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Large-scale cancer genome sequencing has enabled the catalogs of somatic mutations; however, the mutational impact on intrinsically disordered protein regions (IDRs) has not been systematically investigated to date. Here, we comprehensively characterized the mutational landscapes of IDRs and found that IDRs have higher mutation frequencies across diverse cancers. We thus developed a computational method, ROI-Driver, to identify putative driver genes enriching IDR and domain hotspots in cancer. Numerous well-known cancer-related oncogenes or tumor suppressors that play important roles in cancer signaling regulation, development and immune response were identified at a higher resolution. In particular, the incorporation of IDR structures helps in the identification of novel potential driver genes that play central roles in human protein-protein interaction networks. Interestingly, we found that the putative driver genes with IDR hotspots were significantly enriched with predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular pathways. We also identified an appreciable number of clinically relevant genes enriching IDR mutational hotspots that exhibited differential expression patterns and are associated with cancer patient survival. In summary, combinations of mutational effects on IDRs significantly increase the sensitivity of driver detection and are likely to open new therapeutic avenues for various cancers.
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Biologia Computacional/métodos , Proteínas Intrinsicamente Desordenadas , Neoplasias , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Intrinsicamente Desordenadas/química , Mutação , Neoplasias/genética , Neoplasias/metabolismo , Oncogenes , Mapas de Interação de ProteínasRESUMO
With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.
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Glicemia/metabolismo , Insulina , Líquidos Iônicos , Administração Oral , Animais , Cápsulas , Colina/farmacocinética , Colina/farmacologia , Relação Dose-Resposta a Droga , Humanos , Insulina/farmacocinética , Insulina/farmacologia , Líquidos Iônicos/farmacocinética , Líquidos Iônicos/farmacologia , Masculino , Ratos , Ratos Wistar , Terpenos/farmacocinética , Terpenos/farmacologiaRESUMO
Although isolated congenital ventricular septal defects (VSD) can be repaired with a high degree of success, residual shunts (RS) are commonplace postoperatively. Small RS are relatively innocuous and tend to spontaneously close with time, despite the emotional burden it poses for the patient and family. A large RS, however, needs ongoing surveillance and may necessitate reintervention. Factors influencing the incidence of RS as well as the likelihood and expected timing of its spontaneous closure are discussed in this study. The patient records and relevant data of 362 consecutive patients undergoing cardiac operation with isolated congenital VSD closure as primary procedure between January 2017 and December 2017 were included in the study. Postoperative transthoracic echocardiograms were performed at hospital discharge, and during follow-up, at 1 month, 3 months, 6 months and 1 year postoperatively. Residual defects were measured under echocardiogram at every follow-up. Factors expected to be associated with RS occurrence and spontaneous closure were included for logistic and Cox regression statistical analysis. There were 113 cases where RS occurred according to the first postoperative echocardiograms that were performed at discharge, of which 80 were confirmed closed during subsequent follow-up, with a median follow-up of 96 days. A cutoff of 1.25 mm for the initial RS was found to be the best predictor of spontaneous closure at 6-month follow-up. Small shunts had higher closure rate than larger ones by a follow-up duration of 300 days, at which the two groups tended to reach a similar spontaneous closure rate. Longer surgical bypass time distinguished small from larger residual shunts measured upon discharge. Following repair of isolated congenital VSDs, the incidence of a residual shunt is high. The majority spontaneously close within 300 days following surgery. Longer bypass time predicted a larger residual shunt upon discharge. Larger than 1.25 mm shunts had lower short-term closure rate but seemed not to differ from smaller shunts beyond 300 days postoperatively.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Comunicação Interventricular/cirurgia , Complicações Pós-Operatórias/terapia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Período Pós-Operatório , Fatores de RiscoRESUMO
The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through induction of anoikis and inhibition of EMT. Having this dual tumor suppressive effect, its downregulation in the established human lung adenocarcinoma A549 cell line resulted in potentiation of tumorigenicity and metastasis in vivo. However, the exact role of Bit1 in regulating malignant growth and transformation of human lung epithelial cells, which are origin of most forms of human lung cancers, has not been examined. To this end, we have downregulated the endogenous Bit1 expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B cells exhibited enhanced anchorage-independent growth in vitro but failed to form tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part attributable to the repression of E-cadherin expression since forced exogenous E-cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells resulted in increased Erk activation, which functions upstream to promote TLE1-mediated transcriptional repression of E-cadherin. These collective findings indicate that loss of Bit1 expression contributes to the acquisition of malignant phenotype of human lung epithelial cells via Erk activation-induced suppression of E-cadherin expression.
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Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/fisiologia , Anoikis/fisiologia , Caderinas/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Transformação Celular Neoplásica/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Mitocondriais/metabolismo , Células Epiteliais Alveolares/citologia , Antígenos CD , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/patologia , Regulação para Baixo/fisiologia , HumanosRESUMO
While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.
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Sistemas de Liberação de Medicamentos/métodos , Proteínas/administração & dosagem , Proteínas/metabolismo , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular , Endocitose , Proteínas de Fluorescência Verde/administração & dosagem , Proteínas de Fluorescência Verde/metabolismo , Humanos , Microscopia ConfocalRESUMO
The Groucho transcriptional corepressor TLE1 protein has recently been shown to be a putative lung specific oncogene, but its underlying oncogenic activity in lung cancer has not been fully elucidated. In this report, we investigated whether TLE1 regulates lung cancer aggressiveness using the human lung adenocarcinoma cell line A549 as a model system. Through a combination of genetic approaches, we found that TLE1 potentiates epithelial-to-mesenchymal transition (EMT) in A549 cells in part through suppression of the tumor suppressor gene E-cadherin. Exogenous expression of TLE1 in A549 cells resulted in heightened EMT phenotypes (enhanced fibroblastoid morphology and increased cell migratory potential) and in molecular alterations characteristic of EMT (downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal marker Vimentin). Conversely, downregulation of endogenous TLE1 expression in these cells resulted in reversal of basal EMT characterized by a cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Mechanistic studies showed that TLE1 suppresses E-cadherin expression at the transcriptional level in part by recruiting histone deacetylase (HDAC) activity to the E-cadherin promoter. Consistently, the HDAC inhibitor TSA partially reversed the TLE1-induced E-cadherin downregulation and cell migration, suggesting a role for HDACs in TLE1-mediated transcriptional repression of E-cadherin and EMT function. These findings uncover a novel role of TLE1 in regulating EMT in A549 cells through its repressive effect on E-cadherin and provide a mechanism for TLE1 oncogenic activity in lung cancer.
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Adenocarcinoma/metabolismo , Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas Repressoras/fisiologia , Adenocarcinoma de Pulmão , Anoikis , Antígenos CD , Hidrolases de Éster Carboxílico/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas Correpressoras , Regulação para Baixo , Transição Epitelial-Mesenquimal , Histona Desacetilases/metabolismo , Humanos , Proteínas Mitocondriais/metabolismo , Metástase Neoplásica , Regiões Promotoras Genéticas , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/metabolismo , Transcrição GênicaRESUMO
Objective: This study investigates the impact of mild pulmonary vein obstruction, detected via echocardiography before hospital discharge, on the likelihood of reoperation in patients who have undergone repair for Total Anomalous Pulmonary Venous Connection (TAPVC). Method: Utilizing a single-center, retrospective cohort approach, we analyzed 38 cases from October 2017 to December 2023, excluding patients with functionally univentricular circulations or atrial isomerism. Our primary outcome was the necessity for reoperation within one year due to anatomical issues related to the initial TAPVC repair. Mild obstruction was defined as a pulmonary vein flow velocity ≥1.2â m/s. Result: Our findings revealed that 31.6% of patients exhibited pre-discharge mild obstruction. During the median follow-up of 10 months, reoperations were notably higher in the mild obstruction group compared to the normal group, with a significant association between pre-discharge mild obstruction and increased risk of reoperation. Specifically, in the fully adjusted model, mild obstruction was linked to a 13.9-fold increased risk of reoperation. Conclusion: Our results suggest that a pre-discharge echocardiography Doppler velocity threshold of 1.2â m/s could serve as a critical predictor for reoperation, emphasizing the need for targeted follow-up strategies for at-risk patients.
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Objective: This study aimed to investigate the relationship between technical performance scores (TPS) and the early prognosis of tetralogy of Fallot repair (TOF). Methods: A retrospective study was conducted on TOF repair patients at our center from Oct 2017 to Oct 2022. Patients were classified into Class 1 (no residua), Class 2 (minor residua), or Class 3 (major residua) based on TPS derived from predischarge echocardiograms and need for reintervention. Statistical methods were used to assess the association between TPS and early prognosis. Results: A total of 75 TOF repair patients (40% female, 60% male) were analyzed and categorized into TPS1 (24%), TPS2 (53.3%), and TPS3 (22.6%) based on pre-discharge echocardiographic findings. The median follow-up time was 7.0 months. The multivariable Cox regression analysis indicated that TPS3 scores are associated with a 12.68-fold increase in risk compared to TPS1 and TPS2 scores [95% CI = 12.68 (0.9â¼179.28), P = 0.06]. The Spearman rank correlation analysis revealed a weak positive correlation between TPS classification and low cardiac output syndrome (r = 0.26, P = 0.03). However, there were no significant differences in ICU stay or duration of mechanical ventilation among the groups. Conclusion: TPS3 after intracardiac TOF repair is associated with higher risk of early re-intervention, highlighting the importance of close follow-up and monitoring in this patient population. Patients who develop low cardiac output syndrome in the early postoperative period may have residual defects that require prompt identification.
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Objective: This study aimed to explore Kawasaki disease (KD) susceptibility genes and their complications like coronary artery lesions (CAL) using whole exome sequencing (WES). Methods: Between April 1, 2021, and December 31, 2022, our study included 55 pediatric patients diagnosed KD at our center, alongside a cohort of healthy children who sought medical care at our institution during the same timeframe. We extracted peripheral blood DNA from all participants and employed the advanced high-throughput Illumina Next-Generation Sequencing technology for comprehensive analysis. Through bioinformatics evaluation, we identified potential susceptibility genes. Moreover, from the 55 KD patients, we selected 15 for the CAL group and 40 for the non-CAL group. We aimed to investigate whether there were significant differences in the allele frequencies of the targeted susceptibility genes between these subgroups, to explore the risk alleles associated with the development of CAL in KD. Results: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes and alleles differed significantly between KD and non-KD (P < 0.05). No differences existed for IL17RC rs143781415 and VEGFB rs776229557 (P > 0.05). No differences in HLA-DRB1 rs17882084, IL6ST rs781455079, and VEGFB rs776229557 genotypes existed between CAL and non-CAL groups (P > 0.05). However, the IL17RC rs143781415 genotype differed significantly between them (P < 0.05). Conclusions: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes may be potential KD susceptibility gene candidates. Specifically, HLA-DRB1 rs17882084 GA genotype and A allele, and IL6ST rs781455079 TC genotype and C allele may increase KD risk. Additionally, the IL17RC rs143781415 genotype may increase CAL risk in KD patients.
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The fungal pathogen Batrachochytrium dendrobatidis (Bd) causes the disease amphibian chytridiomycosis, which has contributed to population declines in many species of amphibians throughout the world. Previous observational studies have shown that nematodes, waterfowl, lizards, other dipterans, and crayfish have properties which may allow them to harbor and spread Bd; therefore, we sought to determine the carrier capabilities of invertebrates to a further extent in a laboratory setting. We use the insect Drosophila melanogaster as a model organism to quantify the potential relationship between insects and Bd. Our findings show that D. melanogaster can test positive for Bd for up to five days post-exposure and can transmit Bd to conspecifics without suffering mortality. Insects of various types interact with the amphibian habitat and amphibians themselves, making this a potentially important route of transmission between amphibians and of dispersal across the environment.
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Batrachochytrium , Drosophila melanogaster , Animais , Drosophila melanogaster/microbiologia , Batrachochytrium/patogenicidade , Anfíbios/microbiologia , Micoses/veterinária , Micoses/microbiologia , Quitridiomicetos/patogenicidade , Quitridiomicetos/fisiologiaRESUMO
BACKGROUND: The association between body shape and depressive symptoms has been reported in adults. The present study aimed to investigate the association between body shape-specific abdominal obesity and depressive symptoms among multi-regional Asian adults. METHODS: The 2011-2012 China Health and Retirement Longitudinal Study and 2022-2023 Hangzhou study were used as the discovery and validation datasets, respectively. Body shape was assessed by body mass index categories. Abdominal obesity was defined as a body shape index (ABSI) ≥ 75th centile. Depression was measured using 10-item Centre for Epidemiological Studies Depression Scale and Geriatric Depression Scale short 15-item version, respectively. General linear and multinomial logistic models were used to explore the association of ABSI, abdominal obesity with depressive scores and presence, respectively. RESULTS: A total of 12,229 and 1210 participants were included in the discovery and validation datasets, respectively. A non-linear reverse L-shaped association was found between ABSI and depressive scores. Participants with abdominal obesity had higher depressive scores (ß = 0.05, 95%CI = 0.01-0.09; and ß = 0.13, 95%CI = 0.01-0.24; respectively). Stratified analyses showed that abdominal obesity was associated with higher depressive scores (ß = 0.09, 95%CI = 0.00-0.17; and ß = 0.25, 95%CI = 0.05-0.46; respectively) and presence (OR = 1.46, 95%CI = 1.02-2.10; and OR = 3.95, 95%CI = 1.58-9.84; respectively) in overweight adults. Furthermore, abdominal obesity was associated with depressive symptoms among overweight females, but not among males. LIMITATION: Causal links weren't addressed because of the observational study design. CONCLUSION: Abdominal obesity exhibited a positive association with depressive symptoms among Asian overweight adults, particularly in females. Prevention and early diagnosis of depressive symptoms should focus on overweight females.
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Índice de Massa Corporal , Depressão , Obesidade Abdominal , Humanos , Obesidade Abdominal/epidemiologia , Masculino , Feminino , China/epidemiologia , Depressão/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , População do Leste AsiáticoRESUMO
Background: The heterogeneity and dynamic changes of endometrial cells have a significant impact on health as they determine the normal function of the endometrium during the menstrual cycle. Dysfunction of the endometrium can lead to the occurrence of various gynecological diseases. Therefore, deconvolution of immune microenvironment that drives transcriptional programs throughout the menstrual cycle is key to understand regulatory biology of endometrium. Methods: Herein, we comprehensively analyzed single-cell transcriptome of 59,397 cells across ten human endometrium samples and revealed the dynamic cellular heterogeneity throughout the menstrual cycle. Results: We identified two perivascular cell subtypes, four epithelial subtypes and four fibroblast cell types in endometrium. Moreover, we inferred the cell type-specific transcription factor (TF) activities and linked critical TFs to transcriptional output of diverse immune cell types, highlighting the importance of transcriptional regulation in endometrium. Dynamic interactions between various types of cells in endometrium contribute to a range of biological pathways regulating differentiation of secretory. Integration of the molecular biomarkers identified in endometrium and bulk transcriptome of 535 endometrial cancers (EC), we revealed five RNA-based molecular subtypes of EC with highly intratumoral heterogeneity and different clinical manifestations. Mechanism analysis uncovered clinically relevant pathways for pathogenesis of EC. Conclusion: In summary, our results revealed the dynamic immune microenvironment of endometrium and provided novel insights into future development of RNA-based treatments for endometriosis and endometrial carcinoma.
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Congenital heart disease (CHD) is a common birth defect in children. Intelligent auscultation algorithms have been proven to reduce the subjectivity of diagnoses and alleviate the workload of doctors. However, the development of this algorithm has been limited by the lack of reliable, standardized, and publicly available pediatric heart sound databases. Therefore, the objective of this research is to develop a large-scale, high-standard, high-quality, and accurately labeled pediatric CHD heart sound database. METHOD: From 2020 to 2022, we collaborated with experienced cardiac surgeons from three general children's hospitals to collect heart sound signals from 1259 participants using electronic stethoscopes. To ensure the accuracy of the labels, the labels for all data were confirmed by two cardiac experts. To establish the baseline of ZCHsound, we extracted 84 features and used machine learning models to evaluate the performance of the classification task. RESULTS: The ZCHSound database was divided into two datasets: one is a high-quality, filtered clean heart sound dataset, and the other is a low-quality, noisy heart sound dataset. In the evaluation of the high-quality dataset, our random forest ensemble model achieved an F1 score of 90.3% in the classification task of normal and pathological heart sounds. CONCLUSION: This study has successfully established a large-scale, high-quality, rigorously standardized pediatric CHD sound database with precise disease diagnosis. This database not only provides important learning resources for clinical doctors in auscultation knowledge but also offers valuable data support for algorithm engineers in developing intelligent auscultation algorithms.
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Bases de Dados Factuais , Cardiopatias Congênitas , Ruídos Cardíacos , Processamento de Sinais Assistido por Computador , Humanos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/diagnóstico por imagem , Ruídos Cardíacos/fisiologia , Criança , Pré-Escolar , Lactente , Algoritmos , Masculino , Aprendizado de Máquina , Feminino , Recém-Nascido , AdolescenteRESUMO
Background: In this case report, we utilized a three-dimensional printing model to replicate the complex anatomy of a criss-cross heart with double outlet right ventricle-an extremely rare congenital cardiac abnormality. This approach facilitated our understanding of the patient's unique condition and enabled us to plan the surgical procedure with greater precision. Case presentation: Our department received a 13-year-old female patient who presented with a pronounced heart murmur and a decrease in exercise capacity. Subsequent two-dimensional imaging revealed the presence of a criss-cross heart with double outlet right ventricle-an intricate and uncommon cardiac malformation that poses challenges for accurate visualization through conventional two-dimensional modalities. To address this challenge, we constructed and printed a three-dimensional model using computed tomography data, which enabled us to visualize and understand the complex intracardiac structures and plan surgical interventions with greater precision. Using this approach, we successfully performed a right ventricular double outlet repair, and the patient made a full recovery following the procedure. Conclusion: The criss-cross heart with double outlet right ventricle constitutes a complex and uncommon cardiac anomaly that poses considerable challenges in terms of diagnosis and surgical intervention. Employing three-dimensional modeling and printing represents a promising approach, given its potential to enhance the precision and comprehensiveness of the anatomical evaluation of the heart. As a result, this method holds significant promise in facilitating accurate diagnosis, meticulous surgical planning, and ultimately improving clinical outcomes for patients affected by this condition.
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Prenatal anterior mediastinal teratomas are rare. Anterior mediastinal teratomas can cause edema during the perinatal period. Color Doppler ultrasonography and chest computed tomography (CT) are of great value in diagnosing neonatal anterior mediastinal teratomas. Here, we report a case of prenatally diagnosed neonatal anterior mediastinal teratoma. After birth, transthoracic echocardiography and chest enhanced CT showed a large solid mass in the pericardial cavity. Owing to compression of the heart, the tumor was completely removed 1 day after birth, and cardiopulmonary bypass was performed. Pathology results indicated an immature teratoma (Grade I). At 9-month follow-up, the patient remained in good overall condition without observed recurrences.
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OBJECTIVE: To study the effects of ulinastatin on coagulation in children who underwent open-heart surgery with cardiopulmonary bypass (CPB). METHODS: Fifty children who underwent open-heart surgery for ventricular septal defect were randomly divided into two groups: ulinastatin treatment and control. Before CPB, ulinastatin (1.0×10(4) U/kg) was added to CPB priming fluid only in the ulinastatin treatment group. Activated partial thromboplasin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and international normalized ratio (INR) were measured both before and at 1 hr, 6 hrs and 24 hrs after CPB. RESULTS: The PT in the ulinastatin group was more prolonged than in the control group at 1 hr after CPB (18.7 ± 0.7 s vs 15.5 ± 0.5 s) and 6 hrs after CPB (17.5 ± 0.6 s vs 15.0 ± 0.6 s). The APTT in the ulinatatin group was also significantly more prolonged than in the control group at 6 hrs after CPB (38.7 ± 3.1 s vs 35.3 ± 3.1 s) and 24 hrs after CPB (34.2 ± 3.0 s vs 31.1 ± 2.6 s). CONCLUSIONS: Ulinastatin may prolong PT and APTT after CPB, and thus affects coagulation in children.
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Coagulação Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar , Glicoproteínas/farmacologia , Inibidores da Tripsina/farmacologia , Procedimentos Cirúrgicos Cardíacos , Feminino , Humanos , Lactente , Masculino , Tempo de Tromboplastina Parcial , Tempo de ProtrombinaRESUMO
RATIONALE: Double-outlet left ventricle (DOLV) is a rare congenital cardiac malformation in which both great arteries arise entirely or predominantly from the left ventricle. An extracardiac conduit is the first surgical option for repairing DOLV, specifically because its placement of the extracardiac conduit can be customized to accommodate all possible anatomical variations. The bovine jugular veins and homograft valves are often used as conduits. There have been no reports on the use of handmade trileaflet-valved conduits for correcting DORV. PATIENT CONCERNS: A 1-year old male was admitted for significant heart murmur and cyanosis, according to the results of transthoracic echocardiography, computed tomography angiography, and cardioangiography, and was diagnosed with DOLV and pulmonary stenosis. DIAGNOSIS AND INTERVENTIONS: The patient underwent biventricular repair with a handmade trileaflet-valved extracardiac conduit. The postoperative course was uneventful. OUTCOME: Three months after the surgery, TTF indicated mild right ventricular outflow obstruction and pulmonary valve regurgitation. LESSONS: Correction of the left ventricular double outlet with a handmade trileaflet-valved conduit has been shown to have excellent performance, and long-term outcomes should be followed over time.
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Ventrículos do Coração , Estenose da Valva Pulmonar , Masculino , Animais , Bovinos , Humanos , Lactente , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Próteses e Implantes , Ecocardiografia , CianoseRESUMO
Background: The exact incidence and predictors of mortality and left atrioventricular valve (LAVV) re-operation in congenital atrioventricular septal defect (AVSD) repair are still unclear. This study analyzed the middle to long-term outcomes of surgical repair for AVSD. Methods: A total of 150 patients (69 males and 81 females) who underwent AVSD repair at Children's Hospital of Fudan University from January 2013 to December 2021 were divided into complete defect group (C-group, 67 cases), transitional defect group (T-group, 26 cases), and partial defect group (P-group, 57 cases). Outcomes during the peri-operative and 10-year follow-up periods were evaluated. Results: The total mortality was 5.33% (8/150), including seven early deaths (10.4%) and no late deaths in the C-group, no early deaths (0%) and one late death (1.8%) in the P-group, and no early or late deaths in the T-group. Up to the last follow-up, severe LAVV regurgitation had occurred in 27 patients, including 16 in the C-group, four in the T-group, and seven in the P-group. In total, 12 (12/150, 8.0%) patients received LAVV re-operation, including seven in the C-group, three in the T-group, and two in the P-group. Cox regression analysis showed that pre-operative severe pulmonary hypertension (P=0.006) and severe LAVV regurgitation within 24 hours after the first surgery (P=0.023) were independent risk factors for mortality. ≥ Moderate LAVV regurgitation within the first 24 hours after surgery (P=0.014) was an independent risk factor for LAVV re-operation. Conclusions: Complete AVSD repair increased the risk of early death, severe LAVV regurgitation and re-operation. Pre-operative severe pulmonary hypertension and residual severe LAVV regurgitation indicated high risk for mortality. ≥ Moderate LAVV regurgitation within 24 hours after the first surgery predicted a high probability of LAVV re-operation.
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Potato production plays an important role in safeguarding food security in China since the central government implemented the 'Potato-as-Staple-Food' policy in 2015. However, a key challenge facing China's potato production is to realize a tradeoff between economic return and environmental impact. Effective strategies for reducing carbon emission without compromising potato yield remain to be developed. This study conducted a comprehensive assessment by integrating climate, soil, crop, and agricultural input data, crop model and life cycle impact assessment model to quantify potato yields, GHG emission amounts and intensities (GHGI), and economic benefits under the conventional planting pattern (CPP), the lowest GHG emission pattern (LEP), and the highest yield pattern (HYP) across China's potato planting regions including four sub-regions, i.e., North Single planting region (NS), Central Double planting region (CD), South Winter planting region (SW), and Southwest Mixed planting region (SWM). Averaged fresh potato yield, GHG emission amount, and GHGI under the CPP were 21.7 t ha-1, 2815.1 kg CO2eq ha-1, and 137.3 kg CO2eq t-1, respectively, in China's potato planting region. Compared with the CPP, averaged GHG emission amount and GHGI under the LEP could be decreased by 48.2 % and 51.5 % respectively while the fresh potato yield and economic benefit could be enhanced by 8.1 % and 18.5 %, respectively. For the HYP, averaged GHG emission amount and GHGI could be decreased by 24.2 % and 39.8 % respectively while the fresh potato yield and economic benefit could be enhanced by 18.7 % and 39.6 %, respectively, compared with the CPP. Across the four potato planting regions, SW had the largest potential in reducing GHG emissions owing to a high reduction amount of nitrogen application rate. Our study demonstrates that optimizing agronomic management could reduce environmental impact without compromising economic benefit and provides a scientific method for assessing crop potential to realize the climate-smart planting.