Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 426
Filtrar
1.
Genome Biol ; 22(1): 288, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635147

RESUMO

High-throughput biological data analysis commonly involves identifying features such as genes, genomic regions, and proteins, whose values differ between two conditions, from numerous features measured simultaneously. The most widely used criterion to ensure the analysis reliability is the false discovery rate (FDR), which is primarily controlled based on p-values. However, obtaining valid p-values relies on either reasonable assumptions of data distribution or large numbers of replicates under both conditions. Clipper is a general statistical framework for FDR control without relying on p-values or specific data distributions. Clipper outperforms existing methods for a broad range of applications in high-throughput data analysis.

2.
Proc Natl Acad Sci U S A ; 118(41)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607956

RESUMO

Melanotic (Ml) is a mutation in chickens that extends black (eumelanin) pigmentation in normally brown or red (pheomelanin) areas, thus affecting multiple within-feather patterns [J. W. Moore, J. R. Smyth Jr, J. Hered. 62, 215-219 (1971)]. In the present study, linkage mapping using a back-cross between Dark Cornish (Ml/Ml) and Partridge Plymouth Rock (ml + /ml + ) chickens assigned Ml to an 820-kb region on chromosome 1. Identity-by-descent mapping, via whole-genome sequencing and diagnostic tests using a diverse set of chickens, refined the localization to the genomic region harboring GJA5 encoding gap-junction protein 5 (alias connexin 40) previously associated with pigmentation patterns in zebrafish. An insertion/deletion polymorphism located in the vicinity of the GJA5 promoter region was identified as the candidate causal mutation. Four different GJA5 transcripts were found to be expressed in feather follicles and at least two showed differential expression between genotypes. The results showed that Melanotic constitutes a cis-acting regulatory mutation affecting GJA5 expression. A recent study established the melanocortin-1 receptor (MC1R) locus and the interaction between the MC1R receptor and its antagonist agouti-signaling protein as the primary mechanism underlying variation in within-feather pigmentation patterns in chickens. The present study advances understanding the mechanisms underlying variation in plumage color in birds because it demonstrates that the activity of connexin 40/GJA5 can modulate the periodic pigmentation patterns within individual feathers.

3.
Mol Genet Genomics ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609588

RESUMO

Sex form is one of the most important characteristics in papaya cultivation in which hermaphrodite is the preferable form. Self-pollination of H*-TSS No.7, an inbred line derived from a rare X chromosome mutant SR*, produced all-hermaphrodite progeny. The recessive lethal allele controlling the all-hermaphrodite phenomenon was proposed to be the recessive Germination suppressor (gs) locus. This study employed next-generation sequencing technology and genome comparison to identify the candidate Gs gene. One specific gene, monodehydroascorbate reductase 4 (MDAR4) harboring a unique polymorphic 3 bp deletion in H*-TSS No.7 was identified. The function of MDAR4 is known to be involved in the hydrogen peroxide (H2O2) scavenging pathway and is associated with seed germination. Furthermore, MDAR4 showed higher expression in the imbibed seeds than that in the dry seeds indicating its potential role in the seed germination. Perhaps this is the very first report providing the evidences that MDAR4 is the candidate of Gs locus in H*-TSS No.7. In addition, Gs allele-specific markers were developed which would be facilitated for breeding all-hermaphrodite lines.

4.
Appl Environ Microbiol ; : AEM0175821, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613761

RESUMO

Nitroreductases (NTRs) catalyze the reduction of a wide range of nitro-compounds and quinones using NAD(P)H. Although the physiological functions of these enzymes remain obscure, a tentative function of resistance to reactive oxygen species (ROS) via the detoxification of menadione has been proposed. This suggestion is based primarily on the transcriptional or translational induction of an NTR response to menadione, rather than on convincing experimental evidence. We investigated the performance of a fungal NTR from Aspergillus nidulans (AnNTR) exposed to menadione, to address the question of whether NTR is really a ROS defense enzyme. We confirmed that AnNTR was transcriptionally induced by external menadione. We observed that menadione treatment generated cytotoxic levels of O2•-, which requires well-known antioxidant enzymes such as superoxide dismutase, catalase, and peroxiredoxin, to protect A. nidulans against menadione-derived ROS stress. However, AnNTR was counterproductive for ROS defense, since knocking out AnNTR decreased the intracellular O2•- levels, resulting in fungal viability higher than that of the wild type. This observation implies that AnNTR may accelerate the generation of O2•- from menadione. Our in vitro experiments indicated that AnNTR uses NADPH to reduce menadione in a single-electron reaction, and the subsequent semiquinone-quinone redox cycling resulted in O2•- generation. We demonstrated that A. nidulans nitroreductase should be a ROS generator, but not a ROS scavenger, in the presence of menadione. Our results clarified the relationship between nitroreductase and menadione-derived ROS stress, which has long been ambiguous. Importance Menadione is commonly used as an O2•- generator in studies into oxidative stress responses. However, the precise mechanism through which menadione mediates cellular O2•- generation, and the way in which cells respond, remains unclear. Elucidating these events will have important implications for the use of menadione in biological and medical studies. Our results show that the production of Aspergillus nidulans nitroreductase (AnNTR) was induced by menadione. However, the accumulated AnNTR did not protect cells, but instead increased the cytotoxic effect of menadione, through a single-electron reduction reaction. Our finding that nitroreductase is involved in the menadione-mediated O2•- generation pathway has clarified the relationship between nitroreductase and menadione-derived ROS stress, which has long been ambiguous.

5.
Front Immunol ; 12: 676919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594322

RESUMO

Introduction: Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN. Methods: One hundred IgAN patients with various proportions of crescents-24 with 1%-24%, 27 with 25%-49%, 21 with 50%-74% 12 with more than 75%, and 16 without crescents-were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry. Results: IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652-62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0-1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127-66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859-2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058-1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916-11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents. Conclusion: Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34609832

RESUMO

Li-rich Mn-based-layered oxides are considered to be the most felicitous cathode material candidates for commercial application of lithium-ion batteries on account of high energy density. Nevertheless, defects containing an unsatisfactory initial Coulombic efficiency and rapid voltage decay seriously impede their practical utilization. Herein, a coating layer with three distinct crystalline states are employed as a coating layer to modify Li[Li0.2Mn0.54Ni0.13Co0.13]O2, respectively, and the effects of coating layers with distinct crystalline states on the crystal structure, diffusion kinetics, and cell performance of host materials are further explored. A coating layer with high crystallinity enables mitigatory voltage decay and better cyclic stability of materials, while a coating layer with planar defects facilitates Li+ transfer and enhances the rate performance of materials. Consequently, optimizing the crystalline state of coating substances is critical for preferable surface modification.

7.
Biomed Pharmacother ; 144: 112298, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34649219

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.

8.
Cell Death Differ ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465890

RESUMO

Cells coordinate their behaviors with the mechanical properties of the extracellular matrix (ECM). Tumor cells frequently harbor an enhanced nucleotide synthesis, presumably to meet the increased demands for rapid proliferation. Nevertheless, how ECM rigidity regulates nucleotide metabolism remains elusive. Here we show that shift from stiff to soft matrix blunts glycolysis-derived nucleotide synthesis in tumor cells. Soft ECM results in TNF receptor-associated factor 2 (TRAF2)-dependent K29 ubiquitination and degradation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2. Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases. Further, non-phosphoryable or non-ubiquitinatable PRPS1/2 mutations maintain PRPS1/2 expression and nucleotide synthesis at low stiffness, and promote tumor growth and metastasis. Our findings demonstrate that PRPS1/2 stability and nucleotide metabolism is ECM rigidity-sensitive, and thereby highlight a regulatory cascade underlying mechanics-guided tumor metabolism reprogramming.

9.
Plant Cell Environ ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550608

RESUMO

The concentration and homeostasis of intracellular phosphate (Pi) are crucial for sustaining cell metabolism and growth. During short-term Pi starvation, intracellular Pi is maintained relatively constant at the expense of vacuolar Pi. After the vacuolar stored Pi is exhausted, the plant cells induce the synthesis of intracellular acid phosphatase (APase) to recycle Pi from expendable organic phosphate (Po). In this study, the expression, enzymatic activity and subcellular localization of ACID PHOSPHATASE 1 (OsACP1) were determined. OsACP1 expression is specifically induced in almost all cell types of leaves and roots under Pi stress conditions. OsACP1 encodes an acid phosphatase with broad Po substrates and localizes in the endoplasmic reticulum (ER) and Golgi apparatus (GA). Phylogenic analysis demonstrates that OsACP1 has a similar structure with human acid phosphatase PHOSPHO1. Overexpression or mutation of OsACP1 affected Po degradation and utilization, which further influenced plant growth and productivity under both Pi-sufficient and Pi-deficient conditions. Moreover, overexpression of OsACP1 significantly affected intracellular Pi homeostasis and Pi starvation signalling. We concluded that OsACP1 is an active acid phosphatase that regulates rice growth under Pi stress conditions by recycling Pi from Po in the ER and GA. This article is protected by copyright. All rights reserved.

10.
Regen Med ; 16(10): 949-962, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34585967

RESUMO

The stem cell origin theory of endometriosis (EMS) is a significant area of new research but the sources of this have yet to be adequately summarized. Existing treatments for EMS are commonly associated with a high recurrence rate; consequently, there is an urgent need to develop new therapeutic measures for the future treatment of this disease from the view of stem cells and gene therapy. Recently, we described the evidence for the potential sources of EMS stem cells and other key molecules participating in the establishment of lesions, and predict the miRNAs that target these key genes via bioinformatics analysis for further research. This review highlights the origin of EMS stem cells and potential therapy targets.

11.
Int J Pharm ; 608: 121059, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34474115

RESUMO

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.


Assuntos
Melanose , Palmitatos , Animais , Epiderme , Melanócitos , Melanose/tratamento farmacológico , Ratos , Pele
12.
Reprod Sci ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580843

RESUMO

High maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

13.
Top Curr Chem (Cham) ; 379(6): 37, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554348

RESUMO

Traditional drug discovery effectively contributes to the treatment of many diseases but is limited by high costs and long cycles. Quantitative structure-activity relationship (QSAR) methods were introduced to evaluate the activity of compounds virtually, which saves the significant cost of determining the activities of the compounds experimentally. Over the past two decades, many web tools for QSAR modeling with various features have been developed to facilitate the usage of QSAR methods. These web tools significantly reduce the difficulty of using QSAR and indirectly promote drug discovery. However, there are few comprehensive summaries of these QSAR tools, and researchers may have difficulty determining which tool to use. Hence, we systematically surveyed the mainstream web tools for QSAR modeling. This work may guide researchers in choosing appropriate web tools for developing QSAR models, and may also help develop more bioinformatics tools based on these existing resources. For nonprofessionals, we also hope to make more people aware of QSAR methods and expand their use.


Assuntos
Descoberta de Drogas , Internet , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade
14.
J Int Med Res ; 49(9): 3000605211042506, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34551611

RESUMO

Skin aging is an inevitable physiological process and periorbital wrinkling is an active sign of the process. Laser therapy is an effective method for improving periorbital wrinkles and wound care after laser therapy can accelerate the wound healing process. This case report describes a typical case of a 47-year-old male that presented with a 10-year history of gradually-worsening bilateral periorbital wrinkles. These were treated using a 2940 nm erbium (Er):YAG lattice laser combined with recombinant bovine basic fibroblast growth factor (bFGF) gel and hydrogel (HG) treatment on the left side of his face compared with laser therapy and bFGF gel on the right side of his face. HG combined with bFGF gel treatment after 2940 nm Er:YAG lattice laser therapy improved postoperative swelling and pigmentation compared with bFGF gel alone; and it promoted periorbital wrinkle improvement and wound healing. In conclusion, HG combined with GFs after laser therapy could be an alternative therapy for periorbital wrinkles.


Assuntos
Lasers de Estado Sólido , Envelhecimento da Pele , Animais , Bovinos , Érbio , Humanos , Hidrogéis , Lasers de Estado Sólido/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rejuvenescimento , Resultado do Tratamento , Cicatrização
15.
J Am Soc Nephrol ; 32(10): 2561-2578, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34479967

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most common primary GN worldwide. Circulating immune complexes form that are prone to deposition in the mesangium, where they trigger glomerular inflammation. A growing body of evidence suggests that dysregulated expression of microRNAs in IgAN may play a significant role in establishing the disease phenotype. METHODS: We generated single miR-23b-3p(miR-23b) knockout mice using CRISPR-Cas9. RESULTS: In humans, miR-23b levels are downregulated in kidney biopsies and sera of patients with IgAN, and serum miR-23b levels are negatively correlated with serum IgA1 levels. We show that miR-23b-/- mice develop an IgAN-like phenotype of mesangial IgA and C3 deposition associated with development of albuminuria, hypertension, an elevated serum creatinine, and dysregulated mucosal IgA synthesis. Dysregulation of IgA production is likely mediated by the loss of miR-23b-mediated suppression of activation-induced cytidine deaminase in mucosal B cells. In addition, we show that loss of miR-23b increases the susceptibility of the kidney to progressive fibrosis through loss of regulation of expression of gremlin 2 and IgA accumulation through downregulation of the transferrin receptor. CONCLUSIONS: Our findings suggest an indispensable role for miR-23b in kidney disease, and in particular, IgAN. miR-23b may in the future offer a novel therapeutic target for the treatment of IgAN.

16.
Nat Commun ; 12(1): 5285, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489442

RESUMO

The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been intensively studied in the past decade, the direct effects of their interaction on gene expression remain elusive. Here, we quantify the concurrence of DNA methylation and demethylation by the percentage of unmethylated CpGs within a partially methylated read from bisulfite sequencing. After verifying 'methylation concurrence' by its strong association with the co-localization of DNMT and TET enzymes, we observe that methylation concurrence is strongly correlated with gene expression. Notably, elevated methylation concurrence in tumors is associated with the repression of 40~60% of tumor suppressor genes, which cannot be explained by promoter hypermethylation alone. Furthermore, methylation concurrence can be used to stratify large undermethylated regions with negligible differences in average methylation into two subgroups with distinct chromatin accessibility and gene regulation patterns. Together, methylation concurrence represents a unique methylation metric important for transcription regulation and is distinct from conventional metrics, such as average methylation and methylation variation.


Assuntos
Metilação de DNA , Metilases de Modificação do DNA/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Genoma , Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Transcrição Genética , Animais , Cromatina/química , Cromatina/metabolismo , Ilhas de CpG , DNA/genética , DNA/metabolismo , Metilases de Modificação do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ontologia Genética , Histonas/genética , Histonas/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Anotação de Sequência Molecular , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Proto-Oncogênicas/metabolismo , Linfócitos T/citologia , Linfócitos T/metabolismo
17.
Cancer Sci ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533860

RESUMO

Melanoma is a fatal skin malignant tumor with a poor prognosis. We found that long noncoding RNA BASP1-AS1 is essential for the development and prognosis of melanoma. The methylation, RNA sequencing, copy number variation, mutation data, and sample follow-up information of melanoma from The Cancer Genome Atlas (TCGA) were analyzed using weighted gene co-expression network analysis and 366 samples common to the three omics were selected for multigroup clustering analysis. A four-gene prognostic model (BASP1-AS1, LOC100506098, ARHGAP27P1, and LINC01532) was constructed in the TCGA cohort and validated using the GSE65904 series. The expression of BASP1-AS1 was upregulated in melanoma tissues and various melanoma cell lines. Functionally, the ectopic expression of BASP1-AS1 promoted cell proliferation, migration, and invasion in both A375 and SK-MEL-2 cells. Mechanically, BASP1-AS1 interacted with YBX1 and recruited it to the promoter of NOTCH3, initiating its transcription process. The activation of the Notch signaling then resulted in the transcription of multiple oncogenes, including c-MYC, PCNA, and CDK4, which contributed to melanoma progression. Thus, BASP1-AS1 could act as a potential biomarker for cutaneous malignant melanoma.

18.
Global Spine J ; : 21925682211024556, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34569334

RESUMO

STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study. OBJECTIVES: There are few studies examining the balance between preventing venous thrombus embolism (VTE) and reducing blood loss in posterior/transforaminal lumbar interbody fusion (PLIF/TLIF) surgeries. This study aimed to evaluate the efficacy and safety of the combine application of TXA and rivaroxaban in patients undergoing PLIF/TLIF and explore relevant factors related to blood loss and VTE. METHODS: Patients in group A which was the control group received 0.9% NaCl solution intravenously. Group B was treated by an intravenous injection of 2 g tranexamic acid (TXA) and the local use of 1 g intraoperatively. Group C was treated the same as group B intraoperatively, and they received 10 mg rivaroxaban qd treatment postoperatively. Eligible patients with an Autar score ≤ 10 were randomly assigned to group A or group B. Patients with an Autar score >10 were allocated into group C. RESULTS: The intraoperative blood loss and postoperative drainage were lower in groups B and C than in group A (P < .001). The blood transfusion rate in group B was lower than that in group A (P < .001), while the incidence of VTE in group C was lower (P < .001). Four factors were found to be positively correlated with obvious total blood loss (P < .05). The data showed that 5 factors were correlated with the development of a thrombus (P < .1). CONCLUSIONS: The combination of TXA and rivaroxaban in PLIF/TLIF patients is safe and effective in reducing D-dimer levels associated with VTE and reducing blood loss.

19.
Leuk Lymphoma ; : 1-9, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587859

RESUMO

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has led to unprecedented results to date in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), yet its clinical application in elderly patients with R/R DLBCL remains somewhat limited. In this study, a total of 31 R/R DLBCL patients older than 65 years of age were enrolled and received humanized anti-CD19 CAR T-cell therapy. Patients were stratified into a fit, unfit, or frail group according to the comprehensive geriatric assessment (CGA). The fit group had a higher objective response (OR) rate (ORR) and complete response (CR) rate than that of the unfit/frail group, but there was no difference in the part response (PR) rate between the groups. The unfit/frail group was more likely to experience AEs than the fit group. The peak proportion of anti-CD19 CAR T-cells in the fit group was significantly higher than that of the unfit/frail group. The CGA can be used to effectively predict the treatment response, adverse events, and long-term survival.

20.
Epilepsy Behav ; 124: 108309, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536736

RESUMO

OBJECTIVE: This study investigated the long-term response and response patterns to antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: Patients who had been newly diagnosed with epilepsy and had at least 3-year follow-up records were enrolled. Their long-term response and response patterns to AEDs were retrospectively analyzed. Patients were divided into two groups, a controlled group and an uncontrolled group, according to whether 3-year seizure freedom (3YSF) was achieved. Multiple logistic regression analyses were used to identify risk factors associated with a poor drug response. RESULTS: Of the 472 patients with epilepsy, 180 achieved immediate seizure control, 36 achieved early seizure control, 118 achieved late seizure control, and 138 did not achieve 3YSF. Patients who achieved 3YSF (334/472, 70.8%) were categorized into the controlled group. Among them, 53.9% (180/334) achieved 3YSF immediately, 10.8% (36/334) achieved 3YSF within 6 months, and 35.3% (118/334) achieved 3YSF after 6 months. Also in this group, 228 (228/472, 48.3%), 84 (84/472, 17.8%), 15 (15/472, 3.2%), and 7 (7/472, 1.5%) patients achieved 3YSF on the first, second, third, and fourth regimen, respectively. Multivariate analyses showed that multiple seizure types (odds ratio [OR] = 3.903, 95% confidence interval [CI]: 2.098-7.264; P < 0.001] and polytherapy (OR = 5.093, 95% CI: 3.183-8.149; P < 0.001) were independent risk factors for a poor drug response. CONCLUSION: The 3YSF rate in this cohort was 70.8%. More than half of the patients achieved long-term remission immediately after treatment. The probability of attaining 3YSF decreased with the increase in number of drug regimens, especially in patients who experienced failure of two treatment regimens.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...