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China has the largest stroke population and at-risk population in the world. However, it has a lower thrombolytic therapy rate and longer onset-to-needle time/door-to-needle time for patients who had an acute stroke compared with developed countries, which might be due to redundant procedures or inefficient systems. Things are changing due to some new initiatives. Two years ago, a new emergency system in China, Stroke Emergency Map, was first launched as a regional emergency system in Shenzhen, the bustling metropolis just north of Hong Kong. As a result of the Stroke Emergency Map in Shenzhen, the number of thrombolytic cases increased in the last 2 years, from 568 to 809 annually. The Stroke Emergency Map, first pioneered in Shenzhen and now spreading to the rest of China, is a comprehensive and interdisciplinary system. The benefits are not just the immediate improvements in the acute stroke care because the continuous data collection and audit allows for improvements in logistics and future strategies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a predictive model of early neurological deterioration (END) in patients with acute ischemic stroke (AIS).Methods: The present retrospective cohort study considered patients with AIS who were admitted to a tertiary hospital in Shenzhen, China between January 2014 and December 2018. An increase of 2 points or more on the National Institute of Health Stroke Scale (NIHSS) within 7 days indicated END. We selected baseline clinical, laboratory, and neuroimaging variables to construct predictive models through multivariate logistic regression. The receiver operating characteristic curve and calibration plots were calculated.Results: A total of 391 patients with AIS were enrolled in the study. END was observed in 64 (16.4%) cases. A prediction model developed from the initial NIHSS score, middle cerebral artery stenosis, and carotid stenosis of≥ 50% showed good discriminative ability: area under the receiver operating characteristic curve, 0.870 (95%CI, 0.813-0.911); threshold, -1.570; specificity, 84.40%; sensitivity, 75.00%; positive predictive value, 48.48%; and a negative predictive value, 94.52%.Conclusion: Our predictive model developed from the initial NIHSS score, middle cerebral artery stenosis, and carotid stenosis of ≥ 50% could identify patients with AIS who were at risk of developing END. The model requires validation by larger studies performed at other institutions. [ABSTRACT FROM AUTHOR]

Background: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is an acute, potentially life-threatening, yet curable neuro-immunological disease characterized by spasms, muscular rigidity, and brainstem and autonomic dysfunction. The clinical features of glycine receptor (GlyR) antibody-positive PERM may be overlooked, particularly with some unusual symptoms.Case Presentation: A 52-year-old man was admitted to the hospital for evaluation of tension headache for 20 days and mild dysarthria. These symptoms were followed by panic, profuse sweating, severe dysarthria, dizziness, unsteady gait, and paroxysmal muscle spasms. Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal. The patient's condition steadily deteriorated. He repeatedly presented with rigidity, panic attacks, severe anxiety, paroxysmal inspiratory laryngeal stridor, cyanosis of the lips, and intractable epilepsy. Electromyography showed multiple myoclonic seizures, a single generalized tonic-clonic seizure, and a single generalized tonic seizure. Screening for autoimmune encephalitis antibodies revealed anti-GlyR antibodies in his cerebrospinal fluid. Immunomodulatory pulse therapy with steroids and immunoglobulin resulted in expeditious improvement of the symptoms within 2 weeks, and a follow-up at 5 weeks showed consistent clinical improvement.Conclusion: Our case highlights that inspiratory laryngeal stridor is an important symptom of PERM. Our observation widens the spectrum of the clinical presentation of anti-GlyR antibody-positive PERM, where early identification is a key to improving prognosis. [ABSTRACT FROM AUTHOR]

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD‐associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD‐associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD. [ABSTRACT FROM AUTHOR]

To investigate characteristics of intra- and extracranial arterial culprit plaques between patients with single infarct and multiple-infarcts by a head-neck combined high resolution magnetic resonance vessel wall imaging (HR-MRVWI). Forty-three patients with recent ischemic stroke due to large artery atherosclerosis were enrolled. The head-neck combined HR-MRVWI was performed in all patients both pre- and post-contrast administration. Based on diffusion weighted imaging findings, patients were divided into single-infarction and multiple-infarction groups. For patients with anterior circulation ischemic stroke, they were also divided into perforating artery infarction (PAI) and non-PAI groups. Patient demographics, number and location of culprit plaques, artery stenosis percentage, intraplaque hemorrhage, and plaque enhancement were evaluated and compared between single-infarction and multiple-infarction groups, as well as between PAI and non-PAI groups. A total of 83 culprit plaques were identified. The artery stenosis degree was more severe and plaque enhancement more prominent in multiple-infarction group than in single-infarction group. Patients with multiple infarcts also had more culprit plaques per patient than those with single infarct, which contributed to the occurrence of multiple infarcts. For comparison of PAI and non-PAI groups, a higher artery stenosis percentage was observed in non-PAI group, and patients with non-PAI had more culprit plaques per patient, which contributed to a variety of infarct manifestations. A higher stenosis grade and higher number of culprit plaques seem to be associated with a higher number of cerebral infarcts in patients with large artery atherosclerosis. [ABSTRACT FROM AUTHOR]

Emerging evidence shows that perivascular adipose tissue (PVAT) is crucially involved in inflammation and cardiovascular diseases. However, controversial results have been reported regarding the effect of PVAT in atherosclerosis. This study aimed to determine the role of PVAT in disturbed blood flow (d-flow)-induced carotid plaque formation. ApoE −/− male mice underwent partial carotid ligation (PCL) to induce d-flow in the left carotid artery (LCA) and were fed a high-fat diet for 2 weeks. Oil Red O and hematoxylin and eosin stains were used to determine adipose tissue. Thoracic PVAT from ApoE −/− or wild-type female mice were transplanted to the LCA of PCL-treated ApoE −/− mice. Carotid arteries were stained with Sudan IV to detect atherosclerotic lesions. Quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence staining were performed to assess macrophage infiltration. By 2 weeks of the high-fat diet after PCL surgery, de novo adipose tissue was formed around the ligated LCA, where atherosclerotic plaques were also observed. Quantitative real-time reverse transcription polymerase chain reaction analysis of the newly formed PVAT revealed a similar transcription profile to native PVAT. Treatment with bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor γ inhibitor, diminished PVAT formation but increased plaque size and macrophage infiltration. Transplantation of thoracic PVAT from wild-type mice (PVAT-T WT ) rather than from ApoE −/− mice (PVAT-T ApoE−/− ) nearly abrogated LCA plaque macrophage content without affecting plaque size. Mechanistically, PVAT-T ApoE−/− showed higher messenger RNA levels of inflammatory cytokines compared with PVAT-T WT . Our findings suggest that regulated PVAT formation may confer protection against atherosclerosis-prone shear stress, probably through attenuation of focal inflammation. Clinical studies demonstrated that perivascular adipose tissue (PVAT) is anatomically close to atherosclerotic plaques and associated with plaque burden and vascular calcification. Here we showed a beneficial role of PVAT in atherosclerosis protection, suggesting the potential value of PVAT transplantation in disease control and prevention. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease characterized by systemic inflammation, affecting both articular and extra-articular structures. This condition results in inflammation of joints and synovial membranes, accompanied by the development of systemic comorbidities. Despite extensive research, the precise pathogenic mechanisms responsible for RA have yet to be completely understood. RNA methylation, a burgeoning epigenetic alteration, assumes a pivotal function in the regulation of a myriad of biological phenomena, encompassing immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. The N6-methyladenosine (m6A) modification is the most prevalent among the various RNA modifications found in mammalian mRNA. Recent studies have provided evidence of the significant role played by m6A modification in the pathophysiological progression of RA. This review aims to provide a comprehensive analysis of the progress made in research focused on m6A modification in the context of RA, consolidate the underlying mechanisms involved in m6A modification during the initiation of RA and discuss the potential of targeting m6A modification as a viable therapeutic approach for RA. • m6A levels and expression of methylation-related enzymes alters in RA. • m6A levels and methylation-related enzymes are related to disease activities in RA. • methylation-related enzymes play crucial roles in PBMCs, macrophage, and FLSs in RA. [ABSTRACT FROM AUTHOR]

Objectives: To compare visualization of joint intracranial and carotid vessel walls between 5× compressed sensing accelerated three-dimensional DANTE-SPACE sequence (CS VWI) acquired in 5 min and the same sequence accelerated by 2.7× parallel imaging (PI VWI) which takes 9–10 min currently. Methods: Following institutional review board approval and informed consent, 28 subjects including 20 stroke patients underwent PI and CS VWI examinations with an acquired spatial resolution of isotropic 0.55 mm and joint coverage of intracranial and carotid arteries. Quantitative wall thickness measurements of CS VWI and PI VWI were compared on healthy volunteers and patients with wall thickening respectively. Subjective wall visualizations of the two VWI methods on patients were scored by two radiologists blindly and independently using a 4-point scale followed by inter-rater reproducibility analysis. Results: Linear regression analysis of wall thickness measurements showed excellent agreement between CS VWI and PI VWI in both healthy volunteers (r = 0.99) and stroke patients with wall thickening (r = 0.99). Subjective wall visualization score of CS VWI was slightly lower than PI VWI (3.13 ± 0.41 vs. 3.31 ± 0.79) but still had good diagnostic quality (> 3 based on a 4-point scale). The two radiologists' scores agreed excellently, evidenced by the intraclass correlation coefficient (ICC) values being higher than 0.75 (p < 0.001). Conclusions: Compressed sensing expedients joint intracranial and carotid VWI acquired at an isotropic resolution of 0.55 mm in 5 min without compromising quantitative vessel wall thickness measurement or diagnostic wall visualization. Key Points: • CS VWI facilitates comprehensive visualization of intracranial and carotid vessel walls at an acquired isotropic resolution of 0.55 mm in a single 5-min scan. • CS VWI affords comparable vessel wall visualization and morphology measurement as PI VWI with a shortened acquisition time by 45%. • CS VWI alleviates the intensive trade-off between imaging resolution and scan time, and benefits the scan efficiency, motion robustness, and patient tolerance of high-resolution joint intracranial and carotid VWI. [ABSTRACT FROM AUTHOR]

Background: Subacute combined degeneration (SCD) is a demyelinating disease characterized by vitamin B12 deficiency related segmental degeneration of the dorsal or lateral columns of the spinal cord. However, few cases have been reported as a comorbidity of SCD and neuromyelitis optica spectrum disease (NMOSD).Case Presentation: Herein, we describe a female patient (61-year-old) who had sensory deficits, paresthesia, and weakness of the distal extremities for over 2 months. She then received an initial diagnosis of SCD with typical inverted "V-sigh" hyperintensities over the posterior aspect of the spinal cord in magnetic resonance imaging (MRI - T2-weighted imaging), as well as megaloblastic anaemia in blood examinations. From the past history, there was no evidence of a dietary deficiency or gastric abnormalities. However, traditional treatment with vitamin B12 supplementation was ineffective. Hence, a demyelinating antibody examination showed that she had antibodies targeting aquaporin 4 (AQP4) in both the cerebrospinal fluid and serum, leading to the diagnosis of NMOSD. Her clinical symptoms were obviously improved after treatment with intravenous glucocorticoids.Conclusion: People who have nutritional deficiency or altered gastrointestinal function are more likely to develop SCD. This case raises the awareness that the poor therapeutic effects of simple vitamin B12 supplementation could be explained by immunoreactions against AQP4. A better recognition will be of great importance for the correct diagnosis of the comorbidity, as well as for essential treatment and even a better prognosis. [ABSTRACT FROM AUTHOR]

• We studied effects of primed and repopulated microglia on post-ischemic brain injury. • Microglial replacement ameliorates neurodeficits and neuroinflammation post-ischemic stroke. • Newly repopulating microglia may play a protective role in aged mice. • Targeting microglia could be a promising therapeutic strategy for ischemic stroke. As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice. We replaced primed microglia with newly repopulated microglia through pharmacological administration and withdrawal of the colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397. Further, we performed a series of behavioral tests and flow cytometry in mouse models of middle cerebral artery occlusion (MCAO) to study the effects of microglial replacement on ischemic injury in the aged brain. With depletion and subsequent repopulation of microglia in MCAO mice, microglial replacement in aged mice improved neurological function and decreased brain infarction. This protective effect was accompanied by the reduction of peripheral immune cells infiltrating into brains. We showed that the repopulated microglia expressed elevated neuroprotective factors (including Cluster of Differentiation 206, transforming growth factor-β, and interleukin-10) and diminished expression of inflammatory markers (including Cluster of Differentiation 86, interleukin-6, and tumor necrosis factor α). Moreover, microglial replacement protected the blood–brain barrier and relieved neuronal death in aged mice subjected to 60 min of MCAO. These results imply that the replacement of microglia in the aged brain may alleviate brain damage and neuroinflammation, and therefore, ischemic brain damage. Thus, targeting microglia could be a promising therapeutic strategy for ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Existing data suggest that cerebral autoregulation (CA) varies among different subtypes of ischaemic stroke. CA is globally impaired in patients with small artery occlusion (SAO). However, the factors influencing CA impairment in patients remains to be elucidated.Methods: Stroke patients with SAO who underwent brain magnetic resonance imaging (MRI) were prospectively studied. Within 7 days after stroke onset, CA was recorded from the middle cerebral artery blood flow velocity and arterial blood pressure was simultaneously measured. Transfer function analysis was used to derive CA parameters, including gain and phase. Clinical characteristics, mean arterial pressure (MAP), biochemical findings, and cerebral small vessel disease (CSVD) markers on MRI were assessed in each patient. Factors associated with CA parameters were investigated. Univariate and multivariate linear regression analyses were conducted to determine the relationship between clinical factors and CA parameters.Results: Sixty-three SAO patients (age, 56.3 ± 9.9 years; 55 men) were enrolled in the study. In the multiple linear regression analysis, after controlling for relevant clinical factors, MAP on admission (ipsilateral OR = 0.99 and contralateral OR = 0.99, both P < 0.005) was a significant independent predictor of bilateral gain. MAP > 105 mmHg on admission (OR = 0.77, P = 0.019) was significantly associated with ipsilateral gain. Diabetes mellitus was a significant predictive factor for bilateral gain (ipsilateral OR = 1.32 and contralateral OR = 1.22, both P < 0.005). No correlations were found between CA parameters and CSVD characteristics.Conclusion: In SAO-related ischaemic stroke, patients with MAP > 105 mmHg on admission tended to have better ipsilateral CA. Diabetes mellitus appears to be an independent risk factor for CA impairment in patients with SAO-related stroke. CSVD may not be the main factor affecting bilateral CA in patients with SAO. [ABSTRACT FROM AUTHOR]

The hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN1) is predominantly located in key regions associated with epilepsy, such as the neocortex and hippocampus. Under normal physiological conditions, HCN1 plays a crucial role in the excitatory and inhibitory regulation of neuronal networks. In temporal lobe epilepsy, the expression of HCN1 is decreased in the hippocampi of both animal models and patients. However, whether HCN1 expression changes during epileptogenesis preceding spontaneous seizures remains unclear. The aim of this study was to determine whether the expression of HCN1 is altered during the epileptic prodromal phase, thereby providing evidence for its role in epileptogenesis. We utilized a cobalt wire-induced rat epilepsy model to observe changes in HCN1 during epileptogenesis and epilepsy. Additionally, we also compared HCN1 alterations in epileptogenic tissues between cobalt wire- and pilocarpine-induced epilepsy rat models. Long-term video EEG recordings were used to confirm seizures development. Transcriptional changes, translation, and distribution of HCN1 were assessed using high-throughput transcriptome sequencing, total protein extraction, membrane and cytoplasmic protein fractionation, western blotting, immunohistochemistry, and immunofluorescence techniques. In the cobalt wire-induced rat epilepsy model during the epileptogenesis phase, total HCN1 mRNA and protein levels were downregulated. Specifically, the membrane expression of HCN1 was decreased, whereas cytoplasmic HCN1 expression showed no significant change. The distribution of HCN1 in the distal dendrites of neurons decreased. During the epilepsy period, similar HCN1 alterations were observed in the neocortex of rats with cobalt wire-induced epilepsy and hippocampus of rats with lithium pilocarpine-induced epilepsy, including downregulation of mRNA levels, decreased total protein expression, decreased membrane expression, and decreased distal dendrite expression. Alterations in HCN1 expression and distribution are involved in epileptogenesis beyond their association with seizure occurrence. Similarities in HCN1 alterations observed in epileptogenesis-related tissues from different models suggest a shared pathophysiological pathway in epileptogenesis involving HCN1 dysregulation. Therefore, the upregulation of HCN1 expression in neurons, maintenance of the HCN1 membrane, and distal dendrite distribution in neurons may represent promising disease-modifying strategies in epilepsy. • HCN1 alterations in expression and distribution are involved in epileptogenesis rather than being a consequence of seizures. • Being downregulated in two types of epilepsy models suggesting HCN1's involvement in common pathological pathway of epilepsy. • The upregulation of HCN1 expression on membrane and distal dendrite in neurons may be a promising disease-modifying strategy. [ABSTRACT FROM AUTHOR]

With the implementation of energy saving and carbon reduction, the quantitative analysis of solar energy spectral characteristics has been paid more and more attention. Currently, the international test standards provide a spectral distribution with a large span between different wavebands, which makes it difficult to meet the needs of special spectral wavebands. In this paper, based on the principle of spectral splitting, the spectral distribution of solar radiation models (SDSR models) is proposed, and the differences in the spectral distributions of natural outdoor and artificial indoor light sources are evaluated. Firstly, the differences in PV module output power between the outdoor light sources and indoor artificial light sources are assessed in terms of inclination angle and solar radiation, respectively. Secondly, based on that difference, the influencing factors of the spectral distribution of solar radiation are investigated, and the SDSR models of different wavelengths is established based on spectral analysis results. Finally, based on the established SDSR models, the spectral distribution modified models (SDM models) for different inclination angles under artificial light sources is proposed. By comparing the calculated values of the SDM models with the measured data, the calculated values of the model are close to the measured data at different incidence angles. The SDM models proposed in this paper shortens the gap between the spectral distribution of the artificial light source and the outdoor natural light source, and reveal the influence mechanism of the difference in the output power of indoor and outdoor PV modules from the perspective of the spectral distribution. The results can provide guidance for the spectral distribution of solar radiation and the quantitative modification of the artificial light source. • The difference in the output power of PV modules between solar radiation and artificial light sources is evaluated. • The effect of inclination angle and orientation on the spectral distribution of solar radiation is investigated. • The spectral distribution of solar radiation model (SDSR model) at different wavelengths is developed. • The spectral modification models for different wavelengths of of artificial light sources are developed. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (AE) is a common cause of nonviral infectious encephalitis, which can be triggered by herpes simplex virus infection. Previous studies have shown that approximately 27% of herpes simplex encephalitis (HSE) patients produce anti-NMDAR antibodies within 3 months. Immunotherapy is recommended in this situation, but some symptoms usually remain in the 1-year follow-up. Case presentation: A previously healthy 23-year-old Chinese young woman developed epileptic attack followed by psychiatric symptoms of confusion and irritation as well as cognitive deficits. Brain MRI showed hyperintense lesions of the right temporal lobe on DWI and T2 without contrast enhancement effects. Twenty-one days of acyclovir was administered based on the primary diagnosis of HSE. The anti-NMDAR antibody (IgG) was detected positively on day 11 after disease onset. She had improved cognitive function but suffered another grand mal epilepsy after the first course of intravenous immunoglobulin (IVIG) therapy combined with 1000 mg intravenous methylprednisolone. After discussion, another course of IVIG was started for 5 days. Her symptoms were well controlled with only mild cognitive deficits at the 1-year follow-up (mRS = 1). Conclusions: Our case indicated that anti-NMDAR antibodies could develop earlier after HSE compared with previous data from adults. We suggested detecting AE antibodies simultaneously with each CSF analysis. Meanwhile, the second course of IVIG therapy was reasonable when symptoms were not controlled after the first course of IVIG combined with IV steroid treatment. [ABSTRACT FROM AUTHOR]

Abstract The efficacy of neurofeedback is a point of great controversy, because a certain proportion of users cannot properly regulate their brain activities and thereby fail to benefit from neurofeedback. To address the neurofeedback inefficacy problem, the present study is aimed to design and implement a new neurofeedback system that can more effectively and consistently regulate users' brain activities than the conventional way of training users to voluntarily regulate brain activities. The new neurofeedback system delivers external visual stimuli continuously at a specific alpha phase, which is real-time decoded from ongoing alpha wave, to regulate the alpha wave. Experimental results show that the proposed training-free externally-regulated neurofeedback (ER-NF) system can achieve consistent (effective in almost all sessions for almost all users), flexible (either increasing or decreasing peak alpha frequency and alpha power), and immediate (taking or losing effect immediately after stimulation is on or off) modulation effects on alpha wave. Therefore, the ER-NF system holds great potential to be able to more reliably and flexibly modulate cognition and behavior. [ABSTRACT FROM AUTHOR]

• Models of the impact of indoor thermal environment on MDPC thermal comfort were established. • The effect of activity levels on thermal comfort in MDPC was quantitatively analyzed. • The relationship among temperature and humidity in different parts and working time and intensity was established. • The acceptable regions inside MDPC were proposed by the enthalpy-humidity chart. With the outbreak of infectious diseases such as Corona Virus Disease 2019, medical staff work intensively in isolated plots, medical disposable protective clothing (MDPC) has poor air condition and humidity permeability, which seriously reduces the thermal comfort of medical staff. In this paper, the effect of indoor thermal environment and activity levels on thermal comfort inside MDPC was studied by experiment. Five parts of the body were measured inside MDPC and the appropriate movements were chosen to simulate different levels of labor intensity. Meanwhile, physiological parameters and subjective thermal sensation were statistically analyzed. The results showed the influence range of different indoor temperatures on the temperature and humidity inside MDPC was about 1 °C and 10 %, respectively; it indicated that the environment inside MDPC could be improved by reducing indoor temperature, that is, a cross intelligent adjustment mode was proposed. The effect of labor intensity on the temperature inside MDPC was significantly less than that of humidity. Within 20 min, the humidity changes under moderate and heavy labor intensity were even more than 10 %, and the subjective discomfort threshold of the subjects increased by nearly 50 %. Furthermore, the maximum benefit could be obtained by concentrating cooling on back, forehead, chest and upper arm. Theoretical models of working time, labor intensity, and temperature and humidity inside MDPC under different indoor temperatures and different parts were given. In addition, acceptable regions inside MDPC which were approximately parallelogram in the enthalpy-humidity chart. These conclusions could be a reference for future thermal comfort inside MDPC research. [ABSTRACT FROM AUTHOR]

• Coordination polymer nanozymes show pH-dependent peroxidase-like property. • The FNDs achieve high antibacterial activity against E. coli , S. aureus and MRSA. • Developing a novel FNDs-integrated colorimetric microneedle patch. • The FNDs-MNs can recognize normal wounds and bacteria infected wounds. • The FNDs-MNs can efficiently treat MRSA infected wounds. Biomedical patches are playing an indispensable role in wound infection management. Current efforts have focused on designing smart patches with both treating and sensing abilities to recognize wound infections and kill bacteria efficiently. Here, we present intelligent colorimetric microneedle patches (MNs) integrated with Fe ion-gallic acid coordination polymer nanodots (FNDs) for on-demand treatment and real-time report of infected wounds. Such FNDs are fabricated by coordination reactions among polyvinylpyrrolidone (PVP), gallic acid, and Fe ion, and are loaded inside the MNs using a template replication method (FNDs-MNs). Benefitting from the pH-dependent peroxidase mimic activity of the FNDs, the integrated MNs can catalyze H 2 O 2 to generate much more OH at the acidic condition for bacteria killing. Besides, these FNDs-MNs also possess pH and H 2 O 2 dependent color changes, and thus can timely reflect the wound repair and infection states. During the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infected wounds in mice, the FNDs-MNs exhibit obvious color changes at infected stages and achieve on-demand therapeutic effects. Thus, it is believed that such FNDs-MNs have great potentials for efficient wound infection management and will find wide applications in wound care. [ABSTRACT FROM AUTHOR]

• As far as we know, we are the first to assess the carotid plaque occurrence using a machine learning method. • High accuracy is achieved in carotid plaque prediction, even when data are missing. • The underlying causal reasoning for the machine decisions is explainable, enabling subclinical interventions.The proposed method is a promising tool for large-scale screening of stroke. The identification of carotid plaque, one of the most crucial tasks in stroke screening, is of great significance in the assessment of subclinical atherosclerosis and preventing the onset of stroke. However, traditional ultrasound examination is not prevalent or cost-effective for asymptomatic people, particularly low-income individuals in rural areas. Thus, it is necessary to develop an accurate and explainable model for early identification of the risk of plaque prevalence that can help in the primary prevention of stroke. We developed an ensemble learning method to predict the occurrence of carotid plaques. A dataset comprising 1440 subjects (50% with plaques and 50% without plaques) and ten-fold cross-validation were utilized to evaluate the model performance. Four machine learning methods (extreme gradient boosting (XGBoost), gradient boosting decision tree, random forest, and support vector machine) were evaluated. Subsequently, the interpretability of the XGBoost model, which provided the best performance, was analyzed from three aspects: feature importance, feature effect on prediction model, and feature effect on prediction decision for a specific subject. The XGBoost algorithm provided the best performance (sensitivity: 0.8678, specificity: 0.8592, accuracy: 0.8632, F1 score: 0.8621, area under the curve: 0.8635) in carotid plaque prediction and also had excellent performance under missing data circumstances. Further, interpretability analysis showed that the decisions of the XGBoost model were highly congruent with clinical knowledge. The model results are superior to those of state-of-the-art methods. Thus, it is a promising carotid plaque prediction tool that could be used in the primary prevention of stroke. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a prominent contributor to global morbidity and mortality rates. The intricate and diverse mechanisms underlying ischemia-reperfusion injury remain poorly comprehended. RNA methylation, an emerging epigenetic modification, plays a crucial role in regulating numerous biological processes, including immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. Among the various RNA modifications, N6-methyladenosine (m6A) modification stands as the most prevalent in mammalian mRNA. Recent studies have demonstrated the crucial involvement of m6A modification in the pathophysiological progression of ischemic stroke. This review aims to elucidate the advancements in ischemic stroke-specific investigations pertaining to m6A modification, consolidate the underlying mechanisms implicated in the participation of m6A modification during the onset of ischemic stroke, and deliberate on the potential of m6A modification as a viable therapeutic target for ischemic stroke., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Unawareness of the risk factors is one of the most important issues that need to be settled for stroke prevention. We aimed to evaluate the awareness of risk factors for cerebrovascular diseases (CVDs) among acute ischemic stroke patients and to investigate the characteristics of patients who were unaware of their risk factors in Shenzhen, China., Methods: Registered data on awareness of CVD risk factors of patients with confirmed acute ischemic stroke (AIS) from June 2020 to December 2022 were analyzed in May 2023. The data were extracted from the database of Shenzhen Quality Control Center for Management of Cerebrovascular Diseases., Results: Totally, there were 5147 AIS patients with complete data eligible for this study. AIS patients' awareness regarding existing hypertension, diabetes, dyslipidemia, and atrial fibrillation (AF) was 76.1%, 76.2%, 24.2%, and 53.4%, respectively. Patients who were lack of awareness of the CVD risk factors were more likely to be males, individuals with younger ages, and those without medical insurance or a CVD history., Conclusions: The overall awareness of the CVD risk factors was suboptimal among AIS patients in Shenzhen, especially for the existing dyslipidemia. The health education of AIS should be further improved in males as well as individuals without medical insurance or any CVD histories. Age was an independent factor associated with the lack of awareness of the CVD risk factors. The stroke screening program should be extended to younger people.

Background: Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients., Methods: Eighty-nine pairs including 100 men and 78 women matched by sex and age were recruited. Each pair included a hypertensive patient within 48h of AIS onset and a hypertensive patient without stroke. Six circulating fatty acids were methylated before concentration determination which was repeated twice with percent recovery estimated., Results: There were differences in educational level (P = 0.002) and occupation (P < 0.001) between stroke and non-stroke participants. All the 6 fatty acid levels were higher in non-stroke participants (P = 0.017 for palmitoleic acid, 0.001 for palmitic acid, <0.001 for linoleic acid, <0.001 for behenic acid, <0.001 for nervonic acid and 0.002 for lignoceric acid). In logistic regression analysis, AIS was inversely associated with fatty acid levels except for lignoceric acid. After adjustment for education and occupation, the palmitoleic acid and palmitic acid levels were no longer inversely associated with AIS. After further adjustment for systolic blood pressure, smoking, drinking, total cholesterol and triglyceride, the inverse associations of linoleic acid (OR = 0.965, 95%CI = 0.942-0.990, P = 0.005), behenic acid (OR = 0.778, 95%CI = 0.664-0.939, P = 0.009), nervonic acid (OR = 0.323, 95%CI = 0.121-0.860, P = 0.024) with AIS remained significant., Conclusions: Circulating fatty acids except lignoceric acid were inversely associated with AIS. Both USFAs and SFAs may have beneficial effect on stroke prevention in hypertensive population., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Whether minor ischemic stroke (MIS) patients can benefit from intravenous thrombolysis (IVT) remains controversial. The association between the efficacy of IVT and baseline National Institute of Health Stroke Scale (NIHSS) score is unclear in MIS, while the association in moderate and severe stroke is known. This study aimed to explore the effect of IVT in patients with MIS and analyze its efficacy in patients with different baseline NIHSS scores., Methods: Patients with a NIHSS score ≤5 within 4.5 h of stroke onset were screened in 32 centers. Patients with and without IVT were matched to a ratio of 1:1 with propensity scores. An excellent outcome was defined as a modified Rankin Scale (mRS) score ≤1 at three months after stroke onset. Safety outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Multivariate analysis was used to compute the adjusted odds ratio (OR) for excellent outcomes. The effect of IVT was further analyzed in subgroups according to the baseline NIHSS score., Results: Of the 23,853 screened, 3336 patients with MIS who arrived at the hospital within 4.5 h of onset were included. The 1163 patients treated with IVT were matched with 1163 patients without IVT. IVT in minor strokes generated an adjusted OR of 1.38 (95% CI: 1.09-1.75, p  = 0.009) for excellent outcomes. There were no significant differences in mortality (0.17% vs. 0.09%, p =  1.000) and sICH (0.69% vs. 0.86%, p =  0.813) between patients with and without IVT. Subgroup analysis showed that there was no significant effect of IVT in the baseline NIHSS 0-1 or 2-3 subgroups, with adjusted OR of 0.816 (95% CI 0.437-1.53, p  = 0.525) and1.22 (95% CI 0.845-1.77, p  = 0.287), respectively. In patients with NIHSS score of 4-5, IVT was significantly effective, with an adjusted OR of 1.53 (95% CI 1.02-2.30, p  = 0.038)., Conclusion: IVT can improve MIS outcomes. The risks of sICH and mortality did not increase, especially in patients with NIHSS scores 4 to 5, who could benefit from IVT significantly.

Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis. Consequently, these damages are associated with an increased risk of developing severe cardiovascular outcomes including stroke, myocardial infarction, heart failure, and coronary heart disease. Among all the risk factors associated with cardiovascular disease, high blood pressure emerges as the most prominent. However, conventional resting BP measurement methods such as auscultatory or oscillometric methods may fail to identify many individuals with asymptomatic high BP. Recently, exercise BP has emerged as a valuable diagnostic tool for identifying real (high) blood pressure levels and assessing underlying cardiovascular risk, in addition to resting BP measurements in adults. Furthermore, numerous established factors, such as low cardiorespiratory fitness and high body fatness, have been confirmed to contribute to exercise BP and the associated cardiovascular risk. Modifying these factors may help reduce high exercise BP and, consequently, alleviate the burden of cardiovascular disease. A significant body of evidence has demonstrated cardiovascular disease in later life have their origins in early life. Children and adolescents with these cardiovascular risk factors also possess a greater propensity to develop cardiovascular diseases later in life. Nevertheless, the majority of previous studies on the clinical utility of exercise BP have been conducted in middle-to-older aged populations, often with pre-existing clinical conditions. Therefore, there is a need to investigate further of the factors influencing exercise BP in adolescence and its association with cardiovascular risk in early life. Our previously published work showed that exercise BP is a potential useful method to detect adolescents with increased cardiovascular risk. Children and adolescents with cardiovascular risk factors are more likely to develop cardiovascular diseases later in life. However, previous studies on the clinical utility of exercise BP have largely focused on middle-to-older aged populations with pre-existing clinical conditions. Therefore, there is a need to investigate further the factors influencing exercise BP in adolescence and its association with future cardiovascular risk. Our previous studies, which focused on exercise BP measured at submaximal intensity, have shown that exercise BP is a potentially useful method for identifying adolescents at increased cardiovascular risk. Our previous findings suggest that improving cardio-respiratory fitness and reducing body fatness may help to reduce the risk of developing cardiovascular disease and improve overall cardiovascular health. These findings have important implications for the development of effective prevention and early detection strategies, which can contribute to improved public health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Li, Liu, Xu, Feng and Ren.)

Background: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population., Methods: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml., Results: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized β [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3., Conclusions: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease., (© 2024. The Author(s).)

Background: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors., Methods: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay., Results: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908)., Conclusions: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints., (© 2024. The Author(s).)

Background: In the field of medical imaging, the rapid rise of convolutional neural networks (CNNs) has presented significant opportunities for conserving healthcare resources. However, with the wide spread application of CNNs, several challenges have emerged, such as enormous data annotation costs, difficulties in ensuring user privacy and security, weak model interpretability, and the consumption of substantial computational resources. The fundamental challenge lies in optimizing and seamlessly integrating CNN technology to enhance the precision and efficiency of medical diagnosis., Methods: This study sought to provide a comprehensive bibliometric overview of current research on the application of CNNs in medical imaging. Initially, bibliometric methods were used to calculate the frequency statistics, and perform the cluster analysis and the co-citation analysis of countries, institutions, authors, keywords, and references. Subsequently, the latent Dirichlet allocation (LDA) method was employed for the topic modeling of the literature. Next, an in-depth analysis of the topics was conducted, and the topics in the medical field, technical aspects, and trends in topic evolution were summarized. Finally, by integrating the bibliometrics and LDA results, the developmental trajectory, milestones, and future directions in this field were outlined., Results: A data set containing 6,310 articles in this field published from January 2013 to December 2023 was complied. With a total of 55,538 articles, the United States led in terms of the citation count, while in terms of the publication volume, China led with 2,385 articles. Harvard University emerged as the most influential institution, boasting an average of 69.92 citations per article. Within the realm of CNNs, residual neural network (ResNet) and U-Net stood out, receiving 1,602 and 1,419 citations, respectively, which highlights the significant attention these models have received. The impact of coronavirus disease 2019 (COVID-19) was unmistakable, as reflected by the publication of 597 articles, making it a focal point of research. Additionally, among various disease topics, with 290 articles, brain-related research was the most prevalent. Computed tomography (CT) imaging dominated the research landscape, representing 73% of the 30 different topics., Conclusions: Over the past 11 years, CNN-related research in medical imaging has grown exponentially. The findings of the present study provide insights into the field's status and research hotspots. In addition, this article meticulously chronicled the development of CNNs and highlighted key milestones, starting with LeNet in 1989, followed by a challenging 20-year exploration period, and culminating in the breakthrough moment with AlexNet in 2012. Finally, this article explored recent advancements in CNN technology, including semi-supervised learning, efficient learning, trustworthy artificial intelligence (AI), and federated learning methods, and also addressed challenges related to data annotation costs, diagnostic efficiency, model performance, and data privacy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1600/coif). All authors report that this work was supported by the National Natural Science Foundation of China (No. 61972235), the Natural Science Foundation of Shandong Province (No. ZR2018MA004), the Immersion Technology and Evaluation Shandong Engineering Research Center (2022), and the Immersive Smart Devices for Health Care System R&D and Industrial Application Innovation Platform (2022), the Develop a Device for Detecting Trace Pathogenic Microorganisms in Environmental Water Samples Based on Plasma Surface Resonance Technology (2023), and the Modelling of Disease Knowledge Map and Intelligence Information Based on Bibliomics (2023). The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Context: The coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease., Objective: The aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension., Methods: A cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis., Results: The prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male ( B = 1.430, OR = 4.179) and MTHFR (TT) ( B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender ( B = -2.784, P = 0.004), MTHFR genotypes ( B = 1.410, P = 0.005), and FA levels ( B = -0.136, P = 0.030)., Conclusion: The high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Feng, Zhang, Li, Chi and Ren.)

Background: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment., Case Presentation: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion., Conclusions: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research., (© 2024. The Author(s).)

Rationale: Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) represents a demyelinating neurological syndrome characterized by the presence of serum IgG antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG). Concurrently, giant cell arteritis (GCA) constitutes a systemic autoimmune vasculitis., Patient Concerns: In this case, we describe an elderly female patient who presented with the sudden onset of a severe headache, unilateral blindness, and clinical manifestations resembling those of GCA., Diagnosis: Upon conducting a comprehensive analysis of serum antibodies, the diagnosis of MOGAD was established due to the presence of detectable serum MOG-IgG., Interventions: Subsequently, the patient was administered intravenous methylprednisolone therapy, commencing 27 days after the initial onset of symptoms., Outcomes: It is noteworthy that patients afflicted by MOGAD typically manifest severe visual impairment, which, in many instances, exhibits significant improvement following immunotherapeutic interventions. However, this particular patient did not experience any amelioration in visual function despite glucocorticoid therapy., Lessons: This unique case illustrates that the clinical presentation resembling GCA may precede the inaugural manifestation of MOGAD. This suggests the possibility of immune-mediated arterial involvement. The significance of glucocorticoid therapy in the context of immune-related diseases warrants further scrutiny, particularly in cases where MOG-IgG screening should be promptly considered., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Ischemic stroke (IS) is one of most common causes of disability in adults worldwide. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets in IS. Furthermore, immune cell dysfunction plays an important role in the pathogenesis of IS. Hence, in-depth research on immune-related targets in progressive IS is urgently needed., Methods: Expression profile data from patients with IS were downloaded from the Gene Expression Omnibus (GEO) database. Then, differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to identify the significant modules and differentially expressed genes (DEGs). Key genes were obtained and used in functional enrichment analyses by overlapping module genes and DEGs. Next, hub candidate genes were identified by utilizing three machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE). Subsequently, a diagnostic model was constructed based on the hub genes, and receiver operating characteristic (ROC) curves were constructed to validate the performances of the predictive models and candidate genes. Finally, the immune cell infiltration landscape of IS was explored with the CIBERSORT deconvolution algorithm., Results: A total of 40 key DEGs were identified based on the intersection of the DEGs and module genes, and we found that these genes were mainly enriched in the regulation of lipolysis in adipocytes, neutrophil extracellular trap formation and complement and coagulation cascades. Based on the results from three advanced machine learning algorithms, we obtained 7 hub candidate genes (ABCA1, ARG1, C5AR1, CKAP4, HMFN0839, SDCBP and TLN1) as diagnostic biomarkers of IS and developed a reliable nomogram with high predictive performance (AUC = 0.987). In addition, immune cell infiltration dysregulation was implicated in IS, and compared with those in the normal group, IS patients had increased fractions of gamma delta T cells, monocytes, M0 macrophages, M2 macrophages and neutrophils and clearly lower percentages of naive B cells, CD8 T cells, CD4 + memory T cells, follicular helper T cells, regulatory T cells (Tregs) and resting dendritic cells. Furthermore, correlation analysis indicated a significant correlation between the hub genes and immune cells in progressive IS., Conclusion: In conclusion, our study identified 7 hub genes as diagnostic biomarkers and established a reliable model to predict the occurrence of IS. Meanwhile, we explored the immune cell infiltration pattern and investigated the relationship between candidate genes and immune cells in the pathogenesis of IS. Hence, our study provides new insights into the diagnosis and treatment of IS., Competing Interests: The authors declare there are no competing interests., (© 2023 The Authors.)

Introduction: Beta-2-microglobulin (B2M), cystatin C and lipocalin-2 (LCN-2) are established renal biomarkers, yet their roles in stroke have not been fully evaluated. We aimed to investigate the relationship of B2M, cystatin C, and LCN-2 with stroke risk in a general Chinese population., Methods: We used ordinal regression to study the relationship between serum B2M, cystatin C, and LCN-2 with stroke risk in 1060 participants (mean age 45.4 ± 10.8 years, 46% male) from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD) study. Stroke risk was classified into low-risk, middle-risk and high-risk groups according to the China National Stroke Screening Survey criteria. Serum biomarker levels were measured using immunoturbidimetric assays. Participants with valid data on serum biomarker levels and stroke risk were included in the analysis., Results: The number of participants in the low-risk, middle-risk and high-risk stroke risk groups were 663, 143 and 254 respectively. Elevated serum B2M, cystatin C, and LCN-2 levels were associated with being male, overweight/obesity, hypertension, alcohol consumption and smoking. Serum B2M, cystatin C and LCN-2 levels were significantly associated with stroke risk in the overall population (B2M: β  = 0.595, p  < .001; cystatin C: β  = 3.718, p  < .001; LCN-2: β  = 0.564, p  < .001) after adjustment for age., Conclusion: Elevated serum B2M, cystatin C and LCN-2 levels are associated with stroke risk. They may be novel biomarkers for clinicians to assess stroke risk.Key messagesSerum beta-2-microglobulin, cystatin C and lipocalin-2 levels are significantly associated with stroke risk.Beta-2-microglobulin, cystatin C and lipocalin-2 may serve as useful biomarkers for stroke risk stratification in the general population.

Early detection and drug intervention with the appropriate timing and dosage are the main clinical challenges for ischemic stroke (IS) treatment. The conventional therapeutic agents relay fluorescent signals, which require real-time external light excitation, thereby leading to inevitable autofluorescence and poor tissue penetration. Herein, we report endogenous peroxynitrite (ONOO - )-activated BDP-4/Cur-CL NPs that release NIR afterglow signals (λ max 697 nm) for real-time monitoring of the progression of ischemia reperfusion (I/R) brain injury while releasing curcumin for the safe treatment of IS. The BDP-4/Cur-CL NPs exhibited bright NIR afterglow luminescence (maximum 732-fold increase), superb sensitivity (LOD = 82.67 nM), high energy-transfer efficiency (94.6%), deep tissue penetration (20 mm), outstanding antiapoptosis, and anti-inflammatory effects. The activated NIR afterglow signal obtained in mice with middle cerebral artery occlusion (MCAO) showed three functions: (i) the BDP-4/Cur-CL NPs are rapidly activated by endogenous ONOO - , instantly illuminating the lesion area, distinguishing I/R damage from normal areas, which can be successfully used for endogenous ONOO - detection in the early stage of IS; (ii) real-time reporting of in situ generation and dynamic fluctuations of endogenous ONOO - levels in the lesion area, which is of great value in monitoring the evolutionary mechanisms of IS; and (iii) dynamic monitoring of the release of curcumin drug for safe treatment. Indeed, the released curcumin effectively decreased apoptosis, enhanced survival, alleviated neuroinflammation, reduced brain tissue loss, and improved the cognition of MCAO stroke mice. This work is the first example of afterglow luminescence for early diagnosis, real-time reporting, drug tracing, and treatment for IS.

Background: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke., Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation-induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis., Results: The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro., Conclusions: Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia., Competing Interests: Disclosures None.

Background: The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins., Objective: To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH., Methods: We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis., Results: A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79)., Conclusion: Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)