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Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.
Assuntos
Anticorpos Monoclonais Humanizados , Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Idoso , Capacidade Vital , Adulto , Método Duplo-Cego , Idoso de 80 Anos ou mais , Progressão da Doença , Fator de Crescimento do Tecido ConjuntivoRESUMO
The punch tool is a swift and practical instrument in the facial pigmented melanocytic nevus. However, few studies have evaluated the efficacy of the method for facial pigmented nevus. The aim of this study was to evaluate the practicability and effectiveness of removing facial pigmented nevus by punch biopsy technique. This was an observational study of patients with facial pigmented nevus in the Hospital of Plastic Surgery, Weifang Medical University. The ages of patients ranged from 15 to 36 years (average, 25 y). The outcome evaluations included Vancouver Scar Scale (VSS) score, esthetic appearance, and patient satisfaction. Following standard procedures, preoperative surgical excision was performed with safety margins. Anatomopathologic analysis of the surgical specimen was used as the gold standard to evaluate the accuracy of diagnosis by punch biopsy. From January 2019 to January 2020, this punch technique was carried out on 96 patients (151 pigmented nevus) with 35 melanocytic nevus on the forehead, 39 on the cheek, 21 on the eyelid, and 45 on the nose, whereas 11 were on nasolabial folds. The diameters of pigmented nevus are 0.5 to 10 mm on the face. All patients were evaluated at a follow-up visit ranging from 6 to 20 months (average, 11±1.5 mo) and healed with no complication. The histopathological examinations of the skin lesions showed benign outcomes. The mean Vancouver Scar Scale were 1.1±0.4. Ideal cosmetic and functional outcomes were achieved in 94 patients (97.9%). All patients achieved complete satisfaction except 2 patients with partial satisfaction. No recurrences and complications were recorded. This study demonstrated that the punch technique is an effective method to remove facial pigmented melanocytic nevus with acceptable functional and esthetic outcomes without relapse.
Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Adolescente , Adulto Jovem , Adulto , Neoplasias Cutâneas/cirurgia , Cicatriz/patologia , Recidiva Local de Neoplasia , Estética Dentária , Nevo Pigmentado/cirurgiaRESUMO
Head lettuce (Lactuca sativa L.) is an important crop for fresh consumption in China. In Shandong Province, head lettuce is planted in spring and in autumn each year. Because of the on-and-off rain for three weeks, head lettuce plants planted directly into the field in Jiyang City, in July 2017, 20% of the plants rapidly showed symptoms of rotting, water-soaked lesions on roots and stem bases, and then death. The diseased plants first appeared in low-lying areas prone to water accumulation. One-millimeter pieces were excised from water-soaked roots and stem bases, dipped in a 0.2% calcium hypochlorite solution for 10 min, then placed on V8 medium, and incubated in the dark at 28°C for 5 d. Two Pythium-like strains were isolated from the roots and stems. The isolates transferred to CMA and grown for 7 d, and the morphological characteristics of the two isolates on corn meal agar (CMA) were white with dense, cottony, aerial and well-branched mycelia. The two isolates produced sporangia, oogonia, antheridia and oospores. Most of the sporangia were lobate. The oogonia were smooth, nearly globose and terminal. Oospores were globose, smooth and aplerotic. The average dimensions of 50 oogonia and oospores respectively ranged from 19.5 to 25.2 (av. 23.1) µm and 17.8 to 22.3 (av. 19.9) µm. The antheridia were broadly sac-shaped. The isolates morphological characteristics were consistent with P. aphanidermatum (van der Plaats-Niterink, 1981). The COI gene and ITS region of the rDNA were amplified and sequenced using primers FM55/FM52R (Long et al. 2012) and ITS1/ITS4 (White et al. 1990), respectively. The two aligned COI sequences were identical for both isolates, as were the two ITS sequences. BLASTn analysis of the 1,133-bp COI sequence (accession no. MT952703) resulted in a 100% identity with accession number AY129164 from Lactuca sativa, which belongs to P. aphanidermatum, and the 808-bp ITS sequence (accession no. MT921597) showed a 99% identity with Genbank accession number HQ643442 belonging to P. aphanidermatum. Koch's postulates were conducted by first soaking corn kernels for 24 h in water, and then autoclaving for 2 h at 121ËC. Isolate SDHL-1 was grown on CMA for 10 days, after which agar plugs were transferred to the sterilized corn kernels and incubated at 28â for approximately 15 d, until the corn kernels were covered in white hyphae. Ten healthy head lettuce plants were transplanted into a sterilized loam potting soil artificially infested with the corn inoculum (3 g inoculum per 100 g loam mixture). Inoculated plants and noninoculated controls were maintained in a greenhouse at 28°C and 100% relative humidity with a 12-h photoperiod; the experiment was repeated once. All twenty inoculated plants exhibited symptoms within one week similar to those observed. Pythium aphanidermatum was recovered only from the water-soaked roots and stem bases of inoculated plants and the re-isolated cultures again identified based on morphological characteristics and sequencing of the ITS and COI genes. No symptoms were observed on the control plants. Sclerotinia sclerotiorum is reported to cause stem base rot of L. sativa in China (Zhou et al. 2011). To our knowledge, however, this is the first report of root rot of head lettuce caused by Pythium aphanidermatum. Identification of the pathogen will assist in devising strategies to reduce yield loss.
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Pseudorabies virus (PRV) UL2 (pUL2) is a multifunctional protein, which is homologous with herpes simplex virus 1 early protein UL2 (hUL2) and crucial for the viral propagation. Yet, how pUL2 executes its roles in the viral life cycle remain inadequately understood. In order to uncover its effect on the procedure of PRV infection, investigation was performed to examine the subcellular distribution of pUL2 and establish its trafficking mechanism. In the present study, enhanced yellow fluorescent protein or Myc tag fused pUL2 was transiently overexpressed in transfected cells and exhibited an absolutely nuclear accumulation without the existence of other PRV proteins. Additionally, the nuclear trafficking of pUL2 was proved to rely on Ran-, transportin-1, importin ß1, importin α1, α3 and α5. Accordingly, these data will benefit the knowledge of pUL2-mediated biological effects in PRV infection cycle.
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Núcleo Celular/metabolismo , Uracila-DNA Glicosidase/metabolismo , Proteínas Virais/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Células COS , Chlorocebus aethiops , Clonagem Molecular , Uracila-DNA Glicosidase/genética , Proteínas Virais/genéticaRESUMO
Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus, can regulate the antiviral response of NF-κB signaling, which is critical for cell survival, growth transformation, and virus latency. Here, we showed that tegument protein BGLF2 could inhibit TNF-α-induced NF-κB activity. BGLF2 was shown to interplay with the NF-κB subunits p65 and p50, and the Rel homology domain of p65 was the pivotal region to interact with BGLF2. Nonetheless, BGLF2 did not influence the development of p65-p50 dimerization. Yet, overexpression of BGLF2 inhibited the phosphorylation of p65 Ser536 (but not Ser276) and blocked the nuclear translocation of p65. In addition, knockdown of BGLF2 during EBV lytic replication elevated NF-κB activity and the phosphorylation of p65 Ser536. Taken together, these results suggest that the inhibition of NF-κB activation may serve as a strategy to escape the host's antiviral innate immunity to EBV during its lytic infection.-Chen, T., Wang, Y., Xu, Z., Zou, X., Wang, P., Ou, X., Li, Y., Peng, T., Chen, D., Li, M., Cai, M. Epstein-Barr virus tegument protein BGLF2 inhibits NF-κB activity by preventing p65 Ser536 phosphorylation.
Assuntos
Núcleo Celular/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiologia , NF-kappa B/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Proteínas Virais de Fusão/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Células HEK293 , Células HeLa , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Transporte Proteico , Transdução de Sinais , Fator de Transcrição RelA/genética , Proteínas Virais de Fusão/genéticaRESUMO
American ginseng (Panax quinquefolius) is a perennial herb whose dried roots are used for health care products, medicine, and food in China (Yuan et al. 2010). Shandong Province is the main area growing American ginseng and contributes more than 50% of the production in China. Wendeng city, located in the east of Shandong Peninsula, is the primary production area of American ginseng in Shandong Province since it has four distinct seasons, sufficient light, loose soil (pH 5.5ï½7.0), and with thus a similar geographical environment and climate conditions to the American ginseng production area of the United States and Canada. In March 2016, 2-year old American ginseng plants that were planted directly into the ground in the greenhouses in Wendeng city, contained up to 6-10% stunted plants. Water-soaked lesions were observed on the crowns and the tips of fine roots. The leaves of the infected plants became scalded, dark green starting at the top of the plants and gradually move downward. Moreover, the leaves and petioles gradually curled withered and drooped, and the whole plant collapsed. Tissue samples, 10 mm in size, were excised from the water-soaked roots and crowns of diseased plants, rinsed under running water for 24 hours, dipped in a 0.2% calcium hypochlorite solution for 10 minutes, placed on sterile filter paper to dry and then placed on V8 medium (200 mL V8 Campbell Soup, 15 g agar, 0.2 g CaCO3, and 1 L distilled water) and incubated in the dark at 28 °C for 5 days. Five Pythium-like isolates which were arachnoid-cottony on cornmeal agar were isolated and they all produced hyphal swellings, oogonia, antheridia and oospores. Oospores were globose, smooth and plerotic, with some being aplerotic. The dimensions of hyphal swellings, oogonia and oospores respectively ranged from 9.0 to 21.3 (average 14.1) µm, 12.9 to 22.5 (average 18.2) µm, and 12.5 to 20.5 (average 16.7) µm. Finger-like projections were uniformly distributed on the walls of the oogonia and the antheridia were curved rods. The five Pythium-like isolates were identified as P. spinosum based on morphological characteristics (van der Plaats-Niterink, 1981). Genomic DNA was extracted from the isolates of the Pythium sp. using a DNA extraction kit (OMEGA, U.S.A.). The cytochrome c oxidase subunit I (COI) gene and internal transcribed spacer (ITS) region rDNA were amplified and sequenced using primers FM55/FM52R (Long et al. 2012) and ITS1/ITS4, respectively (White et al.1990). The five COI sequences were aligned and were identical for all five isolates, as well as the five ITS sequences. BLASTn analysis of the 538-bp COI sequence (accession no. MT822775) resulted in a 99% identity with that of the P. spinosum strain CBS122663 (accession no. HQ708832.1), and the 916-bp ITS sequence (accession no. MN847595) showed 100% identity with Genbank accession number AB217665 belonging to P. spinosum. Koch's postulates were confirmed. Corn kernels that had been soaked in water for 24 hours in water, autoclaved for 2 hours at 121ËC and allowed to cool were inoculated with agar plugs of P. spinosum grown on corn meal agar medium (CMA) for 10 days. The inoculated corn kernels were incubated at 28 â for 13ï½15 days, until the corn kernels were covered with white hypha of P. spinosum. Ten healthy approximately 2-years old American ginseng plants growing in Wengdeng greenhouses were transplanted into a sterilized potting soil that was artificially infested with the corn inoculum (3 g inoculum per 100 g loam mixture). Inoculated and non-inoculated control plants were maintained in a greenhouse with a roof covered with sunshade net at 28 °C and 100% relative humidity. The experiment was repeated once. Four days after inoculation (DAI), the crown of inoculated plants developed water-soaked symptoms similar to those observed in field. No symptoms developed on the control plants. By 7 DAI, the inoculated fine roots and crowns showed water-soaked lesions identical to those observed in field, whereas control plants remained symptomless. The re-isolated isolate of P. spinosum was identical morphologically and by DNA sequence analysis to the original isolate. To our knowledge, this is the first report of root rot on American ginseng caused by P. spinosum in China and worldwide. Identification of the pathogen will assist in devising strategies to protect this important medicine plant from the pathogen, and to prevent yield losses.
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Pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the definite function of EP0 during PRV infection is not clear. In this study, to determine if EP0 might localize to the nucleus, as it is shown for its homologue in HSV-1, the subcellular localization pattern and molecular determinants for the nuclear import of EP0 were investigated. EP0 was demonstrated to predominantly target the nucleus in both PRV infected- and plasmid-transfected cells. Furthermore, the nuclear import of EP0 was shown to be dependent on the Ran-, importin α1-, α3-, α7-, ß1- and transportin-1-mediated multiple pathways. Taken together, these data will open up new horizons for portraying the biological roles of EP0 in the course of PRV lytic cycle.
Assuntos
Transporte Ativo do Núcleo Celular , Herpesvirus Suídeo 1/metabolismo , Proteínas Virais/metabolismo , Animais , Linhagem Celular , Carioferinas/metabolismo , Ligação ProteicaRESUMO
Although cilostazol was proved to have antitumor biological effects, its function in myocardial ischemia and reperfusion (I/R) injury and the underlying mechanisms were not fully illustrated yet. In this study, a rat model of I/R injury was constructed and quantitative real-time PCR, Western blot, and immunofluorescence (IF) assay were performed. Our results showed that cilostazol increased LC3 II/LC3 I ratio, reduced p62 abundance, and promoted the expressions of LAMP1, LAMP2, cathepsin B, and cathepsin D, indicating that cilostazol could activate autophagy and elevated lysosome activation. Following analysis showed that cilostazol enhanced nuclear protein expression of transcription factor EB (TFEB), an important regulator of autophagy-lysosome pathway. Furthermore, CCI-779, an inhibitor of TFEB, could reverse the effects of cilostazol on autophagic activity and lysosome activation. Importantly, cilostazol suppressed I/R injury-induced apoptosis by decreasing the cleavage of caspase 3 and PARP. Enzyme-linked immunosorbent assay showed that cilostazol reduced the serum levels of CTn1 and CK-MB and decreased infract size caused by I/R injuries. Altogether this study suggested that cilostazol protects against I/R injury by regulating autophagy, lysosome, and apoptosis in a rat model of I/R injury. The protective mechanism of cilostazol was partially through increasing the transcriptional activity of TFEB.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/biossíntese , Cilostazol/farmacologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/antagonistas & inibidores , Modelos Animais de Doenças , Lisossomos/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/cirurgia , Ratos , Ratos Sprague-Dawley , Sirolimo/análogos & derivados , Sirolimo/farmacologiaRESUMO
BACKGROUND: Patients with Cushing's disease (CD) with hypercortisolism have an increased risk of opportunistic infection. However, most CD patients exposed to infections are diagnostic latency, leading to a poor prognosis. METHODS: Six patients in our hospital and an additional six patients in the literature were included in this study. Clinical information of CD patients with pulmonary Cryptococcus neoformans are reviewed. RESULTS: The average baseline total cortisol and ACTH in serum at 8 am of all the patients was 44.85 µg/dL (normal range 4.0-22.3 µg/dL) and 200.3 pg/mL (normal range 0-46 pg/mL), respectively. Lymphopenia was found in 2 out of 6 patients in our hospital. The pulmonary radiologic findings included nodules (4/12), masses with or without a cavity (5/12), infiltration (5/12), and consolidation (4/12). The diagnosis of C.neoformans was established by lung pathology results (7/12), microorganism culture (3/12), and serum cryptococcal polysaccharide antigen (4/12). Lung lobectomy was performed in two patients who had a nodule in one lung lobe. Antifungal drugs were administered, including amphotericin-B (7/12), fluconazole (4/12), flucytosine (2/12) and liposomal amphotericin (1/12). Additional therapies for CD included trans-sphenoidal pituitary adenoma surgery (9/12), adrenalectomy (1/12) and ketoconazole (2/12). Seven patients survived, and five patients died. CONCLUSION: Pulmonary C.neoformans is an uncommon but fatal opportunistic infection in CD patients. Pulmonary nodules or masses should be aggressively investigated to exclude the C.neoformans among CD patients. The infiltration lesions in chest CT scan and lymphopenia are associated with poor prognosis.
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Antifúngicos/uso terapêutico , Criptococose/complicações , Criptococose/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/complicações , Adulto , Pequim , Criptococose/mortalidade , Cryptococcus neoformans/isolamento & purificação , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND/AIMS: Epstein-Barr virus (EBV) BFLF2, the homologue of herpes simplex virus 1 (HSV-1) UL31, is crucial for the efficient viral DNA packaging and primary egress across the nuclear membrane. However, we still do not know its subcellular transport mechanisms. METHODS: Interspecies heterokaryon assays were utilized to detect the nucleocytoplasmic shuttling of BFLF2, and mutation analysis, plasmid transfection and fluorescence microscopy assays were performed to identify the functional nuclear localization sequence (NLS) and nuclear export sequence (NES) of BFLF2 in live cells. Furthermore, the nuclear import and export of BFLF2 were assessed by confocal microscopy, co-immunoprecipitation and immunoblot assays. RESULTS: BFLF2 was confirmed to shuttle between the nucleus and cytoplasm. Two predicted NESs were shown to be nonfunctional, yet we proved that the nuclear export of BFLF2 was mediated through transporter associated with antigen processing (TAP), but not chromosomal region maintenance 1 (CRM1) dependent pathway. Furthermore, one functional NLS, 22RRLMHPHHRNYTASKASAH40, was identified, and the aa22-23, aa22-25, aa28-30 and aa37-40 had an important role in the nuclear localization of BFLF2. Besides, the nuclear import of BFLF2 was demonstrated through Ran-, importin α7-, importin ß1- and transportin-1-dependent mechanism that does not require importin α1, α3 and α5. CONCLUSION: These works are of significance for the further study of the functions of BFLF2 during EBV infection, as well as for further insights into the design of new antiviral drug target and vaccine development against EBV.
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Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiologia , Proteínas Virais/metabolismo , Sequência de Aminoácidos , Animais , Células COS , Núcleo Celular/virologia , Chlorocebus aethiops , Citoplasma/metabolismo , Citoplasma/virologia , Infecções por Vírus Epstein-Barr/virologia , Células HEK293 , Humanos , Camundongos , Células NIH 3T3 , Sinais de Exportação Nuclear , Sinais de Localização NuclearRESUMO
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.
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Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Predisposição Genética para Doença/genética , Proteínas Mutantes/metabolismo , Mutação/genética , Profilinas/genética , Profilinas/metabolismo , Actinas/metabolismo , Sequência de Aminoácidos , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Células Cultivadas , Exoma/genética , Feminino , Cones de Crescimento/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Judeus/genética , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Proteínas Mutantes/genética , Linhagem , Conformação Proteica , Ubiquitinação , População Branca/genéticaRESUMO
BACKGROUND: Smoking has been shown to reduce health-related quality of life (HRQOL) in patients with coronary artery disease (CAD) undergoing percutanous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents (BMS). Drug-eluting stents (DES) have now been widely used and are related to substantial reduction of restenosis and significantly improved HRQOL compared with BMS. This study aimed to evaluate the effects of smoking on HRQOL in patients after PCI in DES era. METHODS: A cohort of 649 patients admitted for CAD and treated with drug-eluting stents were included in this prospective, observational study. Patients were classified as non-smokers (n = 351, 54.1%), quitters (n = 126, 19,4%), or persistent smokers (n = 172, 26.5%) according to their smoking status at the time they first admitted to hospital and during the first year of follow-up. Each patient was prospectively interviewed at baseline, 6 months and 1 year following PCI. HRQOL was assessed with the use of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: For the overall population, HRQOL scores at 1-year follow-up were significantly higher than baseline for all 8 domains. At 1-year follow-up, the HRQOL scores in persistent smokers were still lower than that in non-smokers in 6 domains except for bodily pain and mental health, and than that in quitters in 5 domains except for bodily pain, role emotional and mental health. There were no significant differences with regard to the scores between non-smokers and quitters except role emotional for which non-smokers had higher scores. After adjustment, persistent smokers demonstrated significantly less improvements in HRQOL than non-smokers in 6 domains except for bodily pain and social functioning and significantly less improvement than quitters for general health. Improvements of quitters were comparable to that of non-smokers in all domains. Multivariate linear regression analyses showed persistent smoking was an independent risk factor for PCS and MCS improvements. CONCLUSIONS: Persistent smoking substantially diminishes the potential quality-of-life benefits of DES. Efforts should be made to promote smoking cessation after DES implantation which could greatly improve the health quality outcomes.
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Doença da Artéria Coronariana/psicologia , Stents Farmacológicos/psicologia , Intervenção Coronária Percutânea/psicologia , Fumar/psicologia , Idoso , Angioplastia Coronária com Balão , Doença da Artéria Coronariana/complicações , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Abandono do Hábito de Fumar , Resultado do TratamentoRESUMO
The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 µM/37.0µM, 1.2µM/3.5µM, and 6.3 µM/26.4µM, respectively, while, the intermediate (IDC) was, in order, 18.5µM, 1.8µM, 13.2µM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.
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Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Peixe-Zebra/sangue , Animais , Atorvastatina/farmacologia , Biomarcadores/sangue , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Ezetimiba/farmacologia , Fenofibrato/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Masculino , Triglicerídeos/sangueRESUMO
Purpose To evaluate the diagnostic performance of ultrasonography (US) in the identification and exclusion of biliary atresia with a modified triangular cord thickness metric together with a gallbladder classification scheme, as well as hepatic artery (HA) diameter and liver and spleen size, in a large sample of jaundiced infants. Materials and Methods The ethics committee approved this study, and written informed parental consent was obtained. In 273 infants with conjugated hyperbilirubinemia (total bilirubin level ≥ 31.2 µmol/L, with direct bilirubin level > indirect bilirubin level), detailed abdominal US was performed to exclude biliary atresia. Biliary atresia was found in 129 infants and ruled out in 144. A modified triangular cord thickness was measured at the anterior branch of the right portal vein, and a gallbladder classification scheme was identified that incorporated the appearance of the gallbladder and a gallbladder length-to-width ratio of up to 5.2 when the lumen was visualized, as well as HA diameter and liver and spleen size. Reference standard diagnosis was based on results of one or more of the following: surgery, liver biopsy, cholangiography, and clinical follow-up. Area under the receiver operating characteristic curve (AUC) analysis, binary logistic regression analysis, Fisher exact test, and unpaired t test were performed. Results Triangular cord thickness, HA diameter, ratio of gallbladder length to gallbladder width, liver size, and spleen size exhibited statistically significant differences (all P < .05) between the group with biliary atresia and the group without. AUCs of triangular cord thickness, ratio of gallbladder length to width, and HA diameter were 0.952, 0.844, and 0.838, respectively. Logistic regression analysis demonstrated that these three US parameters were significantly associated (all P < .05) with biliary atresia. The combination of triangular cord thickness and gallbladder classification could yield comparable AUCs (0.915 vs 0.933, P = .400) and a higher sensitivity (96.9% vs 92.2%), compared with triangular cord thickness alone. Conclusion By using the combination of modified triangular cord thickness and gallbladder classification scheme, most infants with biliary atresia could be identified. (©) RSNA, 2015.
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Atresia Biliar/diagnóstico por imagem , Vesícula Biliar/diagnóstico por imagem , Atresia Biliar/classificação , Feminino , Vesícula Biliar/patologia , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/patologia , Humanos , Lactente , Recém-Nascido , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Tamanho do Órgão , Baço/diagnóstico por imagem , Baço/patologia , UltrassonografiaRESUMO
Idiopathic pulmonary fibrosis (IPF), the prototype of interstitial lung diseases, has the worst prognosis and is the only interstitial lung disease for which approved pharmacological treatments are available. Despite being considered a rare disease, IPF patients pose major challenges to both physicians and healthcare systems. It is estimated that a large number of IPF patients reside in BRIC countries (Brazil, Russia, India, and China) given their overall total population of approximately 3 billion inhabitants. Nevertheless, the limited availability of chest imaging in BRIC countries is considered a chief obstacle to diagnosis, since high-resolution computed tomography of the chest is the key diagnostic test for IPF. Further, obtaining reliable lung function tests and providing treatment access is difficult in the more rural areas of these countries. However, IPF might represent an opportunity for BRIC countries: the exponentially increasing demand for the enrollment of IPF patients in clinical trials of new drugs is predicted to face a shortage of patients - BRIC countries may thus play a crucial role in advancing towards a cure for IPF.
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Fibrose Pulmonar Idiopática/genética , Tomografia Computadorizada por Raios X/métodos , Brasil , China , Humanos , Índia , Prognóstico , Federação RussaRESUMO
PURPOSE: We aimed to compare contrast-enhanced ultrasound (CEUS) with contrast-enhanced computed tomography (CECT) for evaluating the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Treatment responses of 130 patients who underwent TACE were evaluated by CEUS and CECT. We initially compared the abilities of CEUS and CECT to detect residual tumour, which were confirmed by histology or angiography. Then, we compared the tumour response to TACE assessed by CEUS and CECT, according to Modified Response Evaluation Criteria in Solid Tumours (mRECIST). RESULTS: The sensitivity and accuracy of detecting residual tumour by CEUS vs. CECT were 95.9 % vs. 76.2 % (p < 0.001) and 96.2 % vs. 77.7 % (p < 0.001), respectively. For target lesions, 13 patients were observed as complete response (CR) by CEUS, compared to 36 by CECT (p < 0.001). For nontarget lesions, 12 patients were observed as CR by CEUS, compared to 22 by CECT (p = 0.006). For overall response, eight patients were observed as CR by CEUS, compared to 31 by CECT (p < 0.001). CONCLUSION: The diagnostic performance of CEUS was superior to CECT for detecting residual tumour after TACE. In clinical, CEUS should be recommended as an optional procedure for assessing the tumour response to TACE. KEY POINTS: ⢠The mRECIST are widely applied for evaluating the response of HCC. ⢠Imaging method has been applied to assess the therapeutic response to TACE. ⢠The diagnostic performance of CEUS was superior to CECT for residual tumours. ⢠CEUS can be a valuable method for assessing tumour response to TACE.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Angiografia/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Estudos de Casos e Controles , Quimioembolização Terapêutica/métodos , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , UltrassonografiaRESUMO
BACKGROUND: Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. METHODS: We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. RESULTS: The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died. CONCLUSIONS: Intrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD's.
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Hiperplasia do Linfonodo Gigante/diagnóstico , Linfonodos/patologia , Adolescente , Adulto , Idoso , Hiperplasia do Linfonodo Gigante/epidemiologia , China/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Biópsia Guiada por Imagem , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Cavidade Torácica , Adulto JovemRESUMO
BACKGROUND: Whole-lung lavage (WLL) is classically the first-line treatment for symptomatic pulmonary alveolar proteinosis (PAP). However, some patients require multiple WLLs because of refractory nature of their PAP. In this instance, these patients may benefit from new treatment regimens, and new therapies should be tried for these patients. CASE PRESENTATION: We describe a 47-year-old Chinese woman who was confidently diagnosed with pulmonary alveolar proteinosis (PAP) after bronchoalveolar lavage and transbronchial lung biopsy. The patient received four sessions of bilateral whole lung lavage (WLL) and one session of WLL in combination with plasmapheresis, each only producing short-term symptomatic relief. The patient was given a trial of combination therapy, which consisted of WLL and Granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation. The patient showed a gradual improvement in oxygenation and her daily activity, as well as a dramatic improvement in her pulmonary CT examination. CONCLUSION: Bilateral WLL, in combination with GM-CSF inhalation, may be an effective treatment option for severe refractory PAP.
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Lavagem Broncoalveolar/métodos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/terapia , Administração por Inalação , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Pulmonary involvement is a common feature of MPA. Although alveolar hemorrhage is the most common pulmonary manifestation of MPA, a few recent studies have described instances of MPA patients with pulmonary fibrosis. Pulmonary fibrosis was seen to predate, be concomitant with, or occur after the diagnosis of MPA. The goal of this study was to describe the clinical features and prognosis of microscopic polyangiitis (MPA) patients whose initial respiratory presentation was pulmonary fibrosis. METHODS: We conducted a retrospective analysis of 19 MPA patients who presented with pulmonary fibrosis at Peking Union Medical College Hospital between 1990 and 2012. RESULTS: Of 67 total MPA cases, 19 patients presented with pulmonary fibrosis. There were 8 males and 11 females, with a median age of 63.6 years. Common clinical manifestations included fever (89.5%), cough (84.2%), dyspnea (78.9%) and velcro rales (84.2%). Eleven patients experienced weight loss, several had kidney involvement, and most had an increased erythrocyte sedimentation rate and C-reactive protein. All were positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA), with 6 patients being positive at the time of their initial diagnosis of pulmonary fibrosis. Every patient had typical features of usual interstitial pneumonia on High-resolution CT. All were treated with corticosteroids and cyclophosphamide, which lead to an improvement in twelve cases. One of the remaining patients progressed slowly, whereas six died. CONCLUSIONS: Patients with MPA, who also presented with pulmonary fibrosis in our cohort, were more likely to be older, female, and have extrapulmonic involvement. Most patients had a delayed positive ANCA. Corticosteroids plus cyclophosphamide was the remission-induction treatment scheme for all cases. The current prognosis for MPA patients with pulmonary fibrosis appears to be poor, suggesting that they may be candidates for new therapies.