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A Gram-staining negative, non-motile, rod-shaped, oxidase negative and catalase positive strain WL0021T was isolated from cricket (Gryllus chinensis) living in the campus of Hohai University. Strain WL0021T was characterized utilizing a polyphasic taxonomy approach. The major fatty acids (> 5%) for strain WL0021T were C16:0 and summed feature 8, and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phospholipid, two aminolipids, and an unidentified polar lipid. Ubiquinone-10 was detected as the predominant respiratory quinone. The results of 16S rRNA gene phylogenetic analyses revealed that strain WL0021T had the highest sequence similarity of 95.3% to Microvirga flavescens c27j1T and strain WL0021T formed a distinct linage within the family Methylobacteriaceae in the phylogenetic trees. Whole genomic DNA G+C content was 48.3%. Combined with the results from this study, strain WL0021T should represent a novel genus in the family Methylobacteriaceae, for which the name Hohaiivirga grylli gen. nov., sp. nov. (type strain WL0021T=GDMCC 1.2420T =JCM 34655T=MCCC 1K05886T) is proposed.
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Composição de Bases , DNA Bacteriano , Ácidos Graxos , Gryllidae , Filogenia , RNA Ribossômico 16S , Gryllidae/microbiologia , RNA Ribossômico 16S/genética , Animais , Ácidos Graxos/química , Ácidos Graxos/análise , DNA Bacteriano/genética , Fosfolipídeos/análise , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.
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Arritmias Cardíacas , Canais de Cálcio , Mutação de Sentido Incorreto , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Potenciais de Ação , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Canais de Cálcio/genética , China , Análise Mutacional de DNA , População do Leste Asiático , Sequenciamento do Exoma , Predisposição Genética para Doença , Frequência Cardíaca/genética , Hereditariedade , Heterozigoto , Linhagem , FenótipoRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities. Studies have shown that Que has therapeutic effects on PAH. However, the effect of quercetin on pulmonary vascular remodeling in PAH and its mechanism remain unclear. METHODS AND RESULTS: In vivo, PAH rats were constructed by intraperitoneal injection of monocrotaline (MCT) at 60 mg/kg. Human pulmonary artery smooth muscle cells (HPASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) 20 ng/mL to construct PAH cell model in vitro. The results showed that in vivo studies, MCT could induce right ventricular wall hyperplasia, narrow the small and medium pulmonary artery cavity, up-regulate the expression of proliferating and migration-related proteins proliferating cell nuclear antigen (PCNA) and osteopontin (OPN), and down-regulate the expression of alpha-smooth muscle actin (α-SMA). Que reversed the MCT-induced results. This process works by down-regulating the transforming growth factor-ß1 (TGF-ß1)/ Smad2/3 signaling pathway. In vitro studies, Que had the same effect on PDGF-BB-induced proliferation and migration cell models. CONCLUSIONS: Que inhibits the proliferation, migration and phenotypic transformation of HPASMCs by down-regulating TGF-ß1/Smad2/Smad3 pathway, thereby reducing right ventricular hyperplasia (RVH) and pulmonary vascular remodeling, providing potential pharmacological and molecular explanations for the treatment of PAH.
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Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Monocrotalina , Músculo Liso Vascular , Miócitos de Músculo Liso , Artéria Pulmonar , Quercetina , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Smad2 , Proteína Smad3 , Fator de Crescimento Transformador beta1 , Remodelação Vascular , Animais , Remodelação Vascular/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/patologia , Proteína Smad2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Quercetina/farmacologia , Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Humanos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/induzido quimicamente , Becaplermina/farmacologia , Osteopontina/metabolismoRESUMO
Background: Liver disease caused by Fasciola is a significant zoonotic and parasitic disease with substantial economic impacts on humans and animals. Many studies have looked at the prevalence of fasciolis worldwide, yet the overall prevalence and risk factors in cattle, ruminants, and humans remains unknown. Methods: We conducted a systematic review and meta-analysis to estimate the global prevalence and risk factors of fascioliasis in humans and domestic ruminants. With this aim, we searched PubMed, ScienceDirect, Web of Science, and Scopus from inception to 8 December 2022 for studies reporting the prevalence of fascioliasis in humans or domestic ruminants post-2000. We then used random effects models to describe the prevalence of fascioliasis; trim-and-fill analysis and Egger's test to assess publication bias; and meta-regression and sensitivity analyses to examine the risk factors for prevalence and heterogeneity. Results: We retrieved 4422 articles, with 371 being included in the analysis, as they concerned fascioliasis in humans and ruminants globally. The pooled prevalence of bovine fasciolosis was 17%, while ovine fasciolosis and human fascioliasis had pooled prevalences of 13% and 5%, respectively. We also conducted subgroup analyses by continents, countries, Fasciola species, sampling years, altitude, rainfall, temperature, humidity, age, sex, feeding mode, and residence. Here, altitude and age emerged as risk factors associated with an increased prevalence of fascioliasis. Both the trim-and-fill analysis and Egger's test confirmed the presence of publication bias, while the sensitivity analysis showed that the omission of any single study did not significantly influence the combined pooled prevalence. Conclusions: Fascioliasis is a widely prevalent zoonosis among humans and livestock worldwide. Strategies targeting risk factors such as altitude and age are urgently needed for prevention and control of this disease, which will consequently reduce Fasciola infection. Additionally, given the inadequacy or absence of data in some countries, greater attention should be paid to Fasciola infection, with further epidemiological studies focussing on improving data quality.
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Doenças dos Bovinos , Fasciola , Fasciolíase , Saúde Global , Animais , Bovinos , Humanos , Animais Domésticos/parasitologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Fasciola/isolamento & purificação , Fasciolíase/epidemiologia , Fasciolíase/veterinária , Saúde Global/estatística & dados numéricos , Prevalência , Fatores de Risco , Ovinos/parasitologiaRESUMO
Successful cell replacement strategies for brain repair depend on graft integration into the neural network, which is affected by the immune response to the grafted cells. Using Parkinson disease as an example, in this chapter, we consider the immune system interaction and its role in autologous vs heterologous graft survival and integration, as well as past and emerging strategies to overcome the immunologic response. We also reflect on the role of nonhuman primate research to assess novel approaches and consider the role of different stakeholders on advancing the most promising new approaches into the clinic.
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Doença de Parkinson , Transplante Autólogo , Humanos , Doença de Parkinson/terapia , Animais , Transplante Autólogo/métodos , Doenças do Sistema Nervoso/terapia , Transplante Heterólogo/métodosRESUMO
NGN2-driven induced pluripotent stem cell (iPSC)-to-neuron conversion is a popular method for human neurological disease modeling. In this study, we present a standardized approach for generating neurons utilizing clonal, targeted-engineered iPSC lines with defined reagents. We demonstrate consistent production of excitatory neurons at scale and long-term maintenance for at least 150 days. Temporal omics, electrophysiological, and morphological profiling indicate continued maturation to postnatal-like neurons. Quantitative characterizations through transcriptomic, imaging, and functional assays reveal coordinated actions of multiple pathways that drive neuronal maturation. We also show the expression of disease-related genes in these neurons to demonstrate the relevance of our protocol for modeling neurological disorders. Finally, we demonstrate efficient generation of NGN2-integrated iPSC lines. These workflows, profiling data, and functional characterizations enable the development of reproducible human in vitro models of neurological disorders.
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Células-Tronco Pluripotentes Induzidas , Proteínas do Tecido Nervoso , Neurônios , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Neurônios/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Diferenciação Celular , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neurogênese/fisiologia , Células CultivadasRESUMO
PURPOSE: Trabeculectomy, a primary surgical treatment for glaucoma, often employs mitomycin C (MMC) to reduce scar formation and improve surgical outcomes. However, the optimal application method of MMC, whether by injection or sponge, remains a subject of debate. This meta-analysis aims to compare injectable and sponge-based MMC application in terms of efficacy and safety, focusing on various clinical outcomes in glaucoma patients. METHODS: A comprehensive literature search of Scopus, MEDLINE, EMBASE, Ovid, Chinese biomedical literature database, China National Knowledge Infrastructure, and Cochrane Library was done for eligible studies that report data of glaucoma patients who were administered MMC by injection or sponge application during trabeculectomy. Outcomes of interest included intraocular pressure (IOP) reduction, bleb appearance grading (height, extent, vascularity), use of anti-glaucoma medications, and rates of complete success, qualified success, and failure. Data were reported as weighted mean differences (WMD) or odds ratios (OR) with confidence intervals (CI). The random-effects inverse-variance model with DerSimonian-Laird estimate of tau2 was employed, with continuity correction applied where necessary. RESULTS: A total of 15 studies with 1276 participants were included. The meta-analysis revealed no significant difference in IOP reduction between patients treated by MMC injection and sponge application (WMD = - 0.434). Significant differences were observed in bleb appearance grading scores for height (WMD = - 0.170) and extent (WMD = 0.174), with substantial heterogeneity. The use of anti-glaucoma medications was significantly lower in the injection group (WMD = - 0.274). However, there were no significant differences in the rates of complete success, qualified success, and failure. The study demonstrated moderate to high heterogeneity across various outcomes. CONCLUSION: This meta-analysis indicated that while both injection and sponge methods of MMC application during trabeculectomy were equally effective for IOP reduction, they differ in their impact on bleb morphology and postoperative medication requirement. The findings highlight the need for individualized treatment approaches in glaucoma surgery, taking into account the specific needs and characteristics of each patient.
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Glaucoma , Pressão Intraocular , Mitomicina , Trabeculectomia , Humanos , Alquilantes/administração & dosagem , Alquilantes/efeitos adversos , Glaucoma/fisiopatologia , Glaucoma/cirurgia , Injeções Intraoculares/efeitos adversos , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Cuidados Intraoperatórios/efeitos adversos , Cuidados Intraoperatórios/métodos , Mitomicina/administração & dosagem , Trabeculectomia/efeitos adversos , Trabeculectomia/métodos , Resultado do TratamentoRESUMO
A high vascular patency was realized in the bulk or surface heparinized small-diameter in situ tissue-engineered vascular grafts (TEVGs) via a rabbit carotid artery replacement model in our previous studies. Those surface heparinized TEVGs could reduce the occurrence of aneurysms, but with a low level of the remodeled elastin, whereas those bulk heparinized TEVGs displayed a faster degradation and an increasing occurrence of aneurysms, but with a high level of the regenerated elastin. To combine the advantages of the bulk and surface graft heparinization to boost the remodeling of elastin and defer the occurrence of aneurysms, a coaxial electro-spinning technique was used to fabricate a kind of small-diameter core/shell fibrous structural in situ TEVGs with a faster degradable poly(lactic-co-glycolic acid) (PLGA) as a core layer and a relatively lower degradable poly(ε-caprolactone) (PCL) as a shell layer followed by the surface heparinization. The in vitro mechanical performance and enzymatic degradation tests revealed the resulting PLGA@PCL-Hep in situ TEVGs possessing not only a faster degradation rate, but also the mechanical properties comparable to those of human saphenous veins. After implanted in the rat abdominal aorta for 12 months, the good endothelialization, low inflammation, and no calcification were evidenced. Furthermore, the neointima layer of regenerated new blood vessels was basically constructed with a well-organized arrangement of elastin and collagen proteins. The results showed the great potential of these in situ TEVGs to be used as a novel type of long-term small-diameter vascular grafts.
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Prótese Vascular , Engenharia Tecidual , Animais , Ratos , Engenharia Tecidual/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Poliésteres/química , Aorta Abdominal/patologia , Implante de Prótese Vascular/métodos , Elastina/metabolismo , Masculino , Alicerces Teciduais/química , Ratos Sprague-Dawley , Humanos , Coelhos , Teste de MateriaisRESUMO
Although enrofloxacin (ENR) is a widely used broad-spectrum antibiotic in veterinary medicine, its residues in animals can pose a risk to human health. Thus, we developed a new method for detecting ENR based on aptamers and AuNPs. In the absence of ENR, the aptamers attached to the surface of the AuNPs via electrostatic interactions to protect the AuNPs from NaCl, and the solution remained red. Conversely, the aptamer bonded with ENR, leading the aptamer to detach from the AuNP surface, and the color of the solution changed from red to blue. Based on this principle, ENR can be qualitatively detected by the naked eye and quantitatively detected by measuring the absorbance ratio at 650 nm and 530 nm. The experimental results showed a good linear relationship within the ENR concentration range of 0-400 nM, with a limit of detection (LOD) of 1.72 nM, which is satisfactory for detection in food safety. Additionally, this method has also been successfully applied to the detection of ENR in tap water, river water, milk, serum and urine, with good recovery rates and RSD values of less than 7%, indicating its great potential for ENR detection in environmental water samples. More importantly, the combination of this method with a smartphone platform provided great convenience for on-site and visual detection of ENR, offering promising applicability prospects.
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Background: High circulatory lipoprotein(a) [Lp(a)] concentration promotes atherosclerosis; however, its efficacy in predicting the extent of atherosclerotic coronary heart disease (CHD) with coronary artery obstruction and major adverse cardiovascular events (MACEs) in diabetic patients remains questionable. This study aimed to examine whether elevated circulating Lp(a) levels exacerbate CHD and to assess their utility in predicting MACEs in individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods: In total, 4332 patients diagnosed with T2DM who underwent coronary angiography (CAG) were included and categorized into two groups (CHD and non-CHD) based on the CAG results. We used a correlation analysis to explore the potential links between the levels of circulating Lp(a) and CHD severity. Cox regression analysis was performed to evaluate MACEs. Results: The concentrations of circulating Lp(a) were markedly elevated in the CHD group and positively correlated with disease severity. Our results indicate that elevated circulating Lp(a) is a crucial risk factor that significantly contributes to both the progression and severity of CHD. The differences between the two groups are evident in the risk of CHD occurrence [odds ratio (OR) = 1.597, 95 % confidence interval (CI): 1.354-1.893, p < 0.001], the different levels of vessel involvement (OR = 1.908 for triple-vessel vs. single-vessel disease, 95 % CI: 1.401-2.711, p < 0.001), and their relation to the Gensini Score (OR = 2.002 for high vs. low GS, 95 % CI: 1.514-2.881, p < 0.001). Over the course of the 7-year follow-up period, the multivariate Cox regression analysis indicated that increased levels Lp(a) levels are independently associated with the occurrence of MACEs [hazard ratio (HR) = 1.915, 95 % CI: 1.571-2.493, p < 0.001]. Conclusion: We confirmed a positive correlation among circulating Lp(a) levels, CHD lesions count, and Gensini scores. Moreover, Lp(a) levels have predictive significance for the occurrence of MACEs in T2DM patients.
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Rice (Oryza sativa L.) husk harbors a substantial proportion of biological metabolites, as one of the most plentiful agriculture by-products in rice milling process, rice husk remains poorly utilized. As a continuing search for potential bioactive molecules from the husk of rice, a totally of twelve conponents (1-12), including six sterol ferulates (1-6), one flavonoid (7), one dipeptide (8), and four phenylpropanoid derivatives (9-12) were obtained. All the chemical structures were elucidated based on comprehensive spectroscopic data. Wherein, compounds 1 and 2 were yield as previous undescribed metabolites, and the comprehensive NMR data for compounds 3 and 4 were first presented in its entirety. Motivated by the similarity of the structural motifs of components 1-6 to that of reported sterol ferulates, the antioxidant and anti-inflammatory effects for compounds 1-6 were evaluated in vitro. Among them, compounds 5/6 had a significant antioxidant activity compare to that of vitamin E in both DPPH and reducing power assay up to the concentration 40 µg/ml; while compounds 1 and 2 exhibited weak suppressive effect on the production of nitric oxide, with the IC50 values of 53.27 ± 1.37 µM.
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Objective: This study aims to assess the risk of neonatal susceptibility to COVID-19 among pregnant women. Methods: We conducted a retrospective cohort study involving 1089 pregnant women ≥28 weeks of gestational age, who were categorized into infected and uninfected groups. Data for all participants were collected through a comprehensive review of electronic medical records and follow-up phone calls. The primary outcome was neonatal infection with SARS-CoV-2, while secondary outcomes included delivery patterns and gestational age at delivery. Results: Maternal vaccination (OR 95%CI:0.63[0.46, 0.85]) and maternal infection with SARS-CoV-2 (OR 95%CI: 0.45[0.34, 0.60]) were found to be associated with a decreased risk of neonatal infection. The infected group exhibited a lower neonatal SARS-CoV-2 infection rate (25.93%) compared to the uninfected group (45.15%). Logistic regression analysis identified several risk factors associated with an increased risk of neonatal infection, including pregnancy BMI (OR 95%CI: 1.04[1.01, 1.08]), age at first pregnancy (OR 95%CI: 1.05[1.01, 1.10]), age at menarche (OR 95%CI: 1.13[1.02, 1.26]), and parturition (Yes vs. No) (OR 95%CI:1.4 [1.04,1.88]). Conclusion: Maternal vaccination and perinatal infection with SARS-CoV-2 play a protective role in preventing neonatal SARS-CoV-2 infection.
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Aims/Background Reliable health-related quality of life data are critical in developing countries, in order to advocate for government agencies to develop national hemophilia care programmes. This study aims to explore the current status and influencing factors of health-related quality of life among adolescents with hemophilia in Hubei Province, so as to provide empirical data for professionals. Methods A total of 84 children with hemophilia aged 8 to 18, who were registered in Tongji Hemophilia Treatment Center and Hubei Hemophilia Home, were selected using a cluster sampling method. The "General Situation Questionnaire of Hemophiliac Adolescents", designed by Tongji Hemophilia Treatment Center, and "the Chinese version of Canadian hemophilia outcomes-kid's life assessment tool (CHO-KLAT)", were used for this study conducted from June 1, 2022 to December 30, 2022. Results 82 completed questionnaires were included. The average age of the 82 adolescents was 13.04 ± 3.29 years and all were males. Among them, 67 were hemophilia A and 15 were hemophilia B. 61 cases were severe type, 19 were moderate type and 2 cases were mild type. The average total score of the CHO-KLAT for adolescents with hemophilia in Hubei Province was 49.49, which was lower than their counterparts in developed countries. The statistically significant influencing factors included residence, annual family income, and disease type. Conclusion This study provides empirical data support for the health management of adolescents with hemophilia, highlighting the importance of improving medical resource access, transfusion convenience, and psychological support in enhancing the quality of life for this group. The results emphasize the need for healthcare systems and policymakers to take specific measures to address these factors to improve the treatment and care conditions for adolescents with hemophilia.
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Hemofilia A , Qualidade de Vida , Humanos , Adolescente , Hemofilia A/terapia , Masculino , Inquéritos e Questionários , China/epidemiologia , Criança , Hemofilia B/terapia , Hemofilia B/psicologiaRESUMO
OBJECTIVES: The aim of this retrospective study was to investigate the influence of chemotherapy on the immune status of individual patients diagnosed with acute lymphoblastic leukemia (ALL) and to elucidate the clinical characteristics of immune reconstitution in ALL patients following chemotherapy. METHODS: Clinical data of children with ALL were gathered, including information on the number of lymphocyte subsets prior to chemotherapy, at the end of therapy, six months, and one year after the end of the treatment. RESULTS: A total of 146 children with ALL were included, and T cells, B cells, and NK cells all decreased to various degrees prior to treatment. The abnormal CD3 + T cell numbers group experienced a considerably higher mortality (21.9% vs. 6.1%) and recurrence rate (31.3% vs. 11.4%) compared to the normal group (P < 0.05). T cells, B cells, and NK cells were all significantly compromised at the end of therapy compared to the beginning of chemotherapy, with B cells being more severely compromised (P < 0.001). At the end of treatment, levels of B cells, CD4 + T cells, CD4/CD8, IgG and IgM in low risk (LR) group were significantly higher than those in intermediate risk (IR) group (P < 0.01), and levels of NK cells in LR group were evidently lower than those in IR group (P < 0.001). Six months after the end of therapy, all the above indicators recovered (P < 0.001) except CD4/CD8 ratio (P = 0.451). CONCLUSIONS: The immune systems of the ALL patients were severely compromised upon therapy withdrawal, particularly the B cells. At six months after the therapy ended, the B cells were basically restored to normal level, while the T-cell compartment was not. The impaired numbers of CD3 + T cell may contribute to a weakened anti-tumor response, potentially leading to a poorer prognosis.
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Reconstituição Imune , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Criança , Masculino , Estudos Retrospectivos , Feminino , Pré-Escolar , Adolescente , Lactente , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/imunologia , Subpopulações de Linfócitos/imunologiaRESUMO
BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.
This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Recidiva Local de Neoplasia , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Resultado do Tratamento , Intervalo Livre de Progressão , Pessoa de Meia-IdadeRESUMO
Transition metals exhibit high reactivity for Fenton-like catalysis in environmental remediation, but how to save consumption and reduce pollution is of great interest. In this study, rationally designed defect-engineered Fe@MoS2 (Fe@D-MoS2) was prepared by incorporating reactive iron onto structural defects generated from the chemical acid-etching, aiming to improve the energetic consumption of the catalyst in Fenton-like applications. Morphological and structural properties were elucidated in details, the Fenton-like reactivity was evaluated with five phenolic contaminants for oxidant activation, radical generation and environmental remediation. Compared to Fe@MoS2, Fe@D-MoS2 exhibited a 18.9-fold increase in phenol degradation (0.09 versus 1.79 min-1). Quenching experiments, electron paramagnetic resonance tests and electrochemical measurements revealed the dominant sulfate and superoxide radicals. Rendered by strong metal-substrate surface and electronic interactions from regulated chemical environment and coordination structure, the inert ≡ Fe(III) was reduced to the reactive ≡ Fe(II) accompanied by the ≡ Mo(IV) oxidation to ≡ Mo(V) in MoS2 lattice, with adjacent sulfur serving as the key electron transfer bridge. Therefore, this work shows that the incorporation of reactive centers is able to boost two-dimensional sulfide materials for environmental catalysis applications.
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Dissulfetos , Ferro , Molibdênio , Oxirredução , Superóxidos , Purificação da Água , Catálise , Ferro/química , Molibdênio/química , Purificação da Água/métodos , Dissulfetos/química , Superóxidos/química , Peróxido de Hidrogênio/química , Poluentes Químicos da Água/química , Recuperação e Remediação Ambiental/métodos , Metais/químicaRESUMO
Optimal plant height is crucial in modern agriculture, influencing lodging resistance and facilitating mechanized crop production. Upland cotton (Gossypium hirsutum) is the most important fiber crop globally; however, the genetic basis underlying plant height remains largely unexplored. In this study, we conducted a genome-wide association study to identify a major locus controlling plant height (PH1) in upland cotton. This locus encodes gibberellin 2-oxidase 1A (GhPH1) and features a 1133-bp structural variation (PAVPH1) located approximately 16 kb upstream. The presence or absence of PAVPH1 influences the expression of GhPH1, thereby affecting plant height. Further analysis revealed that a gibberellin-regulating transcription factor (GhGARF) recognizes and binds to a specific CATTTG motif in both the GhPH1 promoter and PAVPH1. This interaction downregulates GhPH1, indicating that PAVPH1 functions as a distant upstream silencer. Intriguingly, we found that DWARF53 (D53), a key repressor of the strigolactone (SL) signaling pathway, directly interacts with GhGARF to inhibit its binding to targets. Moreover, we identified a previously unrecognized gibberellin-SL crosstalk mechanism mediated by the GhD53-GhGARF-GhPH1/PAVPH1 module, which is crucial for regulating plant height in upland cotton. These findings shed light on the genetic basis and gene interaction network underlying plant height, providing valuable insights for the development of semi-dwarf cotton varieties through precise modulation of GhPH1 expression.
Assuntos
Regulação da Expressão Gênica de Plantas , Giberelinas , Gossypium , Proteínas de Plantas , Gossypium/genética , Gossypium/metabolismo , Gossypium/crescimento & desenvolvimento , Giberelinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Lactonas/metabolismo , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/genética , Estudo de Associação Genômica Ampla , Regiões Promotoras Genéticas/genéticaRESUMO
This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.
Assuntos
Medicamentos de Ervas Chinesas , Humanos , Feminino , Masculino , Adolescente , Criança , Estudos Prospectivos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Pré-Escolar , Lactente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitais , InjeçõesRESUMO
Developing eco-friendly catalysts for effective water purification with minimal oxidant use is imperative. Herein, we present a metal-free and nitrogen/fluorine dual-site catalyst, enhancing the selectivity and utilization of singlet oxygen (1O2) for water decontamination. Advanced theoretical simulations reveal that synergistic fluorine-nitrogen interactions modulate electron distribution and polarization, creating asymmetric surface electron configurations and electron-deficient nitrogen vacancies. These properties trigger the selective generation of 1O2 from peroxymonosulfate (PMS) and improve the utilization of neighboring reactive oxygen species, facilitated by contaminant enrichment at the fluorine-carbon Lewis-acid adsorption sites. Utilizing these insights, we synthesize the catalyst through montmorillonite (MMT)-assisted pyrolysis (NFC/M). This method leverages the role of MMT as an in-situ layer-stacked template, enabling controlled decomposition of carbon, nitrogen, and fluorine precursors and resulting in a catalyst with enhanced structural adaptability, reactive site accessibility, and mass-transfer capacity. The NFC/M demonstrates an impressive 290.5-fold increase in phenol degradation efficiency than the single-site analogs, outperforming most of metal-based catalysts. This work not only underscores the potential of precise electronic and structural manipulations in catalyst design but also advances the development of efficient and sustainable solutions for water purification.
RESUMO
OBJECTIVES: To explore the therapeutic effect of acupuncture combined with paroxetine for mild to moderate depression and the regulatory role of brain derived neurotrophic factor (BDNF) in patients based on DNA methylation. METHODS: A total of 66 patients with mild to moderate depression who met the inclusion and exclusion criteria were randomly divided into an observation (acupuncture+medication) group and a control (medication) group, with 33 patients in each group, and other 25 healthy volunteers were taken as the healthy group. The patients of the control group were treated by oral administration of paroxetine 20 mg/d for 4 weeks. The patients of the observation group were treated by acupuncture stimulation of Zhongwan (CV12), Qihai (CV6), Zusanli (ST36), Sanyinjiao (SP6), Shangxing (GV23), Shuigou (GV26), Shaoshang (LU11), Yinbai (SP1) and Daling (PC7) (for 20 min, 3 times a week for 4 weeks) on the basis of medication treatment (the same as that of the control group). Before treatment, 2 and 4 weeks of treatment, and 2 weeks of follow-up, the therapeutic effect was assessed using Hamilton Depression Scale 17 (HAMD-17). The SPSS25.0 software was used to form a randomized grouping and to randomly select 25 patients from the observation group and 25 patients from the control group for blood collecting and data analysis. The blood samples were taken for assaying serum BDNF content and the methylation degree of BDNF gene promotor I with ELISA and MassARRAY techniques, respectively. RESULTS: 1) In comparison with those before treatment, the total score of HAMD-17, sleep disorder factor score, and anxiety somatization factor score of both the observation and control groups were significantly decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), except sleep disorder factor score in the control group after 2 weeks of the treatment. Compared with the same time-points of the control group, the HAMD-17 total score and sleep disorder factor score of the observation group were decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), while the anxiety somatization factor score was evidently decreased after 2 weeks of treatment (P<0.05). 2) Following 2 weeks of treatment, the total effective rate and markedly effective rate of the observation group were 80%(24/30)and 36.67% (11/30), respectively, being significantly higher than those ï¼»(26.67% and 0 %)ï¼½ of the control group. After 4 weeks of treatment, the markedly effective rate of the observation group was 70.00% (21/30), being significantly higher than that 40% (12/30) of the control group (P<0.05), while the total effective rates of the observation and control groups were the same (100%). 3) Before the treatment, comparison among the healthy, observation and control groups showed no statistical significance in the methylation degree of each site (CpG1.2, CpG5.6, CpG8.9, CpG26, CpG27, CpG31, and CpG33.34) of BDNF gene promotor I, while after 4 weeks of the treatment, the methylation degree of CpG31 was considerably lower in the observation group than in the control group (P<0.05). 4) Before the treatment, the contents of serum BDNF of both observation and control group had no significant difference, but were evidently lower than that of the healthy group (P<0.05). Compared with that before treatment, the serum BDNF contents in both observation and control groups were significantly increased after the treatment (P<0.05), and was significantly higher in the observation group than in the control group (P<0.05). 5) The correlation analysis showed a negative correlation between the BDNF protein content and HAMD-17 score (correlation coefficient ρ=-0.686, P<0.01). CONCLUSIONS: Acupuncture may have an antidepressant role by decreasing CpG31 methylation of BDNF and increasing the serum content of BDNF protein in patients with depression. In addition, acupuncture combined with paroxetine has more advantages in treating mild to moderate depression than oral paroxetine alone, and can improve sleep disorders and anxiety somatization symptoms more quickly.