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1.
Cell ; 187(22): 6235-6250.e19, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39317197

RESUMO

Phytochrome B (phyB) and phytochrome-interacting factors (PIFs) constitute a well-established signaling module critical for plants adapting to ambient light. However, mechanisms underlying phyB photoactivation and PIF binding for signal transduction remain elusive. Here, we report the cryo-electron microscopy (cryo-EM) structures of the photoactivated phyB or the constitutively active phyBY276H mutant in complex with PIF6, revealing a similar trimer. The light-induced configuration switch of the chromophore drives a conformational transition of the nearby tongue signature within the phytochrome-specific (PHY) domain of phyB. The resulting α-helical PHY tongue further disrupts the head-to-tail dimer of phyB in the dark-adapted state. These structural remodelings of phyB facilitate the induced-fit recognition of PIF6, consequently stabilizing the N-terminal extension domain and a head-to-head dimer of activated phyB. Interestingly, the phyB dimer exhibits slight asymmetry, resulting in the binding of only one PIF6 molecule. Overall, our findings solve a key question with respect to how light-induced remodeling of phyB enables PIF signaling in phytochrome research.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Microscopia Crioeletrônica , Luz , Fitocromo B , Transdução de Sinais , Fitocromo B/metabolismo , Fitocromo B/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Arabidopsis/metabolismo , Modelos Moleculares
2.
Cell ; 142(4): 531-43, 2010 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-20723755

RESUMO

Muscle wasting and cachexia have long been postulated to be key determinants of cancer-related death, but there has been no direct experimental evidence to substantiate this hypothesis. Here, we show that in several cancer cachexia models, pharmacological blockade of ActRIIB pathway not only prevents further muscle wasting but also completely reverses prior loss of skeletal muscle and cancer-induced cardiac atrophy. This treatment dramatically prolongs survival, even of animals in which tumor growth is not inhibited and fat loss and production of proinflammatory cytokines are not reduced. ActRIIB pathway blockade abolished the activation of the ubiquitin-proteasome system and the induction of atrophy-specific ubiquitin ligases in muscles and also markedly stimulated muscle stem cell growth. These findings establish a crucial link between activation of the ActRIIB pathway and the development of cancer cachexia. Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival.


Assuntos
Receptores de Activinas Tipo II/antagonistas & inibidores , Caquexia/tratamento farmacológico , Atrofia Muscular/tratamento farmacológico , Miocárdio/patologia , Neoplasias/complicações , Receptores de Activinas Tipo II/genética , Ativinas/metabolismo , Animais , Anorexia/tratamento farmacológico , Anorexia/etiologia , Atrofia/tratamento farmacológico , Atrofia/etiologia , Caquexia/etiologia , Feminino , Humanos , Inibinas/genética , Inibinas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Mioblastos/patologia , Transplante de Neoplasias , Neoplasias/mortalidade , Transdução de Sinais , Transplante Heterólogo , Fator de Necrose Tumoral alfa/metabolismo
3.
Rev Cardiovasc Med ; 25(5): 177, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39076487

RESUMO

Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). Kaplan‒Meier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. Kaplan‒Meier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.

4.
Ann Hematol ; 103(3): 855-868, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112795

RESUMO

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.


Assuntos
Mieloma Múltiplo , Talidomida/análogos & derivados , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Mieloma Múltiplo/tratamento farmacológico , Dexametasona , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Virol J ; 21(1): 212, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39252096

RESUMO

BACKGROUND: Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. METHODS: We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. RESULTS: The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p < 0.001), and developed severe COVID-19 (33.3% vs. 4.7%, p < 0.001) were higher in patients with obinutuzumab than in those with rituximab. Multivariate analyses showed that obinuzumab treatment was associated with higher incidences of prolonged SARS-CoV-2 infection (OR 27.05, 95% CI 3.75-195.22, p = 0.001) and severe COVID-19(OR 15.07, 95% CI 2.58-91.72, p = 0.003). CONCLUSIONS: Our study suggested that patients treated with obinutuzumab had a higher risk of prolonged SARS-CoV-2 infection and severe COVID-19 than those treated with rituximab.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Rituximab , SARS-CoV-2 , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , Adulto , Linfoma de Células B/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Idoso de 80 Anos ou mais
6.
Langmuir ; 40(41): 21804-21813, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39364594

RESUMO

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) has garnered significant attention as a subfield of SERS detection due to its capacity to regulate the band gap between molecules and substrates through pressure modulation. Currently, SERS detection primarily focuses on single molecules at atmospheric pressure with limited investigations conducted under high pressure conditions. Herein, we employed rose-shaped MoS2 nanoflowers as the SERS substrate and realized selective PI-SERS enhancement of R6G molecules in the binary (MV+R6G) and ternary (MV+R6G+RhB) systems. The MoS2 demonstrated an exceptionally low SERS detection limit of 5 × 10-6 M in binary and ternary systems with equimolar amounts of molecules. High-pressure experimental results indicate that MoS2 displays selective enhancement for R6G molecules, as evidenced by the comparison of the PI-SERS peak intensity ratio between MoS2 and the probe molecules. The proposed enhancement mechanism in binary and ternary SERS systems under high pressure involves pressure-induced changes in both the band structures of the MoS2 substrate and molecules, thereby influencing their charge transfer dynamics. Consequently, this approach holds great promise for practical applications in complex SERS systems operating under extreme conditions.

7.
Langmuir ; 40(1): 380-388, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38153039

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has emerged as a highly sensitive trace detection technique in recent decades, yet its exceptional performance remains elusive in semiconductor materials due to the intricate and ambiguous nature of the SERS mechanism. Herein, we have synthesized MoS2 nanoflowers (NFs) decorated with Au nanoparticles (NPs) by hydrothermal and redox methods to explore the size-dependence SERS effect. This strategy enhances the interactions between the substrate and molecules, resulting in exceptional uniformity and reproducibility. Compared to the unadorned Au nanoparticles (NPs), the decoration of Au NPs induces an n-type effect on MoS2, resulting in a significant enhancement of the SERS effect. This augmentation empowers MoS2 to achieve a low limit of detection concentration of 2.1 × 10-9 M for crystal violet (CV) molecules and the enhancement factor (EF) is about 8.52 × 106. The time-stability for a duration of 20 days was carried out, revealing that the Raman intensity of CV on the MoS2/Au-6 substrate only exhibited a reduction of 24.36% after undergoing aging for 20 days. The proposed mechanism for SERS primarily stems from the synergistic interplay among the resonance of CV molecules, local surface plasma resonance (LSPR) of Au NPs, and the dual-step charge transfer enhancement. This research offers comprehensive insights into SERS enhancement and provides guidance for the molecular design of highly sensitive SERS systems.

8.
BMC Ophthalmol ; 24(1): 176, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632531

RESUMO

OBJECTIVE: In this study, we used ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA) to assess changes in retinal thickness (RT) and choroidal parameters in individuals who had received a diagnosis of central serous chorioretinopathy (CSC). METHODS: The study encompassed the evaluation of 59 eyes from 47 patients with a diagnosis of CSC, alongside 33 fellow eyes and 31 eyes from healthy individuals (controls). The parameters assessed included RT, choroidal thickness (CT), choriocapillaris density, vascular density of the large choroidal vessel layer, three-dimensional choroidal vascularity index (3D-CVI), choroidal vessel volume per unit area (mCVV/a), and choroidal stroma volume per unit area (mCSV/a). RESULTS: Metrics including mCVV/a, mCSV/a, 3D-CVI, CT, and RT exhibited significantly elevated values in the eyes affected by CSC compared to those of the control group across nine subfields. Moreover, a substantial number of the subfields in both CSC-affected and fellow eyes exhibited increased values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT when compared with the control group. Additionally, acute and chronic CSC subfields demonstrated significantly elevated values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT in comparison to healthy control eyes. Notably, specific subfields associated with complex and atypical forms of CSC revealed higher metrics compared to those of the control group. CONCLUSION: In conclusion, the UWF SS-OCTA proved to be a valuable tool for exploring the anatomical etiology and clinical classification and diagnosis of CSC.


Assuntos
Coriorretinopatia Serosa Central , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Estudos Transversais , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Corioide/irrigação sanguínea , Estudos Retrospectivos
9.
BMC Geriatr ; 24(1): 799, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350053

RESUMO

BACKGROUND AND AIMS: Despite concerns on the adverse health outcomes of sarcopenic obesity (SO), exploration regarding the applicability of different diagnostic criteria and the optimal screening methods is still lacking. This study aims to compare the prevalence and diagnostic agreement of SO under four diagnostic criteria in Chongming, Shanghai, China and assess the diagnostic value of nine screening methods for SO. METHODS: The study population included older people aged ≥ 65 years. The Asian Working Group for Sarcopenia-2019 (AWGS-2019) was used to diagnose sarcopenia. Obesity was defined using percentage of body fat (PBF), percent of body fat exceeding the 60th percentile (60% PBF), body mass index (BMI) and waist circumference (WC). The four diagnostic criteria for SO were AWGS + PBF, AWGS + 60% PBF, AWGS + BMI and AWGS + WC. Nine screening methods were the sarcopenia questionnaire [the questionnaire with five items to screen for sarcopenia (SARC-F), the addition of calf circumference to the SARC-F (SARC-CalF), and the addition of elderly age and BMI to the SARC-F (SARC-F + EBM)] combined with commonly used obesity indicators. Cohen's kappa compared agreement between diagnostic criteria, whilst sensitivity, specificity, receiver operating characteristics (ROC) and area under the ROC curve (AUC) compared the diagnostic value of nine screening methods. RESULTS: A total of 1407 older people were enrolled. The prevalence of SO ranged from 0.3 to 9.9%. The highest agreement between AWGS + 60% PBF and AWGS + PBF. When the AWGS + PBF was used as the 'gold standard' (due to its high agreement and high prevalence), SARC-CalF + PBF had the highest AUC value, and SARC-F + BMI had the highest sensitivity. The recommended cut-off values for SARC-F + BMI are SARC-F ≥ 1 score and BMI ≥ 19.845 kg/m², and the recommended cut-off values for SARC-CalF + PBF are SARC-CalF ≥ 5 score and PBF ≥ 34.55%. CONCLUSION: The prevalence of SO varied greatly amongst the four diagnostic criteria. AWGS + PBF is recommended for diagnosing SO in older people. SARC-F + BMI and SARC-CalF + PBF can be used as screening methods for SO.


Assuntos
Obesidade , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Idoso , Masculino , Feminino , Prevalência , Obesidade/epidemiologia , Obesidade/diagnóstico , China/epidemiologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Índice de Massa Corporal , Idoso de 80 Anos ou mais , Sensibilidade e Especificidade , Circunferência da Cintura/fisiologia
10.
Br J Cancer ; 128(7): 1377-1390, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36681728

RESUMO

BACKGROUND: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment. This study aims to explore the effect and underlying mechanisms of immunoproteasome inhibition, a novel immunotherapy, on the progression of CRPC. METHODS: The immunoproteasome subunit LMP7 was silenced by using gene knockout or inhibited by the epoxyketone inhibitor ONX 0914 in a mouse CRPC tumour graft model and in interferon-γ-pretreated human CRPC cell lines in vitro. RESULTS: CRPC tissues reveal a significant "tumour-elicited" Th17-type inflammatory response which induces immunoproteasome subunit expression. LMP7 deficiency in host mice or in CRPC tumour grafts had no effect on the "tumour-elicited" Th17-type inflammatory response and tumour progression. However, the selective LMP7 inhibitor ONX 0914 strongly suppressed the "tumour-elicited" Th17-type inflammatory response and CRPC tumour progression. Treatment of wild-type mice receiving LMP7-deficient CRPC tumour grafts with ONX 0914 further suggested that immunoproteasome inhibition prevents CRPC progression through suppressing IL-17-induced angiogenesis and epithelial-mesenchymal transition via inactivation of COX-2/VEGF-A signalling and ß-catenin/Snail signalling. Treatment of LMP7-deficient mice receiving wild-type CRPC tumour grafts with ONX 0914 and inhibition of LMP7 in PC3 and 22Rv.1 cells with ONX 0914 showed that immunoproteasome inhibition also prevents CRPC progression through inducing CRPC cell apoptosis via activation of the unfolded protein response. CONCLUSIONS: We define a critical role of the immunoproteasome in CRPC and propose immunoproteasome inhibition as a promising therapeutic approach to suppress CRPC progression.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Camundongos , Humanos , Animais , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Transdução de Sinais , Interferon gama , Modelos Animais de Doenças , Complexo de Endopeptidases do Proteassoma/metabolismo
11.
BMC Plant Biol ; 23(1): 262, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37198548

RESUMO

BACKGROUND: Leaf litter is the products of metabolism during the growth and development of plantation, and it is also an important component of nutrient cycling in plantation ecosystems. However, leaf litter chemistry and its effects on soil microorganisms in different ages, as well as the interactions between chemical components in leaf litter have been rarely reported. Based on this, this paper took Zanthoxylum planispinum var. dintanensis (hereafter Z. planispinum) plantations of 5-7, 10-12, 20-22, and 28-32 years old as the objects. By using one-way ANOVA, Pearson correlation analysis and redundancy analysis, we investigated leaf litter chemistry and its effects on soil microorganisms in different ages, and to reveal internal correlation of various chemical components in leaf litter, which can provide a scientific basis for the regulation of soil microbial activity in plantations. RESULTS: The variation of organic carbon with plantation age was more stable compared to total nitrogen and phosphorus of leaf litter. Nitrogen resorption was stronger than phosphorus resorption efficiency in Z. planispinum, and resorption efficiencies of leaf nitrogen and phosphorus for different ages were lower than the global average. Total nitrogen was highly significantly positively correlated with lignin, and total potassium was significantly positively correlated with tannin, suggesting the increase of inorganic substances in leaf litter would promote the accumulation of secondary metabolites. The leaf litter chemical traits explained up to 72% of soil microorganisms, where lignin was positively correlated with fungi and negatively correlated with bacteria, indicating that fungi are able to decompose lower quality litter and can break down complex and stable organic compounds more rapidly than bacteria. The nutrient elements carbon and nitrogen in the leaf litter and their interrelationship also have a great impact on soil microorganisms, because carbon is not only the element that provides energy, but also the element with the largest content in the microbiota. CONCLUSIONS: The sustained increase in inorganic nutrients of leaf litter did not favor the decomposition of secondary metabolites, but rather inhibited the degradation of leaf litter. The significant positive effect of the leaf litter chemistry on soil microorganisms indicates the important role of leaf litter in promoting nutrient cycling in Z. planispinum plantations.


Assuntos
Ecossistema , Zanthoxylum , Solo/química , Lignina , Nitrogênio/metabolismo , Carbono , Fósforo/metabolismo , Folhas de Planta/metabolismo
12.
Haemophilia ; 29(1): 123-134, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36163649

RESUMO

INTRODUCTION: The development of inhibitors against factor FIX (FIX) is the most serious complication of FIX replacement therapy in haemophilia B (HB) patients. Currently, only few cohorts of HB inhibitor patients have been reported worldwide. AIM: This Chinese nationwide study of HB inhibitor patients explored their risk factors for FIX inhibitor development and experience on their management. METHODS: We retrospectively analysed patient characteristics, F9 genotypes, treatment strategies and outcomes of HB inhibitor patients registered to the Chinese National Registry and Patient Organization Registry. RESULTS: Forty-four unique HB inhibitor patients were identified in 4485 unique HB patients registered by year 2021 to the two Registries. Inhibitor diagnosis were usually delayed and the low prevalence (.98%) may suggest some inhibitor patients were not identified. Their median age at inhibitor diagnosis was 7.5 (IQR, 3.0-14.8) years. Most patients (95.5%) had high-titre inhibitors. Allergic/Anaphylactic reactions occurred in 59.1% patients. Large deletions and nonsense mutations were the most common F9 mutation types in our FIX inhibitor patients. Patients with large F9 gene deletions were more likely to develop inhibitors (p = .0002), while those with missense mutations had a low risk (p < .0001). Thirteen (29.5%) patients received immune tolerance induction (ITI) therapy using low-dose prothrombin complex concentrate regimens. Twelve completed ITI with three (25.0%) achieving success. Nephrotic syndrome developed in two (16.7%) patients during ITI. CONCLUSION: This study reports the largest Chinese cohort of HB inhibitor patients. Large deletions were most significantly associated with inhibitor development. Low-dose ITI might be feasible for FIX inhibitor eradication.


Assuntos
Fator IX , Hemofilia A , Hemofilia B , Adolescente , Criança , Pré-Escolar , Humanos , China/epidemiologia , Fator IX/antagonistas & inibidores , Fator IX/genética , Hemofilia B/tratamento farmacológico , Hemofilia B/genética , Hemofilia B/diagnóstico , Tolerância Imunológica , Estudos Retrospectivos
13.
Nanotechnology ; 34(30)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37171102

RESUMO

This work demonstrates a facile and efficient methodology to synthesize a composite material of zeolitic imidazolate frameworks (ZIFs) and laser-induced graphene (LIG). This ZIF-67 loaded LIG composite (ZIF-67/LIG) has been adequately characterized for its morphology and structure, and its electrochemical performance has been specifically examined. As supercapacitors (SCs) electrode material, the ZIF-67/LIG composite exhibits superb electrochemical performance, owing to the inherent high porosity, abundant active sites, large specific surface area of ZIF-67, and the excellent conductive three-dimensional hierarchical porous network structure provided by LIG. In three-electrode system, ZIF-67/LIG composite electrode displays outstanding areal specific capacitance (CA) of 135.6 mF cm-2at a current density of 1 mA cm-2with 1 M Na2SO4aqueous electrolyte, which is far greater than that of pristine LIG (7.7 mF cm-2). Furthermore, the ZIF-67/LIG composite has been fabricated into an all-solid-state planar micro-supercapacitor (MSC). This ZIF-67/LIG MSC exhibits an impressiveCAof 38.1 mF cm-2at a current density of 0.20 mA cm-2, a good cycling stability of 80.3% capacitance retention after 3000 cycles, and a high energy density of 5.29µWh cm-2at a power density of 0.1 mW cm-2. All electrochemical results clearly manifest that as-prepared ZIF-67/LIG composite can be a candidate in energy storage field with exciting possibilities.

14.
Platelets ; 34(1): 2157806, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36597010

RESUMO

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.


What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 109/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.


Assuntos
Púrpura Trombocitopênica Idiopática , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Trombopoetina/efeitos adversos , Contagem de Plaquetas , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Hemorragia/induzido quimicamente
15.
J Clin Ultrasound ; 51(4): 624-627, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36807195

RESUMO

Aorto-pulmonary venous fistula combined with pulmonary arteriovenous fistula is a rare condition with an unknown incidence. We experienced a case of descending aorto-pulmonary venous fistula combined with a pulmonary arteriovenous fistula, which was treated with pulmonary arteriovenous fistula embolization and improved.


Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Humanos , Aorta Torácica/diagnóstico por imagem , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores
16.
Molecules ; 28(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138440

RESUMO

Currently, skin injuries have a serious impact on people's lives and socio-economic stress. Shikonin, a naphthoquinone compound derived from the root of the traditional Chinese medicine Shikonin, has favorable biological activities such as anti-inflammatory, antibacterial, immunomodulatory, anticancer, and wound-healing-promoting pharmacological activities. It has been reported that Shikonin can be used for repairing skin diseases due to its wide range of pharmacological effects. Moreover, the antimicrobial activity of Shikonin can play a great role in food and can also reduce the number of pathogenic bacteria in food. This paper summarizes the research on the pharmacological effects of Shikonin in recent years, as well as research on the mechanism of action of Shikonin in the treatment of certain skin diseases, to provide certain theoretical references for the clinical application of Shikonin, and also to provides research ideas for the investigation of the mechanism of action of Shikonin in other skin diseases.


Assuntos
Naftoquinonas , Dermatopatias , Humanos , Anti-Inflamatórios/farmacologia , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Medicina Tradicional Chinesa , Dermatopatias/tratamento farmacológico
17.
BMC Ophthalmol ; 22(1): 110, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260118

RESUMO

PURPOSE: To compare the efficacy and safety of subthreshold micropulse (STMP) laser photocoagulation and half-dose photodynamic therapy (PDT) in the treatment of acute central serous chorioretinopathy (CSC). METHODS: A total of 39 acute CSC patients were included. 18 patients were treated with STMP laser and 21 patients were treated with half-dose PDT. The main outcome measures were best-corrected visual acuity (BCVA) according to Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the proportion of eyes with complete resolution of subretinal fluid, the number of treatments, and the retinal sensitivity by microperimetry during the 12-month study period. RESULTS: The mean number of treatments during the 12-month period was 1.6 in STMP group and 1.3 in half-dose PDT group, respectively (P = 0.174). The proportion of eyes with complete resolution of subretinal fluid was 83.3% in STMP group compared with 90.5% in half-dose PDT group at 12-month (P = 0.647). The mean BCVA at 12-month after treatment was 75.28 ± 12.58 for STMP group and 76.62 ± 11.57 for half-dose PDT group, respectively (P = 0.731). No statistically significant difference was found in the mean retinal sensitivity between the two groups during the 12 months follow-up (P = 0.701 at 3 months; P = 0.725 at 6 months; P = 0.695 at 12 months). CONCLUSIONS: Subthreshold micropulse Laser Photocoagulation is as effective as half-dose PDT for acute CSC, while minimizing the damage effect on retinal.


Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Porfirinas , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/cirurgia , Doença Crônica , Angiofluoresceinografia , Humanos , Lasers , Fotocoagulação , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
18.
BMC Ophthalmol ; 22(1): 480, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482368

RESUMO

In this article, we answered the questions in Lei Gao et al.'s comments on the "effects of refractive accommodation on subfoveal choroidal thickness in silicone oil-filled eyes" one by one.


Assuntos
Óleos de Silicone , Humanos , Óleos de Silicone/efeitos adversos
19.
BMC Ophthalmol ; 22(1): 107, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248008

RESUMO

PURPOSE: To investigate the effects of refractive accommodation on subfoveal choroidal thickness (SFCT) in silicone oil (SO)-filled eyes. METHODS: This retrospective, self-comparative study was conducted on 40 patients with unilateral macula-on rhegmatogenous retinal detachment, who underwent vitrectomy and SO tamponade. The SFCT of SO-filled eyes and the fellow control eyes were measured using optical coherence tomography at their one-month visit after surgery. The patients wore soft contact positive lenses for 24 h in the SO-filled eyes, to correct their refractive error. SFCT and choroidal vascularity index (CVI) were measured before and after wearing the contact lenses. Mean SFCT was compared between SO-filled eyes and the fellow control eyes, and SFCT and CVI were compared before and after refractive error correction in the SO-filled eyes. RESULTS: Mean SFCT of SO-filled eyes (221.52 ± 38.41 um) was less than that of the fellow eyes (273.41 ± 31.30 um) (P < 0.001). After refractive error correction, the mean SFCT increased to 269.28 ± 36.90 um(P < 0.001). However, CVI decreased from 57.01 ± 2.41 to 55.39 ± 2.39 (P < 0.05). CONCLUSIONS: SFCT reduction in SO-filled eyes was primarily due to the hyperopia status. The non-uniform change in CVI suggests that changes in CT are mainly attributed to a greater expansion of the stromal area instead of the choroidal vascular area. TRIAL REGISTRATION: This study protocol was reviewed and approved by the Ethics Committee of the Central Theater General Hospital, approval number No. [2020]058-1, retrospectively registered.


Assuntos
Macula Lutea , Óleos de Silicone , Corioide/irrigação sanguínea , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
20.
J Clin Lab Anal ; 36(4): e24337, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35297094

RESUMO

BACKGROUND: The dysregulated expression of serum circular RNAs (circRNAs) has previously been linked to the prognosis of acute myeloid leukemia (AML) patients, but the clinical and prognostic relevance of serum hsa_circ_0079480 levels in this oncogenic setting have yet to be established. Herein, we assessed the putative prognostic relevance of circulating hsa_circ_0079480 levels in AML patient serum. METHODS: Serum was prepared from blood samples collected from 236 AML patients and 160 healthy controls, with hsa_circ_0079480 levels therein being quantified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) after which the clinical value of these levels was assessed. RESULTS: Acute myeloid leukemia patients were found to exhibit significant hsa_circ_0079480 upregulation in their serum as compared to serum from healthy controls, with such upregulation being most profound in individuals with M4/M5 type disease and to be more common in patients with poor cytogenic risk or high white blood cell counts. Receiver operating characteristic (ROC) curves demonstrated that serum hsa_circ_0079480 levels were able to effectively differentiate between patients with AML and healthy controls. Moreover, the upregulation of serum hsa_circ_0079480 was found to be closely related to clinicopathological findings and to be an independent predictor of reduced overall and relapse-free survival among individuals diagnosed with AML. Furthermore, serum hsa_circ_0079480 levels were markedly decreased after treatment in this patient population, with these levels being lower in patients that achieved complete remission as compared to those patients that did not. CONCLUSION: Levels of hsa_circ_0079480 in patient serum may offer value as a prognostic biomarker in AML.


Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Prognóstico , RNA Circular/genética , Curva ROC
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