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1.
Molecules ; 27(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35056797

RESUMO

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 µM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure-activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

2.
Sci Rep ; 12(1): 51, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996982

RESUMO

This study aimed to compare stent graft with balloon tamponade for ruptured dialysis access during percutaneous transluminal angioplasty. Patients over an 8-year period (2010-2018) were identified from a database of 11,609 procedures. The primary endpoint was target lesion primary patency at 12 months. A total of 143 patients who had rupture dialysis access were enrolled, of whom 52 were salvaged by stent grafts and 91 were salvaged by balloon tamponade. The 6-month target lesion primary patency was greater in the stent graft group than in the balloon tamponade group (66.7% vs. 29.5%, P < 0.001). The benefit of stent grafts was sustained for 12 months (52.5% vs. 9.0%, P < 0.001). The stent grafts increased the median time from the index procedure to the next intervention in the ruptured area by 171 days (260 vs. 89 days) at 12 months. There was no significant difference in the access circuit patency rates at 6 months (25.5% vs. 19.8%, P = 0.203) and 12 months (12.0% vs. 5.8%, P = 0.052). The patency results of the stent grafts remained after the multivariable adjustment analysis. Compared to balloon tamponade alone, stent grafts provided superior target lesion primary patency at 6 and 12 months. The access circuit patency rates were similar.

3.
Chemosphere ; 286(Pt 2): 131628, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34333186

RESUMO

To observe the co-transport of Cd(Ⅱ) with nanoscale As2S3 (nAs2S3) in a soil-packed column under different ionic strength (IS). A soil-packed column experiment with Cd(Ⅱ) and nAs2S3 was conducted. The results show that the transport of Cd(Ⅱ) was facilitated remarkably in the presence of nAs2S3, and nano-associated-Cd(Ⅱ) was the major migration type. However, the co-transport of Cd(Ⅱ) and nAs2S3 was affected by IS. The Cd(Ⅱ) concentration in the effluent to initial Cd(Ⅱ) concentration decreased from 38.75% to 29.95% and 22.28% as IS increased from 1 mM to 10 mM and 50 mM. When IS was 1 mm, 10 mm and 50 mm, the retention of nAs2S3 increased from 74.29% to 78.95% and 85.9% respectively. The agglomeration and sedimentation of nAs2S3 were the main reason for the rise of retention. Due to the increase of retention and reduction in adsorption capacity of nAs2S3 to Cd(Ⅱ), the ratio of migration in the form of nano-associated-Cd(Ⅱ) reduced from 53% (IS 1 mM) to 27.4% (IS 10 mM) and 18.2% (IS 50 mM). During the transport, the IS promoted desorption of Cd(Ⅱ) from nAs2S3 so that more soluble Cd was monitored in the effluent as IS increased. In general, these findings can provide references for controlling the risk caused by the co-transport of nAs2S3 and Cd(Ⅱ) in saline-alkali soil.


Assuntos
Poluentes do Solo , Solo , Adsorção , Cádmio/análise , Concentração Osmolar , Poluentes do Solo/análise
5.
Sci Total Environ ; 805: 150292, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34536857

RESUMO

Since the loss of honeybees in hives could have a greater impact on colony health than those of their foraging bees, it is imperative to know beehives' pesticide exposure via oral ingestion of contaminated in-hive matrices. Here, a 4-year monitoring survey of 64 pesticide residues in pollen, nectar and related beehive matrices (beebread and honey) from China's main honey producing areas was carried out using a modified version of the QuEChERS multi-residue method. The results showed that 93.6% of pollen, 81.5% of nectar, 96.6% of beebread, and 49.3% of honey containing at least one target pesticide were detected either at or above the method detection limits (MDLs), respectively, with up to 19 pesticides found per sample. Carbendazim was the most frequently detected pesticide (present in >85% of the samples), and pyrethroids were also abundant (median concentration = 134.3-279.0 µg/kg). The transfer of pesticides from the environment into the beehive was shown, but the pesticide transference ratio may be affected by complex factors. Although the overall risk to colony health from pesticides appears to be at an acceptable level, the hazard quotient/hazard index (HQ/HI) value revealed that pyrethroids were clearly the most influential contributor, accounting for up to 45% of HI. Collectively, these empirical findings provide further insights into the extent of contamination caused by agricultural pesticide use on honeybee colonies.


Assuntos
Mel , Resíduos de Praguicidas , Praguicidas , Urticária , Animais , Abelhas , Mel/análise , Resíduos de Praguicidas/análise , Praguicidas/análise , Pólen/química
6.
Front Med (Lausanne) ; 8: 769132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869485

RESUMO

Purpose: To explore the therapeutic effect of a dietary supplement on dry eye with meibomian gland dysfunction (MGD). Methods: Sixty patients with MGD-related dry eye were included in this prospective and randomized, placebo-controlled study. All the subjects were treated with eye hot compress, artificial tears, and antibiotic ointment. After that, the patients received dietary supplementary or placebo daily for 12 weeks. The dry eye signs, function of MG, and visual quality of the patients were assessed at 4, 8, and 12 weeks after the treatment. Results: Twelve weeks after the treatment, patients who received dietary supplement had a significantly better improvement of dry eye symptoms, in terms of ocular surface diseases index and tear breaking-up time (TBUT), than those who received placebo (P < 0.05). The functions of MG, in terms of meibum quality and MG exclusion and MG obstruction scores, were significantly improved in both dietary supplement and placebo groups (P < 0.05). Patients who received dietary supplement had a significantly better improvement in the MG structure, in terms of acinar diameter and acinar density, than those who received placebo (P < 0.05). The number of inflammatory cells near MG was significantly lower in the dietary supplement group when compared with the placebo group (P < 0.05). The objective visual quality was significantly improved in the dietary supplement group, but not in the placebo group (P < 0.05). Conclusion: The dietary supplement can effectively improve the symptoms and signs of MGD-related dry eye, reduce the inflammatory reaction of MG, restore the gland structure, and indirectly improve the visual quality.

7.
Aust Crit Care ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34857440

RESUMO

BACKGROUND: Rapid developments in medical care-such as monitoring devices, medications, and working hours restrictions for intensive care personnel-have dramatically increased the demand for intensive care physicians. Therefore, nurse practitioner (NP)-staffed care is becoming increasingly important. This study was aimed to compare the outcomes of daytime NP-staffed and daytime resident-staffed nonsurgical intensive care units (ICU). METHODS: We retrospectively assessed patients admitted to a nonsurgical ICU from March 2017 to December 2017. We collected basic patient data, including age, sex, admission diagnosis, transferring unit, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Primary endpoints were ICU mortality, hospital mortality, and 30-day mortality. Secondary endpoints were 48-h readmission, discharge to nonhome locations, and lengths of ICU and hospital stay. RESULTS: A total of 838 subjects were analysed: 334 subjects in the NP-staffed group and 504 in the resident-staffed group. The NP-staffed group was more likely to come from inpatient units (38.3% vs 16.5% for resident-staffed group; p < 0.001) and had lower disease severity (APACHE II score, 13.9 ± 8.4 vs 15.1 ± 8.2 for resident-staffed group; p = 0.047). After adjusting for age, sex, location before ICU admission, APACHE II score, and significantly different basic characteristics, there were no differences in ICU mortality, hospital mortality, or 30-day mortality between the two groups. Secondary analysis showed the NP-staffed group had a lower discharge rate to nonhome locations (2.1% vs 6.3%; p = 0.023) and shorter hospital stay (12.1 ± 14.1 vs 14.2 ± 14.3 days; p = 0.015). CONCLUSIONS: We observed no difference in mortality between daytime NP-staffed and resident-staffed nonsurgical ICUs. Daytime NP-staffed care is an effective, safe, feasible method for staffing nonsurgical ICUs.

8.
Insect Biochem Mol Biol ; : 103698, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34848284

RESUMO

Histamine-gated chloride channels (HACls) mediate fast inhibitory neurotransmission in invertebrate nervous systems and have important roles in light reception, color processing, temperature preference and light-dark cycle. The fall armyworm, Spodoptera frugiperda is a main destructive pest of grain and row crops. However, the pharmacological characterization of HACls in S. frugiperda remain unknown. In this study, we identified two cDNAs encoding SfHACl1 and SfHACl2 in S. frugiperda. They had similar expression patterns and were most abundantly expressed in the head of larvae and at the egg stage. Electrophysiological analysis with the two-electrode voltage clamp method showed that histamine (HA) and γ-aminobutyric acid (GABA) activated inward currents when SfHACls were singly or collectively expressed with different ratios in Xenopus laevis oocytes. These channels were ≥2000-fold more sensitive to HA than to GABA. They were anion-selective channels, which were highly dependent on changes in external chloride concentrations, but insensitive to changes in external sodium concentrations. The insecticides abamectin (ABM) and emamectin benzoate (EB) also activated these channels with the EC50 to SfHACl1 lower than that to SfHACl2. And the EC50s of ABM and EB to the co-expressed channels gradually increased with increase in the injection ratio of SfHACl2 cRNA. Homology models and docking simulations revealed that HA bound to the large amino-terminal extracellular domain of SfHACl1 and SfHACl2 by forming 4 and 2 hydrogen bonds, respectively. The docking simulations of ABM and EB had similar binding sites in the transmembrane regions. Overall, these findings indicated that HACls act as targets for macrolide, and this study provides theoretical guidance for further derivatization of abamectin insecticides.

9.
Microsc Res Tech ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34951081

RESUMO

The genus Sophora (Fabaceae) is one of the taxonomically challenging genera with high economic and medical values. In this study, the pollen morphology of 43 samples of 27 species, 4 subspecies, and 4 varieties of the genus Sophora and 3 closely related genera was examined using scanning electron microscopy to evaluate the pollen diversity of the genus and its taxonomic significance. Pollen grains of the studied species were tricolporate (rarely six-aperture), and pollen shape varied from suboblate, spheroidal, subprolate to prolate. Echinate external ornamentation was reported for the first time in some species of the genus. Aperture membrane ornamentation and outline in a polar/equatorial view were described for the first time in the genus. Principal component analysis was used to understand the relationship and discrimination between the species and the genera, with six components accounting for 79.92% of the total variance. Taxonomic keys based on pollen morphology were also constructed to easily identify the taxa of the genus through palynological characteristics. Results showed that pollen morphology alone is not sufficient to elucidate or reconstruct taxonomic relationships within the genus Sophora, but palynological assessments can provide some useful information for identifying taxonomically problematic taxa.

10.
Arch Microbiol ; 204(1): 79, 2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-34954815

RESUMO

Genome editing technology has progressed rapidly in recent years. Although traditional gene-editing methods, including homologous recombination, zinc finger endonucleases, and transcription activator-like effector nucleases, have substantial implications for research in genetics and molecular biology, but they have remarkable limitations, including their low efficiency, high error rate, and complex design. A new gene-editing technology, the CRISPR/Cas system, was developed based on studies of archaeal and bacterial immune responses to viruses. Owing to its high target efficiency, simple primer design, and wide applications, the CRISPR/Cas system, whose developers were awarded the Nobel Prize in Chemistry in 2020, has become the dominant genomic editing technology in academia and the pharmaceutical industry. Here, we briefly introduce the CRISPR/Cas system and its main applications for genome engineering, metabolic engineering, and transcriptional regulation in yeast, filamentous fungi, and macrofungi. The polygene and polyploid editing, construction of yeast chromosomes, yeast library creation, regulation of metabolic pathways, and CRISPR activation/CRISPR interference systems are mainly summarized and discussed. The potential applications for the treatment of fungal infections and the further transformation and application of the CRISPR/Cas system in fungi are also proposed and discussed.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Fungos/genética , Saccharomyces cerevisiae/genética , Tecnologia
12.
Int J Mol Sci ; 22(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34948112

RESUMO

The human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways mounted against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages (M1), interferon gamma (IFNγ) CD4 T cells, innate lymphoid cells 1 (NKp44+ ILC1), CD8 T cells (Effector-Memory4, EM4), invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For intracellular protozoa, the tolerable host immunological pathway is TH1-like immunity involving macrophages (M2), interferon gamma (IFNγ)/TGFß CD4 T cells, innate lymphoid cells 1 (NKp44- ILC1), CD8 T cells (EM3), invariant natural killer T 1 (iNKT1) cells, and immunoglobulin A1 (IgA1) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils (N1), interleukin-22 CD4 T cells, innate lymphoid cells 3 (NCR+ ILC3), iNKT17 cells, and IgG2 B cells. For free-living extracellular protozoa, the tolerable host immunological pathway is TH17 immunity involving neutrophils (N2), interleukin-17 CD4 T cells, innate lymphoid cells 3 (NCR- ILC3), iNKT17 cells, and IgA2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), interleukin-5/interleukin-4 CD4 T cells, interleukin-25 induced inflammatory innate lymphoid cells 2 (iILC2), tryptase-positive mast cells (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, chymase- and tryptase-positive mast cells (MCct), interleukin-3/interleukin-4 CD4 T cells, interleukin-33 induced nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, interleukin-9 mast cells (MMC9), thymic stromal lymphopoietin induced innate lymphoid cells 2, interleukin-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. In addition, specific transcription factors important for specific immune responses were listed. This JAK/STAT signaling is key to controlling or inducing different immunological pathways. In sum, Tfh is related to STAT5ß, and BCL6 expression. Treg is related to STAT5α, STAT5ß, and FOXP3. TH1 immunity is related to STAT1α, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1α, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3α and AHR. THαß immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, and ISGF. TH1-like immunity is related to STAT1α, STAT4, STAT5α, and STAT5ß. TH9 immunity is related to STAT6, STAT5α, STAT5ß, and PU.1. TH17 immunity is related to STAT3α, STAT5α, STAT5ß, and RORG. TH3 immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, STAT5α, STAT5ß, and ISGF. This categorization provides a complete framework of immunological pathways against four types of parasitic infections. This framework as well as relevant JAK/STAT signaling can provide useful knowledge to control allergic hypersensitivities and parasitic infections via development of vaccines or drugs in the near future.


Assuntos
Citocinas/imunologia , Imunidade Inata , Leucócitos/imunologia , Doenças Parasitárias/imunologia , Humanos
13.
Pest Manag Sci ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34821014

RESUMO

BACKGROUND: Metabolic resistance is a worldwide concern for weed control but has not yet been well-characterized at the genetic level. Previously, we have identified an Asia minor bluegrass (Polypogon fugax Nees ex Steud.) population AHHY exhibiting cytochrome P450 (P450)-involved metabolic resistance to fenoxaprop-P-ethyl. In this study, we aimed to confirm the metabolic fenoxaprop-P-ethyl resistance in AHHY and uncover the potential herbicide metabolism-related genes in this economically damaging weed species. RESULTS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays indicated the metabolic rates of fenoxaprop-P-ethyl were significantly faster in resistant (R, AHHY) than in susceptible (S, SDTS) plants. The amount of phytotoxic fenoxaprop-P peaked at 12 h after herbicide treatment (HAT) and started to decrease at 24 HAT in both biotypes. R and S plants at 24 HAT were sampled to conduct isoform-sequencing (Iso-Seq) and RNA-sequencing (RNA-Seq). A reference transcriptome containing 24 972 full-length isoforms was obtained, of which 24 329 unigenes were successfully annotated. Transcriptomic profiling identified 28 detoxifying enzyme genes constitutively and/or herbicide-induced up-regulated in R than in S plants. Real-time quantitative polymerase chain reaction (RT-qPCR) confirmed 17 genes were consistently up-regulated in R and its F1 generation plants. They were selected as potential fenoxaprop-P-ethyl metabolism-related genes, including ten P450s, one glutathione-S-transferase, one UDP-glucosyltransferase, and five adenosine triphosphate (ATP)-binding cassette transporters. CONCLUSION: This study revealed that the enhanced rates of fenoxaprop-P-ethyl metabolism in P. fugax were very likely driven by the herbicide metabolism-related genes. The transcriptome data generated by Iso-Seq combined with RNA-Seq will provide abundant gene resources for understanding the molecular mechanisms of resistance in P. fugax.

14.
Pest Manag Sci ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822218

RESUMO

BACKGROUND: Chinese sprangletop (Leptochloa chinensis (L.) Nees) is an invasive grass weed severely infesting rice fields across China. In October 2020, a suspected resistant L. chinensis population HFFD3 that survived the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide cyhalofop-butyl applied at its field-recommended rate was collected from a rice field in Feidong County, Anhui Province, China. This study aimed to determine the resistance profile of HFFD3 to ACCase inhibitors and to investigate its mechanisms of resistance to cyhalofop-butyl. RESULTS: Single-dose testing confirmed that HFFD3 had evolved resistance to cyhalofop-butyl. Two loci encoding plastidic ACCase were each amplified from the susceptible (S) and resistant (R, HFFD3) individual plants. Target gene sequencing and derived cleaved amplified polymorphic sequence assay revealed all the R plants carried a Trp-2027-Leu substitution in their ACCase1,2 copies. Dose-response bioassays revealed that HFFD3 was highly resistant to cyhalofop-butyl and exhibited cross-resistance to metamifop, fenoxaprop-P-ethyl, quizalofop-P-ethyl, and clethodim. Pre-treatment with piperonyl butoxide and 4-chloro-7-nitrobenzoxadiazole considerably reversed the resistance of the R plants to cyhalofop-butyl, by 23% and 43%, respectively. Liquid chromatography-tandem mass spectrometry analysis suggested the metabolic rates of cyhalofop-butyl were significantly faster in the R than in the S plants. CONCLUSION: This study confirmed the first case of an arable weed species featuring cross-resistance to ACCase-inhibiting herbicides due to a novel Trp-2027-Leu mutation of ACCase. Target gene mutation and cytochrome P450s- and glutathione S-transferases-involved enhanced metabolism may have simultaneously participated in the resistance of HFFD3 population to cyhalofop-butyl. This article is protected by copyright. All rights reserved.

15.
Mol Ecol Resour ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837470

RESUMO

The Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a species of a threatened monotypic genus endemic to the Hengduan Mountains. In this study, we present a high-quality, chromosome-level reference genome for A. bracteata, constructed using long reads, short reads and Hi-C technology. We characterized its genetic diversity, population structure, demographic history and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single-copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged ~104.5 million years ago. Whole-genome resequencing based on population genetic analysis revealed that the division of the 14 populations into 10 distinct clusters reflected geographical divergence, and three separate high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicate that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units for the conservation and management of threatened species. Our high-quality genome represents a valuable resource for future studies of the underlying molecular mechanisms of adaptive evolution and provides insight for further comparative genomic analysis with other Velloziaceae species.

17.
Acta Cardiol Sin ; 37(6): 600-607, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34812233

RESUMO

Background: Atrial fibrillation is the most common arrhythmia and it is associated with a higher risk of mortality and morbidity. The goal of this study was to assess the correlation between physical activity (PA) and atrial high rate episodes (AHREs) detected by cardiovascular implantable electronic devices (CIEDs). Methods: We prospectively collected data from 81 patients from March 2017 to June 2019. Device-detected PA (hours per day) through an accelerometer and occurrence/burden of AHREs were determined at each outpatient clinic visit. Modest AHREs and long AHREs were defined as at least 1 episode of AHREs lasting ≥ 12 hours and 24 hours, respectively. The percentage of total AHREs in the follow-up period was defined as the burden of AHREs. Generalized estimating equations were used to explore the association between PA and occurrence/burden of AHREs to account for repeated measures within a participant. Results: The patients had 336 follow-up visits (mean 4.1 visits each). The prevalence rates of device-detected modest AHREs and long AHREs were 4.8% and 3.9%, respectively. More PA (hours per day) was associated with a lower risk of modest AHREs [odds ratio (OR) 0.671, 95% confidence interval (CI) 0.452-0.997, p = 0.048] and long AHREs (OR 0.536, 95% CI 0.348-0.824, p = 0.004) after adjusting for age, sex, and basic characteristics. More PA had a trend of association with fewer AHREs (ß -0.255, 95% CI -0.512 to 0.001, p = 0.051). Conclusions: More PA was associated with a lower risk of AHREs detected by CIEDs in older patients. PA may reduce the risk of AHREs.

18.
Int Heart J ; 62(6): 1442-1444, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34789647

RESUMO

Transthoracic, transesophageal, and intracardiac echocardiography are applicable imaging tools used for increasing the accuracy of tumor positioning during transvenous intracardiac tumor biopsy. However, incorporating echo-images in the extremely rare procedures is usually not easy. By using a contralateral catheter for simultaneous contrast injection and tip positioning, we demonstrated tumor biopsy safely and effectively in 4 cases without the guidance of echocardiography.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34655263

RESUMO

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy, which is a long-term complication of cesarean section. Prompt and accurate diagnosis of CSP is important to decrease maternal mobility and mortality. However, it is difficult to make an early detection for CSP complicated with morbidly adherent placenta. Contrast-enhanced ultrasound with the advantage in blood flow imaging is low-cost, time-saving, safe and more accessible in clinical practice. Here, we report a case with early detection of CSP with placenta increta by contrast-enhanced ultrasound and its successful uterine-sparing surgical management.

20.
Cell Death Discov ; 7(1): 297, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663800

RESUMO

DNA (cytosine-5)-methyltransferase 3A (DNMT3A) mutations occur in ~20% of de novo acute myeloid leukemia (AML) patients, and >50% of these mutations in AML samples are heterozygous missense alterations within the methyltransferase domain at residue R882. DNMT3A R882 mutations in AML patients promote resistance to anthracycline chemotherapy and drive relapse. In this study, we performed high-throughput screening and identified that oridonin, an ent-kaurene diterpenoid extracted from the Chinese herb Rabdosia rubescens, inhibits DNMT3A R882 mutant leukemic cells at a low-micromolar concentration (IC50 = 2.1 µM) by activating both RIPK1-Caspase-8-Caspase-3-mediated apoptosis and RIPK1-RIPK3-MLKL-mediated necroptosis. The inhibitory effect of oridonin against DNMT3A R882 mutant leukemia cells can also be observed in vivo. Furthermore, oridonin inhibits clonal hematopoiesis of hematopoietic stem cells (HSCs) with Dnmt3a R878H mutation comparing to normal HSCs by inducing apoptosis and necroptosis. Overall, oridonin is a potential and promising drug candidate or lead compound targeting DNMT3A R882 mutation-driven clonal hematopoiesis and leukemia.

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