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1.
Anal Methods ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264218

RESUMO

Histidine (His) is a semi-essential amino acid and a unique key neurotransmitter involved in numerous physiological processes. An excessive or deficient amount of His in the body can lead to various related diseases. However, since the chemical structures of L-His and its metabolites (such as histamine (Ha), imidazole-4-acetate (ImA), etc.) are very similar, simple and efficient selective detection of L-His and its related metabolites is of great importance but remains a great challenge. Herein, we successfully designed and synthesized a DMSO-assisted iridium(III) complex (Ir1-DMSO), which can be applied as a "turn-on" photoluminescence (PL) probe for the selective detection and quantification of L-His/Ha. More importantly, Ir1-DMSO exhibited good sensitivity, high selectivity, and anti-interference capability for L-His/Ha/His-containing proteins, which is advantageous due to its simple fabrication and low technical demands. This was attributed to the reaction of Ir1-DMSO with imidazole and amino groups of L-His/Ha. Furthermore, we show the utility of Ir1-DMSO as a PL imaging agent in cultures of E. coli and S. aureus. Considering its diversity of composition and structural flexibility, it can be extended to other solvents and Ir-ligand complexes for various analyses based on specific molecular recognition sensing platforms.

2.
Medicine (Baltimore) ; 103(36): e36401, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252280

RESUMO

RATIONALE: Tachycardia is a common arrhythmia in clinical practice, and its pathogenesis is mostly related to reentry. However, there are also a few tachycardia that are not related to reentry. Actively clarifying the pathogenesis of these non-reentry related tachycardia is of great significance for its treatment. PATIENT CONCERNS: A 55-year-old female patient presented with recurrent palpitations with a fastest heart rate of 180 beats/minute 10 years ago. DIAGNOSIS: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT). INTERVENTIONS: DAVNNT can be cured by radiofrequency ablation of atrioventricular nodal slow path modification. OUTCOMES: The tachycardia has stopped. CONCLUSION: DAVNNT is a rare disease in clinical practice. Its characteristic is not reentration-related arrhythmias, but the phenomenon of increased heart rate caused by electrical conduction down the double pathway of atrioventricular nodal tract and subsequent pathway. Electrophysiological examination helps to clarify the diagnosis and pathogenesis, and catheter ablation can cure the disease.


Assuntos
Ablação por Cateter , Humanos , Feminino , Pessoa de Meia-Idade , Ablação por Cateter/métodos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Eletrocardiografia , Nó Atrioventricular/fisiopatologia , Nó Atrioventricular/cirurgia
3.
Environ Pollut ; 361: 124724, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142430

RESUMO

Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd2+/kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure.

4.
Int Immunopharmacol ; 133: 112081, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38652963

RESUMO

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.


Assuntos
Apoptose , Antígeno B7-H1 , Monócitos , Neutrófilos , Pâncreas , Pancreatite , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Amilases/sangue , Apoptose/efeitos dos fármacos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Ceruletídeo , Citocinas/metabolismo , Modelos Animais de Doenças , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Lipase/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/imunologia , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia
5.
J Steroid Biochem Mol Biol ; 236: 106425, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37984747

RESUMO

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-ß, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2D3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH)2D3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2D3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-ß, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2D3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Fosfotransferases (Aceptor do Grupo Álcool) , Ratos , Animais , Vitamina D/farmacologia , Fator de Necrose Tumoral alfa/genética , Interleucina-6 , Proteína X Associada a bcl-2 , Vitaminas , Lisofosfolipídeos/metabolismo , Esfingosina/metabolismo , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fator de Crescimento Transformador beta
6.
Fish Shellfish Immunol ; 132: 108503, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36581255

RESUMO

In the present study, the polyimmunoglobulin receptor-like (pIgRL) of large yellow croaker (Larimichthys crocea) was first cloned and characterized. LcpIgRL's full-length cDNA was 1610 bp, encoding 377 amino acids, and the protein's predicted molecular weight was 41.9 kDa, containing two immunoglobulin-like structural domains. The transcript levels of LcpIgRL in different tissues of healthy large yellow croaker were examined by real-time fluorescence quantitative PCR, and the results showed that the gills and head kidney had the highest levels. Within 36 h of the large yellow croaker being infected with Vibrio harveyi, pIgRL mRNA first increased and then decreased in all determined tissues, with the highest expression in the skin and hindgut. Furthermore, a recombinant protein of the extracellular region of LcpIgRL was expressed in E. coli BL21, and a murine rLcpIgRL polyclonal antibody was prepared, which could react specifically with the natural LcpIgRL in skin mucus, but no natural LcpIgRL was detected in serum. Meanwhile, it was found that the rLcpIgRL could bind to the recombinant IgM and the natural IgM, indicating that LcpIgRL could mediate the transport of IgM in mucus. In addition, rLcpIgRL binds to Aeromonas hydrophila and V. harveyi, as well as lipopolysaccharide (LPS) and various saccharides, and reduced binding to bacteria was observed under LPS treatment, suggesting that LcpIgRL can bind to bacteria to prevent infection and that saccharide binding is an important mechanism of interaction between pIgRL and bacteria.


Assuntos
Perciformes , Receptores de Imunoglobulina Polimérica , Animais , Camundongos , Receptores de Imunoglobulina Polimérica/genética , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Escherichia coli/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Imunoglobulina M/genética , Proteínas de Peixes/química , Filogenia
7.
Ann Transl Med ; 10(22): 1214, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36544673

RESUMO

Background: With uncontrolled inflammatory progression, acute pancreatitis (AP) can progress to severe acute pancreatitis (SAP). Inflammation and parenchymal cell death are key pathologic responses of AP. Toll-like receptor 4 (TLR4) plays a pro-inflammatory role in AP. Myeloid differentiation primary response protein 88 (MyD88) is the most essential utilized adaptor of TLR4, but its role in AP remains unclear. We investigated the potential role of MyD88 in the pathogenesis of AP. Methods: An AP model was induced by administering either cerulein or L-arginine to wild-type or MyD88-deficient mice. Additionally, receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 (Nec-1) was administered to the MyD88-/- mice. The severity of AP was determined by measuring serum amylase and lipase activities, quantifying pancreatic myeloperoxidase (MPO) activity, and histological examination. The effects of MyD88 deletion on cell death and the inflammatory response were determined by measuring apoptosis, necrosis, and inflammatory cytokines. Western blot was used to assess the necrotic mediators, RIP1 and RIP3. Results: The deletion of MyD88 resulted in more severe acute experimental pancreatitis as assessed by increased amylase and lipase activities, increased pancreatic MPO activity, a reduced anti-inflammatory response, reduced apoptosis, and increased necrosis. Additionally, Nec-1 treatment significantly reduced necrosis in the MyD88-/- mice. Conclusions: The deletion of MyD88 inhibited the TLR4/MyD88-dependent pathway mediated protective immune defense response and enhanced TLR4/MyD88-independent TRIF pathway-mediated pancreatic necrosis, which in turn aggravated the severity of AP. The critical role of MyD88 in immune defense response and cell death indicates that MyD88 represents a potential therapeutic target in the management of AP.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(6): 675-680, 2022 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-35762435

RESUMO

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.


Assuntos
Sepse Neonatal , Sepse , Ácido Ascórbico , Cisteína , Humanos , Recém-Nascido , Metabolômica , Metionina , Piruvatos
10.
World J Gastroenterol ; 28(15): 1588-1600, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35582133

RESUMO

BACKGROUND: The severity of acute pancreatitis in pregnancy (APIP) is correlated with higher risks of maternal and fetal death. AIM: To develop a nomogram that could predict moderately severe and severe acute pancreatitis in pregnancy (MSIP). METHODS: Patients with APIP admitted to West China Hospital between January 2012 and December 2018 were included in this study. They were divided into mild acute pancreatitis in pregnancy (MAIP) and MSIP. Characteristic parameters and laboratory results were collected. The training set and test set were randomly divided at a ratio of 7:3. Least absolute shrinkage and selection operator regression was used to select potential prognostic factors. A nomogram was developed by logistic regression. A random forest model was used to validate the stability of the prediction factors. Receiver operating characteristic curves and calibration curves were used to evaluate the model's predictive performance. RESULTS: A total of 190 patients were included in this study. A total of 134 patients (70.5%) and 56 patients (29.5%) were classified as having MAIP and MSIP, respectively. Four independent predictors (lactate dehydrogenase, triglyceride, cholesterol, and albumin levels) were identified for MSIP. A nomogram prediction model based on these factors was established. The model had areas under the curve of 0.865 and 0.853 in the training and validation sets, respectively. The calibration curves showed that the nomogram has a good consistency. CONCLUSION: A nomogram including lactate dehydrogenase, triglyceride, cholesterol, and albumin levels as independent predictors was built with good performance for MSIP prediction.


Assuntos
Pancreatite , Doença Aguda , Albuminas , Colesterol , Feminino , Humanos , L-Lactato Desidrogenase , Nomogramas , Pancreatite/diagnóstico , Gravidez , Triglicerídeos
11.
J Bone Metab ; 29(1): 51-57, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35325983

RESUMO

BACKGROUND: Spine-hip discordance (SHD) increases fracture risk. However, its prevalence and clinical implications have not been investigated in patients with hip fractures. This study determined the prevalence and association of SHD with mortality and investigated the cause of SHD in patients with hip fractures. METHODS: This study included patients admitted for fragility hip fractures between 2011 and 2020. All patients underwent dual energy X-ray absorptiometry and anteroposterior and lateral views of the lumbosacral spine during admission. Data on demographics, diagnosis, American Society of Anesthesiologists score, and mortality were collected. A T-score difference of more than 1.5 between L1-4 and the femur neck was considered discordant, and 3 groups (lumbar low [LL] discordance, no discordance [ND], and femur neck low [FL] discordance) were compared. In the discordance group, lumbar radiographs were reviewed to determine the cause of discordance. RESULTS: Among 1,220 eligible patients, 130 were excluded due to patient refusal or bilateral hip implantation; therefore, this study included 1,090 patients (271 male and 819 female). The prevalence of LL, ND, and FL was 4.4%, 66.4% and 29.2% in men and 3.9%, 76.1%, and 20.0% women. Mortality was not associated with discordance. The most common causes of discordance were physiological in the LL group and pathological in the FL group for both sexes. CONCLUSIONS: Patients with hip fractures showed lower rates of ND and higher rates of FL compared to the general population. True discordance should be carefully judged for pathological and artifact reasons. The clinical implications of SHD require further investigation.

13.
World J Gastrointest Surg ; 13(10): 1258-1266, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34754393

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) may cause pulmonary embolus, leading to late deaths. The systemic inflammatory and hypercoagulable state of moderate and severe acute pancreatitis (non-mild acute pancreatitis, NMAP) patients may contribute to the development of venous thromboembolism. Accurate prediction of DVT is conducive to clinical decisions. AIM: To develop and validate a potential new prediction nomogram model for the occurrence of DVT in NMAP. METHODS: NMAP patient admission between 2013.1.1 and 2018.12.31 at the West China Hospital of Sichuan University was collected. A total of 220 patients formed the training set for nomogram development, and a validation set was constructed using bootstrapping with 100 resamplings. Univariate and multivariate logistic regression analyses were used to estimate independent risk factors associated with DVT. The independent risk factors were included in the nomogram. The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis, respectively. RESULTS: A total of 220 NMAP patients over 60 years old were enrolled for this analysis. DVT was detected in 80 (36.4%) patients. The final nomogram included age, sex, surgery times, D-dimer, neutrophils, any organ failure, blood culture, and classification. This model achieved good concordance indexes of 0.827 (95%CI: 0.769-0.885) and 0.803 (95%CI: 0.743-0.860) in the training and validation sets, respectively. CONCLUSION: We developed and validated a prediction nomogram model for DVT in older patients with NMAP. This may help guide doctors in making sound decisions regarding the administration of DVT prophylaxis.

14.
J Biol Chem ; 296: 100374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33548228

RESUMO

The recent discovery of the cancer-associated E76K mutation in histone H2B (H2BE76-to-K) in several types of cancers revealed a new class of oncohistone. H2BE76K weakens the stability of histone octamers, alters gene expression, and promotes colony formation. However, the mechanism linking the H2BE76K mutation to cancer development remains largely unknown. In this study, we knock in the H2BE76K mutation in MDA-MB-231 breast cancer cells using CRISPR/Cas9 and show that the E76K mutant histone H2B preferentially localizes to genic regions. Interestingly, genes upregulated in the H2BE76K mutant cells are enriched for the E76K mutant H2B and are involved in cell adhesion and proliferation pathways. We focused on one H2BE76K target gene, ADAM19 (a disintegrin and metalloproteinase-domain-containing protein 19), a gene highly expressed in various human cancers including breast invasive carcinoma, and demonstrate that H2BE76K directly promotes ADAM19 transcription by facilitating efficient transcription along the gene body. ADAM19 depletion reduced the colony formation ability of the H2BE76K mutant cells, whereas wild-type MDA-MB-231 cells overexpressing ADAM19 mimics the colony formation phenotype of the H2BE76K mutant cells. Collectively, our data demonstrate the mechanism by which H2BE76K deregulates the expression of genes that control oncogenic properties through a combined effect of its specific genomic localization and nucleosome destabilization effect.


Assuntos
Proteínas ADAM/genética , Neoplasias da Mama/genética , Histonas/genética , Proteínas ADAM/metabolismo , Neoplasias da Mama/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Histonas/metabolismo , Humanos , Mutação/genética , Nucleossomos , Oncogenes/genética , Polimorfismo de Nucleotídeo Único/genética
15.
Ann Transl Med ; 9(2): 178, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569480

RESUMO

Bosworth fracture-dislocation of ankle is a rare and irreducible type of ankle injury, with a high incidence of complication. This type of fracture was defined originally as entrapment of the proximal fragment of the fibula behind the posterior tubercle of the distal tibia. Recently, many variants of this type of fracture dislocation have been reported, but all of those reports included the syndesmosis ligament injury of ankle. Here, we report a case of a particularly rare variant of Bosworth fracture-dislocation without syndesmosis ligament injury of ankle. A 48-year-old male presented with a Bosworth fracture dislocation with entrapment of proximal fragment behind the tibia. After temporary treatment in emergency department was applied, emergency open reduction and internal fixation with a plate and screws was performed due to irreducibility of the fracture fragment. The fractured lateral malleolus was entrapped behind the tibia and rupture of the interosseous ligament was found intraoperatively. The anterior inferior tibiofibular ligament, a part of syndesmosis ligament of ankle, was grossly intact and no abnormal findings was seen by fluoroscopy with external rotational stress. Moreover, the deltoid ligament was found to be normal in ultrasonography. There were no complications after surgery and the patient showed full functional recovery at 2 years follow up. These fractures will frequently be irreducible and should be considered for open reduction and internal fixation with the careful evaluation of injury mechanisms with syndesmotic stability.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(7): 711-715, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32669166

RESUMO

OBJECTIVE: To study the value of fractional anisotropy (FA) of regions of interest (ROI) on magnetic resonance diffusion tensor imaging (DTI) in bilirubin-induced neurological dysfunction in neonates. METHODS: A total of 91 neonates with hyperbilirubinemia who were hospitalized from January 2017 to January 2018 were enrolled. According to the peak level of total serum bilirubin, they were divided into three groups: mild/moderate increase (n=45), severe increase (n=35), and extremely severe increase (n=11). According to the presence or absence of abnormal neurological manifestations, they were divided into two groups: neurological dysfunction (n=20) and non-neurological dysfunction (n=71). Ten healthy full-term infants were enrolled as the control group. Head DTI was performed for all neonates to measure the FA values of the bilateral globus pallidus, the anterior limb of the internal capsule, the posterior limb of the internal capsule, and the cerebellar dentate nucleus. RESULTS: The extremely severe increase group had significantly lower FA values of the globus pallidus than the control, mild/moderate increase, and severe increase groups (P<0.05). The severe increase group had significantly lower FA values of the globus pallidus than the control group (P<0.05). The extremely severe increase group had significantly lower FA values of the posterior limb of the internal capsule than the control, mild/moderate increase, and severe increase groups (P<0.05). The neurological dysfunction group had significantly lower FA values of the globus pallidus and the posterior limb of the internal capsule than the non-neurological dysfunction group (P<0.05). CONCLUSIONS: Serum bilirubin level combined with the changes in the DTI FA values of the globus pallidus and the posterior limb of the internal capsule can be used to predict the injury of cerebral nuclei and white matter fibers.


Assuntos
Imagem de Tensor de Difusão , Substância Branca , Anisotropia , Bilirrubina , Encéfalo , Imagem de Difusão por Ressonância Magnética , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
18.
Biomater Sci ; 8(6): 1638-1648, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-31970339

RESUMO

The unique conformation transition from a triple helix to single coils for the triple helical ß-d-glucans has paved the way to fabricate various functional nanocomposites through the denaturing-renaturing process. This study firstly reports a novel kind of naturally derived supramolecular polymer micelle consisting of single-stranded chains of curdlan (CUR) and ß-CDs. It is proposed that ß-CDs as the host molecules were threaded onto single ß-glucan chains (denatured triplex CUR) via the host-guest interaction, thereby forming supramolecular micelles. The results from the 1H NMR, FT-IR, XRD and 2D 1H NOESY NMR studies confirmed the formation of the inclusion complex and the existence of the core-shell structure of the supramolecular assembly. TEM images and DLS revealed that the self-organized micelles displayed a regular spherical shape with an average diameter of ∼27 nm. Furthermore, the hydrophobic anticancer drug camptothecin (CPT) was selected as a model drug and successfully encapsulated into the CUR/ß-CD micelles. The drug-loaded micelles exhibited a steady sustained-release pattern regardless of the environmental pH. The flow cytometry and confocal laser scanning microscopy measurements confirmed that the CPT-loaded micelles could be well internalized into HepG 2 cells and continuously release the drug molecules inside the tumor cells. Meanwhile, the in vivo experiments demonstrated that CPT-loaded micelles could effectively inhibit tumor growth in comparison to free drugs. This concept will give a favorable platform to construct intelligent drug delivery systems for potential use.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , beta-Glucanas/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Camptotecina/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Células Hep G2 , Humanos , Camundongos , Micelas , Microscopia Confocal , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Espectroscopia de Infravermelho com Transformada de Fourier , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cancer Manag Res ; 11: 3899-3908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123419

RESUMO

Aim: To assess whether total pancreatectomy (TP) is as feasible, safe, and efficacious as pancreaticoduodenectomy (PD). Materials and Methods: Major databases, including PubMed, EMBASE, Science Citation Index Expanded, Scopus and the Cochrane Library, were searched for studies comparing TP and PD between January 1943 and June 2018. The meta-analysis only included studies that were conducted after 2000. The primary outcomes were morbidity and mortality. Pooled odds ratios (ORs), weighted mean differences (WMDs) or hazard ratios (HRs) with 95 percent confidence intervals (CIs) were calculated using fixed effects or random effects models. The methodological quality of the included studies was evaluated by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Results: In total, 45 studies were included in this systematic review, and 5 non-randomized comparative studies with 786 patients (TP: 270, PD: 516) were included in the meta-analysis. There were no differences in terms of mortality (OR: 1.44, 95% CI: 0.66-3.16; P=0.36), hospital stay (WMD: -0.60, 95% CI: -1.78-0.59; P=0.32) and rates of reoperation (OR: 1.12; 95% CI: 0.55-2.31; P=0.75) between the two groups. In addition, morbidity was not significantly different between the two groups (OR: 1.41, 95% CI: 1.01-1.97; P=0.05); however, the results showed that the TP group tended to have more complications than the PD group. Furthermore, the operation time (WMD: 29.56, 95% CI: 8.23-50.89; P=0.007) was longer in the TP group. Blood loss (WMD: 339.96, 95% CI: 117.74-562.18; P=0.003) and blood transfusion (OR: 4.86, 95% CI: 1.93-12.29; P=0.0008) were more common in the TP group than in the PD group. There were no differences in the long-term survival rates between the two groups. Conclusion: This systematic review and meta-analysis suggested that TP may not be as feasible and safe as PD. However, TP and PD may have the same efficacy.

20.
Sci Rep ; 9(1): 1159, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718559

RESUMO

The safety of minimally invasive distal pancreatectomy (MIDP) and open distal pancreatectomy (ODP) regarding oncological outcomes of pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. Therefore, the aim of this study was to examine the oncological safety of MIDP and ODP for PDAC. Major databases including PubMed, Embase, Science Citation Index Expanded, and the Cochrane Library were searched for studies comparing outcomes in patients undergoing MIDP and ODP for PDAC from January 1994 to August 2018. In total, 11 retrospective comparative studies with 4829 patients (MIDP: 1076, ODP: 3753) were included. The primary outcome was long-term survival, including 3-year overall survival (OS) and 5-year OS. The 3-year OS (hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.89, 1.21; P = 0.66) and 5-year OS (HR: 0.91, 95% CI: 0.65, 1.28; P = 0.59) showed no significant differences between the two groups. Furthermore, the positive surgical margin rate (weighted mean difference (WMD): 0.71, 95% CI: 0.56, 0.89, P = 0.003) was lower in the MIDP group. However, patients in the MIDP group had less intraoperative blood loss (WMD: -250.03, 95% CI: -359.68, -140.39; P < 0.00001), a shorter hospital stay (WMD: -2.76, 95% CI: -3.73, -1.78; P < 0.00001) and lower morbidity (OR: 0.57, 95% CI: 0.46, 0.71; P < 0.00001) and mortality (OR: 0.50, 95% CI: 0.31, 0.81, P = 0.005) than patients in the ODP group. The limited evidence suggested that MIDP might be safer with regard to oncological outcomes in PDAC patients. Therefore, future high-quality studies are needed to examine the oncological safety of MIDP.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Laparoscopia , Neoplasias Pancreáticas/cirurgia , Procedimentos Cirúrgicos Robóticos , Perda Sanguínea Cirúrgica , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Neoplasias Pancreáticas
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