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1.
Front Biosci (Landmark Ed) ; 29(6): 216, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38940040

RESUMEN

The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.


Asunto(s)
Anticuerpos Biespecíficos , Mieloma Múltiple , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/inmunología , Humanos , Inmunoterapia/métodos , Antígenos de Neoplasias/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/inmunología
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124643, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38901233

RESUMEN

Herein, two simple fluorescent signal-on sensing strategies for detecting lead ions (Pb2+) were established based on structure-switching aptamer probes and exonuclease-assisted signal amplification strategies. Two hairpin-structure fluorescent probes with blunt-ended stem arms were designed by extending the base sequence of Pb2+ aptamer (PS2.M) and labelling the probes with FAM (in probe 1) and 2-aminopurine (2-AP) (in probe 2), respectively. In method 1, graphene oxide (GO) was added to adsorb probe 1 and quench the fluorescence emission of FAM to achieve low fluorescent background. In method 2, fluorescent 2-AP molecule inserted into the double-stranded DNA of probe 2 was quenched as a result of base stacking interactions, leading to a simplified, quencher-free approach. The addition of Pb2+ can induce the probes to transform into G-quadruplex structures, exposing single DNA strands at the 3' end (the extended sequences). This exposure enables the activation of exonuclease I (Exo I) on the probes, leading to the cleavage effect and subsequent release of free bases and fluorophores, thereby resulting in amplified fluorescence signals. The two proposed methods exhibit good specificity and sensitivity, with detection limits of 0.327 nM and 0.049 nM Pb2+ for method 1 and method 2, respectively, and have been successfully applied to detect Pb2+ in river water and fish samples. Both detection methods employ the structure-switching aptamer probes and can be completed in two or three steps without the need for complex analytical instruments. Therefore, they have a broad prospect in the sensitive and simple detection of lead ion contamination in food and environmental samples.

3.
Exp Hematol Oncol ; 13(1): 57, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796455

RESUMEN

Hematological malignancies (HMs) encompass a diverse group of blood neoplasms with significant morbidity and mortality. Immunotherapy has emerged as a validated and crucial treatment modality for patients with HMs. Despite notable advancements having been made in understanding and implementing immunotherapy for HMs over the past decade, several challenges persist. These challenges include immune-related adverse effects, the precise biodistribution and elimination of therapeutic antigens in vivo, immune tolerance of tumors, and immune evasion by tumor cells within the tumor microenvironment (TME). Nanotechnology, with its capacity to manipulate material properties at the nanometer scale, has the potential to tackle these obstacles and revolutionize treatment outcomes by improving various aspects such as drug targeting and stability. The convergence of nanotechnology and immunotherapy has given rise to nano-immunotherapy, a specialized branch of anti-tumor therapy. Nanotechnology has found applications in chimeric antigen receptor T cell (CAR-T) therapy, cancer vaccines, immune checkpoint inhibitors, and other immunotherapeutic strategies for HMs. In this review, we delineate recent developments and discuss current challenges in the field of nano-immunotherapy for HMs, offering novel insights into the potential of nanotechnology-based therapeutic approaches for these diseases.

4.
Neuroscience ; 551: 103-118, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38810691

RESUMEN

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

5.
Ann Med ; 56(1): 2338604, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38599340

RESUMEN

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.


There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Células Plasmáticas/patología , Pronóstico , Biomarcadores , Modelos de Riesgos Proporcionales
6.
Langmuir ; 40(16): 8730-8737, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38616350

RESUMEN

An elevated level of blood uric acid (UA) can cause the formation of kidney stones, gout, and other diseases. We recently isolated a few DNA aptamers that can selectively bind to UA. In this work, we investigated the adsorption of a UA aptamer and random sequence DNA onto sodium urate crystals. Both DNA strands adsorbed similarly to urate crystals. In addition, both the UA aptamer and random DNA can inhibit the growth of urate crystals, suggesting a nonspecific adsorption mechanism rather than specific aptamer binding. In the presence of 500 nM DNA, the growth of needle-like sodium urate crystals was inhibited, and the crystals appeared granular after 6 h. To understand the mechanism of DNA adsorption, a few chemicals were added to desorb DNA. DNA bases contributed more to the adsorption than the phosphate backbone. Surfactants induced significant DNA desorption. Finally, DNA could also be adsorbed onto real UA kidney stones. This study provides essential insights into the interactions between DNA oligonucleotides and urate crystals, including the inhibition of growth and interface effects of DNA on sodium urate crystals.

7.
Photobiomodul Photomed Laser Surg ; 42(5): 327-338, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38598279

RESUMEN

Objective: This article aims to review the safety and efficacy of the Er:YAG laser in debonding dental accessories. Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles published between 2010 and 2022 on the removal of dental accessories using erbium laser were searched. The selected articles were then classified according to the accessories used: adhesives, brackets, restorations, or implant crowns. Enamel surface roughness, shear bond strength, adhesive remnant index, duration time (t), pulp chamber temperature (T), morphology (M), and other variables were then noted. Results: The dental accessories and adhesives used were described along with the laser parameters used, such as frequency, pulse width, irradiation time, scanning mode, water-air cooling, and other variables. Conclusions: Laser removal using Er:YAG laser of dental accessories such as brackets, crowns, and veneers is fundamentally safe, time-saving, and does not cause damage to the enamel nor the underlying dentin. However, there was no distinct advantage with laser removal seen, such as those residual adhesives of brackets on the tooth surface and temporary adhesives of restorations.


Asunto(s)
Desconsolidación Dental , Láseres de Estado Sólido , Humanos , Láseres de Estado Sólido/uso terapéutico
8.
Int J Pharm ; 657: 124127, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38621611

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation.


Asunto(s)
Síndrome de Liberación de Citoquinas , Citocinas , Linfohistiocitosis Hemofagocítica , Macrófagos , Nanopartículas , Nitrilos , Pirazoles , Pirimidinas , Animales , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Pirazoles/administración & dosificación , Pirazoles/farmacología , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Ratones , Citocinas/metabolismo , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Modelos Animales de Enfermedad , Masculino , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/administración & dosificación , Humanos
9.
World J Gastrointest Surg ; 16(3): 790-806, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38577095

RESUMEN

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common medical emergency and early assessment of its outcomes is vital for treatment decisions. AIM: To develop a new scoring system to predict its prognosis. METHODS: In this retrospective study, 692 patients with UGIB were enrolled from two centers and divided into a training (n = 591) and a validation cohort (n = 101). The clinical data were collected to develop new prognostic prediction models. The endpoint was compound outcome defined as (1) demand for emergency surgery or vascular intervention, (2) being transferred to the intensive care unit, or (3) death during hospitalization. The models' predictive ability was compared with previously established scores by receiver operating characteristic (ROC) curves. RESULTS: Totally 22.2% (131/591) patients in the training cohort and 22.8% (23/101) in the validation cohort presented poor outcomes. Based on the stepwise-forward Logistic regression analysis, eight predictors were integrated to determine a new post-endoscopic prognostic scoring system (MH-STRALP); a nomogram was determined to present the model. Compared with the previous scores (GBS, Rockall, ABC, AIMS65, and PNED score), MH-STRALP showed the best prognostic prediction ability with area under the ROC curves (AUROCs) of 0.899 and 0.826 in the training and validation cohorts, respectively. According to the calibration curve, decision curve analysis, and internal cross-validation, the nomogram showed good calibration ability and net clinical benefit in both cohorts. After removing the endoscopic indicators, the pre-endoscopic model (pre-MH-STRALP score) was conducted. Similarly, the pre-MH-STRALP score showed better predictive value (AUROCs of 0.868 and 0.767 in the training and validation cohorts, respectively) than the other pre-endoscopic scores. CONCLUSION: The MH-STRALP score and pre-MH-STRALP score are simple, convenient, and accurate tools for prognosis prediction of UGIB, and may be applied for early decision on its management strategies.

10.
Front Immunol ; 15: 1346211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464531

RESUMEN

Multiple myeloma is the second most common malignant hematologic malignancy which evolved different strategies for immune escape from the host immune surveillance and drug resistance, including uncontrolled proliferation of malignant plasma cells in the bone marrow, genetic mutations, or deletion of tumor antigens to escape from special targets and so. Therefore, it is a big challenge to efficiently treat multiple myeloma patients. Despite recent applications of immunomodulatory drugs (IMiDS), protease inhibitors (PI), targeted monoclonal antibodies (mAb), and even hematopoietic stem cell transplantation (HSCT), it remains hardly curable. Summarizing the possible evasion strategies can help design specific drugs for multiple myeloma treatment. This review aims to provide an integrative overview of the intrinsic and extrinsic evasion mechanisms as well as recently discovered microbiota utilized by multiple myeloma for immune evasion and drug resistance, hopefully providing a theoretical basis for the rational design of specific immunotherapies or drug combinations to prevent the uncontrolled proliferation of MM, overcome drug resistance and improve patient survival.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Médula Ósea/patología , Anticuerpos Monoclonales/uso terapéutico , Células Plasmáticas/patología , Inmunoterapia
11.
Biosens Bioelectron ; 251: 116089, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354496

RESUMEN

Benefiting from specific target recognition and trans-cleavage capabilities, the CRISPR/Cas12a system has great application prospects in the design of highly sensitive and rapid fluorescence biosensors. The CRISPR/Cas12a-based fluorophore-quencher molecular beacons exhibit single-color emission and are easily exposed to interference from environmental factors. Herein, we design a CRISPR/Cas12a-derived ratiometric fluorescence sensor for Pb2+ detection based on embedded carbon dots@zeolitic imidazolate framework-8 (CDs@ZIF-8) composites and DNAzyme. The functions of ZIF-8 about encapsulating red emissive CDs in the inner cavity and adsorbing DNA on the outer surface are integrated to establish dual fluorescence signals, thereby reducing the possibility of interference and improving sensing accuracy. The presence of Pb2+ is converted into the change of activator by the GR5 DNAzyme to activate the CRISPR/Cas12a system, which provides signal amplification through multiple turnovers of side branch cutting, achieving highly sensitive detection of Pb2+ with a low detection limit of 18 pM. This method has the advantages of simplicity, universality, and excellent quantitative ability, and has broad prospects in sensing applications.


Asunto(s)
Técnicas Biosensibles , Radioisótopos de Carbono , ADN Catalítico , Sistemas CRISPR-Cas , Plomo
13.
Hepatol Int ; 18(2): 673-687, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37332023

RESUMEN

INTRODUCTION: We aimed to determine the diagnostic criteria of myosteatosis in a Chinese population and investigate the effect of skeletal muscle abnormalities on the outcomes of cirrhotic patients. METHODS: Totally 911 volunteers were recruited to determine the diagnostic criteria and impact factors of myosteatosis, and 480 cirrhotic patients were enrolled to verify the value of muscle alterations for prognosis prediction and establish new noninvasive prognostic strategies. RESULTS: Multivariate analysis showed age, sex, weight, waist circumference, and biceps circumference had a remarkable influence on the L3 skeletal muscle density (L3-SMD). Based on the cut-off of a mean - 1.28 × SD among adults aged < 60 years, the diagnostic criteria for myosteatosis was L3-SMD < 38.93 Hu in males and L3-SMD < 32.82 Hu in females. Myosteatosis rather than sarcopenia has a close correlation with portal hypertension. The concurrence of sarcopenia and myosteatosis not only is associated with poor liver function but also evidently reduced the overall and liver transplantation-free survival of cirrhotic patients (p < 0.001). According to the stepwise Cox regression hazard model analysis, we established nomograms including TBil, albumin, history of HE, ascites grade, sarcopenia, and myosteatosis for easily determining survival probabilities in cirrhotic patients. The AUC is 0.874 (95% CI 0.800-0.949) for 6-month survival, 0.831 (95% CI 0.764-0.898) for 1-year survival, and 0.813 (95% CI 0.756-0.871) for 2-year survival prediction, respectively. CONCLUSIONS: This study provides evidence of the significant correlation between skeletal muscle alterations and poor outcomes of cirrhosis, and establishes valid and convenient nomograms incorporating musculoskeletal disorders for the prognostic prediction of liver cirrhosis. Further large-scale prospective studies are necessary to verify the value of the nomograms.


Asunto(s)
Sarcopenia , Masculino , Adulto , Femenino , Humanos , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Estudios Prospectivos , Músculo Esquelético/patología , Cirrosis Hepática/patología , Pronóstico , Estudios Retrospectivos
14.
Int Immunopharmacol ; 126: 111277, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38061120

RESUMEN

BACKGROUND: Infection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. METHODS: A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. RESULTS: After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum ß2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. CONCLUSION: In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention.


Asunto(s)
Mieloma Múltiple , Nomogramas , Humanos , Pronóstico , Mieloma Múltiple/diagnóstico , Estudios Retrospectivos , Albúminas
15.
Cancer Lett ; 580: 216486, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37984724

RESUMEN

Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor.


Asunto(s)
Mieloma Múltiple , Animales , Humanos , Ratones , Línea Celular Tumoral , Ribonucleoproteína Heterogénea-Nuclear Grupo U , Hidrazinas/farmacología , Carioferinas/genética , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , ARN , Proteínas de Unión al ARN/genética
16.
Ann Med ; 55(2): 2263019, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37983471

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) is one of the most common and severe complications of multiple myeloma (MM). The aim of this study was to learn about the current awareness regarding MM-associated VTE among Chinese hematologists. METHODS: A nationwide, online, questionnaire-based survey was sent to the specialized hematologists in mainland China. The questionnaire investigated respondents' demographic and occupational characteristics, their ability to identify VTE risk factors, and their thromboprophylaxis decisions for different anti-MM regimens. Six clinical vignettes were used to evaluate hematologists' awareness of stratified thromboprophylaxis. The data were analyzed using SPSS software. RESULTS: A total of 518 valid questionnaires were received. Of the 518 hematologists investigated, only 23.7% of them could identify VTE-related risk factors correctly. Most hematologists could select appropriate thromboprophylaxis for common anti-MM regimens such as VCd (bortezomib, cyclophosphamide, and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone), but not for uncommon ones such as VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) and KRd (carfilzomib, lenalidomide, and dexamethasone). The results from the vignettes suggested that only 19.5% of the hematologists could be defined as the 'stratified thromboprophylaxis' group, and the awareness of stratified thromboprophylaxis depended significantly on physicians' age and working seniority. CONCLUSION: The results of our study showed that a large proportion of Chinese hematologists failed to recognize the VTE risk factors, most of them cannot select appropriate thromboprophylaxis for different MM therapeutic regimens and lack awareness of stratified thromboprophylaxis for MM-associated VTE. A standard VTE prevention guideline is urgently needed for the Chinese myeloma group. Continuous education for new professionals should be encouraged. A VTE collaborative group is supposed to be established in each hospital to enhance the overall medical care for VTE patients.


The substantial myeloma patient population and extensive use of immunomodulatory drugs indicate that MM-associated VTE deserves more attention in China.The results from our cross-sectional study showed that a significant proportion of Chinese hematologists failed to identify the VTE risk factors, most of them cannot select appropriate thromboprophylaxis for different MM therapeutic regimens and lack awareness of stratified thromboprophylaxis for MM-associated VTE.


Asunto(s)
Mieloma Múltiple , Tromboembolia Venosa , Humanos , Mieloma Múltiple/complicaciones , Lenalidomida/uso terapéutico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Bortezomib/uso terapéutico , Anticoagulantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico
18.
Asian J Psychiatr ; 90: 103800, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37898099

RESUMEN

To reveal the exact changes of allopregnanolone-mediated γ-aminobutyric acid A receptor pathways and its specific therapeutic targets by Shuyu Capsule treating premenstrual depression, female Wistar rat models of premenstrual depression was established by Forced swimming test (FST). Behavioral tests, enzyme-linked immunosorbent assay (ELISA), interference knockdown adenovirus, and overexpressed vector adenovirus of GABAARδ, RT-qPCR, Western-Blot, and immunohistochemical detecting expressions were applied to identify the therapeutic targets. FST-based rat model indicated that Shuyu capsules alleviated typical premenstrual depression and may regulate alternations of 5α-reductase and 3α-steroid dehydrogenase, enhancing the metabolic pathway of progesterone to allopregnanolone, as well as targeting the GABAARδ subunit, thereby alleviating premenstrual depression of PMDD rat models.


Asunto(s)
Pregnanolona , Receptores de GABA-A , Ratas , Femenino , Animales , Ratas Wistar , Pregnanolona/metabolismo , Pregnanolona/uso terapéutico , Hipocampo/metabolismo , Ácido gamma-Aminobutírico , Redes y Vías Metabólicas
19.
RSC Adv ; 13(45): 31353-31364, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37901263

RESUMEN

The leaf-like zeolitic imidazolate framework (ZIF-L) is a promising porous nanomaterial that has attracted increasing attention as an ideal host material to encapsulate functional fluorescent nanoparticles for designing fluorescent sensors. However, owing to the large particle size, gravity readily facilitates the precipitation of the ZIF-L from the aqueous solution, and thus lead to imperfect experimental results. Herein, we report a simple and rapid synthetic method which uses the polyethyleneimine (PEI)-modified ZIF-L as a host to solve the precipitation problem and construct a dual-emitting system that combines its fluorescence with carbon dots (CDs). Furthermore, CDs@ZIF-L/PEI with dual-emitting centres could be utilised as a ratio fluorescence sensor to detect Hg2+ ions. The sensor exhibited excellent dispersibility and good selectivity for sensing Hg2+ ions, with a limit of detection (LOD) of 14.5 nM. Furthermore, experimental results reveal that the CDs@ZIF-L/PEI fluorescent sensor could be effectively dispersed into agarose and less polar organic solvents such as DMF, MeOH, EtOH and CH3CN, expanding the application scope of the fluorescent sensor.

20.
J Environ Sci (China) ; 134: 44-54, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37673532

RESUMEN

A series of nano-photocatalysts metal-organic frameworks (MOFs)/graphitic carbon nitride (CN) (named MOFCN-x) with high activity have been synthesized by in-situ growth method. Under visible light irradiation, MOFCN-x hybrids show enhanced photocatalytic activity for the debromination of polybromodiphenyl ethers (PBDEs) compared with CN. Among all the hybrids, MOFCN-2 shows the highest reaction rate, which is 3.3 times as high as that in CN. MOFCN-x photocatalysts own stable visible light activity after recycled experiment. It indicates that a moderate amount of MOFs in MOFCN-x can largely enhance the photocatalytic ability by improved visible light absorption, larger specific surface area and better photo-generated charge carriers separation and transfer capabilities. More interestingly, the debromination pathway of PBDEs by MOFCN-x shows obvious selectivity compared with pure CN that bromines at meta-positions are much more susceptible than those at the para- and ortho-positions. The possible photoreductive mechanism has been proposed. This study shows that nanocomposite MOFCN can be an excellent candidate for dealing with halogen pollutants by solar-driven.


Asunto(s)
Contaminantes Ambientales , Estructuras Metalorgánicas , Éteres Difenilos Halogenados , Luz , Halógenos
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