Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

Low expression of TGF-ß2 and matrilin2 in human aqueous humour with acute primary angle closure.

Primary angle-closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label-free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor-ß2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.

Sensitive Dual-Signal ELISA Based on Specific Phage-Displayed Double Peptide Probes with Internal Filtering Effect to Assay Monkeypox Virus Antigen.

The global spread of monkeypox has become a worldwide public healthcare issue. Therefore, there is an urgent need for accurate and sensitive detection methods to effectively control its spreading. Herein, we screened by phage display two peptides M4 (sequence: DPCGERICSIAL) and M6 (sequence: SCSSFLCSLKVG) with good affinity and specificity to monkeypox virus (MPXV) B21R protein. To simulate the state of the peptide in the phage and to avoid spatial obstacles of the peptide, GGGSK was added at the C terminus of M4 and named as M4a. Molecular docking shows that peptide M4a and peptide M6 are bound to different epitopes of B21R by hydrogen bonds and salt-bridge interactions, respectively. Then, peptide M4a was selected as the capture probe, phage M6 as the detection probe, and carbonized polymer dots (CPDs) as the fluorescent probe, and a colorimetric and fluorescent double-signal capture peptide/antigen/signal peptide-displayed phage sandwich ELISA triggered by horseradish peroxidase (HRP) through a simple internal filtration effect (IFE) was constructed. HRP catalyzes H2O2 to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue oxidized TMB, which can further quench the fluorescence of CPDs through IFE, enabling to detect MPXV B21R in colorimetric and fluorescent modes. The proposed simple immunoassay platform shows good sensitivity and reliability in MPXV B21R detection. The limit of detection for colorimetric and fluorescent modes was 27.8 and 9.14 pg/mL MPXV B21R, respectively. Thus, the established double-peptide sandwich-based dual-signal immunoassay provides guidance for the development of reliable and sensitive antigen detection capable of mutual confirmation, which also has great potential for exploring various analytical strategies for other respiratory virus surveillance.

Self-Interface in Rh Nanosheets-Supported Tetrahedral Rh Nanocrystals for Promoting Electrocatalytic Oxidation of Ethanol.

Direct ethanol fuel cells hold great promise as a power source. However, their commercialization is limited by anode catalysts with insufficient selectivity toward a complete oxidation of ethanol for a high energy density, as well as sluggish catalytic kinetics and low stability. To optimize the catalytic performance, rationally tuning surface structure or interface structure is highly desired. Herein, a facile route is reported to the synthesis of Rh nanosheets-supported tetrahedral Rh nanocrystals (Rh THs/NSs), which possess self-supporting homogeneous interface between Rh tetrahedrons and Rh nanosheets. Due to full leverage of the structural advantages within the given structure and construction of interfaces, the Rh THs/NSs can serve as highly active electro-catalysts with excellent mass activity and selectivity toward ethanol electro-oxidation. The in situ Fourier transform infrared reflection spectroscopy showed the Rh THs/NSs exhibit the highest C1 pathway selectivity of 23.2%, far exceeding that of Rh nanotetrahedra and Rh nanosheets. Density function theory calculations further demonstrated that self-interface between Rh nanosheets and tetrahedra is beneficial for C-C bond cleavage of ethanol. Meanwhile, the self-supporting of 2D nanosheets greatly enhance the stability of tetrahedra, which improves the catalytic stability.

Enhancement and suppression of nonsequential double ionization by spatially inhomogeneous fields.

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

Proteomic characteristics of the aqueous humor in Uyghur patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma.

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.

Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/P53 signaling pathway.

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Impact of Stent Size Selection and Vessel Evaluation on Skull Base Cerebrovascular Diseases Treated With Willis Covered Stents: A Multicenter Retrospective Analysis.

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

Systemic inflammatory response index as a predictor of stroke-associated pneumonia in patients with acute ischemic stroke treated by thrombectomy: a retrospective study.

BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. METHODS: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. RESULTS: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774). CONCLUSIONS: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.

The aneurysm occlusion and recurrence of posterior communicating artery aneurysms following the treatment with the pipeline embolization device.

Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.

Association of inflammatory trajectory with subarachnoid hemorrhage mortality.

OBJECTIVE: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality. METHODS: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model. RESULTS: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW. CONCLUSION: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH.

Relationship between stress hyperglycemia ratio and prognosis in patients with aneurysmal subarachnoid hemorrhage: a two-center retrospective study.

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.

A Machine Learning Framework for Screening Plasma Cell-Associated Feature Genes to Estimate Osteoporosis Risk and Treatment Vulnerability.

Osteoporosis, in which bones become fragile owing to low bone density and impaired bone mass, is a global public health concern. Bone mineral density (BMD) has been extensively evaluated for the diagnosis of low bone mass and osteoporosis. Circulating monocytes play an indispensable role in bone destruction and remodeling. This work proposed a machine learning-based framework to investigate the impact of circulating monocyte-associated genes on bone loss in osteoporosis patients. Females with discordant BMD levels were included in the GSE56815, GSE7158, GSE7429, and GSE62402 datasets. Circulating monocyte types were quantified via CIBERSORT, with subsequent selection of plasma cell-associated DEGs. Generalized linear models, random forests, extreme gradient boosting (XGB), and support vector machines were adopted for feature selection. Artificial neural networks and nomograms were subsequently constructed for osteoporosis diagnosis, and the molecular machinery underlying the identified genes was explored. SVM outperformed the other tuned models; thus, the expression of several genes (DEFA4, HLA-DPB1, LCN2, HP, and GAS7) associated with osteoporosis were determined. ANNs and nomograms were proposed to robustly distinguish low and high BMDs and estimate the risk of osteoporosis. Clozapine, aspirin, pyridoxine, etc. were identified as possible treatment agents. The expression of these genes is extensively posttranscriptionally regulated by miRNAs and m6A modifications. Additionally, they participate in modulating key signaling pathways, e.g., autophagy. The machine learning framework based on plasma cell-associated feature genes has the potential for estimating personalized risk stratification and treatment vulnerability in osteoporosis patients.

Stent-to-vessel diameter ratio is associated with in-stent stenosis after flow-diversion treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

Analysis of Adverse Events in the Postanesthesia Unit at a Tertiary Pediatric Hospital.

PURPOSE: The postanesthesia care unit (PACU) is an indispensable part of modern medicine which provides critical care to patients to ensure safe and smooth emergence from anesthesia. The adverse events in the PACU have been widely investigated in adults. However, little is known about the adverse events in pediatric populations. This study was designed to investigate adverse events, including the incidence, disease spectrum, and possible risk factors, in pediatric patients in the PACU at a tertiary pediatric hospital. DESIGN: This is a retrospective observational study. METHODS: Children admitted to the PACU at the Children's Hospital of Fudan University from September 2021 to August 2022 were included in the study. The following adverse events were recorded: hypothermia, fever, adverse airway events, hypotension, hypertension, prolonged length of stay in PACU, pain, reintubation, neurological events, unplanned admission to the intensive care unit, arrhythmia, water-electrolyte imbalance, and bleeding requiring medical intervention. Descriptive analyses, t tests, and χ2 tests were performed. FINDINGS: A total of 16,012 children were included in the study, and 305 adverse events occurred in 237 (1.48%) children. The three most frequently occurring adverse events were prolonged stay in the PACU (8.4%), adverse airway events (5.6%), and abnormal temperature (2.7%). Age, American Society of Anesthesiologists' grade, and general surgery were independent risk factors of both overall adverse events and prolonged stay in the PACU in multivariate logistic regression analysis. Children with adverse events stayed in the PACU significantly longer than those without adverse events (60.04 ± 1.01 vs 95.8 ± 47.25 minutes, P < .05). Compared with the other surgeries, a significantly higher proportion of severe pain (37.5% vs 0%) after thoracic surgery, prolonged stay in the PACU (52.9% vs 36.4%) after general surgery, and neurological events (14.7% vs 0%) after neurological surgery was detected, while a significantly lower proportion of adverse airway events after general surgery (21.1% vs 43%) and neurological surgery (8.8% vs 43%) was detected, respectively. CONCLUSIONS: Our study reports the current incidence and spectrum of adverse events in the PACU at a tertiary pediatric hospital. Patients with young age, high American Society of Anesthesiologists' grade, and those from the general surgery department are at a significantly increased risk of adverse events in the PACU. Significant differences were detected in the proportion of specific adverse events after specific surgeries.

Dual Signal Amplification by Urease Catalysis and Silver Nanoparticles for Ultrasensitive Colorimetric Detection of Nucleic Acids.

Signal amplification techniques are highly desirable for the analysis of low-level targets that are closely related with diseases and the monitoring of important biological processes. However, it is still challenging to achieve this goal in a facile and economical way. Herein, we developed a novel dual signal amplification strategy by combining urease catalysis with the release of Ag+ from silver nanoparticles (AgNPs). This strategy was used for quantifying a DNA sequence (HIV-1) related with human immunodeficiency virus (HIV). DNA target HIV-1 hybridizes with the capture DNA probe on magnetic beads and the reporter DNA probe on AgNPs, forming a sandwich complex. The captured AgNPs are then transformed into numerous Ag+ ions that inactivate numerous ureases. Without catalytic production of ammonia from urea, the substrate solution shows a low pH 5.8 that will increase otherwise. The pH change is monitored by a pH indicator (phenol red), which allows for colorimetric detection. The proposed approach is sensitive, easy to use, economic, and universal, exhibiting a low detection limit of 9.7 fM (i.e., 1.94 attomoles) and a dynamic linear range of 4 orders for HIV-1 sequence detection.

Sensitive Lateral Flow Immunoassay Based on Specific Peptide and Superior Oxidase Mimics with a Universal Dual-Mode Significant Signal Amplification.

Rapid and sensitive antigen detection using a lateral flow immunoassay (LFIA) is crucial for diagnosing infectious diseases due to its simplicity, speed, and user-friendly features. However, it remains a critical issue to explore specific biorecognition elements and powerful signal amplification. In this study, taking SARS-CoV-2 as a proof of concept, a specific peptide, WFLNDSELIML, binding to the SARS-CoV-2 spike (S) antigen was identified by a nonamplified biopanning method, which exhibited high affinity to the target, with a dissociation constant of 9.29 ± 1.55 nM. Molecular docking analysis reveals that this peptide binds to the N-terminal domain of the SARS-CoV-2 S antigen. Then, using this peptide as a capture probe and angiotensin-converting enzyme 2 as a detection probe, a peptide-based lateral flow immunoassay (pLFIA) for the sensitive detection of the SARS-CoV-2 S antigen without any antibody was developed, for which a polydopamine nanosphere (PDA)@MnO2 nanocomposite with excellent oxidase-like activity was used as a colorimetric label, exhibiting dual-mode remarkable signal amplification of natural melanin and on-demand nanozyme catalytic enhancement. The PDA@MnO2-based pLFIA is capable of detecting the SARS-CoV-2 S antigen with a limit of detection of 8.01 pg/mL, which is 18.7 times lower than that of a conventional pLFIA tagged with gold nanoparticles. Additionally, the as-proposed PDA@MnO2-based pLFIA can detect up to 150 transduction units/mL SARS-CoV-2 pseudoviruses spiked in saliva samples. Given the outstanding analytical performance, the proposed PDA@MnO2-based pLFIA may offer a reliable option for the rapid diagnosis of SARS-CoV-2.

BCG-induced trained immunity: history, mechanisms and potential applications.

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.