Overloaded transnidal pressure gradient as the hemodynamic mechanism leading to arteriovenous malformation rupture: a quantitative analysis using intravascular pressure monitoring and color-coded digital subtraction angiography.

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

Three new species and one new record of Deimatidae (Echinodermata, Holothuroidea, Synallactida) discovered in the South China Sea and the Mariana fore-arc area using integrative taxonomic methods.

Deep-sea holothurian specimens were collected during five scientific expeditions (2018-2023) using the submersible vehicle 'Shenhaiyongshi'. Our examination of specimens of Deimatidae from the South China Sea and the Mariana fore-arc area revealed three new species, which were described as Oneirophantaidsseicasp. nov., Oneirophantabrunneannulatasp. nov., and Oneirophantalucernasp. nov. These species were distinguished from each other and from congeners by the arrangement, and number of ventrolateral tube feet and ossicle types. We also reported Oneirophantamutabilismutabilis Théel, 1879 for the first time from the Mariana fore-arc area, and we recorded Deimavalidumvalidum for the second time from the South China Sea. The taxonomy of these new species and new records is discussed, and a phylogenetic analysis based on a concatenated dataset of 16S and COI genes was conducted. Additionally, the inter- and intraspecific genetic divergences we calculated among deimatid species. The results support the assignment of these new species to the genus Oneirophanta and their separation from congeners. A description of the main morphological characters of Oneirophanta species is also provided. The data were collected from geographically diverse areas and suggest that species of Deimatidae were abundant in the Pacific Ocean and occupied a wide range of depths.

Risk factors for delayed postoperative hemorrhage in patients with brain arteriovenous malformations: an analysis of the nationwide multicenter prospective registry MATCH study.

OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

A retrospective study on the relationship between serum electrolyte disorder and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.

A high-quality chromosomal genome assembly of the sea cucumber Chiridota heheva and its hydrothermal adaptation.

BACKGROUND: Chiridota heheva is a cosmopolitan holothurian well adapted to diverse deep-sea ecosystems, especially chemosynthetic environments. Besides high hydrostatic pressure and limited light, high concentrations of metal ions also represent harsh conditions in hydrothermal environments. Few holothurian species can live in such extreme conditions. Therefore, it is valuable to elucidate the adaptive genetic mechanisms of C. heheva in hydrothermal environments. FINDINGS: Herein, we report a high-quality reference genome assembly of C. heheva from the Kairei vent, which is the first chromosome-level genome of Apodida. The chromosome-level genome size was 1.43 Gb, with a scaffold N50 of 53.24 Mb and BUSCO completeness score of 94.5%. Contig sequences were clustered, ordered, and assembled into 19 natural chromosomes. Comparative genome analysis found that the expanded gene families and positively selected genes of C. heheva were involved in the DNA damage repair process. The expanded gene families and the unique genes contributed to maintaining iron homeostasis in an iron-enriched environment. The positively selected gene RFC2 with 10 positively selected sites played an essential role in DNA repair under extreme environments. CONCLUSIONS: This first chromosome-level genome assembly of C. heheva reveals the hydrothermal adaptation of holothurians. As the first chromosome-level genome of order Apodida, this genome will provide the resource for investigating the evolution of class Holothuroidea.

Cloning and functional characterization of the oxidative squalene cyclase gene in the deep-sea holothurian Chiridota sp.

Saponins derived from holothurians have high potential medicinal value. However, the de novo synthesis of the derivatization of triterpenes is still unclear. Oxidative squalene cyclase (OSC) can catalyze 2,3-Oxidosqualene into diverse products that serve as important precursors for triterpene synthesis. However, the function of theOSCgene in Chiridotasp. hasnot been elucidated. In this study, an OSCgenederived from the deep-sea holothurianChiridota sp. was cloned and characterized functionally in a yeast system. The open reading frame of the OSC gene was 2086 bp, which encoded 695 amino acids. The Chiridota sp. OSC gene has a similarity of 66.89 % to the OSC of other holothurian species and 63.51 % to that of Acanthaster planci. The phylogenetic tree showed that the echinozoan OSCsclustered together, and then they formeda sister group to fungi and plant homologs. Chiridota sp. OSC catalyzed 2,3-Oxidosqualene into parkeol.Under high pressure, the relative enzymatic activity and stability of cyclase inChiridota sp. was higher than that in the shallow-sea holothurianStichopus horrens. The newly cloned OSC of Chiridota sp.provideskey information for the interpretation of the saponin synthesis pathway in deep-sea holothurians.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

ITGA2 as a prognostic factor of glioma promotes GSCs invasion and EMT by activating STAT3 phosphorylation.

Glioma is the most common malignant brain tumor in adults with a high mortality and recurrence rate. Integrin alpha 2 (ITGA2) is involved in cell adhesion, stem cell regulation, angiogenesis and immune cell function. The role of ITGA2 in glioma malignant invasion remains unknown. The function and clinical relevance of ITGA2 were analysed by bioinformatics databases. The expression of ITGA2 in parent cells and GSCs was detected by flow cytometry and immunofluorescence double staining. The role of ITGA2 on the malignant phenotype of GSCs and epithelial-mesenchymal transition (EMT) was identified by stem cell function assays and Western blot. The effect of ITGA2 on glioma progression in vivo was determined by the intracranial orthotopic xenograft model. Immunohistochemistry, Spearman correlation and Kaplan-Meier were used to analyse the relationship of ITGA2 with clinical features and glioma prognosis. Biological analysis showed that ITGA2 might be related to cell invasion and migration. ITGA2, enriched in GSCs and co-expressed with SOX2, promoted the invasion and migration of GSCs by activating STAT3 phosphorylation and enhancing EMT. ITGA2 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice. In addition, the expression level of ITGA2 was significantly correlated to the grade of malignancy, N-cadherin and Ki67. High expression of ITGA2 indicated a worse prognosis of glioma patients. As a biomarker for the prediction of prognosis, ITGA2 promotes the malignant invasion of GSCs by activating STAT3 phosphorylation and enhancing EMT, leading to tumor recurrence and poor prognosis.

Automatic Diagnosis of Carotid Atherosclerosis Using a Portable Freehand 3-D Ultrasound Imaging System.

The objective of this study is to develop a deep-learning-based detection and diagnosis technique for carotid atherosclerosis (CA) using a portable freehand 3-D ultrasound (US) imaging system. A total of 127 3-D carotid artery scans were acquired using a portable 3-D US system, which consisted of a handheld US scanner and an electromagnetic (EM) tracking system. A U-Net segmentation network was first applied to extract the carotid artery on 2-D transverse frame, and then, a novel 3-D reconstruction algorithm using fast dot projection (FDP) method with position regularization was proposed to reconstruct the carotid artery volume. Furthermore, a convolutional neural network (CNN) was used to classify healthy and diseased cases qualitatively. Three-dimensional volume analysis methods, including longitudinal image acquisition and stenosis grade measurement, were developed to obtain the clinical metrics quantitatively. The proposed system achieved a sensitivity of 0.71, a specificity of 0.85, and an accuracy of 0.80 for diagnosis of CA. The automatically measured stenosis grade illustrated a good correlation ( r = 0.76) with the experienced expert measurement. The developed technique based on 3-D US imaging can be applied to the automatic diagnosis of CA. The proposed deep-learning-based technique was specially designed for a portable 3-D freehand US system, which can provide a more convenient CA examination and decrease the dependence on the clinician's experience.

Novel predictors of permanent pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: Conduction and rhythm abnormalities requiring permanent pacemakers (PPM) are short-term complications following transcatheter aortic valve replacement (TAVR), and their clinical outcomes remain conflicting. Potential novel predictors of post-TAVR PPM, like QRS duration, QTc prolongation, and supraventricular arrhythmias, have been poorly studied. AIM: To evaluate the effects of baseline nonspecific interventricular conduction delay and supraventricular arrhythmia on post-TAVR PPM requirement and determine the impact of PPM implantation on clinical outcomes. METHODS: A retrospective cohort study that identified patients with TAVR between January 1, 2012 to December 31, 2019. The group was dichotomized into those with post-TAVR PPM and those without PPM. Both groups were followed for one year. RESULTS: Out of the 357 patients that met inclusion criteria, the mean age was 80 years, 188 (52.7%) were male, and 57 (16%) had a PPM implantation. Baseline demographics, valve type, and cardiovascular risk factors were similar except for type II diabetes mellitus (DM), which was more prevalent in the PPM cohort (59.6% vs 40.7%; P = 0.009). The PPM cohort had a significantly higher rate of pre-procedure right bundle branch block, prolonged QRS > 120 ms, prolonged QTc > 470 ms, and supraventricular arrhythmias. There was a consistently significant increase in the odds ratio (OR) of PPM implantation for every 20 ms increase in the QRS duration above 100 ms: QRS 101-120 [OR: 2.44; confidence intervals (CI): 1.14-5.25; P = 0.022], QRS 121-140 (OR: 3.25; CI: 1.32-7.98; P = 0.010), QRS 141-160 (OR: 6.98; CI: 3.10-15.61; P < 0.001). After model adjustment for baseline risk factors, the OR remained significant for type II DM (aOR: 2.16; CI: 1.18-3.94; P = 0.012), QRS > 120 (aOR: 2.18; CI: 1.02-4.66; P = 0.045) and marginally significant for supraventricular arrhythmias (aOR: 1.82; CI: 0.97-3.42; P = 0.062). The PPM cohort had a higher adjusted OR of heart failure (HF) hospitalization (aOR: 2.2; CI: 1.1-4.3; P = 0.022) and nonfatal myocardial infarction (MI) (aOR: 3.9; CI: 1.1-14; P = 0.031) without any difference in mortality (aOR: 1.1; CI: 0.5-2.7; P = 0.796) at one year. CONCLUSION: Pre-TAVR type II DM and QRS duration > 120, regardless of the presence of bundle branch blocks, are predictors of post-TAVR PPM. At 1-year post-TAVR, patients with PPM have higher odds of HF hospitalization and MI.

Comparison of conservative management, microsurgery only, and microsurgery with preoperative embolization for unruptured arteriovenous malformations: A propensity score weighted prospective cohort study.

AIMS: To compare the efficacy and deficiency of conservative management (CM), microsurgery (MS) only, and microsurgery with preoperative embolization (E + MS) for unruptured arteriovenous malformations (AVMs). METHODS: We prospectively included unruptured AVMs undergoing CM, MS, and E + MS from our institution between August 2011 and August 2021. The primary outcomes were long-term neurofunctional outcomes and hemorrhagic stroke and death. In addition to the comparisons among CM, MS, and E + MS, E + MS was divided into single-staged hybrid and multi-staged E + MS for further analysis. Stabilized inverse probability of treatment weighting using propensity scores was applied to control for confounders by treatment indication across the three groups. RESULTS: Of 3758 consecutive AVMs admitted, 718 patients were included finally (266 CM, 364 MS, and 88 E + MS). The median follow-up duration was 5.4 years. Compared with CM, interventions (MS and E + MS) were associated with neurological deterioration. MS could lower the risk of hemorrhagic stroke and death. Multi-staged E + MS was associated with neurological deterioration and higher hemorrhagic risks compared with MS, but the hybrid E + MS operation significantly reduced the hemorrhage risk. CONCLUSION: In this study, unruptured AVMs receiving CM would expect better neurofunctional outcomes but bear higher risks of hemorrhage than MS or E + MS. The single-staged hybrid E + MS might be promising in reducing inter-procedural and subsequent hemorrhage.

Expression and gene regulatory network of S100A16 protein in cervical cancer cells based on data mining.

S100A16 protein belongs to the S100 family of calcium-binding proteins, which is widely distributed in human tissues and highly conserved. S100 calcium-binding proteins possess broad biological functions, such as cancer cell proliferation, apoptosis, tumor metastasis, and inflammation (Nat Rev Cancer 15:96-109, 2015). The S100A16 protein was initially isolated from a cell line derived from astrocytoma. The S100A16 protein, consisting of 103 amino acids, is a small acidic protein with a molecular weight of 11,801.4 Da and an isoelectric point (pI) of 6.28 (Biochem Biophys Res Commun 313:237-244, 2004). This protein exhibits high conservation among mammals and is widely expressed in various human tissues (Biochem Biophys Res Commun 322:1111-1122, 2004). Like other S100 proteins, S100A16 contains two EF-hand motifs that form a helix-loop-helix structural domain. The N-terminal domain and the C-terminal domain of S100A16 are connected by a "hinge" linker.S100A16 protein exhibits distinct characteristics that distinguish it from other S100 proteins. A notable feature is the presence of a single functional Ca2 + binding site located in the C-terminal EF-hand, consisting of 12 amino acids per protein monomer (J Biol Chem 281:38905-38917, 2006). In contrast, the N-terminal EF-hand of S100A16 comprises 15 amino acids instead of the typical 14, and it lacks the conserved glutamate residue at the final position. This unique attribute may contribute to the impaired Ca2 + binding capability in the N-terminal region (J Biol Chem 281:38905-38917, 2006). Studies have shown an integral role of S100 calcium-binding proteins in the diagnosis, treatment, and prognosis of certain diseases (Cancers 12:2037, 2020). Abnormal expression of S100A16 protein is implicated in the progression of breast and prostate cancer, but an inhibitor of oral cancer and acute lymphoblastic leukemia tumor cell proliferation (BMC Cancer 15:53, 2015; BMC Cancer 15:631, 2015). Tu et al. (Front Cell Dev Biol 9:645641, 2021) indicate that the overexpression of S100A16 mRNA in cervical cancer(CC) such as cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to the control specimens. Tomiyama N. and co-workers (Oncol Lett 15:9929-9933, 2018) (Tomiyama, N) investigated the role of S100A16 in cancer stem cells using Yumoto cells (a CC cell line),The authors found upregulation of S100A16 in Yumoto cells following sphere formation as compared to monolayer culture.Despite a certain degree of understanding, the exact biological function of S100A16 in CC is still unclear. This article explores the role of S100A16 in CC through a bioinformatics analysis. Referencing the mRNA expression and SNP data of cervical cancer available through The Cancer Genome Atlas (TCGA) database, we analyzed S100A16 and its associated regulatory gene expression network in cervical cancer. We further screened genes co-expressed with S100A16 to hypothesize their function and relationship to the S100A16 cervical cancer phenotype.Our results showed that data mining can effectively elucidate the expression and gene regulatory network of S100A16 in cervical cancer, laying the foundation for further investigations into S100A16 cervical tumorigenesis.

Diagnostic biomarker for type 2 diabetic peripheral neuropathy via comprehensive bioinformatics analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN. METHODS: In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression. RESULTS: In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes. CONCLUSIONS: Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies.

Recurrence of Cerebral Arteriovenous Malformation Following Complete Obliteration Through Endovascular Embolization.

Arteriovenous malformation (AVM) recurrence after embolization was rarely reported. This study aimed to explore the potential risk factors of recurrence in angiographically obliterated AVMs treated with endovascular embolization. This study reviewed AVMs treated with embolization only in a prospective multicenter registry from August 2011 to December 2021, and ultimately included 92 AVMs who had achieved angiographic obliteration. Recurrence was assessed by follow-up digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression models. Nineteen AVMs exhibited recurrence on follow-up imaging. The recurrence rates after complete obliteration at 6 months, 1 year, and 2 years were 4.35%, 9.78%, and 13.0%, respectively. Multivariate Cox regression analysis identified diffuse nidus (HR 3.208, 95% CI 1.030-9.997, p=0.044) as an independent risk factor for recurrence. Kaplan-Meier analysis confirmed a higher cumulative risk of recurrence with diffuse nidus (log-rank, p=0.016). Further, in the exploratory analysis of the effect of embolization timing after AVM rupture on recurrence after the complete obliteration, embolization within 7 days of the hemorrhage was found as an independent risk factor (HR 4.797, 95% CI 1.379-16.689, p=0.014). Kaplan-Meier analysis confirmed that embolization within 7 days of the hemorrhage was associated with a higher cumulative risk of recurrence in ruptured AVMs (log-rank, p<0.0001). This study highlights the significance of diffuse nidus as an independent risk factor for recurrence after complete embolization of AVMs. In addition, we identified a potential recurrent risk associated with early embolization in ruptured AVMs.

Prediction of stress-related gastrointestinal bleeding in patients with aneurysmal subarachnoid hemorrhage using caudate Hounsfield unit value in ASPECT score.

Background: Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH. Methods: We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan-Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB. Results: The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847-0.983, and p = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p = 0.78). The optimal cut-off value of the right caudate HU was 25.1. Conclusion: Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.

Re-rupture in ruptured brain arteriovenous malformations: a retrospective cohort study based on a nationwide multicenter prospective registry.

BACKGROUND: This study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention. METHODS: This study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan-Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed. RESULTS: The annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, p<0.001), especially in those who underwent surgical resection (annual rupture risk 0.13%). CONCLUSIONS: The risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

Metasurface Absorbers with Film-Coupled Au Nanoclusters to Achieve Broadband and Polarization-Independent Absorption of UV-Vis Light.

Metasurface absorbers (MAs) have attracted widespread interest in the recent study of subwavelength artificial optical metasurfaces, although most reported MAs suffer from the actualities of costly and time-consuming fabrications, narrow working bandwidth, polarization-dependent responses, etc., somewhat limiting their practical applications. Herein, we introduce a facile and low-cost method to fabricate MAs with excellent absorption performances via the self-assembly of synthesized Au nanoclusters (NCs) on a Au film spaced by a nanoscale-thick dielectric SiO2. Interestingly, the proposed MAs with well-designed Au film-coupled Au NCs (i.e., an appropriate surface coverage of Au NCs and the compatible thickness of the SiO2 spacer) exhibited a measured average absorbance above 90% within a broad UV-vis wavelength band (200-800 nm). In addition, owing to the MAs' topological symmetry, their UV-vis absorption behaviors presented polarization insensitivity with the incident light angles ranging from 20 to 50°. It has been demonstrated that the excited different surface plasmon resonance modes between Au NCs and the adjacent Au film were vital; in addition, the light-trapping effects from "V"-shaped structures of Au NCs were favorable for the designed MAs with enhanced light absorption. We believe that such MAs and the potential self-assembly fabrication strategy may facilitate scalable optical applications such as photothermalvoltaics, ultraviolet protection, optical storage, and sensing.