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1.
Cardiol Young ; : 1-10, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602080

RESUMO

Hypertrophic cardiomyopathy is the second most common cardiomyopathy affecting children and adolescents and is the main cause of sudden death of young athletes. The natural prognosis of children with severe hypertrophic obstructive cardiomyopathy is not optimistic, and it is not uncommon for children with hypertrophic obstructive cardiomyopathy who do not respond to medication. Surgical treatment is often the only solution. Conventional surgical methods in the past include classic or modified extended Morrow operation, classic or modified Konno operation, and Ross-Konno operation. In recent years, with the development of minimally invasive surgery, various minimally invasive surgical methods have emerged endlessly. Because the incision of minimally invasive cardiac surgery is significantly smaller than that of traditional surgery, it causes less trauma, recovers quickly after surgery, and has the advantage of no difference in surgical effect compared with traditional median sternotomy. Tally endoscopic transmitral myectomy, RTM, minimally right thoracotomy, and other surgical methods have achieved encouraging results in adults and some older children with hypertrophic obstructive cardiomyopathy. The appearance of transapical beating-heart septectomy has brought the treatment of hypertrophic obstructive cardiomyopathy from the era of cardiopulmonary bypass and cardiac arrest to a new era of minimally invasive beating-heart surgery. In the past, there were few articles about the treatment of children with hypertrophic obstructive cardiomyopathy. This article reviewed the new progress and prognosis of surgical treatment of children with hypertrophic obstructive cardiomyopathy at home and abroad.

2.
Cardiol Young ; : 1-13, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629195

RESUMO

OBJECTIVES: The aims of this study were to evaluate the 16-year experience with  arterial switch operation at Beijing Children's Hospital and to determine early and late mortality and late morbidity, to explore risk factors for late complications and reintervention, and finally to evaluate whether the neoaortic sinotubular junction reconstruction technique reduces late complications of arterial switch operation. METHODS: The clinical data of 185 patients with transposition of the great arteries who underwent arterial switch operation in Beijing Children's Hospital from January 2006 to January 2022 and 30 patients who underwent modified arterial switch operation with neoaortic sinotubular junction reconstruction technique in Fuwai Hospital during the same period were retrospectively analysed. Propensity score matching was also used to match the neoaortic sinotubular junction reconstruction patients in Fuwai Hospital with 30 non-neoaortic sinotubular junction reconstruction patients in Beijing Children's Hospital. RESULTS: There were 13 early deaths (7.03%) and five late deaths (3.01%). Nineteen patients (11.45%) developed new aortic valve regurgitation and 28 patients (16.87%) developed aortic root dilation. Late right ventricular outflow tract obstruction occurred in 33 patients (19.88%). Late reintervention occurred in 18 cases (10.84%). Multivariate analysis showed that aorto-pulmonary diameter mismatch, previous pulmonary artery banding, and mild moderate or above new aortic valve regurgitation at discharge were independent risk factors for late new aortic valve regurgitation and aortic root dilation. Low surgical weight was an independent risk factor specific to new aortic valve regurgitation, and bicuspid native pulmonary valve was an independent risk factor specific to aortic root dilation. Older surgical age and aortic root dilation were independent risk factors for late right ventricular outflow tract obstruction. Older surgical age, operation before 2014, late right ventricular outflow tract obstruction, and late aortic root dilation were independent risk factors for late intervention. Propensity score matching showed that new aortic valve regurgitation and aortic root dilation were not followed up in the neoaortic sinotubular junction reconstruction group, while seven cases of aortic root dilation and five cases of new aortic valve regurgitation occurred in the non-neoaortic sinotubular junction reconstruction group, respectively, and the differences were statistically significant (P = 0.003; P = 0.015). CONCLUSIONS: The increased incidence of new aortic valve regurgitation, aortic root dilation, and right ventricular outflow tract obstruction as children age is a major concern outcome in the future and may mean more late reintervention. neoaortic sinotubular junction reconstruction technique may reduce the incidence of new aortic valve regurgitation and aortic root dilation, and improve the late prognosis of arterial switch operation. Careful follow-up of neo-aortic valve and root function is imperative, especially in patients with aorto-pulmonary diameter mismatch, previous pulmonary artery banding, mild new aortic valve regurgitation at discharge, low surgical weight, and bicuspid native pulmonary valve structures.

3.
Cardiol Young ; : 1-8, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584316

RESUMO

OBJECTIVES: The clinical data of patients with subaortic stenosis who underwent surgical treatment in our centre in the past 12 years were reviewed. The short-term and long-term clinical outcomes were analyzed, and the long-term outcomes of different surgical methods for subaortic stenosis were compared to determine the optimal surgical treatment strategy for subaortic stenosis. METHODS: From December 2010 to December 2022, 90 patients undergoing surgical treatment for subaortic stenosis in our hospital were enrolled. There were 55 males and 35 females with a median age of 72 (46,132) months and an average surgical weight of (21.35 ± 15.84) kg. According to the operation method, 90 patients were divided into group A (50 patients with simple subaortic membrane resection) and group B (40 patients with subaortic membrane and muscle resection or modified Konno procedure). RESULTS: There were three early deaths (3.33%). One late death occurred in group B. There was no significant difference in long-term survival rate between the two groups (p = 0.904). The preoperative left ventricular outflow tract pressure gradient in group B was (91.56 ± 36.98) mm Hg, which was higher than that in group A(51.13 ± 36.04)mm Hg(p < 0.001). There was no significant difference in immediate postoperative left ventricular outflow tract pressure gradient between group B [(5.44 ± 8.43) mm Hg] and group A [(7.82 ± 13.44) mm Hg] (p = 0.343). In the long-term follow-up, left ventricular outflow tract pressure gradient in group B was (5.86 ± 9.53) mm Hg, which was not statistically significant compared with group A (8.83 ± 14.52) mm Hg (p = 0.294). Eleven patients with moderate or greater aortic regurgitation (group A/group B: 3/8) underwent simultaneous aortic valvuloplasty. In group B, moderate or greater aortic regurgitation was significantly improved immediately after operation (p = 0.013) and was not significantly aggravated in long-term follow-up (p = 0.083), and there was no significant improvement in group A after operation and long-term follow-up. CONCLUSIONS: According to the different anatomical lesions of left ventricular outflow tract, the individualised surgical treatment strategy for patients with subaortic stenosis can achieve good long-term outcomes. The long-term survival rate and freedom from reoperation due to late left ventricular outflow tract obstruction after simple subaortic membrane resection and extended left ventricular outflow tract resection are comparable. For patients with moderate or greater aortic regurgitation before extended left ventricular outflow tract resection, simultaneous aortic valvuloplasty is beneficial to improve postoperative aortic valve function.

4.
Vet Res ; 55(1): 33, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493160

RESUMO

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.


Assuntos
Doenças dos Bovinos , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/veterinária , Replicação Viral , Linhagem Celular
5.
Int J Surg ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498395

RESUMO

BACKGROUND: The available evidence regarding the predictive value of troponins and natriuretic peptides for early postoperative outcomes in pediatrics is limited, controversial, and based on small sample sizes. We aimed to investigate the association of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) with the in-hospital adverse outcomes after congenital cardiac surgeries. METHODS: A secondary analysis based on a prospective study of pediatric congenital heart disease (CHD) patients was conducted to investigate the association of NT-proBNP and hs-TnT tested within 6 hours postoperatively with in-hospital adverse events. A multivariate logistic regression analysis with a minimum P value approach was used to identify the optimal thresholds of NT-proBNP and hs-TnT for risk stratification. RESULTS: NT-proBNP and hs-TnT are positively correlated with cardiopulmonary bypass time, mechanical ventilation duration, and pediatric intensive care unit stay. The predictive performance of NT-proBNP is excellent for adverse events in both patients younger than 1 year [area under the curve (AUC): 0.771, 0.693-0.850] and those older than 1 year (AUC: 0.839, 0.757-0.922). However, hs-TnT exhibited a satisfactory predictive value solely in patients aged over 1 year. (AUC: 0.784, 0.717-0.852). NT-proBNP levels of 2000 to 10000 ng/L [Odds Ratio (OR): 3.79, 1.47-9.76) and exceeding 10000 ng/L (OR: 12.21, 3.66-40.80) were associated with a higher risk of postoperative adverse events in patients younger than 1 year. Patients older than 1 year, with NT-proBNP higher than 500 ng/L (OR: 15.09, 6.05-37.66) or hs-TnT greater than 1200 ng/L (OR: 5.50, 1.47-20.59), had a higher incidence of postoperative adverse events. CONCLUSIONS: NT-proBNP and hs-TnT tested within postoperative 6 hours demonstrated significant predictive value for postoperative adverse events in CHD patients older than 1 year. However, among CHD patients younger than 1 year, only NT-proBNP exhibited commendable predictive performance for postoperative adverse events.

6.
Transl Psychiatry ; 14(1): 166, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538614

RESUMO

Melatonin improves chronic stress-induced hippocampal damage and depression-like behaviors, but the mechanism needs further study. This study was to explore the mechanism of melatonin inhibiting microglia pyroptosis. In virtro experiments, melatonin improved corticosterone-induced the ultrastructure and microstructure damage of HAPI cells by inhibiting pyroptosis, thereby increasing cell survival rate. Protein-protein interaction network and molecular autodocking predicted that Cathespin B might be the target of melatonin inhibition of NLRP3-mediated pyroptosis. Melatonin inhibited corticosterone-induced Cathespin B expression. Both Cathepsin B inhibitor CA-074Me and NLRP3 knockout inhibited the HAPI cells pyroptosis. Similarly, melatonin inhibited Cathepsin B agonist Pazopanib-induced activation of Cathepsin B/NLRP3 signaling pathway and HAPI cells pyroptosis. In vivo studies, melatonin inhibited chronic restraint stress (CRS)-induced activation of Cathepsin B/NLRP3 signaling pathway and alleviated hippocampal microglia pyroptosis in rats. Inhibition of microglia pyroptosis improved CRS-induced depression-like behaviors of rats. In addition, inhibition of Cathepsin B and NLRP3 alleviated hippocampal pyroptosis. Melatonin inhibited Pazopanib-induced activation of Cathepsin B/NLRP3 signaling pathway and hippocampal pyroptosis. These results demonstrated that melatonin could alleviate CRS-induced hippocampal microglia pyroptosis by inhibiting Cathepsin B/NLRP3 signaling pathway, thereby improving depression-like behaviors in rats. This study reveals the molecular mechanism of melatonin in the prevention and treatment of chronic stress-related encephalopathy.


Assuntos
Catepsina B , Indazóis , Melatonina , Pirimidinas , Sulfonamidas , Animais , Ratos , Melatonina/farmacologia , Corticosterona , Depressão/tratamento farmacológico , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Transdução de Sinais , Hipocampo
7.
Heart ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346787

RESUMO

BACKGROUND: Staged repair is common for complex conotruncal defects, often involving bidirectional Glenn (BDG) procedure. Following the cavopulmonary shunt, both Fontan completion and biventricular conversion (BiVC) serve as definitive approaches. The optimal strategy remains controversial. METHODS: The baseline, perioperative and follow-up data were obtained for all paediatric patients with conotruncal defects who underwent BDG procedure as palliation in Fuwai Hospital from 2013 to 2022. Patients with single ventricle were excluded. The primary outcome was mortality. The secondary outcome was reintervention, including any cardiovascular surgeries and non-diagnostic catheterisations. RESULTS: A total of 232 patients were included in the cohort, with 142 underwent Fontan (61.2%) and 90 underwent BiVC (38.8%). The median interstage period from BDG to the definitive procedure was 3.83 years (IQR: 2.72-5.42) in the overall cohort, 3.62 years (IQR: 2.57-5.15) in the Fontan group and 4.15 years (IQR: 3.05-6.13) in the BiVC group (p=0.03). The in-hospital outcomes favoured the Fontan group, including duration of cardiopulmonary bypass, aortic cross-clamp, mechanical ventilation and intensive care unit stay. Postoperative mortality was generally low and comparable, as was the reintervention rate (HR=1.42, 95% CI: 0.708 to 2.85, p=0.32). The left ventricular size was smaller at baseline and within the normal range at follow-up for both Fontan and BiVC groups; however, it was significantly larger with BiVC at follow-up. CONCLUSION: In paediatric patients with conotruncal heart defects who underwent BDG procedure, BiVC is a feasible option, especially for patients with certain Fontan risk factors, and are not ideal candidates for successful Fontan completion.

8.
Lancet Reg Health West Pac ; 44: 101002, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38322730

RESUMO

Background: The prevalence and risk factors for failure to thrive (FTT) in pediatric patients with congenital heart disease (CHD) remain ambiguous. We aimed to investigate the prevalence, growth profiles, risk factors, and vulnerable subtypes of CHD associated with FTT in pediatric patients with CHD. Methods: This was a cross-sectional study based on Chinese Database for Congenital Heart Surgery. FTT was defined as either stunting or underweight (height or weight standard deviation score <-2), and they were standardized by references of normal Chinese population. Risk factors was determined with logistic regression model, and growth profiles were delineated in each subgroup. Findings: A total of 13,256 CHD patients were included in this study, with 3994 patients of mild CHD, 7195 patients of moderate CHD and 2067 patients of complex CHD. The prevalence of stunting, underweight and FTT was 24%, 29.3% and 36.9%, respectively. Preoperative anaemia, left ventricle systolic dysfunction, younger age, more complex CHD types, lower birth weight and genetic syndrome were found to be the risk factors for FTT in CHD patients. Interrupted aortic arch was revealed to be the most severe group associated with FTT. Interpretation: FTT is ubiquitous in patients with CHD and exacerbated in high-risk subgroups. Our findings hinted the necessity of early identification and intervention for FTT in patients with CHD during daily practice of pediatrics, as it has the potential to improve outcomes and enhance their quality of life. Furthermore, we advocate for the initiation of prospective research with longitudinal data to comprehensively investigate the association between FTT and CHD across the lifespan. Funding: This study was supported by National High Level Hospital Research Funding (2022-GSP-GG-19), Capital Health Research and Development of Special Fund (2022-1-4032) and National Key R&D Program of China (2022YFC3600202 and 2022YFC3600203).

9.
Pediatr Cardiol ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363311

RESUMO

To investigate the influencing factors of postoperative creatine kinase-MB (CK-MB) elevation in children with congenital heart disease and its peak value in predicting early postoperative mortality. The clinical data of 521 children with congenital heart disease under the age of 14 who underwent elective surgery in Beijing Children's Hospital from December 2018 to December 2020 were retrospectively analyzed. Stepwise multiple linear regression was used to analyze independent risk factors for postoperative CK-MB elevation, receiver operating characteristic (ROC) curve was used to determine the predictive value of postoperative CK-MB peak, CK peak, and LDH peak on mortality, and linear correlation and regression analysis were used to analyze the interdependence among postoperative CK-MB peak, CK peak, and LDH peak, and multivariate Logistic regression was used to identify independent risk factors for early postoperative mortality. Preterm birth (P = 0.004), ventriculotomy (P = 0.009), the re-establish of bypass (P = 0.007), cardiopulmonary bypass time (P = 0.024), deep hypothermic circulatory arrest time (P = 0.000), assisted ventilation time (P = 0.049), CK peak (P = 0.000), and LDH peak (P = 0.000) were independently associated with increased postoperative CK-MB elevation. The ROC curve showed that CK-MB peak had the strongest predictive value for death (AUC = 0.924), followed by LDH peak (AUC = 0.864) and CK peak (AUC = 0.758). The cut-off value of the postoperative CK-MB peak was 144.5 IU/L, with a sensitivity of 87% and a specificity of 97%. CK-MB peak was moderately correlated with CK peak (Pearson Correlation coefficient r = 0.514, P = 0.000) and strongly correlated with LDH peak (Pearson Correlation coefficient r = 0.601, P = 0.000). Multivariate analysis showed that delayed chest closure (OR = 4.865, P = 0.004) and postoperative CK-MB peak (OR = 1.031, P = 0.000) were independent risk factors for postoperative mortality. The postoperative CK-MB peak has a certain predictive value for the early postoperative mortality of children with congenital heart disease. It is affected by many factors, and the risk of mortality is significantly increased in children with severely elevated postoperative CK-MB.

10.
iScience ; 27(1): 108642, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38205249

RESUMO

The epidemiological, etiological, and clinical characteristics vary greatly between pediatric (P-HCM) and adult (A-HCM) hypertrophic cardiomyopathy (HCM) patients, and the understanding of the heterogeneous pathogenesis mechanisms is insufficient to date. In this study, we aimed to comprehensively assess the respective transcriptome signatures and uncover the essential differences in gene expression patterns among A-HCM and P-HCM. The transcriptome data of adults were collected from public data (GSE89714), and novel pediatric data were first obtained by RNA sequencing from 14 P-HCM and 9 infantile donor heart samples. Our study demonstrates the common signatures of myofilament or protein synthesis and calcium ion regulation pathways in HCM. Mitochondrial function is specifically dysregulated in A-HCM, whereas the inhibition of cardiac developing networks typifies P-HCM. These findings not only distinguish the transcriptome characteristics in children and adults with HCM but also reveal the potential mechanism of the higher incidence of septal defects in P-HCM patients.

11.
Eur J Prev Cardiol ; 31(1): 23-37, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37665956

RESUMO

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.


Assuntos
Cardiopatias , Hipertensão , Humanos , Idoso , Pessoa de Meia-Idade , Carga Global da Doença , Teorema de Bayes , Distribuição por Idade , Saúde Global , Cardiopatias/diagnóstico , Hipertensão/diagnóstico , Anos de Vida Ajustados por Qualidade de Vida
12.
J Pediatr ; 264: 113741, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37726085

RESUMO

OBJECTIVE: To assess management strategies for pediatric patients with the challenging combination of congenital heart diseases (CHDs) and airway anomalies. STUDY DESIGN: Patients diagnosed with CHD and airway anomalies in the Pediatric Cardiac Surgery Centre of Fuwai Hospital from January 2016 to December 2020 were included in this retrospective study. Patients were divided into three groups based on different management, including the conservative group, the slide group (slide tracheoplasty), and the suspension group (suspension with external stenting). Patients' data and computed tomography measurements from medical records were reviewed. RESULTS: A total of 139 patients were included in the cohort; 107 had conservative airway treatment (conservative group), 15 had slide tracheoplasty (slide group), and 17 had tracheal suspension operation (suspension group). The top three associated intracardiac anomalies were ventricular septal defect (n = 34, 24%), pulmonary artery sling (n = 22, 16%), and tetralogy of Fallot (n = 15, 11%). Compared with patients with conservative airway management (100 minutes [median], 62-152 [IQR]), the extra airway procedure prolonged cardiopulmonary bypass duration, with 202 minutes (IQR, 119-220) for the slide group and 150 minutes (IQR, 125-161) for the suspension group. Patients who underwent slide tracheoplasty required prolonged mechanical ventilation (129 minutes [median], 56-328 [IQR]). Of the total cohort, 6 in-hospital deaths, all in the conservative group, and 8 mid-to long-term deaths, with 6 in the conservative group, occurred. CONCLUSIONS: Both conservative and surgical management of CHD patients with airway anomalies have promising outcomes. Extra tracheobronchial procedures, especially the slide tracheoplasty, significantly prolonged cardiopulmonary bypass duration. Based on multidisciplinary team assessment, individualized management strategies should be developed for these patients.


Assuntos
Cardiopatias Congênitas , Estenose Traqueal , Criança , Humanos , Lactente , Estudos Retrospectivos , Estenose Traqueal/congênito , Resultado do Tratamento , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/cirurgia , Ponte Cardiopulmonar/métodos , Traqueia/cirurgia
13.
J Agric Food Chem ; 71(50): 20034-20046, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38054647

RESUMO

Lycopene (LYC) exerts a strong neuroprotective and antipyroptotic effects. This study explored the effects and mechanisms of LYC on chronic stress-induced hippocampal microglial damage and depression-like behaviors. The caspase-1 inhibitor VX-765 attenuated chronic restrain stress (CRS)-induced hippocampal microglial pyroptosis and depression-like behaviors. Moreover, the alleviation of CRS-induced hippocampal microglial pyroptosis and depression-like behaviors by LYC was associated with the cathepsin B/NLRP3 pathway. In vitro, the caspase-1 inhibitor Z-YVAD-FMK alleviated pyroptosis in highly aggressively proliferating immortalized (HAPI) cells. Additionally, the alleviation of corticosterone-induced HAPI cell damage and pyroptosis by LYC was associated with the cathepsin B/NLRP3 pathway. Furthermore, the cathepsin B agonist pazopanib promoted HAPI cell pyroptosis, whereas LYC inhibited pazopanib-induced pyroptosis via the cathepsin B/NLRP3 pathway. Similarly, Z-YVAD-FMK inhibited pazopanib-induced HAPI cell pyroptosis. These results suggest that LYC alleviates chronic stress-induced hippocampal microglial pyroptosis via the cathepsin B/NLRP3 pathway inhibition. This study provides a new strategy for treating chronic stress encephalopathy.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Licopeno/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Microglia , Transdução de Sinais , Hipocampo , Inflamassomos/genética , Inflamassomos/metabolismo
14.
Vaccines (Basel) ; 11(12)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38140181

RESUMO

Avian pathogenic Escherichia coli (APEC) is one of the leading pathogens that cause devastating economic losses to the poultry industry. Type I fimbriae are essential adhesion factors of APEC, which can be targeted and developed as a vaccine candidate against multiple APEC serogroups due to their excellent immunogenicity and high homology. In this study, the recombinant strain SG102 was developed by expressing the APEC type I fimbriae gene cluster (fim) on the cell surface of an avirulent Salmonella gallinarum (S. gallinarum) vector strain using a chromosome-plasmid-balanced lethal system. The expression of APEC type I fimbriae was verified by erythrocyte hemagglutination assays and antigen-antibody agglutination tests. In vitro, the level of the SG102 strain adhering to leghorn male hepatoma (LMH) cells was significantly higher than that of the empty plasmid control strain, SG101. At two weeks after oral immunization, the SG102 strain remained detectable in the livers, spleens, and ceca of SG102-immunized chickens, while the SG101 strain was eliminated in SG101-immunized chickens. At 14 days after the secondary immunization with 5 × 109 CFU of the SG102 strain orally, highly antigen-specific humoral and mucosal immune responses against APEC type I fimbriae protein were detected in SG102-immunized chickens, with IgG and secretory IgA (sIgA) concentrations of 221.50 µg/mL and 1.68 µg/mL, respectively. The survival rates of SG102-immunized chickens were 65% (13/20) and 60% (12/20) after challenge with 50 LD50 doses of APEC virulent strains O78 and O161 serogroups, respectively. By contrast, 95% (19/20) and 100% (20/20) of SG101-immunized chickens died in challenge studies involving APEC O78 and O161 infections, respectively. In addition, the SG102 strain effectively provided protection against lethal challenges from the virulent S. gallinarum strain. These results demonstrate that the SG102 strain, which expresses APEC type I fimbriae, is a promising vaccine candidate against APEC O78 and O161 serogroups as well as S. gallinarum infections.

15.
iScience ; 26(11): 108150, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37908310

RESUMO

Recent studies suggest that pleiotropic effects may explain the genetic architecture of cardiovascular diseases (CVDs). We conducted a comprehensive gene-centric pleiotropic association analysis for ten CVDs using genome-wide association study (GWAS) summary statistics to identify pleiotropic genes and pathways that may underlie multiple CVDs. We found shared genetic mechanisms underlying the pathophysiology of CVDs, with over two-thirds of the diseases exhibiting common genes and single-nucleotide polymorphisms (SNPs). Significant positive genetic correlations were observed in more than half of paired CVDs. Additionally, we investigated the pleiotropic genes shared between different CVDs, as well as their functional pathways and distribution in different tissues. Moreover, six hub genes, including ALDH2, XPO1, HSPA1L, ESR2, WDR12, and RAB1A, as well as 26 targeted potential drugs, were identified. Our study provides further evidence for the pleiotropic effects of genetic variants on CVDs and highlights the importance of considering pleiotropy in genetic association studies.

16.
Lancet Reg Health West Pac ; 40: 100958, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024098
18.
Int J Surg ; 109(12): 3788-3795, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678273

RESUMO

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.


Assuntos
Veias Pulmonares , Síndrome de Cimitarra , Ferida Cirúrgica , Humanos , Lactente , Veias Pulmonares/cirurgia , Veias Pulmonares/anormalidades , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Síndrome de Cimitarra/cirurgia , Síndrome de Cimitarra/complicações , Ferida Cirúrgica/complicações , Resultado do Tratamento
19.
Front Microbiol ; 14: 1252272, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711694

RESUMO

Canine circovirus (CanineCV) is a virus associated with respiratory and digestive diseases in dogs and often occurs in coinfections with other pathogens, thereby aggravating the symptoms of infected dogs. CanineCV was first reported in the United States in 2012. Subsequently, it was reported among dogs in Europe, Asia, and South America. To investigate the prevalence of CanineCV in dogs in China, 331 dog samples were collected in this study. The PCR results showed that 9.06% (30/331, 95% CI = 6.2% ~ 12.7%) of the dog samples were CanineCV positive. CanineCV has also been detected in some carnivorous wild animals, indicating the potential risk of cross-species transmission of this virus. And, cats are also one of the most common pets in our daily lives, who is close contact with dogs. Thus, this study first investigated the prevalence of CanineCV in cats. The PCR results showed that 3.42% (14/409, 95% CI = 1.9% ~ 5.7%) of the cat samples were CanineCV positive. Moreover, 14 canine-derived CanineCV whole genomes and the first cat-derived CanineCV whole genome were obtained in this study. Rep and Cap are the major nonstructural proteins and structural proteins of CanineCV, respectively. In nucleic acid homology analyses, these 15 CanineCV strains showed a high degree of variation in Rep (85.9 ~ 99%) and Cap (85.6 ~ 100%). In phylogenetic analyses, the 15 CanineCV strains clustered into 3 different genotypes (genotypes 1, 3, and 4). Among them, the first cat-derived CanineCV belonged to CanineCV-3. In addition, 4 genetic recombination events were predicted in these 15 CanineCV strains, occurring in multiple regions of the genome. In conclusion, this study is the first to provide evidence of CanineCV infection in cats and successfully obtained the first whole genome of cat-derived CanineCV. The complex circulation and high prevalence of CanineCV among dogs and cats emphasize the importance of continuous monitoring of this virus in various animal species.

20.
Innovation (Camb) ; 4(5): 100485, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37609559

RESUMO

Cardiovascular diseases (CVDs) are one of the most urgent threats to humans worldwide, which are responsible for almost one-third of global mortality. Over the last decade, research on flexible electronics for monitoring and treatment of CVDs has attracted tremendous attention. In contrast to conventional medical instruments in hospitals that are usually bulky, hard to move, monofunctional, and time-consuming, flexible electronics are capable of continuous, noninvasive, real-time, and portable monitoring. Notable progress has been made in this emerging field, and thus a number of significant achievements and concomitant research prospects deserve attention for practical implementation. Here, we comprehensively review the latest progress of flexible electronics for CVDs, focusing on new functions provided by flexible electronics. First, the characteristics of CVDs and flexible electronics and the foundation of their combination are briefly reviewed. Then, four representative applications of flexible electronics for CVDs are elaborated: blood pressure (BP) monitoring, electrocardiogram (ECG) monitoring, echocardiogram monitoring, and direct epicardium monitoring. Their operational principles, progress, merits and demerits, and future efforts are discussed. Finally, the remaining challenges and opportunities for flexible electronics for cardiovascular healthcare are outlined.

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