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BACKGROUND: Climate change has led to severe cold events, adversely impacting global crop production. Eggplant (Solanum melongena L.), a significant economic crop, is highly susceptible to cold damage, affecting both yield and quality. Unraveling the molecular mechanisms governing cold resistance, including the identification of key genes and comprehensive transcriptional regulatory pathways, is crucial for developing new varieties with enhanced tolerance. RESULTS: In this study, we conducted a comparative analysis of leaf physiological indices and transcriptome sequencing results. The orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted peroxidase (POD) activity and soluble protein as crucial physiological indicators for both varieties. RNA-seq data analysis revealed that a total of 7024 and 6209 differentially expressed genes (DEGs) were identified from variety "A" and variety "B", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs demonstrated that the significant roles of starch and sucrose metabolism, glutathione metabolism, terpenoid synthesis, and energy metabolism (sucrose and starch metabolism) were the key pathways in eggplant. Weighted gene co-expression network analysis (WGCNA) shown that the enrichment of numerous cold-responsive genes, pathways, and soluble proteins in the MEgrep60 modules. Core hub genes identified in the co-expression network included POD, membrane transporter-related gene MDR1, abscisic acid-related genes, growth factor enrichment gene DELLA, core components of the biological clock PRR7, and five transcription factors. Among these, the core transcription factor MYB demonstrated co-expression with signal transduction, plant hormone, biosynthesis, and metabolism-related genes, suggesting a pivotal role in the cold response network. CONCLUSION: This study integrates physiological indicators and transcriptomics to unveil the molecular mechanisms responsible for the differences in cold tolerance between the eggplant cold-tolerant variety "A" and the cold-sensitive variety "B". These mechanisms include modulation of reactive oxygen species (ROS), elevation in osmotic carbohydrate and free proline content, and the expression of terpenoid synthesis genes. This comprehensive understanding contributes valuable insights into the molecular underpinnings of cold stress tolerance, ultimately aiding in the improvement of crop cold tolerance.
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Solanum melongena , Transcriptoma , Solanum melongena/genética , Solanum melongena/metabolismo , Fisiologia Comparada , Perfilação da Expressão Gênica/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta ao Choque Frio/genética , Amido/metabolismo , Sacarose/metabolismo , Terpenos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Drug-target interactions (DTIs) prediction research presents important significance for promoting the development of modern medicine and pharmacology. Traditional biochemical experiments for DTIs prediction confront the challenges including long time period, high cost and high failure rate, and finally leading to a low-drug productivity. Chemogenomic-based computational methods can realize high-throughput prediction. In this study, we develop a deep collaborative filtering prediction model with multiembeddings, named DCFME (deep collaborative filtering prediction model with multiembeddings), which can jointly utilize multiple feature information from multiembeddings. Two different representation learning algorithms are first employed to extract heterogeneous network features. DCFME uses the generated low-dimensional dense vectors as input, and then simulates the drug-target relationship from the perspective of both couplings and heterogeneity. In addition, the model employs focal loss that concentrates the loss on sparse and hard samples in the training process. Comparative experiments with five baseline methods show that DCFME achieves more significant performance improvement on sparse datasets. Moreover, the model has better robustness and generalization capacity under several harder prediction scenarios.
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Algoritmos , Desenvolvimento de Medicamentos , Desenvolvimento de Medicamentos/métodosRESUMO
Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.3% for nonclinical adverse findings; sensitivity increased to 67.3% and PPV fell to 35.0% when including nonadverse findings. Nonclinical findings were associated with a greater likelihood of a human ADR in that organ category, especially for adverse findings [positive likelihood ratio (LR+) >10 (lower 95% confidence interval [CI] of >5)]. The specificity and negative predictive value (NPV) were very high (>85%). A lack of nonclinical findings in an organ category was associated with a lower likelihood of a human ADR in that organ category. About 40-50% of human ADRs and nonclinical adverse findings, and about 30% of nonclinical nonadverse findings, were attributed to pharmacology. Slightly more than half of the human ADRs with a translating nonclinical finding had findings in animals that could be considered very similar. Overall, 38% of nonclinical findings translated to a human ADR at the organ category level. When nonclinical findings did not translate to humans, the cause was usually higher exposures or longer dosing in animals. All programs with human ADRs attributed to immunogenicity also had nonclinical adverse or nonadverse findings related to immunogenicity. Overall, nonclinical adverse and nonadverse findings were useful in predicting human ADRs, especially at an organ category level, and the majority of human ADRs were predicted by nonclinical toxicity studies.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Animais , Humanos , Valor Preditivo dos TestesRESUMO
BACKGROUND: The combination of targeted therapy and immunotherapy has improved the clinical outcomes of unresectable hepatocellular Carcinoma (HCC). However, the overall prognosis remains suboptimal. This study aims to evaluate the efficacy and safety of a novel combination of radiofrequency ablation (RFA) with lenvatinib plus sintilimab in unresectable HCC. METHODS: In this retrospective study, patients diagnosed with unresectable HCC were included and divided into two cohorts: RFA combined with lenvatinib plus sintilimab (R-L-S group) and lenvatinib plus sintilimab (L-S group). The primary efficacy endpoints were objective response rate (ORR) and progression free survival (PFS). Adverse events were analyzed to assess the safety profiles. RESULTS: The median follow-up periods for the entire cohort were 14.0 months. The R-L-S group (n = 60) had a significantly higher ORR than those with L-S alone (n = 62) (40.0% vs. 20.9%; p = 0.022). Moreover, patients in the R-L-S group had improved median PFS (12 vs. 8 months; p = 0.013) and median overall survival (24 vs. 18 months; p = 0.037), as compared with lenvatinib and sintilimab alone. No significant difference in treatment related adverse event (TRAE) of any grade between the two groups. The most common TRAEs of grade ≥ 3 were fatigue 10.0% (6/60) and hand-foot skin reaction 10.0% (6/60) in the R-L-S group and hand-foot skin reaction 11.3% (7/62) in the L-S group. CONCLUSION: In unresectable HCC patients, the incorporation of RFA to lenvatinib plus sintilimab demonstrated improved efficacy without compromising safety compared with lenvatinib plus sintilimab alone.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.
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BACKGROUND: Dopamine antagonists, 5-HT3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. RESULTS: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT3 antagonists, dopamine antagonists, dexamethasone, and 5-HT3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. CONCLUSIONS: Combined 5-HT3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023454602.
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Antieméticos , Cesárea , Dexametasona , Morfina , Metanálise em Rede , Náusea e Vômito Pós-Operatórios , Humanos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Morfina/administração & dosagem , Morfina/uso terapêutico , Feminino , Antieméticos/uso terapêutico , Antieméticos/administração & dosagem , Cesárea/efeitos adversos , Gravidez , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Antagonistas de Dopamina/administração & dosagem , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND AIM: The latest Barcelona Clinic Liver Cancer (BCLC) staging system suggests considering surgery in patients with resectable BCLC stage 0/A hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH). This study aimed to evaluate the safety and short- and long-term outcomes of laparoscopic hepatectomy for BCLC stage 0/A HCC patients with CSPH. METHODS: We retrospectively reviewed the medical records of 647 HCC patients in BCLC stage 0/A who were treated at five centers between January 2010 and January 2019. Among these patients, 434 underwent laparoscopic hepatectomy, and 213 underwent open hepatectomy. We used Kaplan-Meier analysis to compare the overall survival (OS) rate and recurrence-free survival (RFS) rate between patients with and without CSPH before and after propensity score matching (PSM). Multivariate Cox regression analysis was performed to identify prognostic factors for BCLC stage 0/A patients, and subgroup analyses were also conducted. RESULTS: Among the 434 patients who underwent laparoscopic hepatectomy, 186 had CSPH and 248 did not. The Kaplan-Meier analysis showed that the OS and RFS rates were significantly worse in the CSPH group before and after PSM. Multivariate Cox regression analyses identified CSPH as a prognostic factor for poor OS and RFS after laparoscopic hepatectomy. However, CSPH patients treated laparoscopically had a better short- and long-term prognosis than those treated with open surgery. CONCLUSIONS: CSPH has a negative impact on the prognosis of BCLC stage 0/A HCC patients after laparoscopic hepatectomy. Laparoscopic hepatectomy is still recommended for treatment, but careful patient selection is essential.
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Carcinoma Hepatocelular , Hipertensão Portal , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Hepatectomia , Estudos Retrospectivos , Pontuação de Propensão , Resultado do Tratamento , Prognóstico , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Laparoscopia/efeitos adversosRESUMO
In this paper, a highly sensitive ammonia (N H 3) sensor based on a polymethyl methacrylate/polyaniline (PMMA/PANI) microwire structure is designed and implemented. First, a micron-sized PMMA microwire was fabricated and connected with two tapered single-mode fibers to form a coupling structure; thus, the Mach-Zehnder (MZ) interference was successfully excited due to the good light conductivity of the PMMA. It was demonstrated that the coupling structure behaved with a high refractive index detection sensitivity of 3044 nm/RIU. To make it sensitive to N H 3, the PANI was selected to mix with PMMA and then formed a micron-level PMMA/PANI fiber. The experimental results showed that the PMMA/PANI fiber can selectively sense N H 3 with a high sensitivity of 65.3 pm/ppm. This proposed N H 3 sensor not only solves the problem of sensitive film shedding, but also possesses the advantages of good integration, high sensitivity, good selectivity, and short response time.
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OBJECTIVE: To estimate the impact of traumatic brain injury (TBI) on prevalence of posttraumatic stress disorder (PTSD), depression, and alcohol and substance use disorders. SETTING: A random sample of Veteran's Health Administration data. PARTICIPANTS: A total of 14 116 veterans aged ≥55 with incident late-life TBI between October 1, 1999, and September 31, 2021, were matched 1:3 on age and TBI date to 42 678 veterans without TBI. DESIGN: Retrospective cohort study. MAIN MEASURES: PTSD, depression, and alcohol and substance use disorders were identified using diagnostic codes. Participants were censored after the first diagnosis during the year before and the year after the TBI or matched date. Prevalence rates of PTSD, depression, alcohol, and substance use disorders were compared before and after incident TBI or matched date using Poisson regression. RESULTS: Pre-TBI prevalence rates of disorders were higher among those with TBI relative to those without TBI. Pre-TBI PTSD prevalence rates (per 1000 person-years) were 126.3 (95% CI, 120.2-132.4) compared to 21.5 (95% CI, 20.1-22.9) in the non-TBI cohort. In adjusted models, TBI was not associated with an increase in the prevalence of any of the studied disorders. CONCLUSIONS: Prevalence rates of depression, PTSD, and alcohol and substance use disorders were 5 to 10 times higher among older veterans before incident TBI. We did not observe an increase in the prevalence of these disorders after incident TBI. Older veterans with these disorders may be at increased risk for TBI.
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BACKGROUND: Neuraxial labour analgesia can be initiated with epidural (EPL), combined spinal epidural (CSE) or dural puncture epidural (DPE) and maintained with continuous epidural infusion (CEI), patient-controlled epidural analgesia (PCEA) or programmed intermittent epidural bolus (PIEB), but the optimal analgesia modality is still controversial. OBJECTIVE: To compare the effects of commonly used neuraxial analgesia modalities on the proportion of women needing physician interventions, as defined by the need for physician-administered epidural top-ups for inadequate analgesia in labour. DESIGN: Bayesian network meta-analysis. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science and Wanfang Data were searched from January 1988 to August 2023 without language restriction. ELIGIBILITY CRITERIA: Randomised controlled trials comparing two or more modalities of the following six neuraxial analgesia modalities in healthy labouring women: EPL+CEI+PCEA, EPL+PIEB+PCEA, CSE+CEI+PCEA, CSE+PIEB+PCEA, DPE+CEI+PCEA and DPE+PIEB+PCEA. RESULTS: Thirty studies with 8188 women were included. Compared with EPL+CEI+PCEA, EPL+PIEB+PCEA [odds ratio (OR)â=â0.44; 95% credible interval (CrI), 0.22 to 0.86], CSE+PIEB+PCEA (ORâ=â0.29; 95% CrI, 0.12 to 0.71) and DPE+PIEB+PCEA (ORâ=â0.19; 95% CrI, 0.08 to 0.42) significantly reduced the proportion of women needing physician interventions. DPE+PIEB+PCEA had fewer women needing physician interventions than all other modalities, except for CSE+PIEB+PCEA (ORâ=â0.63; 95% CrI, 0.25 to 1.62). There were no significant differences in local anaesthetic consumption, maximum pain score, and the incidence of instrumental delivery between the different neuraxial modalities. CONCLUSIONS: PIEB+PCEA is associated with a lower risk of physician interventions in labour than CEI+PCEA. DPE or CSE and PIEB+PCEA may be associated with a lower likelihood of physician interventions than other neuraxial modalities. Otherwise, the new neuraxial analgesia techniques do not appear to offer significant advantages over traditional techniques. However, these results should be interpreted with caution due to limited data and methodological limitations. TRIAL REGISTRATION: PROSPERO (CRD42023402540).
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Analgesia Epidural , Analgesia Obstétrica , Metanálise em Rede , Feminino , Humanos , Gravidez , Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente/métodos , Teorema de Bayes , Trabalho de Parto/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
Calmodulin-binding transcription activator (CAMTA) is an important calmodulin-binding protein with a conserved structure in eukaryotes which is widely involved in plant stress response, growth and development, hormone signal transduction, and other biological processes. Although CAMTA genes have been identified and characterized in many plant species, a systematic and comprehensive analysis of CAMTA genes in the Solanaceae genome is performed for the first time in this study. A total of 28 CAMTA genes were identified using bioinformatics tools, and the biochemical/physicochemical properties of these proteins were investigated. CAMTA genes were categorized into three major groups according to phylogenetic analysis. Tissue-expression profiles indicated divergent spatiotemporal expression patterns of SmCAMTAs. Furthermore, transcriptome analysis of SmCAMTA genes showed that exposure to cold induced differential expression of many eggplant CAMTA genes. Yeast two-hybrid and bimolecular fluorescent complementary assays suggested an interaction between SmCAMTA2 and SmERF1, promoting the transcription of the cold key factor SmCBF2, which may be an important mechanism for plant cold resistance. In summary, our results provide essential information for further functional research on Solanaceae family genes, and possibly other plant families, in the determination of the development of plants.
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Solanaceae , Solanum melongena , Resposta ao Choque Frio/genética , Solanum melongena/genética , Solanum melongena/metabolismo , Solanaceae/metabolismo , Filogenia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genéticaRESUMO
INTRODUCTION: This study aims to assess the safety and clinical efficacy of percutaneous splenic embolization (PSE) and splenectomy as approaches to treating cases of traumatic splenic rupture (TSR). MATERIAL AND METHODS: Eligible articles published throughout August 2023 were identified. Endpoints compared between PSE and splenectomy patient groups included operative time, intraoperative hemorrhage, duration of hospitalization, postoperative complication rates, and measures of immune function. RESULTS: Thirteen studies, involving 474 and 520 patients in the PSE and splenectomy groups respectively, were incorporated into this meta-analysis. As compared to the splenectomy group, individuals treated via PSE exhibited a significant reduction in pooled operative time (p < 0.00001) and hospitalization duration (p < 0.00001), with corresponding reductions in rates of intraoperative hemorrhage (p < 0.00001), total complications (p < 0.0001), incisional infection (p < 0.0001), ileus (p = 0.0004), and abdominal infection (p = 0.02). The immune status of these PSE group patients was also improved, as evidenced by significantly higher pooled CD4+ (30 days), CD4+/CD8+ (30 days), and CD3+ (30 days) values (p < 0.0001, 0.0001, and 0.0001, respectively). CONCLUSIONS: Compared to splenectomy, PSE-based TSR treatment can significantly reduce operative time, rate of postoperative complications, and incidence of intraoperative hemorrhage, while improving post-procedural immune functionality.
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The increase in biological data and the formation of various biomolecule interaction databases enable us to obtain diverse biological networks. These biological networks provide a wealth of raw materials for further understanding of biological systems, the discovery of complex diseases and the search for therapeutic drugs. However, the increase in data also increases the difficulty of biological networks analysis. Therefore, algorithms that can handle large, heterogeneous and complex data are needed to better analyze the data of these network structures and mine their useful information. Deep learning is a branch of machine learning that extracts more abstract features from a larger set of training data. Through the establishment of an artificial neural network with a network hierarchy structure, deep learning can extract and screen the input information layer by layer and has representation learning ability. The improved deep learning algorithm can be used to process complex and heterogeneous graph data structures and is increasingly being applied to the mining of network data information. In this paper, we first introduce the used network data deep learning models. After words, we summarize the application of deep learning on biological networks. Finally, we discuss the future development prospects of this field.
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Aprendizado Profundo , Redes Neurais de Computação , Algoritmos , Mineração de Dados , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Interações Medicamentosas , Genótipo , Humanos , Microbiota , Fenótipo , Mapas de Interação de Proteínas , Proteínas/químicaRESUMO
Copper plays a vital role in the host-pathogen interface, potentially making components of the bacterial copper response suitable targets for the development of innovative antimicrobial strategies. The anti-copper arsenal of intracellular pathogens has expanded as an adaptation to survive copper toxicity in order to escape intracellular killing by the host immune system. Herein, we employed transposon insertion sequencing to investigate the genetic mechanisms underlying the survival of Edwardsiella piscicida under copper stress. A novel transcriptional regulator, ETAE_2324 (named CorR), was identified to participate in the response to copper ions by controlling the expression of copA, the core component of cytoplasmic copper homeostasis. Furthermore, CorR regulated the expression of virulent determinant eseB, influencing the in vivo colonization of E. piscicida. Collectively, our results contribute to the comprehension of the underlying mechanism of the adaption of intracellular pathogens to copper stress during bacterial infections.IMPORTANCECopper ions play a pivotal role in the interaction between bacteria and the host during infection. The host's innate immune system employs copper ions for their bactericidal properties, thereby making bacterial copper tolerance a crucial determinant of virulence. Edwardsiella piscicida, a significant marine pathogen, has caused substantial losses in the global aquaculture industry. To comprehensively investigate how E. piscicida responds to copper stress, we utilized transposon insertion sequencing to explore genes associated with copper tolerance in culture media containing different concentrations of copper ions. A novel transcriptional regulator, CorR, was identified to respond to copper ions and regulates the expression of crucial components of copper homeostasis CopA, along with the essential virulence factor EseB. These findings offer valuable insights into the underlying mechanisms that govern bacterial copper tolerance and present novel perspectives for the development of vaccines and therapeutic strategies targeting E. piscicida.
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Infecções por Enterobacteriaceae , Doenças dos Peixes , Animais , Cobre/toxicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Enterobacteriaceae/veterinária , Infecções por Enterobacteriaceae/microbiologia , Íons , Doenças dos Peixes/microbiologiaRESUMO
BACKGROUND: A growing body of evidence suggests adverse health outcomes related to intimate partner violence (IPV), including traumatic brain injury (TBI). However, most research in this area has focused on reproductive-aged women. OBJECTIVE: To examine relationships between IPV (with and without TBI), mental health, and aging-related health outcomes among men and women Veterans across the lifespan. DESIGN: Cross-sectional analysis of Department of Veterans Affairs (VA) administrative data from fiscal years 2000-2019. Descriptive statistics and chi-square analyses were used to compare key comorbidities in matched samples of Veterans with and without IPV (gender-stratified and matched 1:3 based on demographics and index date). Comparisons between those with IPV and TBI relative to IPV alone were also examined. SUBJECTS: Veterans aged 18 + with and without documented IPV in Department of Veterans Affairs (VA) electronic health records (n = 4108 men, 2824 women). MAIN MEASURES: ICD codes were used to identify IPV, TBI, and aging-related medical (sleep disorder, hypertension, diabetes, dementia) and common psychiatric (depression, posttraumatic stress disorder, alcohol use disorder, and substance use disorder) diagnoses. KEY RESULTS: Demographic characteristics were reflective of VA-enrolled Veterans (men: mean age 66, SD 16; 72% non-Hispanic White; women: mean age 47, SD 13; 64% non-Hispanic White). Relative to Veterans without IPV, both men and women with IPV had higher rates of all examined medical (e.g., sleep disorders, men: 33% vs. 52%; women: 45% vs. 63%) and psychiatric diagnoses (e.g., depression, men 32% vs. 74%; women 59% vs. 91%; all ps < .001), with evidence of an additive effect of TBI on some psychiatric outcomes. CONCLUSIONS: IPV is broadly associated with aging-related and mental health, and TBI is a common correlate that may further contribute to psychiatric outcomes. Findings highlight the importance of trauma-informed care and recognizing the potential role of these exposures on men and women Veterans' health across the lifespan.
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Liver cancer is a common malignant tumor, and its clinical stage is closely related to the clinical treatment and prognosis of patients. Currently, the BCLC staging system revised by the BCLC group of University of Barcelona is the globally recognized staging system for liver cancer. However, with the deepening of related research, the current staging system can no longer fully meet the clinical needs. In this work, we propose a novel machine learning method for constructing an automatic hepatocellular carcinoma staging model that incorporates far more clinical variables than any existing staging system. Our model is based on random survival forests, which generates a unique hazard function for each patient. B-splines are used to embed hazard functions into vectors in low-dimensional space and hierarchical clustering method groups similar patients to form staging cohorts. The resulting staging system significantly outperforms the BCLC system in terms of distinctiveness between patients in different stages.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , PrognósticoRESUMO
Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.
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Anemia , Medicamentos Biossimilares , Hematínicos , Nefropatias , Aplasia Pura de Série Vermelha , Humanos , Anemia/tratamento farmacológico , Doença Crônica , Epoetina alfa/uso terapêutico , Hematínicos/uso terapêutico , Nefropatias/induzido quimicamente , Proteínas Recombinantes/uso terapêutico , Aplasia Pura de Série Vermelha/complicações , Aplasia Pura de Série Vermelha/epidemiologiaRESUMO
This study aimed to observe the mechanism and effect of circ_0004771 on cardiomyocyte injury in acute myocardial infarction (AMI). The differences in circ_0004771 expression in the blood of AMI patients and healthy volunteers were observed by Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction. AMI cell models were constructed by hypoxia/reoxygenation (H/R)-induced injury in human cardiomyocytes (AC16 cells). The changes of circ_0004771 expression in AMI cells were observed. After transfection with the knockdown or overexpression of circ_0004771 vector in AMI cells, Cell Counting Kit-8 (CCK-8) assay and propidium iodide/FITC-Annexin V staining were performed to detect cell proliferation and apoptosis levels, extracellular lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity. Expression levels of Mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2), and endoplasmic reticulum (ER) stress proteins (GRP78 and CHOP-1) were observed in each group of cells by western blot method. The expression level of circ_0004771 was significantly reduced in both clinical samples and cells of AMI. When circ_0004771 was knocked down in AMI cells, it resulted in a decrease in cell proliferation level and significant increase in apoptosis level. The inhibition of circ_0004771 expression caused leakage of LDH in AMI cells, accumulation of intracellular MDA, and inhibition of SOD activity. In addition, the knockdown of circ_0004771 significantly increased the levels of p-MEK1/2, p-ERK1/2, GRP78, and CHOP-1 in H/R-induced AC16 cells. However, the overexpression of circ_0004771 resulted in the opposite result as when circ_0004771 was knocked down. A low level of circ_0004771 in AMI activates the MAPK signaling pathway in cardiomyocytes as well as encourages intracellular oxidative stress and ER stress, thereby inhibiting cell proliferation and promoting apoptosis.
Assuntos
MicroRNAs , Infarto do Miocárdio , Humanos , Miócitos Cardíacos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Chaperona BiP do Retículo Endoplasmático , Transdução de Sinais , Infarto do Miocárdio/metabolismo , Apoptose , Hipóxia/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , MicroRNAs/metabolismoRESUMO
BACKGROUND: The market demand for Panax notoginseng (P. notoginseng) is growing rapidly because of its useful properties in food and medicine. However, the frequent adulteration of P. notoginseng seriously affects the health of consumers and is a great challenge to food safety. In this study, low- and high-field nuclear magnetic resonance (LF/HF-NMR) were applied to detect the transverse relaxation distribution of P. notoginseng contaminated with different ratios of Caulis clematidis armandii (CCA) and the components in P. notoginseng and CCA, respectively. RESULTS: Fifty-seven kinds of major and minor components in P. notoginseng and CCA were identified and quantified from their high-resolution NMR spectra, and there were significant differences in ginsenosides, sucrose, and glucose between P. notoginseng and CCA. Furthermore, the partial least squares regression analysis results indicated that LF-NMR parameters (T21 and S21 ) changed linearly as the ratio of CCA increased, and these changes were attributed to the variations in polysaccharide and sucrose in adulterated P. notoginseng. CONCLUSION: In the relaxation time-based pattern recognition models, the authentic P. notoginseng powder could be classified with 100% accuracy from adulterated P. notoginseng when the adulteration ratio was greater than 30%, demonstrating the possibility of LF-NMR, in combination with pattern recognition, for rapid discrimination of food authenticity. © 2022 Society of Chemical Industry.
Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Ginsenosídeos/análise , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Panax/química , Panax notoginseng/química , Pós , SacaroseRESUMO
PURPOSE: This study was designed to assess the clinical efficiency and long-term outcomes of hepatic vein (HV) and accessory hepatic vein (AHV) recanalization in patients with HV-type Budd-Chiari syndrome (BCS). MATERIAL AND METHODS: A total of 27 patients with HV-type BCS underwent AHV recanalization and 94 patients had HV recanalization at our center from January 2012 to December 2019. The treatment effectiveness and long-term outcomes were compared. RESULTS: Technical success was accomplished in all patients, without any procedure-related complications. The clinical success rates were 96.3% (26/27) and 95.7% (90/94) (p = 1.000). In the AHV and HV groups, re-obstruction was observed in 5 and 36 patients, respectively (p = 0.056). The median primary durations of AHV and HV patency were 64 and 49 months, respectively (p = 0.036), while the median secondary durations of AHV and HV patency were 70 and 64 months, respectively (p = 0.134). The median overall survival after AHV and HV recanalization was 73 and 78 months, respectively (p = 0.263). CONCLUSIONS: Our findings suggest that AHV could be employed as a replacement for HV, as a hepatic drainage vein, in HV-type BCS patients.