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1.
J Hepatol ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34736969

RESUMO

BACKGROUND & AIMS: Drug-induced liver injury (DILI) is a leading cause of acute liver failure, and treatment of DILI remains a challenge. MG53 is a muscle-derived tissue-repair protein that circulates in the bloodstream whose physiological role in protection against DILI has not been examined. METHODS: Recombinant MG53 protein (rhMG53) was administered exogenously, using mice with deletion of MG53 or RIPK3. Live cell imaging, histological, biochemical, and molecular studies were used to investigate the mechanisms that underlie the extracellular and intracellular action of rhMG53 in hepatoprotection. RESULTS: Systemic administration of rhMG53 protein, in mice, can prophylactically and therapeutically treat DILI induced through exposure to acetaminophen tetracycline, concanavalin A, carbon tetrachloride, or thioacetamide. Circulating MG53 protects hepatocytes from injury through direct interaction with MLKL at the plasma membrane. Extracellular MG53 can enter hepatocytes and act as an E3-ligase to mitigate RIPK3-mediated MLKL phosphorylation and membrane translocation. CONCLUSIONS: Our data show that the membrane-delimited signaling and cytosolic dual action of MG53 effectively preserves hepatocyte integrity during DILI. rhMG53 may be a potential treatment option for patients with DILI. LAY SUMMARY: Interventions to treat drug-induced liver injury and halt its progression into liver failure are of great value to the medical society. The present study reveals that muscle-liver cross talk, with MG53 as a messenger, serves an important role in liver-cell protection.

2.
Comput Med Imaging Graph ; 94: 101989, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34741846

RESUMO

BACKGROUND AND OBJECTIVE: Real time localization and shape extraction of guide wire in fluoroscopic images plays a significant role in the image guided navigation during cerebral and cardiovascular interventions. Given the complexity of the non-rigid and sparse characteristics of guide wire structures, and the low SNR(Signal Noise Ratio) of fluoroscopic images, traditional handcrafted guide wire tracking methods such as Frangi filter, Hessian Matrix, or open active contour usually produce insufficient accuracy with high computational cost, and may require extra human intervention for proper initialization or correction. The application of deep learning techniques to guide wire tracking is reported to produce significant improvement in guide wire localization accuracy, but the heavy calculation cost is still a concern. METHOD: In this paper we propose a two phase deep learning scheme for accurate and real time guide wire shape extraction in fluoroscopic sequences. In the first phase we train a guide wire localization network to pick image regions containing guide wire structures. From the picked image regions, we train a guide wire shape extraction network in the second phase to mark the guide wire pixels. RESULTS: We report that our proposed method can accurately distinguish about 99% of the guide wire structure pixels, and the falsely detected pixels in the background are close to 0, the average offset from the ground truth is less than 1 pixel. For extreme cases where traditional handcrafted method may fail, our proposed method can still extract guide wire completely and accurately. The processing time for a 512 × 512 pixels image is 78 ms. CONCLUSION: Compared with the traditional filtering based method from our previous work, we show that our proposed method can achieve more accurate and stable performance. Compared with other deep learning methods, our proposed method significantly improve calculation efficiency to meet the real time requirement of clinical applications.

3.
J Cancer Educ ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599456

RESUMO

Compared to other races/ethnicities, the Latino population has a lower rate of adherence to colorectal cancer (CRC) screening guidelines. Previous studies have identified a variety of barriers to CRC screening in Latino populations but have not explored factors associated with barriers. The purpose of this study was to identify barriers to CRC screening and associated factors in a Midwest Latino population visiting an urban Federally Qualified Health Center (FQHC). We conducted a cross-sectional investigation of 68 Latinos at a FQHC from June to October 2017. We examined factors associated with scheduling, psychological, and financial barriers using t-test, ANOVA, and multiple linear regression analyses. Our participants reported low educational level, low income, and limited access to insurance or a primary care provider. Scheduling barriers are the highest barrier compared with psychological and financial barriers. Being married or coupled was the only predictor of higher scheduling barriers (P < .05). Being married or coupled was associated with higher psychological barriers in both univariate and multivariate analysis (P < .05). Higher education level was associated with higher psychological barriers in univariate (P < .05) but not multivariate analysis. Participants with lower vs. higher English proficiency had a higher financial barrier score in univariate (P < .05) but not multivariate analysis. Despite interventions targeting CRC screening barriers, including the provision of free at-home testing, perceived barriers persist. Bilingual patient navigators may help address needs for those with limited English proficiency to find and schedule free or reduced-fee colonoscopy services. People who are well educated are also at high risk of psychological barriers and should be targeted and given more education on the importance of CRC screening.

4.
Front Cardiovasc Med ; 8: 739598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568467

RESUMO

Congenital heart defects (CHDs) represent the most common human birth defects. Our previous study indicates that the malfunction of microRNAs (miRNAs) in cardiac neural crest cells (NCCs), which contribute to the development of the heart and the connected great vessels, is likely linked to the pathogenesis of human CHDs. In this study, we attempt to further search for causative single-nucleotide variants (SNVs) from CHD patients that mediate the mis-regulating of miRNAs on their downstream target genes in the pathogenesis of CHDs. As a result, a total of 2,925 3'UTR SNVs were detected from a CHD cohort. In parallel, we profiled the expression of miRNAs in cardiac NCCs and found 201 expressed miRNAs. A combined analysis with these data further identified three 3'UTR SNVs, including NFATC1 c.*654C>T, FGFRL1 c.*414C>T, and CTNNB1 c.*729_*730insT, which result in the malfunction of miRNA-mediated gene regulation. The dysregulations were further validated experimentally. Therefore, our study indicates that miRNA-mediated gene dysregulation in cardiac NCCs could be an important etiology of congenital heart disease, which could lead to a new direction of diagnostic and therapeutic investigation on congenital heart disease.

5.
Cancer Res ; 81(21): 5572-5581, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34518211

RESUMO

Oxidative phosphorylation (OXPHOS) is an active metabolic pathway in many cancers. RNA from pretreatment biopsies from patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy demonstrated that the top canonical pathway associated with worse outcome was higher expression of OXPHOS signature. IACS-10759, a novel inhibitor of OXPHOS, stabilized growth in multiple TNBC patient-derived xenografts (PDX). On gene expression profiling, all of the sensitive models displayed a basal-like 1 TNBC subtype. Expression of mitochondrial genes was significantly higher in sensitive PDXs. An in vivo functional genomics screen to identify synthetic lethal targets in tumors treated with IACS-10759 found several potential targets, including CDK4. We validated the antitumor efficacy of the combination of palbociclib, a CDK4/6 inhibitor, and IACS-10759 in vitro and in vivo. In addition, the combination of IACS-10759 and multikinase inhibitor cabozantinib had improved antitumor efficacy. Taken together, our data suggest that OXPHOS is a metabolic vulnerability in TNBC that may be leveraged with novel therapeutics in combination regimens. SIGNIFICANCE: These findings suggest that triple-negative breast cancer is highly reliant on OXPHOS and that inhibiting OXPHOS may be a novel approach to enhance efficacy of several targeted therapies.

6.
Microvasc Res ; 139: 104257, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534572

RESUMO

OBJECTIVE: Amiodarone is the first choice for the treatment of arrhythmia, but it is easy to cause extravasation during infusion, after extravasation, it often cause skin injury. The healing of skin injury induced by amiodarone is an inflammatory process. Chrysin, a natural flavonoid, has been investigated to have anti-inflammatory and antioxidant effects. It was reported that chrysin can promote wound healing. So this study aims to investigate the effect of chrysin on amiodarone extravasation-induced skin injury model in rats. METHODS: The rat model of skin extravasation injury was established by subcutaneous injection of 0.5 mL of amiodarone. After successful modeling, the rats were randomly assigned to the five groups: control group, 10% DMSO group, and low-dose, medium-dose, and high-dose chrysin groups (10, 20 and 40 mg/mL). The extravasation injury model was given locally on the same day for seven days. On day 0, 3, 7 and 10 of administration, the lesion's image were taken to calculate the area, and the tissue of the lesion were collected for H&E staining. Then, the level of IL-6 and TNF-α were measured by ELISA, and the protein expression level of bFGF in the wound tissue were detected by immunohistochemical staining. RESULTS: It was found that chrysin groups (20 and 40 mg/mL) compared to contronl group and 10% DMSO solvent group significantly decreased area injury, IL-6 and TNF-α(P < 0.05) on day 3, 7, 10. On the other hand, the chrysin group (40 mg/mL) compared to contronl group and 10% DMSO group significantly increase bFGF(P < 0.05) on day 3, 7. CONCLUSION: Chrysin were effective in reducing injury area, reducing inflammation, and promoting the secretion of bFGF, it can promote the healing of skin injury induced by amiodarone extravasation in rats. These findings provide a good theoretical and experimental basis for the prevention and treatment of amiodarone extravasation-induced skin injury, and provide evidence for finding potential healing agents for the prevention and treatment of amiodarone and other corrosive extravasation-induced injuries from the molecular and cytological levels, thus solving the clinical problems.

7.
Front Oncol ; 11: 705627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422660

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous disease with variable responses to therapy. Cytogenetic and genomic features are used to classify AML patients into prognostic and treatment groups. However, these molecular characteristics harbor significant patient-to-patient variability and do not fully account for AML heterogeneity. RNA-based classifications have also been applied in AML as an alternative approach, but transcriptomic grouping is strongly associated with AML morphologic lineages. We used a training cohort of newly diagnosed AML patients and conducted unsupervised RNA-based classification after excluding lineage-associated genes. We identified three AML patient groups that have distinct biological pathways associated with outcomes. Enrichment of inflammatory pathways and downregulation of HOX pathways were associated with improved outcomes, and this was validated in 2 independent cohorts. We also identified a group of AML patients who harbored high metabolic and mTOR pathway activity, and this was associated with worse clinical outcomes. Using a comprehensive reverse phase protein array, we identified higher mTOR protein expression in the highly metabolic group. We also identified a positive correlation between degree of resistance to venetoclax and mTOR activation in myeloid and lymphoid cell lines. Our approach of integrating RNA, protein, and genomic data uncovered lineage-independent AML patient groups that share biologic mechanisms and can inform outcomes independent of commonly used clinical and demographic variables; these groups could be used to guide therapeutic strategies.

8.
Cell Rep Med ; 2(7): 100349, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34337565

RESUMO

Uncoupling of mRNA expression from copy number (UECN) might be a strategy for cancer cells to a tolerate high degree of aneuploidy. To test the extent and role of UECN across cancers, we perform integrative multiomic analysis of The Cancer Genome Atlas (TCGA) dataset, encompassing ∼5,000 individual tumors. We find UECN is common in cancers and is associated with increased oncogenic signaling, proliferation, and immune suppression. UECN appears to be orchestrated by complex regulatory changes, with transcription factors (TFs) playing a prominent role. To further dissect the regulatory mechanisms, we develop a systems-biology approach to identify candidate TFs, which could serve as targets to disrupt UECN and reduce tumor fitness. Applying our approach to TCGA data, we identify 21 putative targets, 42.8% of which are validated by independent sources. Together, our study indicates that UECN is likely an important mechanism in development of aneuploid tumors and might be therapeutically targetable.

9.
Food Chem ; 363: 130323, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34247035

RESUMO

Resveratrol, in wines, has been implicated to be primarily responsible for the French paradox, remaining controversial. Herein, we elucidated the representative vasodilation-increasing polyphenols from concord grape juice (CGJ) using ex vivo-to-in vivo extrapolation (EVIVE). We verified the interference-free antioxidant response of CGJ post-dose supernatant of deproteinated serum (CPSDS, as ex vivo proxy) in isolated aortic rings, and in healthy, and H2O2-treated endothelial cells (H-ECs). Syringic acid and ferulic acid (SF) were detected in CGJ and post-dose rat serum (PRS). In isolated aortic rings and H-ECs, polyphenols alone, or in combination, at doses equivalent to those detected in PRS, quantitatively reflected endothelium-dependent vasodilation of CPSDS, as evidenced by nitric oxide (NO) formation-mediated antioxidation-sensitive activation of Src kinase with subsequent PI3/Akt-dependent phosphorylation of endothelial NO synthase. Using EVIVE, SF closely reflected CGJ in coronary flow-mediated vasodilation. Hence, SF application in precision ethnomedicine may redefine antioxidant-sensitive vasoprotective resveratrol of the French paradox.


Assuntos
Vasodilatação , Vitis , Animais , Ácidos Cumáricos , Células Endoteliais , Endotélio , Endotélio Vascular , Ácido Gálico/análogos & derivados , Peróxido de Hidrogênio , Óxido Nítrico , Ratos , Resveratrol
10.
Artigo em Inglês | MEDLINE | ID: mdl-34232885

RESUMO

Analyzing single-cell sequencing data from large cohorts is challenging. Discrepancies across experiments and differences among participants often lead to omissions and false discoveries in differentially expressed genes. We find that the Van Elteren test, a stratified version of the widely used Wilcoxon rank-sum test, elegantly mitigates the problem. We also modified the common language effect size to supplement this test, further improving its utility. On both simulated and real patient data we show the ability of Van Elteren test to control for false positives and false negatives. A comprehensive assessment using receiver operating characteristic (ROC) curve shows that Van Elteren test achieves higher sensitivity and specificity on simulated datasets, compared with nine state-of-the-art differential expression analysis methods. The effect size also estimates the differences between cell types more accurately.

11.
Ann Pharmacother ; : 10600280211033938, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282636

RESUMO

BACKGROUND: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. OBJECTIVE: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. METHODS: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. RESULTS: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. CONCLUSION AND RELEVANCE: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

13.
Cell Rep ; 36(3): 109432, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34270918

RESUMO

Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach to coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observe that the choice of cytokines modulates the expansion, phenotype, and hierarchy of antigenic recognition by SARS-CoV-2 T cells. Culture with interleukin (IL)-2/4/7, but not under other cytokine-driven conditions, results in more than 1,000-fold expansion in SARS-CoV-2 T cells with a retained phenotype, function, and hierarchy of antigenic recognition compared with baseline (pre-expansion) samples. Expanded cytotoxic T lymphocytes (CTLs) are directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T cells cannot be expanded efficiently from the peripheral blood of non-exposed controls. Because corticosteroids are used for management of severe COVID-19, we propose an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.

14.
Molecules ; 26(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299565

RESUMO

For the long-term operation of municipal solid waste incineration (MSWI), online monitoring and feedback control of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) can be used to control the emissions to national or regional standards. In this study, 500 PCDD/F samples were determined by thermal desorption gas chromatography coupled to tunable-laser ionization time-of-flight mass spectrometry (TD-GC-TLI-TOFMS) for 168 h. PCDD/F emissions range from 0.01 ng I-TEQ/Nm3 to 2.37 ng I-TEQ/Nm3, with 44% of values below 0.1 ng I-TEQ/Nm3 (the national standard). In addition, the temperature of the furnace outlet, bed pressure, and oxygen content are considered as key operating parameters among the 13 operating parameters comprising four temperature parameters, four pressure parameters, four flow parameters, and oxygen content. More specifically, maintaining the furnace outlet temperature to be higher than 800 °C, or bed pressure higher than 13 kPa, or the oxygen content stably and above 10% are effective methods for reducing PCDD/F emissions. According to the analysis of the Pearson coefficients and maximal information coefficients, there is no significant correlation between operating parameters and PCDD/F I-TEQ. Only when there is a significant change in one of these factors will the PCDD/F emissions also change accordingly. The feedback control of PCDD/F emissions is realized by adjusting the furnace outlet temperature, bed temperature, and bed pressure to control the PCDD/F to be less than 0.1 ng I-TEQ/Nm3.

15.
Sci Rep ; 11(1): 12388, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117319

RESUMO

Sample barcoding is essential in mass cytometry analysis, since it can eliminate potential procedural variations, enhance throughput, and allow simultaneous sample processing and acquisition. Sample pooling after prior surface staining termed live-cell barcoding is more desirable than intracellular barcoding, where samples are pooled after fixation and permeabilization, since it does not depend on fixation-sensitive antigenic epitopes. In live-cell barcoding, the general approach uses two tags per sample out of a pool of antibodies paired with five palladium (Pd) isotopes in order to preserve appreciable signal-to-noise ratios and achieve higher yields after sample deconvolution. The number of samples that can be pooled in an experiment using live-cell barcoding is limited, due to weak signal intensities associated with Pd isotopes and the relatively low number of available tags. Here, we describe a novel barcoding technique utilizing 10 different tags, seven cadmium (Cd) tags and three Pd tags, with superior signal intensities that do not impinge on lanthanide detection, which enables enhanced pooling of samples with multiple experimental conditions and markedly enhances sample throughput.


Assuntos
Separação Celular/métodos , Leucócitos Mononucleares/citologia , Espectrometria de Massas/métodos , Células Cultivadas , Humanos , Imunoensaio/métodos , Leucócitos Mononucleares/classificação , Análise de Célula Única/métodos
16.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34138753

RESUMO

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-ß activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-ß signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-ß axis as a potentially useful therapeutic target in GBM.


Assuntos
Glioblastoma/imunologia , Integrinas/imunologia , Células Matadoras Naturais/imunologia , Proteínas de Neoplasias/imunologia , Células-Tronco Neoplásicas/imunologia , Fator de Crescimento Transformador beta/imunologia , Animais , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/terapia , Xenoenxertos , Humanos , Integrinas/genética , Células Matadoras Naturais/patologia , Masculino , Camundongos , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/imunologia , Fator de Crescimento Transformador beta/genética
17.
Front Pharmacol ; 12: 617678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093177

RESUMO

Background: Pharmacist-led clinical pathways/order sets (PLCOs) were first applied for designated diseases and surgical operations, such as cancer. They were not used in pharmacotherapy until recently. After screening a large number of publications, we found that PLCOs were rarely accessible. Objective: To evaluate the effects and the changes of relevant medical outcomes of PLCOs. Methods: Articles from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and China Biology Medicine disc (CBM) were systematically retrieved. Clinical research comparing cancer patients' clinical effects with or without clinical pathway/order sets was performed. Two reviewers performed quality assessment, and the data were abstracted independently. A narrative synthesis of the extracted data was performed due to heterogeneity. Results: Nine studies were identified, including six uncontrolled before-after studies and three case-series studies. The scopes of PLCOs of included research can be divided into two types, one focusing on chemotherapy agents and the other on the managements of chemotherapy-induced complications. The PLCOs shortened hospital length of stay, decreased initial antibiotic time intervals in patients with febrile neutropenia, reduced medication error incidence, and increased physicians' adherence rate to clinical pathway/order sets. Moreover, three articles included economic effects showing positive savings on medication costs through PLCOs. Conclusion: PLCOs can have beneficial effects on medication effectiveness, safety, and economic outcomes. Nevertheless, clinical pathway/order sets need to be further optimized and expanded to other clinical areas.

18.
Sci Rep ; 11(1): 9858, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972647

RESUMO

Early recognition and rapid initiation of high-quality cardiopulmonary resuscitation (CPR) are key to maximising chances of achieving successful return of spontaneous circulation in patients with out-of-hospital cardiac arrests (OHCAs), as well as improving patient outcomes both inside and outside hospital. Mechanical chest compression devices such as the LUCAS-2 have been developed to assist rescuers in providing consistent, high-quality compressions, even during transportation. However, providing uninterrupted and effective compressions with LUCAS-2 during transportation down stairwells and in tight spaces in a non-supine position is relatively impossible. In this study, we proposed adaptations to the LUCAS-2 to allow its use during transportation down stairwells and examined its effectiveness in providing high-quality CPR to simulated OHCA patients. 20 volunteer emergency medical technicians were randomised into 10 pairs, each undergoing 2 simulation runs per experimental arm (LUCAS-2 versus control) with a loaded Resusci Anne First Aid full body manikin weighing 60 kg. Quality of CPR compressions performed was measured using the CPRmeter placed on the sternum of the manikin. The respective times taken for each phase of the simulation protocol were recorded. Fisher's exact tests were used to analyse categorical variables and median test to analyse continuous variables. The LUCAS-2 group required a longer time (~ 35 s) to prepare the patient prior to transport (p < 0.0001) and arrive at the ambulance (p < 0.0001) compared to the control group. The CPR quality in terms of depth and rate for the overall resuscitation period did not differ significantly between the LUCAS-2 group and control group, though there was a reduction in both parameters when evaluating the device's automated compressions during transport. Nevertheless, the application of the LUCAS-2 device yielded a significantly higher chest compression fraction of 0.76 (p < 0.0001). Our novel adaptations to the LUCAS-2 device allow for uninterrupted compressions in patients being transported down stairwells, thus yielding better chest compression fractions for the overall resuscitation period. Whether potentially improved post-OHCA survival rates may be achieved requires confirmation in a real-world scenario study.


Assuntos
Reanimação Cardiopulmonar/instrumentação , Parada Cardíaca Extra-Hospitalar/terapia , Treinamento por Simulação/métodos , Transporte de Pacientes/métodos , Auxiliares de Emergência , Feminino , Humanos , Masculino , Manequins , Ombro , Macas (Leitos) , Resultado do Tratamento
19.
Biopreserv Biobank ; 19(5): 386-393, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34042506

RESUMO

Objective: To establish a structured and integrated platform of clinical data and biobank data, and a client to retrieve these data. Study Design: Initially, the hospital information system (HIS) and biobank information system (BIS) were integrated through the patients' ID numbers. Then, natural language processing (NLP) was used to process the integrated unstructured clinical information. A query interface was designed for this system, which enabled researchers to retrieve clinical or biobank data. Finally, several queries were listed and manually checked to test the retrieval performance of the system. Results: The construction of the biobank screening system (BSS) was completed, and the data were structured. The BSS took an average of 2 seconds to perform a search for target patients/samples. The retrieval results were consistent with the HIS and BIS. For complex queries, we manually checked the retrieved patients/samples, and the system's accuracy was 100%. Conclusion: This NLP-based system improved biological sample screening and using of clinical data. We will continue to improve this system, enhance resource sharing, and promote the development of translational medicine.


Assuntos
Inteligência Artificial , Registros Eletrônicos de Saúde , Bancos de Espécimes Biológicos , China , Humanos , Processamento de Linguagem Natural
20.
Front Immunol ; 12: 631353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017325

RESUMO

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.


Assuntos
Técnicas de Reprogramação Celular/métodos , Reprogramação Celular/fisiologia , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/prevenção & controle , Células-Tronco Mesenquimais/metabolismo , Animais , Reprogramação Celular/efeitos dos fármacos , Reprogramação Celular/imunologia , Citocinas/farmacologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos NOD , Controle de Qualidade
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