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BACKGROUND: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. METHODS: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice. FINDINGS: Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups. INTERPRETATION: Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine. FUNDING: Funding bodies are described in the Acknowledgments section.
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Epítopos de Linfocito B , Virus de la Influenza B , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Ratones , Virus de la Influenza B/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Femenino , Epítopos de Linfocito B/inmunología , Virus de la Influenza A/inmunología , Anticuerpos Antivirales/inmunología , Epítopos de Linfocito T/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Estaciones del Año , Subtipo H3N2 del Virus de la Influenza A/inmunología , HumanosRESUMEN
Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding.
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COVID-19 , SARS-CoV-2 , Aguas Residuales , COVID-19/epidemiología , China/epidemiología , Aguas Residuales/virología , Humanos , Heces/virología , Betacoronavirus , Pandemias , Monitoreo Epidemiológico Basado en Aguas Residuales , ARN Viral/análisis , Esparcimiento de Virus , Carga ViralRESUMEN
AIMS: Heritable dilated cardiomyopathy (DCM) or DCM associated with congenital or acquired left ventricular diseases carries a significant mortality risk. Pulmonary artery banding (PAB) has been proposed as an alternative to heart transplantation. This study aimed to delineate the clinical development, ventricular reverse remodelling, and functional regeneration of the dilated left ventricle, presenting as a pioneering approach in China. METHODS AND RESULTS: This prospective study was initiated in November 2021, involving paediatric patients with a significant dilated left ventricle and preserved right ventricle who underwent surgical PAB. The baseline characteristics and clinical information during follow-up were collected. Seven patients (five boys) with a median age of 240 (148, 1028) days have been included thus far. No procedural or follow-up mortality was observed. The modified Ross functional class improved from treatment to follow-up of 348 (200, 629) days, and the median left ventricular ejection fraction increased from 27.0 (15.0, 34.0) % before surgery to 61.0 (52.0, 68.0) % (P < 0.05); the median left ventricular end-diastolic diameter and corresponding Z-scores decreased from 43.0 (40.0, 55.0) mm [+9.4 (+7.7, +11.7)] to 33.0 (29.0, 39.0) mm [+1.8 (+1.3, +3.8)] (P < 0.05). Functional regeneration of the left ventricle was observed in five patients. Three of them underwent balloon dilation of the PAB to relieve excessively elevated right ventricular pressures. CONCLUSIONS: The application of PAB should adhere to strict criteria. Initial results are promising for infants and even toddlers with a dilated left ventricle and limited probability of spontaneous recovery. PAB can be an alternative when there is a shortage of donor transplants and assist devices, especially for low- and middle-income countries.
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China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.
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Cell membrane surface tension has emerged as a pivotal biophysical factor governing cell behavior and fate. This review systematically delineates recent advances in techniques for cell membrane surface tension quantification, mechanosensing mechanisms, and regulatory roles of cell membrane surface tension in modulating major cellular processes. Micropipette aspiration, tether pulling, and newly developed fluorescent probes enable the measurement of cell membrane surface tension with spatiotemporal precision. Cells perceive cell membrane surface tension via conduits including mechanosensitive ion channels, curvature-sensing proteins (e.g. BAR domain proteins), and cortex-membrane attachment proteins (e.g. ERM proteins). Through membrane receptors like integrins, cells convert mechanical cues into biochemical signals. This conversion triggers cytoskeletal remodeling and extracellular matrix interactions in response to environmental changes. Elevated cell membrane surface tension suppresses cell spreading, migration, and endocytosis while facilitating exocytosis. Moreover, reduced cell membrane surface tension promotes embryonic stem cell differentiation and cancer cell invasion, underscoring cell membrane surface tension as a regulator of cell plasticity. Outstanding questions remain regarding cell membrane surface tension regulatory mechanisms and roles in tissue development/disease in vivo. Emerging tools to manipulate cell membrane surface tension with high spatiotemporal control in combination with omics approaches will facilitate the elucidation of cell membrane surface tension-mediated effects on signaling networks across various cell types/states. This will accelerate the development of cell membrane surface tension-based biomarkers and therapeutics for regenerative medicine and cancer. Overall, this review provides critical insights into cell membrane surface tension as a potent orchestrator of cell function, with broader impacts across mechanobiology.
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[This corrects the article DOI: 10.3389/fpubh.2024.1354515.].
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Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) globally exhibits a high prevalence and serves as a potential precursor to multidrug-resistant tuberculosis (MDR-TB). Recognizing the spatial distribution of Hr-TB and identifying associated factors can provide strategic entry points for interventions aimed at early detection of Hr-TB and prevention of its progression to MDR-TB. This study aims to analyze spatial patterns and identify socioeconomic, demographic, and healthcare factors associated with Hr-TB in Shanghai at the county level. Method: We conducted a retrospective study utilizing data from TB patients with available Drug Susceptible Test (DST) results in Shanghai from 2010 to 2016. Spatial autocorrelation was explored using Global Moran's I and Getis-Ord Gi∗ statistics. A Bayesian hierarchical model with spatial effects was developed using the INLA package in R software to identify potential factors associated with Hr-TB at the county level. Results: A total of 8,865 TB patients with DST were included in this analysis. Among 758 Hr-TB patients, 622 (82.06%) were new cases without any previous treatment history. The drug-resistant rate of Hr-TB among new TB cases in Shanghai stood at 7.20% (622/8014), while for previously treated cases, the rate was 15.98% (136/851). Hotspot areas of Hr-TB were predominantly situated in southwestern Shanghai. Factors positively associated with Hr-TB included the percentage of older adult individuals (RR = 3.93, 95% Crl:1.93-8.03), the percentage of internal migrants (RR = 1.35, 95% Crl:1.15-1.35), and the number of healthcare institutions per 100 population (RR = 1.17, 95% Crl:1.02-1.34). Conclusion: We observed a spatial heterogeneity of Hr-TB in Shanghai, with hotspots in the Songjiang and Minhang districts. Based on the results of the models, the internal migrant population and older adult individuals in Shanghai may be contributing factors to the emergence of areas with high Hr-TB notification rates. Given these insights, we advocate for targeted interventions, especially in identified high-risk hotspots and high-risk areas.
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Migrantes , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Anciano , China/epidemiología , Estudios Retrospectivos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Teorema de Bayes , Tuberculosis Resistente a Múltiples Medicamentos/diagnósticoRESUMEN
Backgrounds: The diagnostic delay of tuberculosis (TB) contributes to further transmission and impedes the implementation of the End TB Strategy. Therefore, we aimed to describe the characteristics of patient delay, health system delay, and total delay among TB patients in Shanghai, identify areas at high risk for delay, and explore the potential factors of long delay at individual and spatial levels. Method: The study included TB patients among migrants and residents in Shanghai between January 2010 and December 2018. Patient and health system delays exceeding 14 days and total delays exceeding 28 days were defined as long delays. Time trends of long delays were evaluated by Joinpoint regression. Multivariable logistic regression analysis was employed to analyze influencing factors of long delays. Spatial analysis of delays was conducted using ArcGIS, and the hierarchical Bayesian spatial model was utilized to explore associated spatial factors. Results: Overall, 61,050 TB patients were notified during the study period. Median patient, health system, and total delays were 12 days (IQR: 3-26), 9 days (IQR: 4-18), and 27 days (IQR: 15-43), respectively. Migrants, females, older adults, symptomatic visits to TB-designated facilities, and pathogen-positive were associated with longer patient delays, while pathogen-negative, active case findings and symptomatic visits to non-TB-designated facilities were associated with long health system delays (LHD). Spatial analysis revealed Chongming Island was a hotspot for patient delay, while western areas of Shanghai, with a high proportion of internal migrants and industrial parks, were at high risk for LHD. The application of rapid molecular diagnostic methods was associated with reduced health system delays. Conclusion: Despite a relatively shorter diagnostic delay of TB than in the other regions in China, there was vital social-demographic and spatial heterogeneity in the occurrence of long delays in Shanghai. While the active case finding and rapid molecular diagnosis reduced the delay, novel targeted interventions are still required to address the challenges of TB diagnosis among both migrants and residents in this urban setting.
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Migrantes , Tuberculosis , Femenino , Humanos , Anciano , Diagnóstico Tardío , Teorema de Bayes , China/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
Previous studies reported that the association between statins use and influenza infection was contradictory. A systematic review and meta-analysis of longitudinal studies were performed to determine the association between statins use and influenza susceptibility. The literature search was conducted in PubMed, Embase, and Web of Science, from each database's inception to 21 May 2023. The fixed effect model and random effects model were used for data synthesis. In our study, a total of 1,472,239 statins users and 1,486,881 statins non-users from five articles were included. The pooled risk ratio (RR) of all included participants was 1.05 (95% CI: 1.03-1.07), and there were still significant differences after adjusting for vaccination status. Of note, RR values in statins users were 1.06 (95% CI: 1.03-1.08) in people aged ≥60 years old and 1.05 (95% CI: 1.03-1.07) in participant groups with a higher proportion of females. Administration of statins might be associated with an increased risk of influenza infection, especially among females and elderly people. For those people using statins, we should pay more attention to surveillance of their health conditions and take measures to prevent influenza infection.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Gripe Humana , Humanos , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Longitudinales , Susceptibilidad a Enfermedades , Femenino , Masculino , Persona de Mediana Edad , Anciano , Factores de RiesgoRESUMEN
Fluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Femenino , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Estudios Retrospectivos , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad Microbiana , China/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Genómica , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.
This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.
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Cardiopatías , Hipertensión , Humanos , Anciano , Persona de Mediana Edad , Carga Global de Enfermedades , Teorema de Bayes , Distribución por Edad , Salud Global , Cardiopatías/diagnóstico , Hipertensión/diagnóstico , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Progressive reduction of sodium intake is an attractive approach for addressing excessive salt intake, but evidence for this strategy in real practice is limited. We aimed to determine the feasibility, effectiveness, and safety of a progressive sodium intake reduction intervention in real-world setting. METHODS: We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to either progressive reduction (PR, 24 facilities) or no reduction (NR, 24 facilities) of the supply of study salt to the kitchens of these facilities for 2 years. The primary efficacy outcome was systolic blood pressure (SBP) at any scheduled follow-up visit. Secondary efficacy outcomes included diastolic blood pressure (DBP) at any scheduled follow-up visit, and major adverse cardiovascular events (comprising non-fatal stroke, non-fatal myocardial infarction, hospitalized non-fatal heart failure, or vascular death) and total mortality. The perception of food saltiness, the addition of out-of-study salt in meals, and 24-h urinary sodium excretion were used as process indicators. RESULTS: Pre-specified analysis per randomization found no effect of the intervention on the 2-year overall mean systolic and diastolic blood pressure (SBP, DBP) and any other outcomes. However, post hoc analysis showed that the intervention effect on blood pressure varied over multiple follow-up visits (p for interaction < 0.046) and presented favorable differences at the 24-month visit (SBP = - 3.0 mmHg, 95%CI = - 5.6, - 0.5; p = 0.020; DBP = - 2.0 mmHg, 95%CI - 3.4, - 0.63; p = 0.004). The effect on 24-h sodium was non-significant (- 8.4 mmol, 95%CI = - 21.8 to 4.9, p = 0.216), though fewer participants with NR than with PR reported food tasting bland (odds ratio 0.46; 95%CI 0.29 to 0.73; p = 0.001). Reporting of bland food taste and other process measures indicated that intervention delivery and adherence were not fully achieved as designed. CONCLUSIONS: The experience of this real-world study demonstrated that achieving acceptability and sustainability of the progressive sodium intake reduction strategy among older adults was challenging, but it has shown potential for effectiveness in these and potentially other residential settings if the lessons of DECIDE-Salt are applied in further studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03290716).
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Hipertensión , Cloruro de Sodio Dietético , Anciano , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Cloruro de Sodio Dietético/efectos adversosRESUMEN
Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.
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Background: To date, most vaccines, including the COVID-19 vaccine, are mainly administered by intramuscular injection, which might lead to vaccine hesitancy in some populations due to needle fear. Alternatively, needle-free immunization technology is extensively developed to improve the efficacy and acceptance of vaccination. However, there is no study to report the perception and willingness toward various immunization routes of the COVID-19 vaccine in the general population. Methods: A cross-sectional survey was conducted nationwide using an online questionnaire. Bivariate analyses were undertaken to assess variable associations among the participants who reported a hesitancy to receive the COVID-19 booster vaccination. Multivariable logistic regression with a backward step-wise approach was used to analyze the predicted factors associated with the willingness to receive the COVID-19 booster vaccination. Results: A total of 3,244 valid respondents were included in this survey, and 63.2% of participants thought they had a good understanding of intramuscular injection, but only 20.7, 9.2, 9.4, and 6.0% of participants had a self-perceived good understanding of inhalation vaccine, nasal spray vaccine, oral vaccine, and microneedle patch vaccine. Correspondingly, there was high acceptance for intramuscular injection (76.5%), followed by oral inhalation (64.4%) and nasal spray (43.0%). Those participants who were only willing to receive an intramuscular vaccine had less vaccine knowledge (OR = 0.78; 95% CI: 0.65-0.94) than those who were willing to receive a needle-free vaccine (OR = 1.97; 95% CI: 1.52-2.57). Some factors were found to be associated with vaccine hesitancy toward booster COVID-19 vaccination. Conclusion: Needle-free vaccination is a promising technology for the next generation of vaccines, but we found that intramuscular injection was still the most acceptable immunization route in this survey. One major reason might be that most people lack knowledge about needle-free vaccination. We should strengthen the publicity of needle-free vaccination technology, and thus improve the acceptance and coverage of vaccination in different populations.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Estudios Transversales , Rociadores Nasales , COVID-19/prevención & control , Vacunación , Inmunización , China , PercepciónRESUMEN
BACKGROUND: The modified L-shaped incision technique (MLIT) was successfully applied to the repair of supracardiac total anomalous pulmonary venous connection (TAPVC) with promising mid-term outcomes. It is, however, unclear whether or not MLIT could be an alternative to sutureless technique (ST). METHODS: All patients ( n =141) who underwent MLIT or ST repair for supracardiac TAPVC between June 2009 and June 2022 were included and a propensity score-matched analysis was performed to reduce the heterogeneity. RESULTS: MLIT was performed in 80.9% (114/141), whereas ST was performed in 19.1% (27/141). Patients who underwent MLIT repair had a lower incidence of pulmonary veinous obstruction (PVO)-related reintervention (1.8 vs. 18.5%, P =0.002), and late mortality (2.6 vs. 18.2%, P =0.006). Overall survival at 10 years was 92.5% (87.7-97.7%) for MLIT and 66.8% (44.4-100%) for ST ( P =0.012). Freedom from postoperative PVO at 10 years was 89.1% (83.2-95.5%) for MLIT and 79.9% (65.6-97.4%) for ST ( P =0.12). Cox proportional hazards regression identified prolonged mechanical ventilation duration, postoperative PVO, respiratory dysfunction, and low cardiac output syndrome were associated with postoperative death and PVO-related reintervention. CONCLUSIONS: The MLIT strategy is a safe, technologically feasible, and effective approach for supracardiac TAPVC, which is associated with more favorable and promising freedom from death and PVO-related reintervention.
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Venas Pulmonares , Síndrome de Cimitarra , Herida Quirúrgica , Humanos , Lactante , Venas Pulmonares/cirugía , Venas Pulmonares/anomalías , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Síndrome de Cimitarra/cirugía , Síndrome de Cimitarra/complicaciones , Herida Quirúrgica/complicaciones , Resultado del TratamientoRESUMEN
Growing evidence supports the efficacy of ketogenic diets for inducing weight loss, but there are also potential health risks due to their unbalanced nutrient composition. We aim at assessing relative effectiveness of a balanced diet and ketogenic diet for reversing metabolic syndrome in a diet-induced C57BL/6J mouse model. Mice were fed high-fat diet to induce obesity. Obese individuals were then fed either ketogenic or balanced diets as an obesity intervention. Serum, liver, fat and faecal samples were analysed. We observed that both diet interventions led to significant decrease in body weight. The ketogenic intervention was less effective in reducing adipocyte cell size and led to dyslipidaemia. The composition of the gut microbiome in the balanced diet intervention was more similar to the non-obese control group and had improved functional attributes. Our results indicate intervention with balanced diets ameliorates obesity more safely and effectively than ketogenic diets in diet-induced obesity mouse model.
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Dieta Cetogénica , Microbioma Gastrointestinal , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/metabolismoRESUMEN
Background: Hepatocellular carcinoma (HCC), the main type of liver cancer, is the second most lethal tumor worldwide, with a 5-year survival rate of only 18%. Driver genes facilitate cancer cell growth and spread in the tumor microenvironment. Here, a comprehensive driver gene signature for the prognosis of HCC was developed. Methods: HCC driver genes were analyzed comprehensively to develop a better prognostic signature. The dataset of HCC patients included mRNA sequencing data and clinical information from the TCGA, the ICGC, and the Guangxi Medical University Cancer Hospital cohorts. First, LASSO was performed to develop a prognostic signature for differentially expressed driver genes in the TCGA cohort. Then, the robustness of the signature was assessed using survival and time-dependent ROC curves. Furthermore, independent predictors were determined using univariate and multivariate Cox regression analyses. Stepwise multi-Cox regression analysis was employed to identify significant variables for the construction of a nomogram that predicts survival rates. Functional analysis by Spearman correlation analysis, enrichment analysis (GO, KEGG, and GSEA), and immunoassay (ssGSEA and xCell) were performed. Result: A 4-driver gene signature (CLTC, DNMT3A, GMPS, and NRAS) was successfully constructed and showed excellent predictive efficiency in three cohorts. The nomogram indicated high predictive accuracy for the 1-, 3-, and 5-year prognoses of HCC patients, which included clinical information and risk score. Enrichment analysis revealed that driver genes were involved in regulating oncogenic processes, including the cell cycle and metabolic pathways, which were associated with the progression of HCC. ssGSEA and xCell showed differences in immune infiltration and the immune microenvironment between the two risk groups. Conclusion: The 4-driver gene signature is closely associated with the survival prediction of HCC and is expected to provide new insights into targeted therapy for HCC patients.
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With the continuous development of deep learning technology, object detection has received extensive attention across various computer fields as a fundamental task of computational vision. Effective detection of objects in remote sensing images is a key challenge, owing to their small size and low resolution. In this study, a remote sensing image detection (RSI-YOLO) approach based on the YOLOv5 target detection algorithm is proposed, which has been proven to be one of the most representative and effective algorithms for this task. The channel attention and spatial attention mechanisms are used to strengthen the features fused by the neural network. The multi-scale feature fusion structure of the original network based on a PANet structure is improved to a weighted bidirectional feature pyramid structure to achieve more efficient and richer feature fusion. In addition, a small object detection layer is added, and the loss function is modified to optimise the network model. The experimental results from four remote sensing image datasets, such as DOTA and NWPU-VHR 10, indicate that RSI-YOLO outperforms the original YOLO in terms of detection performance. The proposed RSI-YOLO algorithm demonstrated superior detection performance compared to other classical object detection algorithms, thus validating the effectiveness of the improvements introduced into the YOLOv5 algorithm.
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The frequent SARS-CoV-2 variants have caused a continual challenge, weakening the effectiveness of current vaccines, and thus it is of great importance to induce robust and conserved T cellular immunity for developing the next-generation vaccine against SARS-CoV-2 variants. In this study, we proposed a conception of enhancing the SARS-CoV-2 specific T cell functionality by fusing autophagosome-associated LC3b protein to the nucleocapsid (N) (N-LC3b). When compared to N protein alone, the N-LC3b protein was more effectively targeted to the autophagosome/lysosome/MHC II compartment signal pathway and thus elicited stronger CD4+ and CD8+ T cell immune responses in mice. Importantly, the frequency of N-specific polyfunctional CD4+ and CD8+ T cells, which can simultaneously secrete multiple cytokines (IFN-γ+/IL-2+/TNF-α+), in the N-LC3b group was significantly higher than that in the N alone group. Moreover, there was a significantly improved T cell proliferation, especially for CD8+ T cells in the N-LC3b group. In addition, the N-LC3b also induced a robust humoral immune response, characterized by the Th1-biased IgG2a subclass antibodies against the SARS-CoV-2 N protein. Overall, these findings demonstrated that our strategy could effectively induce a potential SARS-CoV-2 specific T cellular immunity with enhanced magnitude, polyfunctionality, and proliferation, and thus provided insights to develop a promising strategy for the design of a novel universal vaccine against SARS-CoV-2 variants and other emerging infectious diseases.
Asunto(s)
Linfocitos T CD8-positivos , COVID-19 , Humanos , Animales , Ratones , SARS-CoV-2 , Linfocitos T CD4-Positivos , Vacunas contra la COVID-19/metabolismo , COVID-19/metabolismo , Autofagia , Transducción de Señal , Anticuerpos AntiviralesRESUMEN
There is a paucity of high-quality evidence on the effectiveness and safety of salt reduction strategies, particularly for older people, who have the most to benefit but are at higher risk of adverse effects. Here, we conducted a clinical trial in which 48 residential elderly care facilities in China (1,612 participants including 1,230 men and 382 women, 55 years or older) were cluster-randomized using a 2 × 2 factorial design to provision of salt substitute (62.5% NaCl and 25% KCl) versus usual salt and to a progressively restricted versus usual supply of salt or salt substitute for 2 years. Salt substitute compared with usual salt lowered systolic blood pressure (-7.1 mmHg, 95% confidence interval (CI) -10.5 to -3.8), meeting the primary outcome of the trial, whereas restricted supply compared with usual supply of salt or salt substitute had no effect on systolic blood pressure. Salt substitute also lowered diastolic blood pressure (-1.9 mmHg, 95% CI -3.6 to -0.2) and resulted in fewer cardiovascular events (hazard ratio (HR) 0.60, 95% CI 0.38-0.96), but had no effect on total mortality (HR 0.84, 95% CI 0.63-1.13). From a safety standpoint, salt substitute increased mean serum potassium and led to more frequent biochemical hyperkalemia, but was not associated with adverse clinical outcomes. In contrast, salt restriction had no effect on any study outcome. The results of this trial indicate that use of salt substitute, but not efforts to restrict salt supply, may achieve blood pressure lowering and deliver health benefits to residents of elderly care facilities in China. Clinicaltrials.gov registration: NCT03290716.