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1.
Cytokine ; 149: 155725, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634653

RESUMO

BACKGROUND: Over-activation of the NLRP3 inflammasome can lead to sepsis. NLRP3 is an essential protein in the classical pathway of pyroptosis. This study assessed the use of serum NLRP3 level as a potential inflammatory biomarker in septic patients. METHODS: Patients were categorized into five groups: healthy controls (n = 30), ICU controls (n = 22), infection (n = 19), septic non-shock (n = 33), and septic shock (n = 83). Serum NLRP3 levels were measured by enzyme-linked immunosorbent assay for all patients upon enrollment. Clinical parameters and laboratory test data (APACHE II, SOFA, and lactate) were also assessed. Moreover, the ability of serum NLRP3 levels to predict sepsis was determined by the area under the curve (AUC) analysis. RESULTS: The NLRP3 levels in the septic shock group was significantly higher (431.89, 386.61-460.21 pg/mL) than that in the healthy control group (23.24, 9.38-49.73 pg/mL), ICU control group (74.82, 62.71-85.93 pg/mL), infection group (114.34, 99.21-122.56 pg/mL), and septic non-shock group (136.99, 128.80-146.98 pg/mL; P<0.001 for all comparisons). Additionally, the AUC indicated that the ability of serum NLRP3 levels to predict sepsis and septic shock incidences was not lower than that of the SOFA score. Patients with higher NLRP3 serum levels (>147.72 pg/mL) had significantly increased 30-day mortality rate. CONCLUSIONS: NLRP3 is useful for the early identification of high-risk septic patients, particularly septic shock patients. Moreover, elevated NRLP3 levels could result in poor septic prediction outcomes.

2.
Theor Appl Genet ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665265

RESUMO

KEY MESSAGE: YrFDC12 and PbcFDC, co-segregated in chromosome 4BL, and significantly interacted with Yr30/Pbc1 to enhance stripe rust resistance and to promote pseudo-black chaff development. Cultivars with durable resistance are the most popular means to control wheat stripe rust. Durable resistance can be achieved by stacking multiple adult plant resistance (APR) genes that individually have relatively small effect. Chinese wheat cultivars Ruihua 520 (RH520) and Fengdecun 12 (FDC12) confer partial APR to stripe rust across environments. One hundred and seventy recombinant inbred lines from the cross RH520 × FDC12 were used to determine the genetic basis of resistance and identify genomic regions associated with stripe rust resistance. Genotyping was carried out using 55 K SNP array, and eight quantitative trait loci (QTL) were detected on chromosome arms 2AL, 2DS, 3BS, 4BL, 5BL (2), and 7BL (2) by inclusive composite interval mapping. Only QYr.nwafu-3BS from RH520 and QYr.nwafu-4BL.2 (named YrFDC12 for convenience) from FDC12 were consistent across the four testing environments. QYr.nwafu-3BS is likely the pleiotropic resistance gene Sr2/Yr30. YrFDC12 was mapped in a 2.1-cM interval corresponding to 12 Mb and flanked by SNP markers AX-111121224 and AX-89518393. Lines harboring both Yr30 and YrFDC12 displayed higher resistance than the parents and expressed pseudo-black chaff (PBC) controlled by loci Pbc1 and PbcFDC12, which co-segregated with Yr30 and YrFDC12, respectively. Both marker-based and pedigree-based kinship analyses revealed that YrFDC12 was inherited from founder parent Zhou 8425B. Fifty-four other wheat cultivars shared the YrFDC12 haplotype. These results suggest an effective pyramiding strategy to acquire highly effective, durable stripe rust resistance in breeding.

3.
Chin Med J (Engl) ; 134(19): 2299-2305, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34629416

RESUMO

BACKGROUND: Functional mitral regurgitation (FMR) is common in critically ill patients and may cause left atrial (LA) pressure elevation. This study aims to explore the prognostic impact of synergistic LA pressure elevation and FMR in patients with shock. METHODS: We retrospectively screened 130 consecutive patients of 175 patients with shock from April 2016 to June 2017. The incidence and impact of FMR and early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio (E/e') ≥ 4 within 6 h of shock on the prognosis of patients were evaluated. Finally, the synergistic effect of FMR and E/e' were assessed by combination, grouping, and trend analyses. RESULTS: Forty-four patients (33.8%) had FMR, and 15 patients (11.5%) had E/e' elevation. A multivariate analysis revealed FMR and E/e' as independent correlated factors for 28-day mortality (P = 0.043 and 0.028, respectively). The Kaplan-Meier survival analysis revealed a significant difference in survival between patients with and without FMR (χ2 = 7.672, P = 0.006) and between the E/e' ≥ 14 and E/e' < 14 groups (χ2 = 19.351, P < 0.010). Twenty-eight-day mortality was significantly different among the four groups (χ2 = 30.141, P < 0.010). The risk of 28-day mortality was significantly higher in group 4 (E/e' ≥ 14 with FMR) compared with groups 1 (E/e' < 14 without FMR) and 2 (E/e' < 14 with FMR) (P = 0.001 and 0.046, respectively). CONCLUSIONS: Patients with shock can be identified by the presence of FMR. FMR and E/e' are independent risk factors for a poor prognosis in these patients, and prognosis is worst when FMR and E/e' ≥ 14 are present. It may be possible to improve prognosis by reducing LA pressure and E/e'. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03082326.


Assuntos
Insuficiência da Valva Mitral , Choque , Humanos , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos
4.
Ultrasonics ; 118: 106561, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500338

RESUMO

Angiogenesis involves the activation of endothelial cells (ECs). Low-intensity pulsed ultrasound (LIPUS), which delivers ultrasound waves at a low intensity, can induce the angiogenic potential of ECs. However, the underlying cellular mechanisms remain to be elucidated. In this study, the LIPUS parameters were 1.5 MHz pulsed frequency, 200 us pulse duration, 1.0 kHz repetition rate, and 30 mW/cm2 energy intensity. First, we evaluated the effects of LIPUS on the proliferation and angiogenic differentiation of the EC line EA.hy926. The results showed that LIPUS could induce cell proliferation, promote migration, and increase mRNA level inKDR and CD144.Also, the mRNA level and secretion of VEGF were enhanced. We then investigated the role of the AKT signaling pathway in this process. We observed that the expression of p-AKT was upregulated which means that the AKT signaling pathway could be activated by LIPUS, while inhibitor LY294002 of the AKT signaling pathway effectively blocked LIPUS-induced angiogenesis. Finally,we applied confocal Raman microscopy to track biomolecular changes in cells after LIPUS treatment. Spectral analysis showed DNA methylation changes. An Infinium Methylation assay suggested that399 sites were significantly different. After KEGG enrichment analysis, we found seven genes (IRS1, GNG7, COL4A1, FOXO3, COL4A2, CDK4 and EGF) which were closely related to AKT signaling pathway. We verified that AKT signaling pathway inhibition partially blocked LIPUS-induced DNA methylation changes. Ourstudy demonstrated that LIPUS couldpromote the proliferation and angiogenic differentiation of ECs via the AKT signaling pathway. LIPUS could also alter DNA methylation of ECs via the activation of AKT signal.

5.
Nat Commun ; 12(1): 5350, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504089

RESUMO

Relationships between biodiversity and multiple ecosystem functions (that is, ecosystem multifunctionality) are context-dependent. Both plant and soil microbial diversity have been reported to regulate ecosystem multifunctionality, but how their relative importance varies along environmental gradients remains poorly understood. Here, we relate plant and microbial diversity to soil multifunctionality across 130 dryland sites along a 4,000 km aridity gradient in northern China. Our results show a strong positive association between plant species richness and soil multifunctionality in less arid regions, whereas microbial diversity, in particular of fungi, is positively associated with multifunctionality in more arid regions. This shift in the relationships between plant or microbial diversity and soil multifunctionality occur at an aridity level of ∼0.8, the boundary between semiarid and arid climates, which is predicted to advance geographically ∼28% by the end of the current century. Our study highlights that biodiversity loss of plants and soil microorganisms may have especially strong consequences under low and high aridity conditions, respectively, which calls for climate-specific biodiversity conservation strategies to mitigate the effects of aridification.


Assuntos
Biodiversidade , Clima Desértico , Fungos/metabolismo , Desenvolvimento Vegetal , Plantas/metabolismo , Solo/química , China , Ecossistema , Fungos/classificação , Fungos/crescimento & desenvolvimento , Geografia , Concentração de Íons de Hidrogênio , Modelos Teóricos , Plantas/classificação , Microbiologia do Solo , Especificidade da Espécie , Água/metabolismo
6.
Biomed Eng Online ; 20(1): 78, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353324

RESUMO

PURPOSE: A real-time automatic cataract-grading algorithm based on cataract video is proposed. MATERIALS AND METHODS: In this retrospective study, we set the video of the eye lens section as the research target. A method is proposed to use YOLOv3 to assist in positioning, to automatically identify the position of the lens and classify the cataract after color space conversion. The data set is a cataract video file of 38 people's 76 eyes collected by a slit lamp. Data were collected using five random manner, the method aims to reduce the influence on the collection algorithm accuracy. The video length is within 10 s, and the classified picture data are extracted from the video file. A total of 1520 images are extracted from the image data set, and the data set is divided into training set, validation set and test set according to the ratio of 7:2:1. RESULTS: We verified it on the 76-segment clinical data test set and achieved the accuracy of 0.9400, with the AUC of 0.9880, and the F1 of 0.9388. In addition, because of the color space recognition method, the detection per frame can be completed within 29 microseconds and thus the detection efficiency has been improved significantly. CONCLUSION: With the efficiency and effectiveness of this algorithm, the lens scan video is used as the research object, which improves the accuracy of the screening. It is closer to the actual cataract diagnosis and treatment process, and can effectively improve the cataract inspection ability of non-ophthalmologists. For cataract screening in poor areas, the accessibility of ophthalmology medical care is also increased.

7.
Chin Med J (Engl) ; 134(17): 2017-2024, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432651

RESUMO

ABSTRACT: Acute respiratory distress syndrome (ARDS) is one of the most common severe diseases seen in the clinical setting. With the continuous exploration of ARDS in recent decades, the understanding of ARDS has improved. ARDS is not a simple lung disease but a clinical syndrome with various etiologies and pathophysiological changes. However, in the intensive care unit, ARDS often occurs a few days after primary lung injury or after a few days of treatment for other severe extrapulmonary diseases. Under such conditions, ARDS often progresses rapidly to severe ARDS and is difficult to treat. The occurrence and development of ARDS in these circumstances are thus not related to primary lung injury; the real cause of ARDS may be the "second hit" caused by inappropriate treatment. In view of the limited effective treatments for ARDS, the strategic focus has shifted to identifying potential or high-risk ARDS patients during the early stages of the disease and implementing treatment strategies aimed at reducing ARDS and related organ failure. Future research should focus on the prevention of ARDS.


Assuntos
Síndrome do Desconforto Respiratório , Humanos , Unidades de Terapia Intensiva , Síndrome do Desconforto Respiratório/etiologia , Resultado do Tratamento
8.
Sci Transl Med ; 13(608)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433637

RESUMO

Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response to immune checkpoint blockade (ICB) therapy. Bispecific T cell engager (BiTE) molecules induce redirected lysis of cancer cells by polyclonal T cells and have demonstrated promising clinical activity against solid tumors in some patients. However, little is understood about the key factors that govern clinical responses to these therapies. Using an immunocompetent mouse model expressing a humanized CD3ε chain (huCD3e mice) and BiTE molecules directed against mouse CD19, mouse CLDN18.2, or human EPCAM antigens, we investigated the pharmacokinetic and pharmacodynamic parameters and immune correlates associated with BiTE efficacy across multiple syngeneic solid-tumor models. These studies demonstrated that pretreatment tumor-associated T cell density is a critical determinant of response to BiTE therapy, identified CD8+ T cells as important targets and mediators of BiTE activity, and revealed an antagonistic role for CD4+ T cells in BiTE efficacy. We also identified therapeutic combinations, including ICB and 4-1BB agonism, that synergized with BiTE treatment in poorly T cell-infiltrated, immunotherapy-refractory tumors. In these models, BiTE efficacy was dependent on local expansion of tumor-associated CD8+ T cells, rather than their recruitment from circulation. Our findings highlight the relative contributions of baseline T cell infiltration, local T cell proliferation, and peripheral T cell trafficking for BiTE molecule-mediated efficacy, identify combination strategies capable of overcoming resistance to BiTE therapy, and have clinical relevance for the development of BiTE and other T cell engager therapies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34284697

RESUMO

A genetic polymorphism (rs968697 T > C) in the HMGA2 gene has recently been linked to an increased risk of hepatoblastoma. However, no studies have been conducted to investigate the effect of the polymorphism on the risk of colorectal cancer (CRC). The study aimed to explore whether the rs968697 polymorphism had a significant impact on CRC risk. A total of 500 CRC patients and 500 age and gender matched healthy individuals were genotyped by using the SNaPshot method. Quantitative real-time PCR technology was used to detect the relative expression of the HMGA2 gene in 30 pairs of primary CRC and adjacent non-cancerous tissues. Results: HMGA2 rs968697 polymorphism was significantly associated with CRC risk [CC vs. TT: OR = 0.20, 95%CI = 0.06-0.70, P = 0.01; (CC + CT) vs. TT: OR = 0.71, 95%CI = 0.53-0.96, P = 0.02; CC vs. (CT + TT): OR = 0.21, 95%CI = 0.06-0.73, P = 0.01; C vs. T: OR = 0.67, 95%CI = 0.51-0.89, P < 0.01]. The analysis based on tumor stage indicated that the CRC patients with HMGA2 rs968697 C allele were less likely to have high-stage tumors. Furthermore, the genotype-tissue expression analysis revealed that the rs968697 CC genotype was linked to the low expression of HMGA2 gene. The in silico analysis revealed that the rs968697 polymorphism in the promoter region of the HMGA2 gene could influence transcription factor binding, including ATF6, DBP, CDPCR3, DR3, NRSF, PAX8, PPARA, SZF11, TAXCREB and POLR2A. In conclusion, our findings suggested that the HMGA2 rs968697 polymorphism was linked to CRC risk and could be used as a biomarker to detect CRC risk.

10.
Ann Intensive Care ; 11(1): 108, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255224

RESUMO

INTRODUCTION: Right ventricle (RV) dilation in combination with elevated central venous pressure (CVP), which is a state of RV congestion, is seen as a sign of RV failure (RVF). On the other hand, RV systolic function is usually assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). This study aimed to investigate the prevalence and prognostic value of RVF and RV systolic dysfunction (RVSD) in septic patients. METHODS: Mechanically ventilated sepsis and septic shock patients were included. We collected haemodynamic and echocardiographic parameters as well as prognostic information including mechanical ventilation duration, length of ICU stay and 30-day mortality. RVF was defined as a right and left ventricular end-diastolic area ratio ≥ 0.6 in combination with CVP ≥ 8 mmHg. RVSD was defined as TAPSE < 16 mm or FAC < 35%. RESULTS: A total of 215 patients were enrolled in this study, and the patients were divided into 4 groups: patients with normal RV function (normal, n = 101), patients with RVF but without RVSD (RVF only, n = 38), patients with RVSD but without RVF (RVSD only, n = 44), and patients with combined RVF-RVSD (RVF/RVSD, n = 32). The RVF/RVSD group and RVSD only group had a lower cardiac index than the RVF only group and normal groups (p < 0.05). At 30 days after ICU admission, 50.0% of patients had died in the RVF/RVSD group, which was much higher than the mortality in the RVF only group (13.2%) and normal group (13.9%) (p < 0.05). In a Cox regression analysis, the presence of RVF/RVSD was independently associated with 30-day mortality (HR 3.004, 95% CI:1.370-6.587, p = 0.006). In contrast, neither the presence of RVF only nor the presence of RVSD only was associated with 30-day mortality (HR 0.951, 95% CI:0.305-2.960, p = 0.931; HR 1.912, 95% CI:0.853-4.287, p = 0.116, respectively). CONCLUSION: The presence of combined RVF-RVSD was associated with 30-day mortality in mechanically ventilated septic patients. Additional studies are needed to confirm and expand this finding.

13.
J Clin Ultrasound ; 49(7): 704-714, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117639

RESUMO

PURPOSE: The primary objective was to demonstrate the relationship between lung ultrasound (LUS) manifestations and the outcomes of intensive care unit (ICU) patients. The secondary objective was to determine the characteristics of LUS manifestations in different subgroups of ICU patients. METHODS: This prospective multi-center cohort study was conducted in 17 ICUs. A total of 1702 patients admitted between August 31, 2017 and February 16, 2019 were included. LUS was performed according to the bedside lung ultrasound in emergency (BLUE)-plus protocol, and LUS scores were calculated. Data on the outcomes and oxygenation indices were analyzed and compared between different primary indication groups. RESULTS: The LUS scores were significantly higher for non-survivors than for survivors and were significantly different between the oxygenation index groups, with higher scores in the lower oxygenation index groups. The LUS score was an independent risk factor for the 28-day mortality. The area under the receiver operating characteristic curve was 0.663 for prediction of the 28-day mortality and 0.748 for prediction of an oxygenation index ≤100. CONCLUSIONS: The LUS score based on the BLUE-plus protocol was an independent risk factor for the 28-day mortality and was important for the prediction of an oxygenation index ≤100. An early LUS score within 24 hours of ICU admission helps predicting the outcome of ICU patients.


Assuntos
Unidades de Terapia Intensiva , Pulmão , Estudos de Coortes , Humanos , Pulmão/diagnóstico por imagem , Estudos Prospectivos , Ultrassonografia
14.
Nanoscale ; 13(23): 10579-10586, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34100510

RESUMO

As a new two-dimensional elemental layered semiconductor, black phosphorus (b-P) has received tremendous attention due to its excellent physical and chemical properties and has potential applications in the fields of catalysis, energy, and micro/nano-optoelectronic devices. However, studies have found that b-P is very unstable and will decompose within a few minutes under humid air conditions. Element doping is an effective method for adjusting the physical and chemical properties of crystals. Theoretical and experimental studies have confirmed that the stability of b-P crystals is significantly improved after arsenic doping, and the crystals also exhibit excellent photoresponse and electrical transport performances. In this work, we investigate the physical properties of a component of black arsenic phosphorus crystals (b-As0.084P0.916) and the potential applications in field effect transistors (FETs) and broadband photodetectors. An obvious ambipolar behavior is observed in the transfer characteristics of b-As0.084P0.916 based FETs, with drain current modulation on the order of 105 and the highest charge-carrier mobility of up to 147 cm2 V-1 s-1. The physisorption of atmospheric species on the surface of the FETs is the main factor for the formation of Schottky contacts between the Au electrodes and the b-As0.084P0.916 crystal. Temperature-dependent electrical characteristics show that the Fermi level shifts from the valence band to the middle level between the conduction band and valence band as the temperature decreases. In addition, the FETs also exhibit excellent photoresponse properties from the visible to near-infrared region (450-2200 nm), with a responsivity of 37 A W-1, a specific detectivity of 7.18 × 1010 Jones, and a fast response speed (τrise ≈ 0.04 s and τdecay ≈ 0.14 s). These results suggest that b-As0.084P0.916 crystals are a promising candidate for future electronic and optoelectronic devices.

15.
Adv Sci (Weinh) ; 8(14): e2100075, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34021718

RESUMO

With the increasing demand for detection accuracy and sensitivity, dual-band polarimetric image sensor has attracted considerable attention due to better object recognition by processing signals from diverse wavebands. However, the widespread use of polarimetric sensors is still limited by high noise, narrow photoresponse range, and low linearly dichroic ratio. Recently, the low-dimensional materials with intrinsic in-plane anisotropy structure exhibit the great potential to realize direct polarized photodetection. Here, strong anisotropy of 1D layered bismuth sulfide (Bi2 S3 ) is demonstrated experimentally and theoretically. The Bi2 S3 photodetector exhibits excellent device performance, which enables high photoresponsivity (32 A W-1 ), Ion /Ioff ratio (1.08 × 104 ), robust linearly dichroic ratio (1.9), and Hooge parameter (2.0 × 10-5 at 1 Hz) which refer to lower noise than most reported low-dimensional materials-based devices. Impressively, such Bi2 S3 nanowire exhibits a good broadband photoresponse, ranging from ultraviolet (360 nm) to short-wave infrared (1064 nm). Direct polarimetric imaging is implemented at the wavelengths of 532 and 808 nm. With these remarkable features, the 1D Bi2 S3 nanowires show great potential for direct dual-band polarimetric image sensors without using any external optical polarizer.

16.
Anal Chem ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945260

RESUMO

Surface-enhanced Raman spectroscopy (SERS) is a promising ultrasensitive analysis technology due to outstanding molecular fingerprint identification. However, the measured molecules generally need to be adsorbed on a SERS substrate, which makes it difficult to detect weakly adsorbed molecules, for example, the volatile organic compound (VOC) molecules. Herein, we developed a kind of a SERS detection method for weak adsorption molecules with Au@ZIF-8 core-shell nanoparticles (NPs). The well-uniformed single- and multicore-shell NPs can be synthesized controllably, and the shell thickness of the ZIF-8 was able to be precisely controlled (from 3 to 50 nm) to adjust the distance and electromagnetic fields between metal nanoparticles. After analyzing the chemical and physical characterization, Au@ZIF-8 core-shell NPs were employed to detect VOC gas by SERS. In contrast with multicore or thicker-shell nanoparticles, Au@ZIF-8 with a shell thickness of 3 nm could efficiently probe various VOC gas molecules, such as toluene, ethylbenzene, and chlorobenzene. Besides, we were capable of observing the process of toluene gas adsorption and desorption using real-time SERS technology. As observed from the experimental results, this core-shell nanostructure has a promising prospect in diverse gas detection and is expected to be applied to the specific identification of intermediates in catalytic reactions.

17.
FEBS Open Bio ; 11(6): 1659-1672, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33932138

RESUMO

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m6 A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m6 A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.

18.
J Int Med Res ; 49(5): 3000605211013176, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33990145

RESUMO

OBJECTIVE: To investigate the effect of focused ultrasonography on clinical outcomes of septic shock. METHODS: Patients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay. RESULTS: Ninety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation. CONCLUSIONS: The initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.


Assuntos
Choque Séptico , Hidratação , Hemodinâmica , Humanos , Choque Séptico/diagnóstico por imagem , Choque Séptico/tratamento farmacológico , Ultrassonografia , Vasoconstritores/uso terapêutico
19.
Clin Transl Oncol ; 23(9): 1942-1954, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33826083

RESUMO

PURPOSE: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC). METHODS: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model. RESULTS: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression. CONCLUSION: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.

20.
Signal Transduct Target Ther ; 6(1): 165, 2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33895786

RESUMO

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Simulação por Computador , Reposicionamento de Medicamentos , Modelos Biológicos , SARS-CoV-2/metabolismo , Humanos
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