Lower serum uric acid to serum creatinine ratio as a predictor of poor functional outcome after mechanical thrombectomy in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT-treated AIS patients. METHODS: Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death. RESULTS: Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score (ρ = -0.095, p = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282-0.428, p < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724-0.788, p < 0.001). CONCLUSION: The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90-day functional outcome in AIS patients undergoing MT.

Effect of Additives on CO2 Adsorption of Polyethylene Polyamine-Loaded MCM-41.

Organic amine-modified mesoporous carriers are considered potential CO2 sorbents, in which the CO2 adsorption performance was limited by the agglomeration and volatility of liquid amines. In this study, four additives of ether compounds were separately coimpregnated with polyethylene polyamine (PEPA) into MCM-41 to prepare the composite chemisorbents for CO2 adsorption. The textural pore properties, surface functional groups and elemental contents of N for MCM-41 before and after functionalization were characterized; the effects of the type and amount of additives, adsorption temperature and influent velocity on CO2 adsorption were investigated; the amine efficiency was calculated; and the adsorption kinetics and regeneration for the optimized sorbent were studied. For 40 wt.% PEPA-loaded MCM-41, the CO2 adsorption capacity and amine efficiency at 60 °C were 1.34 mmol/g and 0.18 mol CO2/mol N, when the influent velocity of the simulated flue gas was 30 mL/min, which reached 1.81 mmol/g and 0.23 mol CO2/mol N after coimpregnating 10 wt.% of 2-propoxyethanol (1E). The maximum adsorption capacity of 2.16 mmol/g appeared when the influent velocity of the simulated flue gas was 20 mL/min. In addition, the additive of 1E improved the regeneration and kinetics of PEPA-loaded MCM-41, and the CO2 adsorption process showed multiple adsorption routes.

Associations between prenatal exposure to phthalates and birth weight: A meta-analysis study.

Previous studies have suggested that phthalates are associated with birth weight. However, most phthalate metabolites have not been fully explored. Therefore, we conducted this meta-analysis to assess the relationship between phthalate exposure and birth weight. We identified original studies that measured phthalate exposure and reported its association with infant birth weight in relevant databases. Regression coefficients (ß) with 95% confidence intervals (CIs) were extracted and analyzed for risk estimation. Fixed-effects (I2 ≤ 50%) or random-effects (I2 > 50%) models were adopted according to their heterogeneity. Overall summary estimates indicated negative associations of prenatal exposure to mono-n-butyl phthalate (pooled ß = -11.34 g; 95% CI: -20.98 to -1.70 g) and mono-methyl phthalate (pooled ß = -8.78 g; 95% CI: -16.30 to -1.27 g). No statistical association was found between the other less commonly used phthalate metabolites and birth weight. Subgroup analyses indicated that exposure to mono-n-butyl phthalate was associated with birth weight in females (ß = -10.74 g; 95% CI: -18.70 to -2.79 g). Our findings indicate that phthalate exposure might be a risk factor for low birth weight and that this relationship may be sex specific. More research is needed to promote preventive policies regarding the potential health hazards of phthalates.

[Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of three children with KBG syndrome. METHODS: Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. RESULTS: All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype. CONCLUSION: The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.

[Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene].

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION: The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.

Dual Antiplatelet Therapy Plus Argatroban Prevents Early Neurological Deterioration in Branch Atherosclerosis Disease.

[Figure: see text].

Impact of persistent subclinical hypothyroidism on clinical outcomes in non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Data on the association of subclinical hypothyroidism (SCH) with the severity of coronary artery disease and major adverse cardiovascular and cerebral events (MACCE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) are limited and conflicting. OBJECTIVE: We established the baseline rate of SCH and followed the trajectory of thyroid-stimulating hormone (TSH) values during and after hospitalisation for PCI for up to six months and determined whether persistent SCH was associated with the severity of coronary artery disease and MACCE in patients with NSTE-ACS after PCI. DESIGN: Population-based prospective cohort study. PATIENTS: We included patients with NSTE-ACS who underwent PCI with simple balloon angioplasty or stent implantation for coronary heart disease. MEASUREMENTS: Thyroid function tests of patients before PCI and 1 day, 1 week, 1 and 6 months after PCI were performed. Cases showing transient SCH were excluded. Patients were divided into two groups based on the results of four TSH tests: 0.27-4.2 mIU/L (n = 1472, 89.7%) and >4.2 mIU/L (n = 170, 10.4%). The risk factors for the severity of coronary artery lesions were estimated using multinomial logistic regression analysis. Univariate and multivariate Cox regression analyses were used to study the relationship between TSH and MACCE. RESULTS: Among 1642 patients, there were 1070 males (65.2%) and 572 females (34.8%), with an average age of 62.5 ± 9.6 years. SCH patients had a wider range of diseased vessels and a higher number of diseased vessels (p < .05). TSH level was an independent risk factor for moderate [odds ratio (OR) = 1.144, 95% confidence interval (95% CI): 1.057-1.237, p = .001] and severe (OR = 1.131, 95% CI: 1.043-1.226, p = .003) coronary artery lesions. After adjusting for covariates, the risk of MACCE [hazard ratio (HR): 4.067, p < .001], nonfatal myocardial infarction (HR: 14.724, p = .003), and unplanned PCI (HR: 5.028, p < .001) were higher in the SCH group than in the euthyroidism group. There were no significant differences in the incidence of heart failure (HR: 6.012, p = .175), nonfatal stroke (HR: 2.039, p = .302), unplanned coronary artery bypass grafting (CABG) (HR: 1.541, p = .57), or cardiac death (HR: 2.704, p = .375) between the two groups. CONCLUSIONS: Preoperative TSH levels and changes in thyroid hormone levels several months post-PCI in NSTE-ACS patients are highly significant in practice. Persistent SCH is associated with severe coronary artery lesions and MACCE, and may be a predictor for evaluating the prognosis of PCI-treated NSTE-ACS patients.

Risk factors for early neurological deterioration in acute isolated pontine infarction without any causative artery stenosis.

BACKGROUND: This study aimed to investigate the risk predictors for early neurological deterioration (END) in isolated acute pontine infarction without any causative artery stenosis. METHODS: In this retrospective study, patients with isolated acute pontine infarction within 72 h of symptom onset were enrolled between October 2017 and December 2021. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 2 points within the first week postadmission. Patients were divided into the END and the non-END groups. Multiple logistic regression analysis was used to evaluate independent predictors of END in patients with isolated acute pontine infarction. RESULTS: A total of 153 patients were included in the final study (62 females; mean age, 67.27 ± 11.35 years), of whom 28.7% (47 of 153) experienced END. Multiple logistic regression analyses showed that infarct volume (adjusted odds ratio [aOR], 1.003; 95% CI, 1.001-1.005; P = 0.002) and basilar artery branch disease  (aOR, 3.388; 95% CI, 1.102-10.417; P = 0.033) were associated with END. The combined ROC analysis of the infarct volume and basilar artery branch disease for predicting END showed that the sensitivity and specificity were 80.9% and 72.6%, respectively. CONCLUSION: Basilar artery branch disease and infarct volume were associated with END in acute isolated pontine infarction and may be useful prognostic factors for neurological progression.

[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Bainbridge-Ropers syndrome].

OBJECTIVE: To explore the clinical features and genetic basis for a child with Bainbridge-Ropers syndrome (BRPS). METHODS: Clinical data of the child were retrospectively analyzed. Copy number variation sequencing (CNV-seq) and trio based whole exome sequencing (trio-WES) were carried out. Prenatal diagnosis was provided for a at risk fetus from the pedigree, and genotype phenotype correlation was summarized through a literature review. RESULTS: The proband, a 6-year-old boy, has presented with feeding difficulties, specific craniofacial features, global developmental delay and intellectual disability, which has not improved after rehabilitation treatment. CNV-seq analysis of the patient showed no obvious abnormalities. A de novo heterozygous truncating variation, c.1448dupT (p.T484Nfs*5), was identified in the ASXL3 gene by trio-WES, which was a previously reported pathogenic variant. So far 14 Chinese patients with BRPS and ASXL3 variants have been reported. All patients have shown specific craniofacial features and delayed motor and speech development, and harbored 12 loss of function ASXL3 variants, which were de novo in origin and have clustered in exons 11 and 12 of the ASXL3 gene. CONCLUSION: The heterozygous frameshift c.1448dupT (p.T484Nfs*5) variant of the ASXL3 gene probably underlay the disorder in this patient. BRPS should be considered in infants with feeding difficulties, special craniofacial features, global developmental delay and hand anomalies, and WES can help to delineate the pathogenesis and establish the definite diagnosis.

Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome.

BACKGROUND: The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS. METHODS: A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). RESULTS: The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan-Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201-1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019). CONCLUSIONS: The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.

Proprotein convertase subtilisin/kexin 9 inhibitor downregulates microRNA-130a-3p expression in hepatocytes to alleviates atherosclerosis progression.

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have been shown to regulate lipid metabolism and reduce the risk of cardiovascular events. This study explores the effect and potential mechanism of PCSK9 inhibitors on lipid metabolism and coronary atherosclerosis. HepG2 cells were incubated with PCSK9 inhibitor. ApoE-/- mice were fed with a high fat to construct an atherosclerosis model, and then treated with PCSK9 inhibitor (8 mg/kg for 8 w). PCSK9 inhibitor downregulated microRNA (miRNA)-130a-3p expression in a dose-dependent manner. And, miR-130a-3p could bind directly to the 3' untranslated region (3'-UTR) region of LDLR to down-regulate LDLR expression in HepG2 cells, as confirmed by the luciferase reporter gene assay. In addition, miR-130a-3p overexpression significantly attenuated the promoting effect of PCSK9 inhibitor on LDLR and DiI-LDL uptake in HepG2 cells. More importantly, in vivo experiments confirmed that PCSK9 inhibitor could significantly inhibit miR-130a-3p levels and promote LDLR expression in liver tissues, thus regulating serum lipid profile and alleviating the progression of coronary atherosclerosis. PCSK9 inhibitor could moderately improve coronary atherosclerosis by regulating miR-130a-3p/LDLR axis, providing an exploitable strategy for the treatment of coronary atherosclerosis.

Microparticulated Polygonatum sibiricum polysaccharide shows potent vaccine adjuvant effect.

Adjuvants are necessary for protein vaccines and have been used for nearly 100 years. However, developing safe and effective adjuvants is still urgently needed. Polysaccharides isolated from traditional Chinese medicine are considered novel vaccine adjuvant sources. This study aimed to investigate the adjuvant activity and immune-enhancing mechanisms of the microparticulated Polygonatum sibiricum polysaccharide (MP-PSP) modified by calcium carbonate. PSP demonstrated adjuvant activity, and MP-PSP further showed a higher humoral response compared to PSP. Subsequently, MP-PSP was elucidated to improving the immunity by slowing the rate of antigen release and activating dendritic cells along with interleukin-6 secretion through toll-like receptor 4 signaling, followed by T follicular helper cell and B cell interactions. Moreover, MP-PSP had a good safety profile in vaccinated mice. Thus, MP-PSP may be a promising vaccine adjuvant and warrants further investigation.

Lipoprotein Subfractions as Markers for Predicting the Presence and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography.

Patients with coronary artery disease (CAD) often have normal blood cholesterol profiles that make it difficult to identify those at risk. The role of lipoprotein subfractions in the development of CAD has attracted increasing attention, and can further stratify risks. We enrolled 1578 patients undergoing coronary angiography and not taking any lipid-lowering drugs; 1033 of them were diagnosed with CAD. The severity of CAD was assessed using Gensini score (GS) and divided into 3 groups. Multivariate regression analysis showed that low-density lipoprotein particle 6 (LDL-P6) and lipoprotein (a) (Lp(a)) were independent risk factors for CAD, apart for the traditional risk factors. In receiver-operating characteristic (ROC) analysis for predicting the presence of CAD, the area under the ROC curve of traditional risk factors combined with Lp(a) and LDL-P6 for predicting CAD was .723, which was better than for traditional risk factors (P = .023). The plasma LDL-P6 and Lp(a) concentrations in the highest tertile GS group were significantly higher than that in the lowest GS group (P < .001). Stepwise linear regression analysis demonstrated positive correlations between Lp(a), LDL-P6 and GS (P = .007 and P < .001). LDL-P6 and Lp(a) are useful markers for predicting the presence and severity of CAD.

Highly porous BiOBr@NU-1000 Z-scheme heterojunctions for synergistic efficient adsorption and photocatalytic degradation of tetracycline.

Designing an effective photoactive heterojunction having dual benefits towards photoenergy conversion and pollutant adsorption is regarded as an affordable, green method for eliminating tetracycline (TC) from wastewater. In this regard, a series of BiOBr@NU-1000 (BNU-X, X = 1, 2 and 3) heterojunction photocatalysts are constructed. BNU-X preserves the original skeleton structure of the parent NU-1000, and its high porosity and specific surface area enable superior TC adsorption. At the same time, BNU-X is an effective Z-scheme photocatalyst that improves light trapping, promotes photoelectron-hole separation, and shows excellent photocatalytic degradation efficiency towards TC with the value of the photodegradation kinetic rate constant k being 2.2 and 24.8 times those of NU-1000 and BiOBr, respectively. The significant increase in the photocatalytic activity is ascribed to the construction of an efficient Z-scheme photocatalyst, which promotes the formation of superoxide radicals (˙O2-) and singlet oxygen (1O2) as the main oxidative species in the oxidation system. This research has the advantage of possibilities for the development of porous Z-scheme photocatalysts based on photoactive MOF materials and inorganic semiconductors for the self-purification and photodegradation of organic contaminants.

Astaxanthin Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis.

Increasing evidence points to the critical role of calcium overload triggered by mitochondrial dysfunction in the development of alcoholic liver disease (ALD). As an important organelle for aerobic respiration with a double-layered membrane, mitochondria are pivotal targets of alcohol metabolism-mediated lipid peroxidation, wherein mitochondria-specific phospholipid cardiolipin oxidation to 4-hydroxynonenal (4-HNE) ultimately leads to mitochondrial integrity and function impairment. Therefore, it is absolutely essential to identify effective nutritional intervention targeting mitochondrial redox function for an alternative therapy of ALD, in order to compensate for the difficulty in achieving alcohol withdrawal due to addiction. In this study, we confirmed the significant advantages of astaxanthin (AX) against alcohol toxicity among various carotenoids via cell experiments and identified the potential in mitochondrion morphogenesis and calcium signaling pathway by bioinformatics analysis. The ALD model of Sprague-Dawley (SD) rats was also generated to investigate the effectiveness of AX on alcohol-induced liver injury, and the underlying mechanisms were further explored. AX intervention attenuated alcohol-induced oxidative stress and lipid peroxidation as well as mitochondrial dysfunction characterized by degenerative morphology changes and collapsed membrane potential. Also, AX reduced the production of 4-HNE by activating the Nrf2-ARE signaling pathway, which is closely associated with the redox balance of mitochondria. In addition, relieved mitochondrial Ca2+ accumulation caused by AX was observed both in vivo and in vitro. Furthermore, we revealed the structure-activity relationship of AX and mitochondrial membrane channel proteins MCU and VDAC1, implying potential acting targets. Altogether, our data indicated a new mechanism of AX intervention which protects against alcohol-induced liver injury through restoring redox balance and Ca2+ homeostasis in mitochondria, as well as provided novel insights into the development of AX as a therapeutic option for the management of ALD.

Changes in the gut microbiota structure and function in rats with doxorubicin-induced heart failure.

Objectives: The rat model of heart failure (HF) induced by doxorubicin (DOX), a broad spectrum and highly effective chemotherapeutic anthracycline with high-affinity to myocardial tissue that causes severe dose-dependent irreversible cardiotoxicity has been widely recognized and applied in HF pathogenesis and drug therapy studies. The gut microbiota (GM) has attracted significant attention due to its potential role in HF, and research in this area may provide beneficial therapeutic strategies for HF. Considering the differences in the route, mode, and total cumulative dose of DOX administration used to establish HF models, the optimal scheme for studying the correlation between GM and HF pathogenesis remains to be determined. Therefore, focusing on establishing the optimal scheme, we evaluated the correlation between GM composition/function and DOX-induced cardiotoxicity (DIC). Methods: Three schemes were investigated: DOX (at total cumulative doses of 12, 15 or 18 mg/kg using a fixed or alternating dose via a tail vein or intraperitoneal injection) was administered to Sprague Dawley (SD) for six consecutive weeks. The M-mode echocardiograms performed cardiac function evaluation. Pathological changes in the intestine were observed by H&E staining and in the heart by Masson staining. The serum levels of N-terminal pre-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by ELISA. The GM was analysed by 16S rRNA gene sequencing. Key findings: Strikingly, based on the severity of cardiac dysfunction, there were marked differences in the abundance and grouping of GM under different schemes. The HF model established by tail vein injection of DOX (18 mg/kg, alternating doses) was more stable; moreover, the degree of myocardial injury and microbial composition were more consistent with the clinical manifestations of HF. Conclusions: The model of HF established by tail vein injection of doxorubicin, administered at 4mg/kg body weight (2mL/kg) at weeks 1, 3 and 5, and at 2mg/kg body weight (1mL/kg) at weeks 2, 4 and 6, with a cumulative total dose of 18mg/kg, is a better protocol to study the correlation between HF and GM.

Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing.

Designing a modified virus that can be controlled to replicate will facilitate the study of pathogenic mechanisms of virus and virus-host interactions. Here, we report a universal switch element that enables precise control of virus replication after exposure to a small molecule. Inteins mediate a traceless protein splicing-ligation process, and we generate a series of modified vesicular stomatitis virus (VSV) with intein insertion into the nucleocapsid, phosphoprotein, or large RNA-dependent RNA polymerase of VSV. Two recombinant VSV, LC599 and LY1744, were screened for intein insertion in the large RNA-dependent RNA polymerase of VSV, and their replication was regulated in a dose-dependent manner with the small molecule 4-hydroxytamoxifen, which induces intein splicing to restore the VSV replication. Furthermore, in the presence of 4-hydroxytamoxifen, the intein-modified VSV LC599 replicated efficiently in an animal model like a prototype of VSV. Thus, we present a simple and highly adaptable tool for regulating virus replication.

Effects of SARS-CoV-2 Omicron BA.1 Spike Mutations on T-Cell Epitopes in Mice.

T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2d) and C57BL/6 mice (H-2b) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4+ T-cell epitopes and most of which were CD8+ T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2b and H-2d mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity.

FT3/FT4 Enhances Risk Assessment in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Based on GRACE 2.0 Score.

Little is known about the association between the free triiodothyronine/free thyroxine (FT3/FT4) ratio and clinical outcomes in euthyroid patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). A total of 1448 euthyroid patients with NSTE-ACS who underwent PCI were included in this prospective study. Multivariate Cox regression analysis revealed that there was a significantly increased risk of stroke (hazard ratio [HR] 11.380, 95% confidence interval [CI]: 1.386-93.410, P = .024) and major adverse cardiovascular and cerebrovascular events (MACCEs) (HR 3.364, 95% CI: 1.595-7.098, P = .001) in patients in lower FT3/FT4 tertiles. The combined model of FT3/FT4 ratio and the Global Registry of Acute Coronary Events (GRACE) score provided the added value of risk assessment by improving C-statistics, integrated discrimination improvement (IDI), and the net reclassification index (NRI) (all P < .05). Thus, in euthyroid patients with NSTE-ACS undergoing PCI, the FT3/FT4 ratio was not only an independent prognostic indicator of long-term MACCE but also enhanced risk discrimination when combined with the GRACE risk score, which suggests that the calculation of FT3/FT4 before and after PCI may contribute to risk stratification in this particular patient group.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.