additionally, it demonstrated low cytotoxicity and hemolysis while maintaining good stability. Notably, AC7 displays the antibacterial mechanism with superior abilities in cell membrane disruption and potential DNA binding in vitro, as well as effectively disrupting biofilms. Moreover, the murine skin wound model infected with drug-resistant Pseudomonas aeruginosa was employed to evaluate the anti-infective efficacy and therapeutic potential of AC7. It was observed that AC7 displays a remarkable capacity to inhibit wound colonization, reduce levels of inflammatory cytokines (TNF-α) and inflammatory cells (white blood cells (WBC), monocytes (MONO), lymphocytes (LYMPH), neutrophils (GRAN)), promote the levels of IL-10 and VEGF, and enhance wound healing. Overall, these findings demonstrate the potential of AC7 as a viable alternative to traditional antibiotics.

Effect of continuous instant pressure drop treatment on the rheological properties and volatile flavor compounds of whole highland barley flour.

Continuous instant pressure drop (CIPD) treatment effectively reduces microbial contamination in whole highland barley flour (WHBF). Base on it, this study further investigated its effects on flour properties (especially rheological properties) and volatile compounds (VOCs) profile of WHBF, and compared it with that of ultraviolet-C (UV-C), ozone and hot air (HA) treatments. The results showed that the damaged starch content (6.0%) of CIPD-treated WHBF was increased, leading to a rough surface and partial aggregation of starch particle, thereby increasing the particle size (18.06 µm of D10, 261.46 µm of D50 and 534.44 µm of D90). Besides, CIPD treatment exerted a positive influence on the structure and rheological properties of WHBF, including an elevation in pasting temperature and viscosity. Notably, CIPD-treated WHBF exhibited higher storage modulus and loss modulus compared to the other three groups of sterilization treatments, contributing to the formulation of a better-defined and stable gel strength (tan δ = 0.38). UV-C and ozone, as cold sterilization techniques, also induced alterations in specific characteristics of WHBF. UV-C treatment led to changes in WHBF's crystallinity, while ozone treatment caused modifications in the secondary protein structure of WHBF. A total of 68 VOCs were identified in raw WHBF (including 3 acids, 19 alcohols, 25 aldehydes, 1 alkene, 8 esters, 2 ethers, 3 furans, and 7 ketones). The maximum flavor-contributing VOC in CIPD-treated WHBF remained dimethyl sulfide monomer (cabbage aroma), consistent with the raw WHBF. Conversely, in HA-treated WHBF, the maximum flavor-contributing VOC shifted to 2-furanmethanethiol monomer (roasted coffee aroma), altering the initial flavor presentation. These findings will provide strong support for the application of CIPD technology in the powdery foods industry.

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.