Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters.

The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility. Significantly, the evolutionary trajectory of SARS-CoV-2 has shown continual progression, with a recent global shift observed from XBB to BA.2.86, exemplified by the emergence of the predominant JN.1 subvariant. This phenomenon highlights the need for vaccines that can provide broad-spectrum antigenic coverage. In this study, we utilized a NS1-deleted (dNS1) influenza viral vector to engineer an updated live-attenuated vectored vaccine called dNS1-XBB-RBD. This vaccine encodes the receptor-binding domain (RBD) protein of the XBB.1.5 strain. Our findings demonstrate that the dNS1-XBB-RBD vaccine elicits a similar systemic and mucosal immune response compared to its prototypic form, dNS1-RBD. In hamsters, the dNS1-XBB-RBD vaccine provided robust protection against the SARS-CoV-2 immune-evasive strains XBB.1.9.2.1 and Beta. Remarkably, nasal vaccination with dNS1-RBD, which encodes the ancestor RBD gene, also effectively protected hamsters against both the XBB.1.9.2.1 and Beta strains. These results provide valuable insights about nasal influenza-vectored vaccine and present a promising strategy for the development of a broad-spectrum vaccine against COVID-19 in the future.

Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Use of the systemic inflammation response index (SIRI) as a novel prognostic marker for patients on peritoneal dialysis.

BACKGROUND: The systemic inflammatory response index (SIRI), a novel inflammation maker, has proven to be associated with prognostic outcomes in various diseases. However, few studies have been conducted assessing how SIRI may influence outcomes of patients on peritoneal dialysis (PD). Herein, we assessed the predictive value of SIRI on mortality all-cause mortality, including cardiovascular disease (CVD) in PD patients. METHODS: A total of 646 PD patients were enrolled in this study. PD patients received regular PD treatments at the Zhujiang Hospital from 1 January 2011 to 31 December 2018. SIRI values could be computed as follows: neutrophil count × monocyte count/lymphocyte count. Patients were divided into two groups according to the median level of SIRI. Cox regression analysis and Kaplan-Meier methods were applied to analyze the relationship between SIRI and mortality outcomes in PD patients. RESULTS: During the median 31-month follow-up period, 97 (15.0%) PD patients died from all-causes, and 47 (49.0%) died of CVD. Kaplan-Meier analyses revealed that a high SIRI corresponded to the high mortality of all-cause deaths, including CVD (both p < 0.001) in patients on PD. After adjusting for potential confounders, the higher SIRI level was significantly associated with an increased all-cause mortality (HR: 2.007, 95% CI: 1.304-3.088, p = 0.002) and cardiovascular mortality (HR: 2.847, 95% CI: 1.445-5.608, p = 0.002). CONCLUSIONS: SIRI was a promising predictor of mortality in PD patients, with a higher SIRI corresponding to increased risk of mortality.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

Impact of the caFFR-Guided Functional SYNTAX Score on Ventricular Tachycardia/Fibrillation Development in Patients With Acute Myocardial Infarction.

Aims: To explore the relationship between the severity of coronary artery disease (CAD) and the occurrence of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with acute myocardial infarction (AMI). Methods: We retrospectively enrolled 705 patients with AMI, who were hospitalized and underwent percutaneous coronary intervention (PCI), in Nanfang Hospital from July 2017 to July 2020. Logistic regression analysis and backward stepwise approach were taken to select the correlation factors. The left and the receiver operating characteristic curves (ROC) analysis were plotted to observe the discriminative power of the SYNTAX score (SS)/caFFR-guided functional SS (FSScaFFR) on the incident VT/VF. Results: About 58 (8.2%) patients experienced life-threatening VT/VF. The FSScaFFR (OR: 1.155; 95% CI: 1.047 to 1.273; p = 0.004) was an independent predictor of VT/VF after AMI. The ROC analysis showed that the discriminative power of FSScaFFR on the incident VT/VF was significantly better than SS (0.759 vs.0.695, p < 0.0001). Patients with VT/VF were categorized into 2 groups according to the interval between the onset of AMI and the VT/VF. The logistic regression analysis revealed that FSScaFFR was a significant independent correlation of early- and late-VT/VF. Conclusion: The incident VT/VF in patients with AMI is closely associated with the severity of CAD evaluated by SS and FSScaFFR. Compared to SS, FSScaFFR has a higher correlation with VT/VF, and FSScaFFR was demonstrated to be an independent correlation factor of incident VT/VF after AMI.

The Association Between Visceral Adiposity Index and Worsening Renal Function in the Elderly.

Background: Visceral adiposity index (VAI) is an indicator of visceral fat accumulation and dysfunction. However, little is known about whether VAI is associated with worsening renal function (WRF) in the elderly. Therefore, our study aimed to explore the association between VAI and WRF among the elderly population. Methods: In total, 5,583 elderly participants (aged ≥ 65 years) who participated in the annual health checkups at least twice between January 2017 and July 2021 were enrolled and divided into four groups according to the VAI quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The secondary endpoint was rapid kidney function decline (RKFD), defined as decline in eGFR of 40%. To evaluate the association between VAI and WRF, three Cox regression models were conducted, where VAI was treated as a continuous variable and a categorical variable (Q1 as reference), respectively. Subgroup analysis in participants with different baseline characteristics was also performed. Results: During a median of 2.46 year follow-up, 931 (16.68%) participants developed CKD. After fully adjusting for confounding factors, VAI was significantly associated with incident CKD (HR, 1.052; 95% CI: 1.029-1.076, p < 0.001), and RKFD (HR, 1.077; 95% CI: 1.041-1.114, p < 0.001). Moreover, compared to those with the lowest VAI quartiles, subjects with the highest quartiles had a higher risk of incident CKD (HR, 1.286; 95% CI: 1.033-1.601, p = 0.024), and RKFD (HR, 1.895; 95% CI: 1.086-3.307, p = 0.025). The risk of incident CKD also tended to increase with elevated VAI quartiles (all p-values for trend <0.05). This positive association remained consistent among participants with different genders, baseline weights, or kidney functions. Conclusion: In our study, elevated VAI was associated with increased risk of incident CKD and RKFD in the elderly population.

Nomogram to predict rapid kidney function decline in population at risk of cardiovascular disease.

BACKGROUND: To develop a reliable model to predict rapid kidney function decline (RKFD) among population at risk of cardiovascular disease. METHODS: In this retrospective study, key monitoring residents including the elderly, and patients with hypertension or diabetes of China National Basic Public Health Service who underwent community annual physical examinations from January 2015 to December 2020 were included. Healthy records were extracted from regional chronic disease management platform. RKFD was defined as the reduction of estimated glomerular filtration rate (eGFR) ≥ 40% during follow-up period. The entire cohort were randomly assigned to a development cohort and a validation cohort in a 2:1 ratio. Cox regression analysis was used to identify the independent predictors. A nomogram was established based on the development cohort. The concordance index (C-index) and calibration plots were calculated. Decision curve analysis was applied to evaluate the clinical utility. RESULTS: A total of 8455 subjects were included. During the median follow-up period of 3.72 years, the incidence of RKFD was 11.96% (n = 1011), 11.98% (n = 676) and 11.92% (n = 335) in the entire cohort, development cohort and validation cohort, respectively. Age, eGFR, hemoglobin, systolic blood pressure, and diabetes were identified as predictors for RKFD. Good discriminating performance was observed in both the development (C-index, 0.73) and the validation (C-index, 0.71) cohorts, and the AUCs for predicting 5-years RKFD was 0.763 and 0.740 in the development and the validation cohort, respectively. Decision curve analysis further confirmed the clinical utility of the nomogram. CONCLUSIONS: Our nomogram based on five readily accessible variables (age, eGFR, hemoglobin, systolic blood pressure, and diabetes) is a useful tool to identify high risk patients for RKFD among population at risk of cardiovascular disease in primary care. Whereas, further external validations are needed before clinical generalization.

Nomogram to predict risk of incident chronic kidney disease in high-risk population of cardiovascular disease in China: community-based cohort study.

AIMS: To develop a nomogram for incident chronic kidney disease (CKD) risk evaluation among community residents with high cardiovascular disease (CVD) risk. METHODS: In this retrospective cohort study, 5730 non-CKD residents with high CVD risk participating the National Basic Public Health Service between January 2015 and December 2020 in Guangzhou were included. Endpoint was incident CKD defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 during the follow-up period. The entire cohorts were randomly (2:1) assigned to a development cohort and a validation cohort. Predictors of incident CKD were selected by multivariable Cox regression and stepwise approach. A nomogram based on these predictors was developed and evaluated with concordance index (C-index) and area under curve (AUC). RESULTS: During the median follow-up period of 4.22 years, the incidence of CKD was 19.09% (n=1094) in the entire cohort, 19.03% (727 patients) in the development cohort and 19.21% (367 patients) in the validation cohort. Age, body mass index, eGFR 60-89 mL/min/1.73 m2, diabetes and hypertension were selected as predictors. The nomogram demonstrated a good discriminative power with C-index of 0.778 and 0.785 in the development and validation cohort. The 3-year, 4-year and 5-year AUCs were 0.817, 0.814 and 0.834 in the development cohort, and 0.830, 0.847 and 0.839 in the validation cohort. CONCLUSION: Our nomogram based on five readily available predictors is a reliable tool to identify high-CVD risk patients at risk of incident CKD. This prediction model may help improving the healthcare strategies in primary care.

Right coronary artery-left ventricular fistula with giant right coronary artery of diffuse ectasia: a case report.

BACKGROUND: Coronary artery fistula complicated with giant coronary artery ectasia (CAE) is a rare cardiac malformation, and its surgical indications and treatment strategies still need further discussion. CASE SUMMARY: In this case, a 41-year-old man had complained of occasional dizziness for 2 years, but he did not seek medical attention until he started to feel palpitations. A right coronary artery (RCA)-left ventricular (LV) fistula with giant RCA of diffuse ectasia was firstly revealed by transthoracic echocardiography. A widened left ventricle and significantly constricted right atrium and right ventricle were also detected by three-dimensional coronary artery computed tomography. Surgical treatment, including the repair of the RCA-LV fistula, the resection and reconstruction of the dilated RCA and coronary artery bypass grafting (CABG) under hypothermic cardiopulmonary bypass, were performed to correct the malformation. The patient presented a favourable health condition without any discomfort at the 1-year follow-up. DISCUSSION: CAE can be caused by various congenital or acquired factors. Surgical treatment, such as transcatheter embolization excision, surgical ligation or resection for symptomatic patients with CAE three times or larger than the reference diameter, has been reported to have satisfactory results. Additionally, CABG can be selected if myocardial perfusion is compromised and the distal branch is of reasonable size. In this case, the giant ectasia of the RCA may have been a consequence of the congenital RCA-LV fistula. Atherosclerosis, with calcified plaques in the RCA, and the patient's long-term history of smoking may have contributed to the development of giant ectasia of the RCA.

Prognostic Value of YKL-40 in Patients with Glioblastoma: a Systematic Review and Meta-analysis.

YKL-40 is the most highly expressed gene in glioblastoma compared with normal brain tissues. Previous studies assessing the association between YKL-40 and survival in glioblastoma patients reported varying magnitude of estimates. The objective of this meta-analysis was to determine the prognostic value of YKL-40 in glioblastoma patients. PubMed and Embase databases were searched for studies relating to YKL-40 and prognosis of glioblastoma patients. Studies reporting estimates for overall survival by YKL-40 expression in glioblastoma patients were considered eligible. A meta-analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) and 95 % confidence interval (95%CI). Eight studies were ultimately considered eligible and included into the meta-analysis. Those eight studies included 1241 glioblastoma patients. Meta-analysis of those studies showed that high YKL-40 expression was associated with worse overall survival in glioblastoma patients (HR = 1.46, 95%CI 1.33-1.61, P < 0.001). Meta-analysis of studies with adjusted estimates and high quality showed that high YKL-40 expression was independently associated with worse overall survival in glioblastoma patients (HR = 1.50, 95%CI 1.35-1.66, P < 0.001). Both subgroup analysis and sensitivity analysis validated the obvious association between high YKL-40 expression and worse overall survival in glioblastoma patients. High YKL-40 expression is independently and markedly associated with worse overall survival in glioblastoma patients. YKL-40 is a good predictive biomarker of prognosis in glioblastoma patients.