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1.
J Nat Prod ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39315450

RESUMO

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5-seco-abietane diterpenoids including serra A (1), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (2-3) and five known compounds were isolated from Isodon serra (I. serra). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. In silico, serras A-C (1-3) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A (1) with hPXR demonstrated agonist activity with an EC50 value of 15 µM. Serra A (1), graciliflorin F (4), gerardianin C (5), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (6), rabdosin D (7), and 15-hydroxysalprionin (8) exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 µM.

2.
NPJ Biofilms Microbiomes ; 10(1): 83, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266570

RESUMO

At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832-1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.


Assuntos
Líquido da Lavagem Broncoalveolar , Aprendizado de Máquina , Microbiota , Infecções Respiratórias , Humanos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Masculino , Feminino , Transcriptoma , Pessoa de Meia-Idade , Idoso , Klebsiella pneumoniae/imunologia , Klebsiella pneumoniae/genética , Adulto
3.
Mol Pharm ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235393

RESUMO

Spinal cord injury (SCI) is a highly disabling neurological disorder. Its pathological process comprises an initial acute injury phase (primary injury) and a secondary injury phase (subsequent chronic injury). Although surgical, drug, and cell therapies have made some progress in treating SCI, there is no exact therapeutic strategy for treating SCI and promoting nerve regeneration due to the complexity of the pathological SCI process. The development of novel drug delivery systems to treat SCI is expected to significantly impact the individualized treatment of SCI due to its unique and excellent properties, such as active targeting and controlled release. In this review, we first describe the pathological progression of the SCI response, including primary and secondary injuries. Next, we provide a concise overview of newly developed nanoplatforms and their potential application in regulating and treating different pathological processes of SCI. Then, we introduce the existing potential problems and future clinical application perspectives of biomedical engineering-based therapies for SCI.

4.
J Anim Sci Biotechnol ; 15(1): 113, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135090

RESUMO

BACKGROUND: High-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition. RESULTS: Newly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD. CONCLUSIONS: The results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota-bile acid profile pathways.

5.
Expert Opin Drug Saf ; : 1-8, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39157892

RESUMO

BACKGROUND: Vancomycin (VAN) is empirically used with other broad-spectrum antibiotics, such as piperacillin-tazobactam (PTZ) or carbapenem (CBP). However, conflicting literature on the rates of acute kidney injury (AKI) of VAN with PTZ has been reported. RESEARCH DESIGN AND METHODS: A multicenter, retrospective cohort study of the risk of AKI was conducted in patients receiving VAN and concomitant PTZ or CBP from January 2019 and June 2023. RESULTS: In total, 514 eligible patients were included. AKI occurred in a total of 91 patients (17.70%). The prevalence of AKI was significantly higher in the VAN+PTZ group than in the VAN+CBP group (23.37% vs 15.27%, p = 0.028). The survival curves depicting the time to AKI showed the increased incidence and more rapid onset of AKI among patients in the VAN+PTZ group compared to those of the VAN+CBP group (HR 2.186, 95%CI 1.351-3.538, p = 0.0015). VAN+PTZ was associated with a consistently higher AKI rate over VAN+CBP (HR 1.762, 95%CI 1.111-2.795, p = 0.0161) throughout the 14-day combination therapy. VAN with concomitant PTZ, duration of combination therapy ≤ 4 days and VAN trough concentration > 20 mg/L were independent risk factors associated with AKI. CONCLUSION: The prevalence of AKI was found to be higher in patients receiving VAN+PTZ therapy compared to those receiving VAN+CBP therapy based on creatinine-defined AKI.

6.
BMC Cardiovasc Disord ; 24(1): 402, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090542

RESUMO

BACKGROUND: The efficacy of dapagliflozin in patients with acute heart failure remains unclear. OBJECTIVE: To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure. METHODS: In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People's Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM). RESULTS: A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385-1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441-1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P<0.001), lower total loop diuretic dose during hospitalization (106.06 ± 31.23 mg vs. 144.50 ± 45.39 mg, P = 0.038) and a decreased number of diuretic types used (11.88% vs. 23.12%, P = 0.008). CONCLUSIONS: DAPA reduced the dose of intravenous loop diuretics. However, it did not improve all-cause readmission for 90 days or readmission for heart failure after discharge.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Readmissão do Paciente , Pontuação de Propensão , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Doença Aguda , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Fatores de Tempo , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/administração & dosagem , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Quimioterapia Combinada , China/epidemiologia , Idoso de 80 Anos ou mais , Medição de Risco
7.
Angew Chem Int Ed Engl ; : e202411323, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213167

RESUMO

Fluorene derivatives have been widely developed in OLEDs because of its efficient fluorescence quantum efficiency, but for which unique rigid biphenyl planar structure and large conjugated system, we hypothesize that they have a great potential for room temperature phosphorescence (RTP) applications, and confirmed this conjecture by subjecting polyvinyl alcohol (PVA) and phosphors to thermal annealing. The cross-linked structure formed during thermal annealing judiciously modulates the phosphorescence emission characteristics of the fluorenol with the synergistic interaction between PVA and fluorenol. Specifically, the lifetime exhibited a substantial increase from 1352.2 ms to 2874.1 ms, accompanied by a quantum yield augmentation from 4.8% to 11.3%, which substantiate that cross-linked induced by thermal annealing effectively amplifies the phosphorescent intensity and stability of the phosphors, facilitating ultralong phosphorescent emission at ambient conditions. Furthermore, an effective probe based on this film is developed for its highly sensitive, quantitative and immediate detection of volatile organic compounds. This investigation not only proffers a novel paradigm for the development of advanced RTP materials but also imparts insightful considerations for optimizing the performance of polymers in conjunction with functional materials, encompassing bioimaging, sensing, and optoelectronic devices.

8.
Adv Sci (Weinh) ; 11(34): e2402025, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38976572

RESUMO

As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.


Assuntos
Biomarcadores , Lisofosfolipídeos , Aprendizado de Máquina , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Suínos , Biomarcadores/metabolismo , Lisofosfolipídeos/metabolismo , Metabolômica/métodos , Multiômica
9.
Aust Crit Care ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969541

RESUMO

OBJECTIVES: Advances in critical care technology have lowered mortality rates among critically ill individuals. Nonetheless, survivors and their families may develop new physical, mental, cognitive, and social challenges due to paediatric intensive care unit (PICU) treatments, impacting their quality of life. The aim of this study was to investigate the survival journey and post-traumatic growth process of children and their families following PICU admission within the Chinese cultural context. METHODS: Twenty-six children who have been or are currently admitted to the PICU, alongside their parents and three PICU nurses, were chosen through purposive and theoretical sampling. Data collection involved face-to-face interviews and observations, with data analysis conducted through continuous comparison, open coding, and selective coding techniques. FINDINGS: A model outlining the survival journey and post-traumatic growth process of critically ill children and their families post PICU admission has been established. This model encompasses two central trajectories: an upward trajectory consisting of confusion, charging, action, and sublimation phases and a downward trajectory comprising confusion, doubt and fear, inhibition (including confrontation and avoidance), and drowning phases. CONCLUSIONS: Critically ill children and their families encounter diverse survival experiences and psychological journeys following traumatic events in the PICU. The survival experience has alternative upwards or downwards trajectories that are flexible/adaptable. Hence, offering timely psychological support can alter their developmental trajectories and foster post-traumatic growth.

10.
FASEB J ; 38(14): e23812, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39041354

RESUMO

The application of metagenomic next-generation sequencing (mNGS) in pathogens detection of cerebrospinal fluid (CSF) is limited because clinical, microbiological, and biological information are not well connected. We analyzed the 428 enrolled patients' clinical features, pathogens diagnostic efficiency of mNGS in CSF, microbial community structure and composition in CSF, and correlation of microbial and clinical biomarkers in CSF. General characteristics were unspecific but helpful in formulating a differential diagnosis. CSF mNGS has a higher detection rate (34.6%) compared to traditional methods (5.4%). mNGS detection rate was higher when the time from onset to CSF collection was ≤20 days, the CSF leukocytes count was >200 × 106/L, the CSF protein concentration was >1.3 g/L, or CSF glucose concentration was ≤2.5 mmol/L in non-postoperative bacterial CNS infections (CNSi). CSF was not strictly a sterile environment, and the potential pathogens may contribute to the dysbiosis of CSF microbiome. Furthermore, clinical biomarkers were significantly relevant to CNS pathogens. Clinical data are helpful in choosing a proper opportunity to obtain an accurate result of mNGS, and can speculate whether the mNGS results are correct or not. Our study is a pioneering study exploring the CSF microbiome in different CNSIs.


Assuntos
Infecções do Sistema Nervoso Central , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Metagenômica/métodos , Idoso , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/diagnóstico , Adolescente , Biomarcadores/líquido cefalorraquidiano , Criança , Adulto Jovem , Líquido Cefalorraquidiano/microbiologia , Idoso de 80 Anos ou mais , Pré-Escolar , Metagenoma
11.
Heliyon ; 10(12): e33204, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022099

RESUMO

Sine oculis homeoprotein 1 (SIX1), a prominent representative of the homeodomain transcription factors within the SIX family, has attracted significant interest owing to its role in tumorigenesis, cancer progression, and prognostic assessments. Initially recognized for its pivotal role in embryonic development, SIX1 has emerged as a resurgent factor across a diverse set of mammalian cancers. Over the past two decades, numerous investigations have emphasized SIX1's dual significance as a developmental regulator and central player in oncogenic processes. A mounting body of evidence links SIX1 to the initiation of diverse cancers, encompassing enhanced cellular metabolism and advancement. This review provides an overview of the multifaceted roles of SIX1 in both normal development and oncogenic processes, emphasizing its importance as a possible therapeutic target and prognostic marker. Additionally, this review discusses the natural product agents that inhibit various pro-oncogenic mechanisms associated with SIX1.

12.
Front Physiol ; 15: 1396301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022305

RESUMO

Dietary calcium supply is essential for bone development and egg production in laying hens. This study investigated the effects of low dietary calcium and lipopolysaccharide (LPS) induced immune challenge in aged laying hens. A total of thirty-two Hy-Line Brown laying hens at 80 weeks old with an average laying rate of 62% were randomly divided into two groups and fed a normal calcium diet (3.57% Ca, NCA) or low calcium diet (2.08% Ca, LCA). At 88 weeks, the experiment was designed using a 2 × 2 factorial arrangement, and hens were intraperitoneally injected with saline (SAL) or LPS (0.5 mg/kg, 0.5 mg/kg, or 1.5 mg/kg body weight) once every 48 h intervals over 5 days. Production performance, egg quality, and bone physiology were evaluated. Results showed that LPS challenge decreased the hen-day egg production, egg mass, and eggshell traits (p < 0.05), but increased (p < 0.05) the calcium content of the tibia compared to SAL-injected hens. LCA diet decreased (p < 0.05) the hen-day egg production, and eggshell traits such as weight, percentage, strength, and thickness compared to the NCA diet. LCA diet increased the serum alkaline phosphatase (ALP) activity (p < 0.01) and tibial expression of ALP (p < 0.05) compared to NCA diet. LPS injection suppressed both the serum ALP activity (p < 0.05) and tibial expression of ALP (p < 0.001) compared to SAL injection. Furthermore, LPS injection increased (p < 0.05) the expression of both pro and anti-inflammatory cytokines in the spleen and tibia. The expression of cathepsin K ( Cts K ) and matrix metalloproteinase 9 ( MMP-9 ) were downregulated by LPS injection (p < 0.001). Broken and shell-less egg production and calcium content of eggshell, as well as tibial mRNA expression of osteocalcin ( Ocn ), tumor necrosis factor-alpha ( TNF-α ) and tartrate-resistant acid phosphatase ( TRAP ) were affected by the interaction (p < 0.05) of diet and injection. Therefore, this study demonstrated that to certain extents, low dietary calcium and LPS challenge dysregulated bone homeostasis and metabolism, with detrimental effects on the performance and eggshell quality of aged laying hens.

13.
Front Med (Lausanne) ; 11: 1391269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050529

RESUMO

Purpose: This study investigates the prevalence and progression of myopia among primary and secondary school students in Xuzhou City, China, during one academic year. Methods: The study employed a prospective research design and utilized a whole-group sampling method to conduct non-cycloplegic spot photo screenings on 37,938 students from 44 primary and secondary schools in Xuzhou City, China. A one-year study was conducted to gather spherical equivalent refraction (SER), and subsequent analysis was carried out to explore the disparities in myopia prevalence among primary and secondary school students within the same academic year, as well as the progression of myopia. Results: During the 2022 academic year, the overall prevalence of myopia in the first and second semesters was 62.6 and 64.2% respectively, indicating an increasing trend. Particularly in primary school (Grades 1-6), the prevalence of myopia increased with higher grade levels, and significant variations in myopia prevalence were observed mainly in grades 1-3 and 7 (p < 0.05). The incidence rate of myopia in middle school remained stable, while in primary school, there was a positive correlation between myopia incidence and the grade level, with the highest rate of 20.1% in grade 6. Among the myopic population, the median value of spherical equivalent refraction slightly decreased between the two semesters. The proportion of high myopia increased among students in grades 5-8. Conclusion: Our study revealed that within one academic year, the prevalence of myopia and the severity of myopia have significantly increased in Xuzhou City, China, accompanied by an increase in the proportion of high myopia. For different grade levels, we should adopt personalized prevention and control measures, with a particular focus on lower grade levels and students who have just entered a new grade.

14.
Int J Nanomedicine ; 19: 7383-7398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050878

RESUMO

Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment ("cold" environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the "cold" microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on "vascular-immune" crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and "cold" TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of "vascular-immune" crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy.


Assuntos
Imunoterapia , Neoplasias , Neovascularização Patológica , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Imunoterapia/métodos , Neovascularização Patológica/imunologia , Neovascularização Patológica/terapia , Animais , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina , Nanopartículas/química
15.
Sci Data ; 11(1): 738, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972877

RESUMO

The role of China is increasingly pivotal in climate change mitigation, and the formulation of energy conservation and emission reduction policies requires city-level information. The effectiveness of national policy implementation is contingent upon the support and involvement of local governments. Accurate data on final energy consumption is vital to formulate and implement city-level energy transitions and energy conservation and emission reduction policies. However, there is a dearth of data sources pertaining to China's city-level final energy consumption. To address these gaps, we developed computational modeling techniques along with top-down and downscaling methods to estimate China's city-level final energy consumption. In this way, we compiled a final energy consumption inventory for 331 Chinese cities from 2005 to 2021, covering seven economic sectors, 30 fossil fuels, and four clean power sources. Moreover, we discussed the validity of the estimation results from multiple perspectives to enhance estimation accuracy. This dataset can be utilized for analysis in various cutting-edge research fields such as energy transition dynamics, transition risk management strategies, and policy formulation processes.

16.
World J Clin Cases ; 12(18): 3378-3384, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983416

RESUMO

BACKGROUND: Insulin injection is the basic daily drug treatment for diabetic patients. AIM: To evaluate the comparative impacts of continuous subcutaneous insulin infusion (CSII). METHODS: Based on the treatment modality received, the patients were allocated into two cohorts: The CSII group and the multiple daily injections (MDI) group, with each cohort comprising 210 patients. Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5, homocysteine, and C1q/TNF-related protein 9. Furthermore, outcomes such as fasting plasma glucose, 2-hour postprandial glucose levels, pain assessment scores, and the incidence of complications were evaluated post-treatment. RESULTS: The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group (P < 0.05). Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group (60.00%) in contrast to the MDI group (36.19%) (P < 0.05). Additionally, the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group (P < 0.05). However, there were no significant variances observed in other pregnancy outcomes between the two groups (P > 0.05). A statistical analysis revealed a significant difference in the incidence of complications between the groups (χ 2 = 11.631, P = 0.001). CONCLUSION: The utilization of CSII via an insulin pump, as opposed to MDI, can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery. This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar, reducing the likelihood of adverse pregnancy outcomes and complications. The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.

17.
Cell Rep Med ; 5(7): 101648, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38986624

RESUMO

Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNPcancer cell@MVDC). This approach transforms immune-cold tumors, increases migratory DCs, activates T cells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. In vivo imaging reveals superior cNPcancer cell@MVDC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments.


Assuntos
Vacinas Anticâncer , DNA Mitocondrial , Células Dendríticas , Neoplasias Pulmonares , Nanopartículas , Neoplasias Pancreáticas , Células Dendríticas/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Humanos , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/imunologia , Camundongos , Vacinas Anticâncer/imunologia , Nanopartículas/química , Linhagem Celular Tumoral , Imunoterapia/métodos , Feminino , Movimento Celular , Camundongos Endogâmicos C57BL
18.
Cancer Lett ; 598: 217104, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-38969163

RESUMO

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).


Assuntos
Citometria de Fluxo , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Masculino , Feminino , Citometria de Fluxo/métodos , Pessoa de Meia-Idade , Adulto Jovem , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente
19.
Photodiagnosis Photodyn Ther ; 49: 104267, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009205

RESUMO

OBJECTIVE: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. METHODS: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. RESULTS: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95 % CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95 % CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02 mm; 95 % CI: -0.07, 0.03) was less than the control group's (0.22 mm; 95 % CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19 µm; 95 % CI: 18.48, 39.91) compared to that of the control group (-6.59 µm; 95 % CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. CONCLUSIONS: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.

20.
Int J Biol Macromol ; 277(Pt 2): 134307, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39084435

RESUMO

Though the heparin-protamine complex (HP complex) is a crucial system utilized in clinical settings, the metabolic pathways of this complex remain inadequately understood. Herein, the enzymatic degradation of the heparin-protamine complex by trypsin and its broader implications were investigated. By utilizing fluorescent gold nanoclusters liganded with the HP complex (AuNCs-HP complex), we observed significant morphological and spectral changes during enzymatic degradation. Experiments showed that AuNCs-HP complex could be degraded and cleaved into small fragments by trypsin. Moreover, the AuNCs-HP complex demonstrated its potential as a highly sensitive spectral sensing platform, enabling precise measurement of trypsin activity with an outstanding detection limit (0.34 ng mL-1). Additionally, we explored its utility for specific tumor cell detection, focusing on lung adenocarcinoma cells, and successfully identified their presence through distinctive fluorescence changes. These remarkable findings not only contribute valuable insights into targeted degradation systems but also offer promising opportunities for cancer biomarker detection. The AuNCs-HP complex serves as an innovative tool for real-time trypsin activity monitoring, paving the way for advanced biomedical applications.


Assuntos
Adenocarcinoma de Pulmão , Ouro , Heparina , Neoplasias Pulmonares , Nanopartículas Metálicas , Protaminas , Tripsina , Humanos , Heparina/química , Protaminas/química , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Tripsina/metabolismo , Tripsina/química , Ouro/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas/química , Células A549 , Espectrometria de Fluorescência/métodos , Linhagem Celular Tumoral
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