Effects of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetes patients: a post-hoc analysis of the MARCH study.

PURPOSE: While metformin is known to regulate thyroid stimulating hormone (TSH) levels, the effects of acarbose on thyroid function remain unreported. Our study was designed to evaluate the impact of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetic patients. METHODS: In the MARCH study, 788 patients with type 2 diabetes were randomly assigned to treat with acarbose (300 mg) or metformin (1,500 mg) for 48 weeks. Thyroid function was assessed at baseline, 24 weeks, and 48 weeks, and the thyroid feedback quantile index (TFQI) and parameterized thyroid feedback quantile index (PTFQI) were calculated. Generalized estimating equations adjusted for confounders were used to analyze changes over time. RESULTS: Eighty-four patients with subclinical hypothyroidism (SCH) exhibited a decrease in TSH levels (p = 0.001) with no significant differences between the two treatment groups (p = 0.460). Both TFQI (p = 0.029) and PTFQI (p < 0.001) also decreased over time. Mediation analysis revealed that these change over time were not mediated by BMI (all p < 0.05). Among the 489 euthyroid subjects, no significant changes in TSH levels were observed (p > 0.05). Stratification by baseline TSH levels revealed significant increases in TSH, TFQI, and PTFQI (all p < 0.05) in the normal-low TSH group and significant decreases in PTFQI (all p < 0.05) in the normal-high TSH group after treatment with acarbose and metformin. CONCLUSIONS: Acarbose and metformin have similar buffering effects on TSH levels, the TFQI and the PTFQI. In patients with lower TSH levels, acarbose and metformin do not further decrease TSH levels. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR-TRC-08000231.

Efficient conversion of hemicellulose into high-value product and electric power by enzyme-engineered bacterial consortia.

As an abundant agricultural and forestry biomass resource, hemicelluloses are hard to be effectively degraded and utilized by microorganisms due to the constraints of membrane and metabolic regulations. Herein, we report a synthetic extracellular metabolic pathway with hemicellulose-degrading-enzymes controllably displayed on Escherichia coli surface as engineered bacterial consortia members for efficient utilization of xylan, the most abundant component in hemicellulose. Further, we develop a hemicellulose/O2 microbial fuel cell (MFC) configuring of enzyme-engineered bacterial consortia based bioanode and bacterial-displayed laccase based biocathode. The optimized MFC exhibited an open-circuit voltage of 0.71 V and a maximum power density (Pmax) of 174.33 ± 4.56 µW cm-2. Meanwhile, 46.6% (w/w) α-ketoglutarate was produced in this hemicellulose fed-MFC. Besides, the MFC retained over 95% of the Pmax during 6 days' operation. Therefore, this work establishes an effective and sustainable one-pot process for catalyzing renewable biomass into high-value products and electricity in an environmentally-friendly way.

The prognostic significance of synchronous metastasis in glioblastoma multiforme patients: a propensity score-matched analysis using SEER data.

Background: Glioblastoma multiforme (GBM) with synchronous metastasis(SM) is a rare occurrence. We extracted the data of GBM patients from the SEER database to look into the incidence of SM in GBM, determine the prognostic significance of SM in GBM, and assess therapeutic options for patients presenting with SM. Methods: From 2004 to 2015, information on GBM patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching (PSM) method was employed to mitigate confounding factors between SM and non-SM groups, subsequently investigating the prognostic significance of SM in patients with GBM. Multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic variables for GBM patients with SM. A forest plot was used to visualize the results. Results: A cohort of 19,708 patients was obtained from the database, among which 272 (1.4%) had SM at the time of diagnosis. Following PSM at a 3:1 ratio, in both univariate and multivariate cox regression analysis, SM (HR = 1.27, 95% CI: 1.09-1.46) was found to be an independent predictive predictor for GBM patients. Furthermore, the Cox proportional hazard forest plot demonstrated that independent risk variables for GBM patients with SM included age (Old vs. Young, HR = 1.44, 95% CI: 1.11-1.88), surgery (biopsy vs. no surgery, HR = 0.67, 95% CI: 0.46-0.96;Subtotal resection vs. no surgery, HR = 0.47, 95% CI: 0.32-0.68;Gross total resection vs. no surgery, HR = 0.44, 95% CI: 0.31-0.62), radiotherapy (HR = 0.58, 95% CI: 0.41-0.83), and chemotherapy (HR = 0.51, 95% CI: 0.36-0.72). Conclusion: The predictive value of SM in GBM was determined by this propensity-matched analysis using data from the SEER database. Radiotherapy, chemotherapy, and surgery constitute an effective treatment regimen for patients with SM. A more positive approach toward the use of aggressive treatment for GBM patients with SM may be warranted.

Contrast-enhanced ultrasound findings of sclerotic nodules in Wilson disease: A case report.

RATIONALE: Wilson disease is an autosomal recessive genetic disease found by Samuel Alexander Kinnier Wilson and prevalent in childhood and adolescents. PATIENT CONCERNS: An 18-year-old female patient presented to our hospital with a continuous decrease of 3 blood cell lines for more than 10 days, and diagnosed as decompensated cirrhosis. Ultrasonography showed diffuse lesions in the hepatic parenchyma, with multiple hypoechoic light masses in the parenchyma, the outline was still clear, and the internal echo was uneven. Contrast-enhanced ultrasound showed that the nodules were enhanced rapidly and uniformly, with an initial enhancement time of 9 seconds and a peak time of 17.2 seconds. The washing time was slightly earlier than that of the hepatic parenchyma and showed slightly higher enhancement in the delayed phase. Finally, ultrasound-guided biopsies showed unexplained liver cirrhosis. DIAGNOSES: Combined with clinical examination, it was inferred to be Wilson disease. It is difficult to diagnose hepatolenticular degeneration because of its concealed incidence, complex clinical manifestations, expensive detection of the ATP7B gene, and lack of other specific imaging signs. OUTCOMES: After admission, the patient was given symptomatic support treatment such as liver protection. INTERVENTIONS: The patient was discharged after improvement of symptoms. LESSONS: Here, the results of contrast-enhanced ultrasound in our case may provide a new idea for the diagnosis of Wilson.

Fontan circulation and systemic disease - a retrospective cohort analysis over 35 years of follow-up: Fontan systemic disease at 35 years.

BACKGROUND: The Fontan operation provides lifesaving palliation for individuals with single ventricle (SV) physiology. Given recent concerns of systemic disease (SD) for patients with a Fontan circulation, we sought to 1) quantify the increase in SD incidence associated with the Fontan circulation; 2) identify the risk factor of SD; 3) assess the association between SD and mortality in patients with a Fontan circulation. METHODS: A matched retrospective cohort study design was adopted. From the Quebec Congenital Heart Disease (CHD) Database with up to 35 years of follow-up, patients who survived at least 30 days after the Fontan operation were identified. For each Fontan patient, patients with isolated ventricular septal defect (VSD) with the same sex and age were identified and 20 of them were randomly selected to form the control group. The presence of SD was defined as at least one hospitalization due to extra-cardiac complications including liver, respiratory, gastrointestinal or renal disease. Time-to-event analysis including Kaplan-Meier curve analysis and Cox proportional hazard models were conducted to assess the cumulative risk of SD, risk factors of SD, and the association between SD and 10-year mortality. RESULTS: A total of 533 patients with Fontan circulation were identified and matched with 10,280 VSD patients. The cumulative probabilities of SD at 10- and 35-years follow-up were 59.02% and 89.66% in patients with a Fontan circulation, 4-7 times of the probabilities in VSD patients (8.68% and 23.34%, respectively; LogRank tests p<0.0001). In Fontan patients, cardiovascular complications were associated with a 4.1-fold (95% CI: 3.52-4.88) higher risk of developing SD. Multisystem disease (>1 extra-cardiac organ affected) disease was associated with a 3.38-fold (95%CI: 1.73-6.60) increase in 10-year mortality risk when comparing to the absence of SD. CONCLUSIONS: This population-based study demonstrated that patients with a Fontan circulation had increased risk of SD, which in turn led to higher risk of mortality. These findings underscore the need for more systematic surveillance of cardiac and systemic disease for patients after Fontan operation.

CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses.

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10-15) and LAG3 (rs67706382, p = 6.16× 10-16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial. Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS. Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023). Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control. Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment. Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients. Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Transition Metal-Gallium Intermetallic Compounds with Tailored Active Site Configurations for Electrochemical Ammonia Synthesis.

Gallium (Ga) with a low melting point can serve as a unique metallic solvent in the synthesis of intermetallic compounds (IMCs). The negative formation enthalpy of transition metal-Ga IMCs endows them with high catalytic stability. Meanwhile, their tunable crystal structures offer the possibility to tailor the configurations of active sites to meet the requirements for specific catalytic applications. Herein, we present a general method for preparing a range of transition metal-Ga IMCs, including Co-Ga, Ni-Ga, Pt-Ga, Pd-Ga, and Rh-Ga IMCs. The structurally ordered CoGa IMCs with body-centered cubic (bcc) structure are uniformly dispersed on the nitrogen-doped reduced graphene oxide substrate (O-CoGa/NG) and deliver outstanding nitrate reduction reaction (NO3RR) performance, making them excellent catalysts to construct highly efficient rechargeable Zn-NO3- battery. Operando studies and theoretical simulations demonstrate that the electron-rich environments around the Co atoms enhance the adsorption strength of *NO3 intermediate and simultaneously suppress the formation of hydrogen, thus improving the NO3RR activity and selectivity.

Human intermediate prostate cancer stem cells contribute to the initiation and development of prostate adenocarcinoma.

BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

Universal All-In-One Lateral Flow Immunoassay with Triple Signal Amplification for Ultrasensitive and Simple Self-Testing of Treponema pallidum Antibodies.

Lateral flow immunoassay (LFIA) is valued for its simplicity and rapidity for on-site screening, however, it experienced false negatives in real sample analysis due to low sensitivity. Although many signal amplification techniques can improve the sensitivity, they usually require additional complicated steps. To address these issues, taking Treponema pallidum (T. pallidum) antibodies as a model detecting target, herein, we report an all-in-one LFIA (AIO-LFIA) with triple-step signal amplification to significantly improve sensitivity while maintaining simplicity. This LFIA utilizes a biotin-streptavidin system for initial signal amplification, followed by introducing a release controller with a specific imprinted structure for timed multicomponent release, which avoids the extra steps when adding components in traditional LFIA. Particularly, a 3D-printed programmed metal in situ growth (MISG) device is integrated to localize signal enhancement at specific sites, overcoming limitations of traditional MISG and substantially reducing reagent usage and assay time, and the nitrocellulose membrane surface was much cleaner than the conventional approach, which facilitates signal readout. After optimization, the proposed AIO-LFIA is capable of visual detection down to 1 pg/mLT. pallidum antibodies in 15 min, 1000-fold lower than the gold nanoparticle-based LFIA. In clinical testing of 152 samples, the AIO-LFIA can distinguish all positive samples, outperforming commercial LFIA which missed those positive samples with relatively low antibody levels. Thus, this study presents a universal ultrasensitive and reliable AIO-LFIA strategy for infectious diseases self-testing, providing an effective promising prospect to address the challenge over emerging infectious diseases in the future.

Risk factors for the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a common neurosurgical disorder with high morbidity and poor prognosis, and the associated delayed cerebral ischemia (DCI) is a key factor contributing to poor prognosis. Despite extensive research on the risk factors associated with DCI development, the evidence remains conflicting. Therefore, this meta-analysis of case-control studies aimed to investigate the risk factors for DCI occurrence during hospitalization in patients with aSAH. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible studies published before November 20, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary outcome was DCI occurrence during hospitalization in patients with aSAH. RESULTS: A total of 42 studies involving 21,726 patients with aSAH were included. The pooled meta-analysis showed that female sex; Hunt-Hess, modified Fisher, and World Federation of Neurosurgical Societies (WFNS) scale scores of 4-5, 3-4, and 4-5, respectively; vasospasm; combined intraventricular hemorrhage (IVH); pre-existing hypertension; hydrocephalus; intracranial infections (ICI); and high white blood cell (WBC) count on admission were independent risk factors for the development of postoperative DCIs in patients with aSAH. CONCLUSIONS: Patients with aSAH who have a Hunt-Hess scale score ≥4, a modified Fisher scale score ≥3, a WFNS scale score ≥4, IVH, pre-existing hypertension, cerebral vasospasm, a high WBC count on admission, ICI, and female sex are at high risk of DCI and hence should be carefully monitored in the intensive care unit.

Cellular and Molecular Network Characteristics of TARM1-Related Genes in Mycobacterium tuberculosis Infections.

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape's cytoHubba plug-in. Furthermore, protein-protein interaction (PPI) networks were analyzed through STRING, while mRNA-RNA-binding protein (RBP) and mRNA-transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers.

Risk of cardiovascular events after influenza infection-related hospitalizations in adults with congenital heart disease: A nationwide population based study.

BACKGROUND: Cardiovascular complications due to viral infection pose a significant risk in vulnerable patients such as those with congenital heart disease (CHD). Limited data exists regarding the incidence of influenza and its impact on cardiovascular outcomes among this specific patient population. METHODS: A retrospective cohort study was designed using the Canadian Congenital Heart Disease (CanCHD) database-a pan-Canadian database of CHD patients with up to 35 years of follow-up. CHD patients aged 40 to 65 years with influenza virus-associated hospitalizations between 2010 and 2017 were identified and 1:1 matched with CHD patients with limb fracture hospitalizations on age and calendar time. Our primary endpoint was cardiovascular complications: heart failure, acute myocardial infarction, atrial arrhythmia, ventricular arrhythmia, heart block, myocarditis, and pericarditis. RESULTS: Of the 303 patients identified with incident influenza virus-associated hospitalizations, 255 were matched to 255 patients with limb fracture hospitalizations. Patients with influenza virus-related hospitalizations showed significantly higher cumulative probability of cardiovascular complications at 1 year (0.16 vs. 0.03) and 5 years (0.33 vs. 0.15) compared to patients hospitalized with bone fracture. Time-dependent hazard function modeling demonstrated a significantly higher risk of cardiovascular complications within 9 months postdischarge for influenza-related hospitalizations. This association was confirmed by Cox regression model (average hazard ratio throughout follow-up: 2.48; 95% CI: 1.59-3.84). CONCLUSIONS: This pan-Canadian cohort study of adults with CHD demonstrated an association between influenza virus-related hospitalization and risk of cardiovascular complications during the 9 months post discharge. This data is essential in planning surveillance strategies to mitigate adverse outcomes and provides insights into interpreting complication rates of other emerging pathogens, such as COVID-19.

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.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats.

BACKGROUND: Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism-like behavior of IMH offspring. METHODS: The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid-stimulating hormone (TSH) were detected using enzyme-linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open-field test, three-chamber sociability test, and Morris water maze, to explore the autistic-like behavior of 40-day-old offspring rats. RESULTS: The ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly. CONCLUSION: The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic-like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

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.

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.

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.

Associations between Life's Essential 8 and depression among US adults.

Few studies have examined the association of Life's Essential 8 (LE8) with depression among US adults. This is a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2020. LE8 score was measured as the mean score of eight metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipid, blood glucose, and blood pressure). CVH was categorized into low, moderate, and high according to tertiles of LE8 score. Depression was defined based on the 9-Item Patient Health Questionnaire (PHQ-9). Weighted logistic regressions were conducted to assess the associations of depression with CVH. Compared with participants with low CVH, the fully adjusted ORs of depression were 0.45 (0.37, 0.55) in the moderate CVH and 0.21 (0.15, 0.30) in the high CVH participants, respectively. The results remained robust in subgroup and sensitivity analyses. All eight LE8 metrics were negatively associated with depression, while nicotine exposure and sleep health were identified as two major metrics contributing to the association. Better CVH evaluated by LE8 was associated with decreased depression prevalence among US adults. Adherence to a higher CVH score, especially targeting smoking cessation and proper sleep duration, might be beneficial for prevention of depression.