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PURPOSE: To investigate the differences in survival after venous thromboembolism (VTE) and anticoagulation efficacy and safety between catheter (CRVTE) and non-catheter-related VTE (NCRVTE) in cancer patients. METHODS: A retrospective research was conducted, and consecutive cancer (digestive, respiratory, genitourinary, blood and lymphatic, and the other cancers) patients with VTE were enrolled. The anticoagulation therapies included low-molecular-weight heparin (LMWH), warfarin, new type of direct oral anticoagulants (NDOACs), LMWH combined with warfarin, and LMWH combined with NDOACs. Data were collected from the electronic medical record database of our hospital and were analyzed accordingly by Kruskal-Wallis H Test, Chi-square test, Fisher's exact test, Logistic regressions, Kaplan-Meier analysis, and Cox regressions. RESULTS: 263 patients were included, median age in years (interquartile range) was 64(56-71) and 60.5% were male. VTE recurrence rate was 16.7% in CRVTE group which was significantly lower than 34.8% in NCRVTE group (P = .032). Heart diseases were independently associated with VTE recurrence (P = .025). Kaplan-Meier survival estimates at 1, 2, and 3 years for CRVTE group were 62.5%, 60.0%, and 47.5%, respectively, compared with 47.9% (P = .130), 38.7% (P = .028), and 30.1% (P = .046), respectively, for NCRVTE group. Cox regression showed surgery (P = .003), anticoagulation therapy types (P = .009), VTE types (P = .006) and cancer types (P = .039) were independent prognostic factors for 3-year survival after VTE. Nonmajor and major bleeding were not significantly different (P = .417). Anticoagulation therapy types were independently associated with the bleeding events (P = .030). CONCLUSIONS: Cancer patients with CRVTE potentially have a better anticoagulation efficacy and survival compared to NCRVTE, and the anticoagulation safety seems no significant difference.
Assuntos
Anticoagulantes , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/tratamento farmacológico , Masculino , Feminino , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.
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Coma , Medicamentos de Ervas Chinesas , Humanos , Masculino , Coma/etiologia , Coma/tratamento farmacológico , Coma/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Eletroencefalografia , Terapias Complementares/métodos , Lesões Encefálicas Traumáticas/complicações , Medicina Tradicional Chinesa/métodosRESUMO
Intracranial infections are the most serious and common postoperative complications with significant mortality and morbidity. Myroides odoratimimus (M. odoratimimus), a Gram-negative environmental species and an opportunistic microorganism, predominantly infects immunocompromised individuals. Limited clinical experiences and documented multidrug resistance have resulted in a scarcity of data on the treatment of M. odoratimimus infections. As far as we know, this is the first reported case of an intracranial M. odoratimimus infection with external ventricular drains (EVD) that was effectively treated with a combination of intravenous and intraventricular tigecycline in an immunocompetent adult host.
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The objective of this study was to investigate the inhibitory effect of chlorogenin 3-O-ß-chacotrioside derivatives against H5N1 subtype of the highly pathogenic avian influenza (HPAI) viruses and its molecular mechanism. A series of novel small molecule pentacyclic triterpene derivatives were designed and synthesized and their antiviral activities on HPAI H5N1 viruses were detected. The results displayed that the derivatives UA-Nu-ph-5, XC-27-1 and XC-27-2 strongly inhibited wild-type A/Duck/Guangdong/212/2004 H5N1 viruses with the IC50 values of 15.59 ± 2.4 µM, 16.83 ± 1.45 µM, and 12.45 ± 2.27 µM, respectively, and had the selectivity index (SI) > 3, which was consistent with the efficacy against A/Thailand/kan353/2004 pseudo-typed viruses. Four dealt patterns were compared via PRNT. The prevention dealt pattern showed the strongest inhibitory effects than other patterns, suggesting that these derivatives act on the entry process at the early stages of H5N1 viral infection, providing protection for cells against infection. Further studies through hemagglutinin inhibition (HI) and neuraminidase inhibitory (NAI) assay confirmed that these derivatives inhibited H5N1 virus replication by interfering with the viral hemagglutinin function. The derivatives could recognize specifically HA protein with binding affinity constant KD values of 2.57 × 10-4 M and 3.67 × 10-4 M. In addition, through site-directed mutagenesis combined with a pseudovirion system, we identified that the high-affinity docking sites underlying interaction were closely associated with amino acid residues I391 and T395 of HA. However, the potential binding sites of the derivatives with HA did not locate at HA1 sialic acids receptor binding domain (RBD). Taken together, these study data manifested that chlorogenin 3-O-ß-chacotrioside derivatives generated antiviral effect against HPAI H5N1 viruses by targeting the hemagglutinin fusion machinery.
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Antivirais/química , Antivirais/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , Sobrevivência Celular , Embrião de Galinha , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Testes de Neutralização , Ligação Proteica , Relação Estrutura-Atividade , Internalização do VírusRESUMO
Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible.
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Antivirais/farmacologia , Farmacorresistência Viral/genética , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Oseltamivir/farmacologia , Sequência de Aminoácidos , Animais , Sequência de Bases , China , Cães , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Mutação , Neuraminidase/genética , RNA Viral , Estações do AnoRESUMO
Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKß phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKß phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury.
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Ciclina D1/genética , Citoproteção/genética , Receptores ErbB/metabolismo , NF-kappa B/metabolismo , Transcrição Gênica , Regulação para Cima/genética , Animais , Hipóxia Celular/genética , Ciclina D1/metabolismo , Regulação para Baixo/genética , Células PC12 , Regiões Promotoras Genéticas , RatosRESUMO
A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized and their anti-proliferative activities on cancer cell lines were investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited cell proliferation of a panel of different human cancer cell lines including A549, HepG2, OVCAR-3, HeLa and K562 and SGC-790 cell lines, and displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we found EM-d-Rha (3-(2",3"-Di-O-acetyl-α-L-rhamnopyranosyl-(1â4)-2',3'-di-O-acetyl-α-L-rhamnopyranosyl)-emodin) substantially induced cellular apoptosis of HepG2 and OVCAR-3 cells in the early growth stage. Furthermore, EM-d-Rha led to the decrease of mitochondrial transmembrane potential, and up-regulated the express of cells apoptosis factors in a concentration- and time-dependent manner. The results indicated the EM-d-Rha may inhibit the growth and proliferation of HepG2 cells through the pathway of apoptosis induction, and the possible molecular mechanism may due to the activation of intrinsic apoptotic signal pathway.
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Antineoplásicos/farmacologia , Emodina/análogos & derivados , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias/patologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Células Hep G2 , Humanos , Técnicas In Vitro , Células MCF-7 , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Hypercholesterolemia contributes to cardiovascular diseases, but its direct effect on lung is little known. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to exert numerous effects that are dependent and independent of their cholesterol-lowering property. The authors hypothesized that atorvastatin would attenuate hypercholesterolemia-induced lesion in lung. Fifteen rabbits were randomly divided into control group, high-cholesterol forage group, and atrovastatin treatment group. Body weight and blood lipid were measured. All lung tissue and pulmonary arteries were collected for histopathology and immunohistochemistry. Alveolar macrophages (AMs) were cultured and activation of nuclear factor (NF)-κB was detected. Concentrations of interleukin (IL)-6 were measured in serum, bronchoalveolar lavage fluid (BALF), and culture supernatants of AMs. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) of high-cholesterol forage group were higher than control group (P < .05). There were infiltrating of AMs and lymphocytes in lung tissue of high-cholesterol forage group. NF-κB activity in AMs and concentrations of IL-6 in serum, BALF, and culture supernatants of AMs were higher than those of control group (P < .01), and so were all vascular remodeling indexes. TC and LDL-C and other indexes of atrovastatin treatment group were decreased (P < .05). Hypercholesterolemia induced pulmonary inflammatory Infiltration and vascular remodeling. Atorvastatin attenuated inflammatory infiltration and vascular remodeling in lung of hypercholesterolemia rabbits.
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Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Pneumopatias/etiologia , Macrófagos Alveolares/metabolismo , Pirróis/uso terapêutico , Animais , Atorvastatina , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Interleucina-6/sangue , Lipídeos/sangue , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Masculino , NF-kappa B/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Pirróis/farmacologia , Coelhos , Distribuição AleatóriaRESUMO
OBJECTIVE: To study the protective mechanisms of the astragaloside against ischemia-reperfusion lung injury in rats. METHODS: Ischemia-reperfusion lung injury was induced in SD rats. Astragalus armour glucoside was dissolved in 1% of sodium carboxymethyl cellulose at different concentrations (8, 6, and 3 mg/ml) was intragastrically administered in the rats at the dose of 1 ml/100 g. Cellular and subcellular structural changes in the lung tissue were observed at the end of the experiment using optical and transmission electron microscope, with the wet/dry ratio of the lung tissue and myeloperoxidase (MPO) activity measured. RESULTS: The wet/dry ratio and myeloperoxidase activity in the lung tissue were significantly higher in the model group than in the sham-operated group (P<0.05), and were significantly lowered by the treatment with astragalus armour glucoside at different doses (P<0.01 or 0.05), and the effect was especially obvious in rats receiving a moderate dose. Pulmonary capillary expansion, erythrocyte leakage and exudate in the alveolar space with obvious pathological changes in the type I and II epithelial cells were observed in model group. Pulmonary capillary expansion was reduced in rats treated with high, medium and low dose of Astragalus armour glucoside, and the medium dose group showed the most obvious effect, in which no edema fluid in the alveolar space or erythrocyte leakage was found with also reduced type II lung epithelial cell degranulation. CONCLUSION: Astragaloside has obvious antioxidant effect in rats with ischemia-reperfusion lung injury, and a medium dose produces the best effect.
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Precondicionamento Isquêmico , Pulmão/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Feminino , Pulmão/patologia , Masculino , Fitoterapia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Saponinas/uso terapêutico , Triterpenos/uso terapêuticoRESUMO
OBJECTIVE: To study the mechanism of the effect of low-frequency rotary constant magnetic field on high-fat and high-protein diet-induced fatty liver in rats. METHODS: Fatty liver model was established in SD rats by feeding on a high-fat and high-protein diet daily. The enzyme activity changes in the serum and liver homogenate were detected at 10, 14, and 18 weeks, and the pathological changes of the liver were observed with optical and electron microscopy. RESULTS: In magnetic field intervention group, the concentration of alanine aminotransferase and aspartate transaminase were significantly decreased, and the activity of lipoprotein lipase, hepatic lipase, superoxide dismutase and the concentration of malondialdehyde in the liver homogenate were significantly increased. Under optical microscope and electron microscope, the rats in the model group showed diffusive adipose degeneration in the hepatic cells with large lipid droplets, which became large vacuoles after fat extraction, indicating fatty necrosis. In magnetic field intervention group, remarkably smaller lipid droplets and lessened hepatic cell adipose degeneration were observed. CONCLUSION: Low-frequency rotary constant magnetic field has beneficial effect on fat metabolism, leading to reduced lipid peroxidation and structural recovery of the degenerated hepatic cells.