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Abstract Objectives To evaluate the ability of sphericity in glioblastomas (GBMs) for predicting overall survival (OS) and the survival benefit from gross tumour resection (GTR). Methods Preoperative MRI scans were retrospectively analysed in IDH-wildtype GBM patients from two datasets. After MRI preprocessing and tumour segmentation, tumour sphericity was calculated based on the tumour core region. The prognostic value of tumour surface regularity was evaluated via Kaplan–Meier (K-M) plots, univariate and multivariate Cox proportional hazards analyses. In different surface regularity subgroups, the OS benefit from GTR was evaluated via K-M plots and the restricted mean survival time (RMST). Results This study included 367 patients (median age, 62.0 years [IQR, 54.5–70.5 years]) in the discovery cohort and 475 patients (median age, 63.6 years [IQR, 56.2–71.3 years]) in the validation cohort. Sphericity was an independent predictor of OS in the discovery (p = 0.022, hazard ratio (HR) = 1.45, 95% confidence interval (CI) 1.06–1.99) and validation groups (p = 0.007, HR = 1.38, 95% CI: 1.09–1.74) according to multivariate analysis. Age, extent of resection, and surface regularity composed a prognostic model that separated patients into subgroups with distinct prognoses. Patients in the surface-irregular subgroup benefited from GTR, but patients in the surface-regular subgroup did not in the discovery (p

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Researchers have been widely attracted by the lining block falling accident of Fukuoka tunnel in Japan, with the main reason that the cold joints have cause the lining blocks falling. This article constructs a numerical calculation model of the Fukuoka tunnel lining, which is based on cohesive fatigue damage units. It analyzes the damage and deformation of lining blocks with cold joints under aerodynamic fatigue loads. The study also explores the extents of aerodynamic load amplitude, pouring intervals, and block positioning on the damage to cold joint units. The study shows that this method is suitable for analyzing the damage process of lining blocks with cold joints under aerodynamic fatigue loads. The discrepancy between the predicted detachment time (40 years) and the actual time (25 years) is attributed to unclear design parameters, the exclusion of train vibration loads, and the deterioration of concrete performance. The timing of cohesive unit damage is accelerated with increasing aerodynamic load amplitude and pouring intervals, while it is delayed when the block position is lower. The greater the normal force on the lining block with cold joints, the more likely the cold joint interface elements are to be damaged.

Abstract Background To investigate the efficacy and safety of endoscopic electrocoagulation haemostasis via a percutaneous transhepatic approach for the treatment of grade IV haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children. Methods The clinical data of 14 children with severe HC, who were admitted to Hebei Yanda Hospital between July 2017 and January 2020, were analysed retrospectively. There were nine males and five females, with an average age of 8.6 years (range: 3 to 13 years). After an average of 39.6 (7 to 96) days of conservative treatment in the hospital’s haematology department, the bladders of all patients were filled with blood clots. A small 2-cm incision was made in the suprapubic area to enter the bladder and quickly clear the blood clots, and a percutaneous transhepatic approach to electrocoagulation and haemostasis was performed. Results In the 14 children, a total of 16 operations were performed, with an average operation time of 97.1 (31 to 150) min, an average blood clot of 128.1 (80 to 460) mL and an average intraoperative blood loss of 31.9 (20 to 50) mL. There were three cases of postoperative bladder spasm remission after conservative treatment. During the follow-up period of 1 to 31 months, one patient improved after one operation, 11 patients were cured after one operation, and two patients were cured after recurrent haemostasis by secondary electrocoagulation, four of whom died of postoperative non-surgical blood-related diseases and severe lung infections. Conclusion Percutaneous electrocoagulation haemostasis can quickly remove blood clots in the bladders of children after allo-HSCT with grade IV HC. It is a safe and effective minimally invasive treatment.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the COVID-19 pandemic, has profoundly impacted global healthcare systems and the trajectory of economic advancement. As nations grapple with the far-reaching consequences of this unprecedented health crisis, the administration of COVID-19 vaccines has proven to be a pivotal strategy in managing this crisis. Protein-based vaccines have garnered significant attention owing to their commendable safety profile and precise immune targeting advantages. Nonetheless, the unpredictable mutations and widespread transmission of SARS-CoV-2 have posed challenges for vaccine developers and governments worldwide. Monovalent and multivalent vaccines represent two strategies in COVID-19 vaccine development, with ongoing controversy surrounding their efficacy. This review concentrates on the development of protein-based COVID-19 vaccines, specifically addressing the transition from monovalent to multivalent formulations, and synthesizes data on vaccine manufacturers, antigen composition, pivotal clinical study findings, and other features that shape their distinct profiles and overall effectiveness. Our hypothesis is that multivalent vaccine strategies for COVID-19 could offer enhanced capability with broad-spectrum protection.

Objectives: To evaluate the ability of sphericity in glioblastomas (GBMs) for predicting overall survival (OS) and the survival benefit from gross tumour resection (GTR). Methods: Preoperative MRI scans were retrospectively analysed in IDH-wildtype GBM patients from two datasets. After MRI preprocessing and tumour segmentation, tumour sphericity was calculated based on the tumour core region. The prognostic value of tumour surface regularity was evaluated via Kaplan–Meier (K-M) plots, univariate and multivariate Cox proportional hazards analyses. In different surface regularity subgroups, the OS benefit from GTR was evaluated via K-M plots and the restricted mean survival time (RMST). Results: This study included 367 patients (median age, 62.0 years [IQR, 54.5–70.5 years]) in the discovery cohort and 475 patients (median age, 63.6 years [IQR, 56.2–71.3 years]) in the validation cohort. Sphericity was an independent predictor of OS in the discovery (p = 0.022, hazard ratio (HR) = 1.45, 95% confidence interval (CI) 1.06–1.99) and validation groups (p = 0.007, HR = 1.38, 95% CI: 1.09–1.74) according to multivariate analysis. Age, extent of resection, and surface regularity composed a prognostic model that separated patients into subgroups with distinct prognoses. Patients in the surface-irregular subgroup benefited from GTR, but patients in the surface-regular subgroup did not in the discovery (p < 0.001 vs. p = 0.056) and validation datasets (p < 0.001 vs. p = 0.11). Conclusions: The high surface regularity of IDH-wildtype GBM is significantly correlated with better OS and does not benefit substantially from GTR. Critical relevance statement: The proposed imaging marker has the potential to increase the survival prediction efficacy for IDH-wildtype glioblastomas (GBMs), offering a valuable indicator for clinical decision-making. Key Points: Sphericity is an independent prognostic factor in IDH-wildtype glioblastomas (GBMs). High sphericity in IDH-wildtype GBM is significantly correlated with better survival. GBM patients with low sphericity could receive survival benefits from gross tumour resection. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of patients with non-lesional epilepsy (NLE) is relatively challenging because of the absence of a clear focus on imaging, and the underlying pathological mechanism remains unclear. The neuronal activity and functional connectivity of NLE patients are significantly abnormal, and the neuronal activity of epilepsy patients is closely related to cerebral blood flow (CBF). Neurovascular coupling (NVC) offers insights into the relationship between neuronal activity and CBF. Hence, we intend to explore the alterations of NVC in NLE patients and their influences on cognitive function. Methods: Clinical data of 24 patients with NLE (15 female; age range 19–40 years; median age 30.5 years) and 39 healthy controls (27 female; age range 19–40 years; median age 30 years) were collected, and resting-state functional magnetic resonance imaging (rs-fMRI) and 3D arterial spin labeling (ASL) were performed. The imaging indexes of amplitude of low-frequency fluctuation (ALFF) and CBF were calculated, respectively, by post-processing analysis. The differences in CBF, ALFF and CBF/ALFF ratio between the two groups were analyzed, along with correlation with clinical data of NLE patients. Results: Compared with the healthy controls, the CBF of the right parahippocampal gyrus was significantly decreased, and the CBF/ALFF ratio of the right inferior parietal, but supramarginal and angular gyri was significantly increased in NLE patients (p < 0.001). Moreover, the CBF/ALFF ratio was positively correlated with epilepsy depression score (r = 0.546, p = 0.006). Conclusion: NLE patients showed abnormal local NVC, which was associated with the severity of depression. The combined application of rs-fMRI and ASL can comprehensively evaluate the neuronal activity and cerebral blood perfusion in patients with NLE. The abnormal NVC is of great significance for us to explore the central mechanism of the occurrence and development of NLE. [ABSTRACT FROM AUTHOR]

Introduction: The occurrence of Gleason grade group upgrading (GGU) significantly impacts treatment strategy developments. We aimed to develop an optimal predictive model to assess the risk of GGU in patients with localized prostate cancer (PCa), by comparing traditional logistic regression (LR) with seven machine learning algorithms. Methods: A retrospective collection of clinical data was conducted on patients who underwent radical prostatectomy at Wuhan Central Hospital (January 2017 to December 2023, n = 177) and Jiangxi Cancer Hospital (July 2019 to February 2024, n = 87). The least absolute shrinkage and selection operator regression was employed to filter the clinical characteristics of patients. Subsequently, models were conducted using multivariate LR, along with seven diverse machine learning algorithms: extreme gradient boosting, decision tree, multilayer perceptron, naive Bayes, K-nearest neighbors, random forest, and support vector machine. By employing the receiver operating characteristic curves, accuracy, brier score, recall, calibration curves, and decision curve analysis (DCA), we compared the predictive capabilities and clinical utility of eight models to identify the optimal one. Results: In the evaluation of eight models, the LR model demonstrated superior performance. In the modeling set, it achieved an area under curve (AUC) of 0.826 (95% CI: 0.808–0.845), accuracy of 0.765, and a brier score of 0.167. In the validation set, it kept good results with an AUC of 0.819 (95% CI: 0.758–0.880), accuracy of 0.725, and a brier score of 0.180. The calibration curves, brier score, and DCA also demonstrated the excellent calibration and net benefit of the LR model. Conclusions: After conducting a comprehensive multi-model comparison, we concluded that the LR model was optimal for predicting GGU, which was confirmed by external validation. Our study also revealed percent free prostate-specific antigen density as a predictive factor for GGU, offering a novel approach for managing localized PCa patients. [ABSTRACT FROM AUTHOR]

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its immunogenicity against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of 12 September 2023, 429 participants aged ≥18 years were randomized into the groups SCTV01E (N = 215) and SCTV01E-2 (N = 214). Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in the SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group than in the SCTV01E group. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase in nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine-related serious adverse events (SAEs), adverse events of special interest (AESIs), or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without raising safety concerns, highlighting its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

Summary: Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator of interferon genes (STING)-TBK1-IRF3-type I interferon (IFN-I) signalingcascade. Here, we report that the HIV-1 p6 protein suppresses HIV-1-stimulated expression of IFN-I and promotes immune evasion. Mechanistically, the glutamylated p6 at residue Glu6 inhibits the interaction between STING and tripartite motif protein 32 (TRIM32) or autocrine motility factor receptor (AMFR). This subsequently suppresses the K27- and K63-linked polyubiquitination of STING at K337, therefore inhibiting STING activation, whereas mutation of the Glu6 residue partially reverses the inhibitory effect. However, CoCl2, an agonist of cytosolic carboxypeptidases (CCPs), counteracts the glutamylation of p6 at the Glu6 residue and inhibits HIV-1 immune evasion. These findings reveal a mechanism through which an HIV-1 protein mediates immune evasion and provides a therapeutic drug candidate to treat HIV-1 infection.

Objective: Ischemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients. Methods: We studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group. Results: The iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR. Conclusion: ESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke. [ABSTRACT FROM AUTHOR]

Introduction: During an immune response, macrophages undergo systematic metabolic rewiring tailored to support their functions. Branched-chain amino acid (BCAA) metabolism has been reported to modulate macrophage function; however, its role in macrophage alternative activation remain unclear. We aimed to investigate the role of BCAA metabolism in macrophage alternative activation. Method: The metabolomics of BMDM-derived M0 and M2 macrophages were analyzed using LC-MS. BCAAs were supplemented and genes involved in BCAA catabolism were inhibited during M2 macrophage polarization. The expression of M2 marker genes was assessed through RT-qPCR, immunofluorescence, and flow cytometry. Results and discussion: Metabolomic analysis identified increased BCAA metabolism as one of the most significantly rewired pathways upon alternative activation. M2 macrophages had significantly lower BCAA levels compared to controls. BCAA supplementation promoted M2 macrophage polarization both in vitro and in vivo and increased oxidative phosphorylation in M2 macrophages. Blocking BCAA entry into mitochondria by knockdown of SLC25A44 inhibited M2 macrophage polarization. Furthermore, M2 macrophages polarization was suppressed by knockdown of Branched-chain amino-acid transaminase 2 (BCAT2) and branched chain keto acid dehydrogenase E1 subunit alpha (BCKDHA), both of which are key enzymes involved in BCAA oxidation. Overall, our findings suggest that BCAA catabolism plays an important role in polarization toward M2 macrophages. [ABSTRACT FROM AUTHOR]

Abstract Background Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. Methods This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. Results The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742–0.806) and 0.820 (95% CI: 0.762–0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. Conclusions The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.

Abstract Background Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. Methods We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. Results In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268–9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455–0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346–2.760, P

Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.

In China, online sales continue to grow against the generally adverse effects of the COVID-19 pandemic on economic development. Although advertisers favor online targeted advertising for its precision, consumers may find it intrusive and avoid it. This study constructed a conceptual model based on Stimulus-Organism-Response (SOR) theory, Approach-Avoidance Theory, and Brand Avoidance Theory to investigate the influence mechanism of consumers’ perceived risk on the avoidance behavior of online targeted advertising via an online survey. Collected 436 validated data was analyzed through structural equation method in AMOS statistical software. Results showed that the positively influenced advertising avoidance, and negative emotions mediated the relationship between perceived performance risk, time-loss risk, freedom risk, and advertising avoidance, but perceived privacy risk did not influence advertising avoidance through negative emotions. Perceived COVID-19 risk moderates the effect of negative emotions on advertising avoidance. The findings provide important insights for helping governments, advertisers and online platforms into which risk perceptions influence advertising avoidance, and suggests ways to mitigate consumers risk perceptions for the mutual benefit of brands and users.

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01–1.08) and 1.93 (95% CI: 1.11–3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99–1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80–2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.

Introduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson's disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients. Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients. Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson's Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively). Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients. [ABSTRACT FROM AUTHOR]

Purpose: Stroke-associated pneumonia (SAP), a common complication in acute ischemic stroke (AIS) patients, is associated with poor prognosis after AIS. Inflammation plays an important role in the development of SAP. In this study, we aimed to explore the association between the monocyte-to-lymphocyte ratio (MLR) and SAP in AIS patients.Methods: We continuously enrolled 972 AIS patients. SAP was diagnosed by two trained neurologists and confirmed by radiography, meeting the modified Centers for Disease Control and Prevention criteria. MLR values were measured for all participants, and all patients were evenly classified into three tertiles according to the MLR levels. We used the values that Youden's index max points corresponded to represent the optimal cutoffs, which represented the balance in sensitivity and specificity.Results: 104 (10.7%) patients were diagnosed with SAP. SAP patients showed a significant increased (P < 0.001) MLR when compared with non-SAP. The optimal cutoff points of MLR were (T1) 0.3843. The incidence of SAP was significantly higher in the third MLR tertile than the first and second MLR tertiles (21.7 vs. 4 vs. 6.5%, respectively, P < 0.001). After adjusting for confounding and risk factors, multivariate regression analysis showed that the third MLR tertile was an independent variable predicting the occurrence of SAP (odds ratio = 3.503, 95%CI = 1.066–11.515, P = 0.039).Conclusions: Our study showed that higher MLR was significantly associated with SAP in AIS patients. MLR is beneficial for clinicians to recognize patients with a high risk of SAP at an early stage and is an effective way to improve clinical care of SAP patients. Higher MLR could be a helpful and valid biomarker for predicting SAP in clinical practice.

Background: Hemorrhagic transformation (HT) is a frequent, often asymptomatic event that occurs after acute ischemic stroke (AIS). Liver fibrosis, usually subclinical, is common and crucial in the development of liver disease. We aimed to investigate the association between liver fibrosis and HT in patients with AIS.Methods: We performed a single-center and retrospective study. A total of 185 consecutive participants with HT and 199 age- and sex-matched stroke patients without HT were enrolled in this study. We calculated one validated fibrosis index—Fibrosis-4 (FIB-4) score—to assess the extent of liver fibrosis. HT was detected by routine CT or MRI and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. HT was also classified into asymptomatic or symptomatic. We used logistic regression models adjusted for previously established risk factors to assess the risks for HT.Results: The median FIB-4 score was significantly higher among patients who developed HT than among those without HT, whereas standard hepatic assays were largely normal. Patients were assigned to groups of high FIB-4 score and low FIB-4 score based on the optimal cutoff value. Compared with the subjects in the low-FIB-4-score group, incidence of HT for the high-FIB-4-score group was significantly higher. After adjustment for potential confounders, the patients with high FIB-4 score had 3.461-fold risk of HT in AIS compared to the patients with low FIB-4 score [odds ratio, 3.461 (95% CI, 1.404–8.531)].Conclusion: Liver fibrosis, measured by FIB-4 score, was independently associated with the risk of HT in AIS patients.

Abstract Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication. However, how exactly NS3 exerts these functions remains unknown. Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6) as a novel NS3-interacting protein via yeast two-hybrid analysis, co-immunoprecipitation, and glutathione S-transferase pull-down assays. Furthermore, we observed that TRAF6 overexpression significantly inhibited CSFV replication, and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages. Additionally, TRAF6 was degraded during CSFV infection or NS3 expression exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that TRAF6 degradation might contribute to persistent CSFV replication. Moreover, nuclear factor-kappa B (NF-κB) activity and interferon (IFN)-β and interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells, whereas TRAF6-knockdown cells exhibited decreased NF-κB activity and IFN-β and IL-6 levels. Notably, TRAF6 overexpression did not reduce CSFV replication following inhibition of NF-κB activation by p65 knockdown. Our findings revealed that TRAF6 inhibits CSFV replication via activation of NF-κB-signalling pathways along with increases in the expression of its targets IFN-β and IL-6. This work addresses a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection.

Giardia duodenalis, formerly known as Giardia lamblia, is an important zoonotic protozoan parasite. It mainly infects the intestines of humans, dogs, cats and domestic animals, causing diarrhea, abdominal pain, indigestion and weight loss. At present, all the clinical drugs for the treatment of Giardia have problems such as side effects and drug resistance to varying degrees, and the development of new drugs for the treatment of Giardia is still a hot issue. There is growing interest in using probiotics as an anti-intestinal parasite strategy. The present study aimed to assess the effect of supernatants of Bifidobacterium Animalis Subsp. lactis BB-12 on giardia the growth of giardia trophozoites. In this study, the Bifidobacterium animalis subsp. lactis BB-12 were cultured in BBL liquid medium, and the effects of the supernatants on the growth and adhesion of trophozoites of Giardia were observed. The results showed that the growth of Giardia flagellate was significantly inhibited by the supernatant. The influence of the supernatant on the morphology of the trophozoites was observed by microscope, and it was found that the surface of the trophozoites was uneven, the shape was atrophied, the surface cell membrane was broken to some extent, and the contents were spilt. In summary, the results of this study suggest that the fresh-cultured supernatants of the probiotic Bifidobacterium Animalis subsp. lactis BB-12 have anti-Giardia effects.