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1.
Ultrason Sonochem ; 103: 106773, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244247

RESUMO

The use of a resin to selectively separate thiomolybdate from a tungsten (W) feed solution is a well-known protocol for achieve high-purity W products; however, the regeneration of saturated resin is laborious. In this study, poly(diallyl dimethyl ammonium chloride) (PDADMA) was used to modify ultrasound-pretreated montmorillonite (Mt) for W and molybdenum (Mo) separation for the first time, and the resultant tetrathiomolybdate (MoS42-)-loaded composite was further tested to remove heavy metals instead of regeneration. Among the three variables of ultrasound pretreatment, that is, Mt concentration, ultrasound power, and treatment time, the Mt concentration exhibited the most significant influence followed by ultrasound power on the separation performance of W and Mo. Compared to the distance of the interlayer space and the surface charge of the modified Mt, the PDADMA content showed a closer correlation with the W/Mo separation coefficient. Assisted by Box-Behnken design, with Mt concentration of 6.9 g/L, ultrasound power of 593.8 W, and treatment time of 13.8 min, the composite with the greatest separation coefficient was obtained. The adsorption of Cu(II) on the optimal W/Mo separation-derived composite was ascribed to the formation of Cu-S complexes, while that of Pb(II) was attributed to complexation and surface precipitation. In contrast, ion exchange with the initially loaded anions, reduction by sulfide to Cr(III), and formation of Cr(III)-S complexes accounted for Cr(VI) removal. The adsorption of Cu(II) and Pb(II) equilibrated faster and showed higher acid-resistance than that of Cr(VI). The adsorption capacities for Cu(II), Pb(II), and Cr(VI) were 0.535, 1.398, and 0.882 mmol/g, respectively. Applying PDADMA to modify Mt as a reagent for W/Mo separation was feasible, and the derived composite was capable of removing cationic and anionic heavy metals.

2.
Nat Microbiol ; 8(5): 934-945, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37012420

RESUMO

Clonal bacterial populations rely on transcriptional variation across individual cells to produce specialized states that increase fitness. Understanding all cell states requires studying isogenic bacterial populations at the single-cell level. Here we developed probe-based bacterial sequencing (ProBac-seq), a method that uses libraries of DNA probes and an existing commercial microfluidic platform to conduct bacterial single-cell RNA sequencing. We sequenced the transcriptome of thousands of individual bacterial cells per experiment, detecting several hundred transcripts per cell on average. Applied to Bacillus subtilis and Escherichia coli, ProBac-seq correctly identifies known cell states and uncovers previously unreported transcriptional heterogeneity. In the context of bacterial pathogenesis, application of the approach to Clostridium perfringens reveals heterogeneous expression of toxin by a subpopulation that can be controlled by acetate, a short-chain fatty acid highly prevalent in the gut. Overall, ProBac-seq can be used to uncover heterogeneity in isogenic microbial populations and identify perturbations that affect pathogenicity.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Transcriptoma , Análise de Sequência de RNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
3.
Bioact Mater ; 23: 526-538, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36514389

RESUMO

Drug-eluting balloon (DEB) angioplasty has emerged as an effective treatment for cardiovascular and cerebrovascular diseases. However, distal embolism and late lumen restenosis could be caused by drug loss during DEB handling and rapid drug metabolization. Here, a drug-loaded balloon equipped with tip-separable microneedles on the balloon surface (MNDLB) was developed. Inbuilt near-infrared (NIR) ring laser inside the catheter inner shaft was introduced to activate the biodegradable microneedle tips for the first time. The drug-loaded tips thus could be embedded in the vasculature and then released antiproliferative drug - paclitaxel slowly via polymer degradation for more than half a year. A significant increase in drug delivery efficiency and superior therapeutic effectiveness compared with the standard DEB were demonstrated using an atherosclerosis rabbit model.

4.
Biosens Bioelectron ; 222: 114921, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36521205

RESUMO

Neutrophil recruitment to the inflamed endothelium is a multistep process and is of utmost importance in the development of the hallmark vaso-occlusive crisis in sickle cell disease (SCD). However, there lacks a standardized, clinically feasible approach for assessing neutrophil recruitment to the inflamed endothelium for individualized risk stratification and therapeutic response prediction in SCD. Here, we describe a microfluidic device functionalized with E-selectin, a critical endothelial receptor for the neutrophil recruitment process, as a strategy to assess neutrophil binding under physiologic flow in normoxia and clinically relevant hypoxia in SCD. We show that hypoxia significantly enhances neutrophil binding to E-selectin and promotes the formation of neutrophil-platelet aggregates. Moreover, we identified two distinct patient populations: a more severe clinical phenotype with elevated lactate dehydrogenase levels and absolute reticulocyte counts but lowered fetal hemoglobin levels associated with constitutively less neutrophil binding to E-selectin. Mechanistically, we demonstrate that the extent of neutrophil activation correlates with membrane L-selectin shedding, resulting in the loss of ligand interaction sites with E-selectin. We also show that inhibition of E-selectin significantly reduces leukocyte recruitment to activated endothelial cells. Our findings add mechanistic insight into neutrophil-endothelial interactions under hypoxia and provide a clinically feasible means for assessing neutrophil binding to E-selectin using clinical whole blood samples, which can help guide therapeutic decisions for SCD patients.


Assuntos
Anemia Falciforme , Técnicas Biossensoriais , Humanos , Selectina E/uso terapêutico , Células Endoteliais/metabolismo , Infiltração de Neutrófilos , Adesão Celular , Endotélio/metabolismo , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/metabolismo , Dispositivos Lab-On-A-Chip , Hipóxia
5.
Ther Apher Dial ; 27(3): 540-551, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36461764

RESUMO

INTRODUCTION: Studies focusing on catheter removal and the pathogenic spectrum of peritoneal dialysis-associated peritonitis (PDAP) need to be updated. METHODS: Data were collected from four peritoneal dialysis (PD) centers. Peritonitis rates were compared using Poisson regression and Logistic regression was used to examine the risk factors for catheter removal. RESULTS: The PD duration (odds ratio [OR], 1.021; 95% confidence interval [CI], 1.010-1.032), number of previous PDAP episodes (OR, 1.267; 95% CI, 1.039-1.545), dialysate white cell count >100 × 106 /L on Day 5 of PDAP (OR, 6.088; 95% CI, 3.277-11.312), Pseudomonas aeruginosa (OR, 4.122; 95% CI, 1.071-15.874) and polymicrobial infections (OR, 3.257; 95% CI, 1.519-6.982) were independent predictors of catheter removal (p < 0.05). The prevalence of polymicrobial peritonitis and fungal peritonitis has increased (p < 0.05). CONCLUSION: Attention should be paid to patients with long PD duration or a history of previous episodes of PDAP characteristics.


Assuntos
Diálise Peritoneal , Peritonite , Humanos , Estudos Retrospectivos , Diálise Peritoneal/efeitos adversos , Fatores de Risco , Peritonite/epidemiologia , Peritonite/etiologia , Peritonite/tratamento farmacológico , Catéteres/efeitos adversos
6.
J Mater Chem B ; 10(38): 7836-7846, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36070240

RESUMO

Acute limb ischemia (ALI) is the most severe manifestation of peripheral artery disease, accompanied by pH/temperature-microenvironment changes in two different phases. In the acute phase, temperature and pH are significantly decreased, and reactive oxygen species (ROS) are excessively generated owing to the sharp reduction of blood perfusion. Afterwards, in the chronic phase, although the temperature gradually recovers, angiogenesis is delayed due to chronic vascular injury, skeletal muscle cell apoptosis and endothelial cell dysfunction. Current therapeutic strategies mainly focus on recanalization; however, their effects on scavenging ROS in the acute phase and promoting angiogenesis in the chronic phase are quite limited. Herein, an injectable pH and temperature dual-responsive poloxamer 407 (PF127)/hydroxymethyl cellulose (HPMC)/sodium alginate (SA)-derived hydrogel (FHSgel), encapsulating melatonin and diallyl trisulfide-loaded biodegradable hollow mesoporous silica nanoparticles (DATS@dHMSNs), is developed, which can intelligently respond to the different phases of ALI. In the acute phase of ischemia, the decreased pH results in the rapid release of melatonin to scavenge excessive ischemia-induced ROS. On the other hand, in the chronic repair phase, the recovered temperature triggers the sustained release of DATS@dHMSNs from the FHSgel, thus generating hydrogen sulfide (H2S) to enhance the angiogenesis and microcirculation reconstruction of ischemic limbs.


Assuntos
Sulfeto de Hidrogênio , Melatonina , Alginatos/uso terapêutico , Compostos Alílicos , Celulose , Preparações de Ação Retardada/uso terapêutico , Humanos , Hidrogéis/uso terapêutico , Sulfeto de Hidrogênio/farmacologia , Concentração de Íons de Hidrogênio , Isquemia/tratamento farmacológico , Poloxâmero/uso terapêutico , Espécies Reativas de Oxigênio , Dióxido de Silício/uso terapêutico , Sulfetos
7.
Front Endocrinol (Lausanne) ; 13: 936573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909563

RESUMO

Background: The optimal break-in period (BI) of urgent-start peritoneal dialysis (USPD) initiation for patients with end-stage renal disease (ESRD) and diabetes is unclear. We aimed to explore the safety and applicability of a BI ≤24 h in patients with ESRD and diabetes. Methods: We used a retrospective cohort design wherein we recruited patients with ESRD and diabetes who underwent USPD at five institutions in China between January 2013 and August 2020. The enrolled patients were grouped according to BI. The primary outcomes were mechanical and infectious complication occurrences, whereas the secondary outcome was technique survival. Results: We enrolled 310 patients with diabetes, of whom 155 and 155 patients were in the BI ≤24 h and BI >24 h groups, respectively. The two groups showed a comparable incidence of infectious and mechanical complications within 6 months after catheter insertion (p>0.05). Logistic regression analysis revealed that a BI ≤24 h was not an independent risk factor for mechanical or infectious complications. Kaplan-Meier estimates showed no statistically significant between-group differences in technique survival rates (p>0.05). Cox multivariate regression analysis revealed that a BI ≤24 h was not an independent risk factor for technique failure. Conclusion: USPD initiation with a BI ≤24 h may be safe and feasible for patients with ESRD and diabetes.


Assuntos
Diabetes Mellitus , Falência Renal Crônica , Diálise Peritoneal , Humanos , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Estudos Retrospectivos , Fatores de Tempo
8.
Bioact Mater ; 18: 91-103, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387173

RESUMO

Thromboembolism is the leading cause of cardiovascular mortality. Currently, for the lack of targeting, short half-life, low bioavailability and high bleeding risk of the classical thrombolytic drugs, pharmacological thrombolysis is usually a slow process based on micro-pumping. In addition, frequently monitoring and regulating coagulation functions are also required during (and after) the process of thrombolysis. To address these issues, a targeted thrombolytic and anticoagulation nanoplatform (UCATS-UK) is developed based on upconversion nanoparticles (UCNPs) that can convert 808 or 980 nm near-infrared (NIR) light into UV/blue light. This nanoplatform can target and enrich in the thrombus site. Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase (UK) and nitric oxide (NO). Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform. Combined with the unique fluorescent imaging capability of UCNPs, this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging, diagnosis and treatment.

9.
Ren Fail ; 44(1): 450-460, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35272577

RESUMO

PURPOSE: Urgent start peritoneal dialysis (USPD) is an effective therapeutic method for end-stage renal disease (ESRD). However, whether it is safe to initiate peritoneal dialysis (PD) within 24 h unclear. We examined the short-term outcomes of a break-in period (BI) of 24 h for patients undergoing USPD. METHODS: This real-world, multicenter, retrospective cohort study evaluated USPD patients from five centers from January 2013 to August 2020. Patients were divided into BI ≤ 24 h or BI > 24 h groups. The Primary outcomes included incidence of mechanical and infectious complications. The secondary outcome was technique failure. Moreover, we presented a subgroup analysis for patients who did not receive temporary hemodialysis (HD). RESULTS: A total of 871 USPD patients were included: 470 in the BI ≤ 24 h and 401 in the BI > 24 h groups. Mechanical and infectious complications did not differ between the two groups across the follow-up timepoints (2 weeks, 1 month, 3 months, and 6 months) (p > 0.05). Multiple logistic regression analysis revealed that BI ≤ 24 h was not an independent risk factor for mechanical complications, catheter migration, or infectious complications (p > 0.05). A BI ≤ 24 h was not an independent significant risk factor for technique failure by multivariate Cox regression analysis (p > 0.05). The subgroup analysis of patients who did not receive temporary HD returned the same results. CONCLUSION: Initiating PD within 24 h of catheter insertion was not associated with increased mechanical complications, infectious complications, or technique failures.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Adulto , China , Estudos de Viabilidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
10.
Elife ; 112022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35088712

RESUMO

During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm (PM) development such as the human segmentation clock in vitro using human pluripotent stem cells (hPSCs); however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human PM organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological, and functional features of PM development, including formation of somite-like structures in vitro. Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA-sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their in vivo counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spine development and disease in vitro.


Humans are part of a group of animals called vertebrates, which are all the animals with backbones. Broadly, all vertebrates have a similar body shape with a head at one end and a left and right side that are similar to each other. Although this is not very obvious in humans, vertebrate bodies are derived from pairs of segments arranged from the head to the tail. Each of these segments or somites originates early in embryonic development. Cells from each somite then divide, grow and specialize to form bones such as the vertebrae of the vertebral column, muscles, skin, and other tissues that make up each segment. Studying different animals during embryonic development has provided insights into how somites form and grow, but it is technically difficult to do and only provides an approximate model of how somites develop in humans. Being able to make and study somites using human cells in the lab would help scientists learn more about how somite formation in humans is regulated. Budjan et al. grew human stem cells in the lab as three-dimensional structures called organoids, and used chemical signals similar to the ones produced in the embryo during development to make the cells form somites. Various combinations of signals were tested to find the best way to trigger somite formation. Once the somites formed, Budjan et al. measured them and studied their structure and the genes they used. They found that these lab-grown somites have the same size and structure as natural somites and use many of the same genes. This new organoid model provides a way to study human somite formation and development in the lab for the first time. This can provide insights into the development and evolution of humans and other animals that could then help scientists understand diseases such as the development of abnormal spinal curvature that affects around 1 in 10,000 newborns.


Assuntos
Células-Tronco Pluripotentes , Somitos , Animais , Diferenciação Celular , Humanos , Mesoderma , Organoides
11.
Exp Hematol ; 107: 14-19, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34921959

RESUMO

The JAK2-V617F mutation is the most common cause of myeloproliferative neoplasms. Although experiments have revealed that this gain-of-function mutation is associated with myeloid blood cell expansion and increased production of white cells, red cells, and platelets, the transcriptional consequences of the JAK2-V617F mutation in different cellular compartments of the bone marrow have not yet been fully elucidated. To study the direct effects of JAK2-V617F on bone marrow cells in patients with myeloproliferative neoplasms, we performed joint single-cell RNA sequencing and JAK2 genotyping on CD34+-enriched cells from eight patients with newly diagnosed essential thrombocythemia or polycythemia vera. We found that the JAK2-V617F mutation increases the expression of interferon-response genes (e.g., HLAs) and the leptin receptor in hematopoietic progenitor cells. Furthermore, we sequenced a population of CD34- bone marrow monocytes and found that the JAK2 mutation increased expression of intermediate monocyte genes and the fibrocyte-associated surface protein SLAMF7 in these cells.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Células da Medula Óssea/metabolismo , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Trombocitemia Essencial/genética
12.
IEEE Trans Pattern Anal Mach Intell ; 44(1): 50-62, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32750808

RESUMO

Rendering bridges the gap between 2D vision and 3D scenes by simulating the physical process of image formation. By inverting such renderer, one can think of a learning approach to infer 3D information from 2D images. However, standard graphics renderers involve a fundamental step called rasterization, which prevents rendering to be differentiable. Unlike the state-of-the-art differentiable renderers (Kato et al. 2018 and Loper 2018), which only approximate the rendering gradient in the backpropagation, we propose a natually differentiable rendering framework that is able to (1) directly render colorized mesh using differentiable functions and (2) back-propagate efficient supervisions to mesh vertices and their attributes from various forms of image representations. The key to our framework is a novel formulation that views rendering as an aggregation function that fuses the probabilistic contributions of all mesh triangles with respect to the rendered pixels. Such formulation enables our framework to flow gradients to the occluded and distant vertices, which cannot be achieved by the previous state-of-the-arts. We show that by using the proposed renderer, one can achieve significant improvement in 3D unsupervised single-view reconstruction both qualitatively and quantitatively. Experiments also demonstrate that our approach can handle the challenging tasks in image-based shape fitting, which remain nontrivial to existing differentiable renders.

13.
STAR Protoc ; 2(3): 100673, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34337442

RESUMO

In many biological applications, the readout of somatic mutations in individual cells is essential. For example, it can be used to mark individual cancer cells or identify progenies of a stem cell. Here, we present a protocol to perform single-cell RNA-seq and single-cell amplicon-seq using 10X Chromium technology. Our protocol demonstrates how to (1) isolate CD34+ progenitor cells from human bone marrow aspirate, (2) prepare single-cell amplicon libraries, and (3) analyze the libraries to assign somatic mutations to individual cells. For complete details on the use and execution of this protocol, please refer to Van Egeren et al. (2021).


Assuntos
Mutação , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Antígenos CD34 , Células da Medula Óssea/fisiologia , Primers do DNA , Biblioteca Gênica , Humanos
14.
Medicine (Baltimore) ; 100(19): e25345, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106586

RESUMO

ABSTRACT: This study explored the effect of percutaneous intervertebral foraminoscopic discectomy (PIFD) in the treatment of lumbar disc herniation (LDH).This retrospective study collected a total of 88 patient cases for inclusion. Epidemiological and clinical data of patients with LDH at the First Affiliated Hospital of Jiamusi University between May 2017 and January 2020 were retrospectively analyzed. Of those, 44 patients received PIFD and were allocated to an intervention group. The other 44 patients administrated fenestration discectomy (FD), and were assigned to a control group. We compared surgery time (minute), incision length (cm), duration of hospital stay after surgery (day), pain intensity (as checked by Visual Analogue Scale (VAS), health-related quality of life (as examined by Oswestry Disability Index, ODI), and complications between 2 groups.There were not significant differences in surgery time (minute) (P = .56), VAS (P = .33) and ODI (P = .46) after surgery between 2 groups. However, there were significant differences in incision size (cm) (P < .01) and length of hospital stay (day) (P < .01) after surgery between 2 groups. When compared before the surgery, patients in both groups had significant improvements in VAS (P < .01) and ODI (P < .01) after the surgery. Moreover, both groups had similar safety profiles (P > .05).The findings of this study showed that both PIFD and FD benefit patients with LDH. However, PIFD can benefit patients more than FD in the incision size and duration of hospital stay after surgery.


Assuntos
Discotomia Percutânea , Endoscopia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Qualidade de Vida , Estudos Retrospectivos , Canal Medular , Resultado do Tratamento
15.
Biomacromolecules ; 22(6): 2718-2728, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34081446

RESUMO

Modifying the side chain of poly(meth)acrylate with moieties originating from biocompatible polymers can be an effective method for developing novel blood-compatible polymers. Inspired by biocompatible poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx), four water-soluble poly(tertiary amide acylate) analogues bearing a pendant tertiary amide were synthesized. The results of hemolysis and cell viability tests showed that all the poly(tertiary amide acylate) analogues were compatible with red blood cells, HeLa cells, and normal human dermal fibroblasts as PMeOx or PEtOx. Among the four poly(tertiary amide acylate) analogues, poly[2-(N-methylpropionamido)ethyl acrylate] (PPEA) and poly[2-(N-ethylacetamido)ethyl acrylate] (PEAE) showed thermosensitivity in aqueous solution; especially, PPEA (10 mg mL-1) exhibited a lower critical solution temperature of 37 °C. Water-insoluble copolymers were prepared to investigate the possibility of applying these synthesized polymers as blood-compatible coatings. The poly[n-butyl methacrylate70-co-2-(N-methylacetamido)ethyl methacrylate30] (coPAEM) coatings significantly suppressed plasma protein adsorption, denaturation degree of adsorbed fibrinogen, and platelet adhesion. Intermediate water (IW), whose content can generally indicate the blood compatibility of polymers, was found in all hydrated homopolymers and copolymers by differential scanning calorimetry. The present work demonstrated that the tertiary amide moiety in the side chain of poly(meth)acrylate was an effective contributor to blood compatibility and IW.


Assuntos
Amidas , Materiais Biocompatíveis , Acrilatos , Células HeLa , Humanos , Oxazóis , Polímeros , Água
16.
Cell Stem Cell ; 28(3): 514-523.e9, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621486

RESUMO

Some cancers originate from a single mutation event in a single cell. Blood cancers known as myeloproliferative neoplasms (MPNs) are thought to originate when a driver mutation is acquired by a hematopoietic stem cell (HSC). However, when the mutation first occurs in individuals and how it affects the behavior of HSCs in their native context is not known. Here we quantified the effect of the JAK2-V617F mutation on the self-renewal and differentiation dynamics of HSCs in treatment-naive individuals with MPNs and reconstructed lineage histories of individual HSCs using somatic mutation patterns. We found that JAK2-V617F mutations occurred in a single HSC several decades before MPN diagnosis-at age 9 ± 2 years in a 34-year-old individual and at age 19 ± 3 years in a 63-year-old individual-and found that mutant HSCs have a selective advantage in both individuals. These results highlight the potential of harnessing somatic mutations to reconstruct cancer lineages.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Adolescente , Adulto , Diferenciação Celular , Criança , Células-Tronco Hematopoéticas , Humanos , Janus Quinase 2/genética , Pessoa de Meia-Idade , Mutação/genética , Transtornos Mieloproliferativos/genética , Adulto Jovem
17.
ACS Biomater Sci Eng ; 6(12): 6790-6799, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33320605

RESUMO

Disability and even death from acute thrombosis remain a grave menace to public health. At present, the traditional drugs represented by urokinase (UK) in clinical thrombolysis can cause side effects of bleeding when the dosage is excess. Therefore, a more effective and safer method of thrombolysis is urgently needed. In this paper, a multifunctional dual-drug sequential release thrombolysis platform (UK-UH@PDA@HMSNs) consisting of polydopamine (PDA)-modified hollow mesoporous silicon (HMSNs) loading with UK and unfractionated heparin (UH) was constructed with a double physical assistance (NIR-II and bubbles). With the aid of near infrared-II (NIR-II, 1064 nm, 1.0 W cm-2) laser, the photothermal effect of PDA could be motivated to facilitate the UH release, thereby accelerating the dissolution of thrombus. Afterward, the local hyperthermia effect could expedite the phase transition of l-menthol in HMSNs to generate bubbles to promote the release of UK, thereby realizing the sequential release of two thrombolytic drugs. Importantly, this method deftly conquered the inherent obstacle that UK and UH cannot be combined directly. In vivo and in vitro experiments proved that the thrombolytic efficiency of UK-UH@PDA@HMSNs stimulated by NIR-II was nearly 3 times than that of UK alone. Collectively, the proposed dual physical assistance and sequential dual-drug delivery system significantly improved the efficiency of thrombolysis under the premise of limiting drug doses; the risk of death from intracranial hemorrhage thus could be decreased radically.


Assuntos
Nanopartículas , Trombose Venosa , Liberação Controlada de Fármacos , Heparina , Humanos , Ativador de Plasminogênio Tipo Uroquinase , Trombose Venosa/tratamento farmacológico
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(12): 1740-1746, 2020 Dec 30.
Artigo em Chinês | MEDLINE | ID: mdl-33380390

RESUMO

OBJECTIVE: To analyze the clinical characteristics and treatment outcomes of the first episode of peritoneal dialysis-associated peritonitis (PDAP) in patients receiving long-term peritoneal dialysis. METHODS: The clinical data of patients with the first episode of PDAP in 4 general hospitals in Jilin Province from 2013 to 2019 were collected retrospectively. According to the duration of dialysis, the patients were divided into long-term (≥36 months) and short-term (< 36 months) dialysis groups for comparison of the clinical data, treatment outcomes and long-term prognostic events. RESULTS: A total of 625 patients with PDAP were enrolled, including 93 on long-term and 532 on short-term dialysis. Compared with those on short-term dialysis, the patients on long-term dialysis had significantly higher hemoglobin levels and lower glomerular filtration rates when the first episode of PDAP occurred (P < 0.05), were more susceptible to gram-negative bacterial infections (P < 0.05), and had significantly lower initial treatment response rate (P=0.009) and complete cure rate (P=0.018) and higher extubation rate (P=0.017). Multivariate logistic regression analysis showed that in patients on long-term dialysis, the risks of extubation and treatment failure for the first episode of PDAP were 3.05 times (OR: 3.05, 95%CI: 1.35-6.91, P=0.008) and 2.81 times (OR: 2.81, 95%CI: 1.45-5.44, P=0.002) those in patients with short-term dialysis, respectively. Fungal infection (OR: 45.40, 95%CI: 1.488-1385.5, P=0.029) and mixed bacterial infection (OR: 16.50, 95%CI: 1.106-246.123, P=0.042) were independent risk factors for treatment failure of the first episode of PDAP in patients on long-term dialysis. Maintenance peritoneal dialysis, technical failure, or all-cause mortality did not differ significantly between the two groups. Multivariate Cox regression analysis suggested that long-term dialysis was not an independent risk factor for technical failure (OR: 1.36, 95%CI: 0.84-2.19, P=0.206) or all-cause mortality (OR: 1.51, 95%CI: 0.97-2.35, P=0.068) in patients with PDAP. CONCLUSIONS: Compared with those on short-term dialysis, patients on long-term dialysis are prone to gram-negative bacterial infection when the first episode of PDAP occurs with worse treatment outcomes but similar long-term outcomes. Long-term dialysis is an independent risk factor of extubation and treatment failure for the first episode of PDAP, and fungal and mixed bacterial infections are independent risk factors for treatment failure of the first PDAP in patients with long-term dialysis.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Peritonite , Humanos , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Peritonite/epidemiologia , Peritonite/etiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
World J Diabetes ; 11(10): 435-446, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33133391

RESUMO

BACKGROUND: The number of end-stage renal disease patients with diabetes mellitus (DM) who are undergoing peritoneal dialysis is increasing. Peritoneal dialysis-associated peritonitis (PDAP) is a serious complication of peritoneal dialysis leading to technical failure and increased mortality in patients undergoing peritoneal dialysis. The profile of clinical symptoms, distribution of pathogenic organisms, and response of PDAP to medical management in the subset of end-stage renal disease patients with DM have not been reported previously. Discrepant results have been found in long-term prognostic outcomes of PDAP in patients with DM. We inferred that DM is associated with bad outcomes in PDAP patients. AIM: To compare the clinical features and outcomes of PDAP between patients with DM and those without. METHODS: In this multicenter retrospective cohort study, we enrolled patients who had at least one episode of PDAP during the study period. The patients were followed for a median of 31.1 mo. They were divided into a DM group and a non-DM group. Clinical features, therapeutic outcomes, and long-term prognostic outcomes were compared between the two groups. Risk factors associated with therapeutic outcomes of PDAP were analyzed using multivariable logistic regression. A Cox proportional hazards model was constructed to examine the influence of DM on patient survival and incidence of technical failure. RESULTS: Overall, 373 episodes occurred in the DM group (n = 214) and 692 episodes occurred in the non-DM group (n = 395). The rates of abdominal pain and fever were similar in the two groups (P > 0.05). The DM group had more infections with coagulase-negative Staphylococcus and less infections with Escherichia coli (E. coli) as compared to the non-DM group (P < 0.05). Multivariate logistic regression analysis revealed no association between the presence of diabetes and rates of complete cure, catheter removal, PDAP-related death, or relapse of PDAP (P > 0.05). Patients in the DM group were older and had a higher burden of cardiovascular disease, with lower level of serum albumin, but a higher estimated glomerular filtration rate (P < 0.05). Cox proportional hazards model confirmed that the presence of diabetes was a significant predictor of all-cause mortality (hazard ratio = 1.531, 95% confidence interval: 1.091-2.148, P < 0.05), but did not predict the occurrence of technical failure (P > 0.05). CONCLUSION: PDAP patients with diabetes have similar symptomology and are predisposed to coagulase-negative Staphylococcus but not E. coli infection compared those without. Diabetes is associated with higher all-cause mortality but not therapeutic outcomes of PDAP.

20.
Medicine (Baltimore) ; 99(31): e21300, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756111

RESUMO

BACKGROUND: Published trials reported that high-energy extracorporeal shock wave therapy (HEEPSWT) can effectively treat early stage femoral head osteonecrosis (ESFHO). However, their results are still inconsistent. Thus, this study will systematically and comprehensively explore the effectiveness and safety of HEEPSWT for ESFHO. METHODS: We will retrieve the electronic databases of Cochrane Library, EMBASE, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, VIP database, and China National Knowledge Infrastructure from inception to the present. All randomized controlled trials that focusing on the effectiveness and safety of HEEPSWT for ESFHO will be considered. Two researchers will undertake literature selection, information collection, and risk of bias evaluation separately. If disagreements occur, we will invite a third researcher for consultation and a final decision will be made. Cochrane risk of bias tool, and Grades of Recommendation, Assessment, Development and Evaluation will be utilized to assess the risk of bias and quality of evidence, respectively. We will perform statistical analysis using RevMan 5.3 software. RESULTS: This study will provide a detailed summary of exist evidence related to the effectiveness and safety of HEEPSWT for ESFHO. CONCLUSION: The results of this study synthesize the evidence regarding the HEEPSWT for ESFHO, which may help to guide clinical management in the future. SYSTEMATIC REVIEW REGISTRATION: INPLASY202060055.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Necrose da Cabeça do Fêmur/terapia , Ondas de Choque de Alta Energia/uso terapêutico , Humanos , Revisões Sistemáticas como Assunto
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