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1.
Genes (Basel) ; 12(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807422

RESUMO

Chinese ginseng (Panax ginseng C. A. Meyer) is a highly cherished traditional Chinese medicine, with several confirmed medical effects and many more asserted health-boosting functions. Somatic chromosomal instability (CIN) is a hallmark of many types of human cancers and also related to other pathogenic conditions such as miscarriages and intellectual disabilities, hence, the study of this phenomenon is of wide scientific and translational medical significance. CIN also ubiquitously occurs in cultured plant cells, and is implicated as a major cause of the rapid decline/loss of totipotency with culture duration, which represents a major hindrance to the application of transgenic technologies in crop improvement. Here, we report two salient features of long-term cultured callus cells of ginseng, i.e., high chromosomal stability and virtually immortalized totipotency. Specifically, we document that our callus of ginseng, which has been subcultured for 12 consecutive years, remained highly stable at the chromosomal level and showed little decline in totipotency. We show that these remarkable features of cultured ginseng cells are likely relevant to the robust homeostasis of the transcriptional expression of specific genes (i.e., genes related to tissue totipotency and chromosomal stability) implicated in the manifestation of these two complex phenotypes. To our knowledge, these two properties of ginseng have not been observed in any animals (with respect to somatic chromosomal stability) and other plants. We posit that further exploration of the molecular mechanisms underlying these unique properties of ginseng, especially somatic chromosomal stability in protracted culture duration, may provide novel clues to the mechanistic understanding of the occurrence of CIN in human disease.

2.
Cell Death Dis ; 12(4): 329, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771975

RESUMO

Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understanding of ERα regulation is critical to shape evolutional treatments for breast cancer. By exploring the regulatory mechanisms of ERα at levels of post-translational modifications, we identified the deubiquitinase USP15 as a novel protector for preventing ERα degradation and a critical driver for breast cancer progression. Specifically, we demonstrated that USP15 promoted the proliferation of ERα+, but not ERα- breast cancer, in vivo and in vitro. Meanwhile, USP15 knockdown notably enhanced the antitumor activities of tamoxifen on breast cancer cells. Importantly, USP15 knockdown induced the downregulation of ERα protein via promoting its K48-linked ubiquitination, which is required for proliferative inhibition of breast cancer cells. These findings not only provide a novel treatment for overcoming resistance to endocrine therapy, but also represent a therapeutic strategy on ERα degradation by targeting USP15-ERα axis.

4.
Hum Pathol ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33713695

RESUMO

Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive neoplasm associated with a rearrangement of the NUT gene on chromosome 15q14. To date, genomic alterations of NCs, especially those in the lung are poorly understood. In this study, immunohistochemistry staining, fluorescence in situ hybridization, and two next-generation sequencing panels (NGS) of 56 and 701 genes were utilized to explore the clinical, pathological, and genetic profiling of pulmonary NCs. Six pulmonary NCs were confirmed with a mean age of 41 years (range: 22-69 years) and a median survival time of 6.5 months (range: 2-19 month). Morphologically, typical abrupt keratinization was observed in four out of six cases (67%), and two patients presented a mixed pattern of classical squamous component and micropapillary adenocarcinoma morphology. We also identified a case with NUT gene amplification instead of rearrangement. Further, NGS analysis demonstrated the following fusions: BRD4-NUTM1 (2/4 cases) and NSD3-NUTM1 (2/4 cases), and highlighted 53 gene mutations, including 50 (94.3%, 50/53) single nucleotide variations (SNVs) and three (5.7%, 3/53) long insertions/deletions. SNVs of MUC16 were the most common, and occurred in three cases (75%). Moreover, SNVs of EPHA8, FANCA, TRIO, and USP6 were detected in two out of four cases (50%). These 53 mutated genes were involved in 13 functional pathways based on enrichment analysis, especially in the PI3K-Akt signaling pathway. Finally, none of the cases showed obvious copy number variations, and had low tumor mutational burden and stable microsatellite sites.

5.
Med Image Anal ; 69: 101975, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33550007

RESUMO

The outbreak of COVID-19 around the world has caused great pressure to the health care system, and many efforts have been devoted to artificial intelligence (AI)-based analysis of CT and chest X-ray images to help alleviate the shortage of radiologists and improve the diagnosis efficiency. However, only a few works focus on AI-based lung ultrasound (LUS) analysis in spite of its significant role in COVID-19. In this work, we aim to propose a novel method for severity assessment of COVID-19 patients from LUS and clinical information. Great challenges exist regarding the heterogeneous data, multi-modality information, and highly nonlinear mapping. To overcome these challenges, we first propose a dual-level supervised multiple instance learning module (DSA-MIL) to effectively combine the zone-level representations into patient-level representations. Then a novel modality alignment contrastive learning module (MA-CLR) is presented to combine representations of the two modalities, LUS and clinical information, by matching the two spaces while keeping the discriminative features. To train the nonlinear mapping, a staged representation transfer (SRT) strategy is introduced to maximumly leverage the semantic and discriminative information from the training data. We trained the model with LUS data of 233 patients, and validated it with 80 patients. Our method can effectively combine the two modalities and achieve accuracy of 75.0% for 4-level patient severity assessment, and 87.5% for the binary severe/non-severe identification. Besides, our method also provides interpretation of the severity assessment by grading each of the lung zone (with accuracy of 85.28%) and identifying the pathological patterns of each lung zone. Our method has a great potential in real clinical practice for COVID-19 patients, especially for pregnant women and children, in aspects of progress monitoring, prognosis stratification, and patient management.


Assuntos
/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
6.
Arch Virol ; 166(5): 1305-1312, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33638089

RESUMO

Echovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.


Assuntos
Echovirus 6 Humano/genética , Infecções por Echovirus/epidemiologia , Infecções por Echovirus/virologia , Proteínas do Capsídeo/genética , China/epidemiologia , Echovirus 6 Humano/classificação , Echovirus 6 Humano/isolamento & purificação , Evolução Molecular , Genótipo , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Humanos , Epidemiologia Molecular , Filogenia , Prevalência , RNA Viral/genética
7.
Thorac Cancer ; 12(6): 993-994, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33569901

RESUMO

A 53-year-old man was admitted to our hospital with a history of a right lung nodule which had gradually increased in size. Wedge resection of the right middle lobe using video-assisted thoracoscopic surgery (VATS) was performed and revealed a yellowish, soft, well circumscribed nodule. Histological analysis confirmed the diagnosis of an uncommon lipolymph node. The patient recovered well from surgery, and there has been no recurrence in the lung for over one-year of follow-up. To the best of our knowledge, this is the first report of a lipolymph node in the lung.

8.
Chronobiol Int ; 38(3): 318-333, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33557625

RESUMO

This meta-analysis investigates the relationship between both shift work and long working hours and risk of developing metabolic syndrome (MetS). PubMed, EMBASE, and Web of Science databases were searched from the outset to December 10, 2019. Two reviewers independently screened studies, extracted data, and assessed the risk of bias of included studies. A total of 36 (30 cross-sectional, 5 cohort, and a nested case-control) studies, involving 274,263 participants, were included. The pooled odds ratio of shift work and development of MetS was 1.35 (95% confidence interval: 1.24-1.48), and the pooled odds ratio of long working hours and development of MetS was 1.19 (95% confidence interval: 0.97-1.46). In the subgroup analysis stratified by gender, the pooled odds ratios for male and female shift workers were 1.25 (95% confidence interval: 1.14-1.37) and 1.47 (95% confidence interval: 1.18-1.82), respectively. The dose-response (number of years of shift work and development of MetS) analysis showed the pooled odds ratio for 5 years of shift work was 1.07 (95% confidence interval: 1.05-1.09) and for 10 years of shift work 1.11 (95% confidence interval: 1.06-1.15). Our meta-analysis confirmed shift work is significantly associated with risk of metabolic syndrome, but the relationship between long working hours and MetS was not substantiated. Additionally, there was a nonlinear dose-response relationship between the number of years of shift work and risk of MetS, showing positive relationship to about 20 years of shift work but not for longer than 20 years. Prospective cohort studies regarding specific shift work schedules are needed to confirm these results.

9.
Cancer Biol Med ; 18(1): 184-198, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628593

RESUMO

Objective: Patient-derived xenograft (PDX) models have shown great promise in preclinical and translational applications, but their consistency with primary tumors in phenotypic, genetic, and pharmacodynamic heterogeneity has not been well-studied. This study aimed to establish a PDX repository for non-small cell lung cancer (NSCLC) and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients. Methods: A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice. Based on the successful establishment of the NSCLC PDX model, we compared the expressions of vimentin, Ki67, EGFR, and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining. In addition, we detected whole gene expression profiling between primary tumors and PDX generations. We also performed whole exome sequencing (WES) analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities. Finally, paclitaxel, cisplatin, doxorubicin, atezolizumab, afatininb, and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents. Results: A large collection of serially transplantable PDX models for NSCLC were successfully developed. The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients' tumor samples. WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors. Similar to clinical patients, PDX models responded differentially to the standard-of-care treatment, including chemo-, targeted- and immuno-therapeutics. Conclusions: Our established PDX models of NSCLC faithfully reproduced the molecular, histopathological, and therapeutic characteristics, as well as the corresponding tumor heterogeneities, which provides a clinically relevant platform for drug screening, biomarker discovery, and translational research.

10.
Theranostics ; 11(5): 2098-2107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500713

RESUMO

Rationale: This study aimed to use computed tomography (CT) images to assess PD-L1 expression in non-small cell lung cancer (NSCLC) and predict response to immunotherapy. Methods: We retrospectively analyzed a PD-L1 expression dataset that consisted of 939 consecutive stage IIIB-IV NSCLC patients with pretreatment CT images. A deep convolutional neural network was trained and optimized with CT images from the training cohort (n = 750) and validation cohort (n = 93) to obtain a PD-L1 expression signature (PD-L1ES), which was evaluated using the test cohort (n = 96). Finally, a separate immunotherapy cohort (n = 94) was used to assess the prognostic value of PD-L1ES with respect to clinical outcome. Results: PD-L1ES was able to predict high PD-L1 expression (PD-L1 ≥ 50%) with areas under the receiver operating characteristic curve (AUC) of 0.78 (95% confidence interval (CI): 0.75~0.80), 0.71 (95% CI: 0.59~0.81), and 0.76 (95% CI: 0.66~0.85) in the training, validation, and test cohorts, respectively. In patients treated with anti-PD-1 antibody, low PD-L1ES was associated with improved progression-free survival (PFS) (median PFS 363 days in low score group vs 183 days in high score group; hazard ratio [HR]: 2.57, 95% CI: 1.22~5.44; P = 0.010). Additionally, when PD-L1ES was combined with a clinical model that was trained using age, sex, smoking history and family history of malignancy, the response to immunotherapy could be better predicted compared to either PD-L1ES or the clinical model alone. Conclusions: The deep learning model provides a noninvasive method to predict high PD-L1 expression of NSCLC and to infer clinical outcomes in response to immunotherapy. Additionally, this deep learning model combined with clinical models demonstrated improved stratification capabilities.

11.
Lung Cancer ; 153: 120-125, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33486417

RESUMO

OBJECTIVES: To investigate the phenomenon of pseudo-small cell transformation (SCT) by reviewing SCT cases from the past 2 years. MATERIALS & METHODS: A total of 11 cases with reported SCT cases from 7282 lung cancer cases treated in West China Hospital of Sichuan University were identified between January 2017 and March 2018. All initial lung adenocarcinoma pathological slides of SCT patients were reviewed carefully by independent, blinded pathologists. Immunohistochemistry was used to identify the expression of EGFRL858R, RB1 and TP53. RESULTS: Surprisingly, 8 of 11 previously SCT samples actually contained variable, but discernible amounts of SCLC components, varying from less than 1%-5%. Dubious small-cell components were found in two other patients. Only one patient's sample had no SCLC component on previous adenocarcinoma sections and was therefore defined as a real SCT case. In the current study, we found that at least 72.7 % (8/11) of SCT cases were actually pseudo-SCT. The immunohistochemistry results showed that the EGFRL858R protein was only expressed in the adenocarcinoma component, but not in the SCLC component, indicating that they may not originate from identical cell clones. RB1 deletion and mutated TP53 overexpression were observed in either pseudo-SCT or real SCT. CONCLUSIONS: Our findings indicated that most SCT may be pseudo-SCT in real world. Pseudo-SCT may lead to bias conclusion from previous researches about SCT. The real mechanism of SCT deserves further investigation.

12.
Chemistry ; 27(18): 5761-5768, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33469957

RESUMO

Nanoscale composites for high-performance electrodes employed in flexible, all-solid-state supercapacitors are being developed. A series of binder-free composites, each consisting of a transition bimetal oxide, a metal oxide, and a metal nitride grown on N-doped reduced graphene oxide (rGO)-wrapped nickel foam are obtained by using a universal strategy. Three different transition metals, Co, Mo, and Fe, are separately compounded with nickel ions, which originate from the nickel foam, to form three composites, NiCoO2 @Co3 O4 @Co2 N, NiMoO4 @MoO3 @Mo2 N, and NiFe2 O4 @Fe3 O4 @Fe2 N, respectively. These as-prepared active materials have similar regular variation patterns in their properties, including better conductivity and battery-mimicking pseudocapacitance, which result in their high whole-electrode capacitance performance [2598.3 F g-1 (39.85 F cm-2 ), 3472.6 F g-1 (41.43 F cm-2 ) and 1907.5 F g-1 (3.41 F cm-2 ) for the composites incorporating Co, Mo, and Fe, respectively]. The as-assembled flexible, all-solid-state NiCoO2 @Co3 O4 @Co2 N//KOH/PVA//NiCoO2 @Co3 O4 @Co2 N device can be easily bent and exhibits high energy density and power density of 92.8 Wh kg-1 and 1670.4 W kg-1 , respectively. The universality of this design strategy could allow it to be employed in producing hybrid materials for high-performance energy-storage devices.

13.
Angew Chem Int Ed Engl ; 60(15): 8521-8525, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33496038

RESUMO

Solid electrolyte interphase (SEI) has been widely employed to describe the new phase formed between anode and electrolyte in working batteries. Significant advances have been achieved on the structure and composition of SEI as well as on the possible ion transport mechanism. However, the nucleation and growth mechanism of SEI catches little attention, which requires the establishment of isothermal electrochemical crystallization theory. Herein we explore the virgin territory of electrochemically crystallized SEI. By using potentiostatic method to regulate the decomposition of anions, an anion-derived SEI forms on graphite surface at atomic scale. After fitting the cur-rent-time transients with Laviron theory and Avrami formula, we conclude that the formation of anion-derived interface is surface reaction controlled and obeys the two-dimensional (2D) progressive nucleation and growth model. Atomic force microscope (AFM) images emphasize the conclusion, which reveals the mystery of isothermal electrochemical crystallization of SEI.

14.
Biotechnol Lett ; 43(3): 711-717, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33386498

RESUMO

OBJECTIVES: To select a microbial consortium from intertidal sludge and evaluate its ability to convert crude glycerol from biodisel to high value-added products such as 1,3-propanediol (1,3-PDO) and lactic acid (LA). RESULTS: A microbial consortium named CJD-S was selected from intertidal sludge and exhibited excellent performance for the conversion of crude glycerol to 1,3-PDO and LA. The composition of CJD-S was determined to be 85.99% Enterobacteriaceae and 13.75% Enterococcaceae by 16S rRNA gene amplicon high-throughput sequencing. In fed-batch fermentation with crude glycerol under nonsterile conditions, the highest concentrations of 1,3-PDO and LA were 41.47 g/L and 45.86 g/L, respectively. CONCLUSIONS: The selected microbial consortium, CJD-S, effectively converted crude glycerol to 1,3-PDO and LA under nonsterile conditions and can contribute to the sustainable development of the biodiesel industry.

15.
BMC Bioinformatics ; 22(1): 32, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499802

RESUMO

BACKGROUND: Anatomical distance has been identified as a key factor in the organizational principles of the human brain. On the other hand, criticality was proposed to accommodate the multiscale properties of human brain dynamics, and functional criticality based on resting-state functional magnetic resonance imaging (rfMRI) is a sensitive neuroimaging marker for human brain dynamics. Hence, to explore the effects of anatomical distance of the human brain on behaviors in terms of functional criticality, we proposed a revised algorithm of functional criticality called the distance-based vertex-wise index of functional criticality, and assessed this algorithm compared with the original neighborhood-based functional criticality. RESULTS: We recruited two groups of healthy participants, including young adults and middle-aged participants, for a total of 60 datasets including rfMRI and intelligence as well as emotional intelligence to study how human brain functional criticalities at different spatial scales contribute to individual behaviors. Furthermore, we defined the average distance between the particular behavioral map and vertices with significant functional connectivity as connectivity distance. Our results demonstrated that intelligence and emotional intelligence mapped to different brain regions at different ages. Additionally, intelligence was related to a wider distance range compared to emotional intelligence. CONCLUSIONS: For different age groups, our findings not only provided a linkage between intelligence/emotional intelligence and functional criticality but also quantitatively characterized individual behaviors in terms of anatomical distance.


Assuntos
Mapeamento Encefálico , Encéfalo , Inteligência Emocional , Imagem por Ressonância Magnética , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Adulto Jovem
16.
J Affect Disord ; 281: 406-412, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359931

RESUMO

BACKGROUND: Little was known on whether drinking habits and water sources affected cognitive function. This study aimed to examine the associations of drinking habits and water sources with the incidence of cognitive impairment in the Chinese elderly population. METHODS: Data were drawn from the Chinese Longitudinal Healthy Longevity Survey. All participants aged ≥ 60 years at baseline were potential eligible. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (CMMSE). Participants with the CMMSE score ≤ 24 were identified as cognitive impairment. Drinking habits included preferring to drink boiled water or un-boiled water. Water sources included well, surface water, spring, and tap water. RESULTS: This study included 18034 participants. Participants drinking un- boiled water were more likely to develop cognitive impairment than those drinking boiled water (P< 0.001; HR: 1.269; and 95% CI: 1.128-1.427). Compared to drinking from a well, drinking from tap water at childhood, around aged 60 years, and present was associated with a lower incidence of cognitive impairment (all P< 0.001; HR: 0.672, 0.735, and 0.765; and 95% CI: 0.540-0.836, 0.686-0.788, and 0.723-0.810, respectively). LIMITATIONS: The underline mechanisms behind the associations of drinking habits and water sources with the incidence of cognitive impairment were not fully explained. CONCLUSIONS: Participants drinking un- boiled water were more likely to develop cognitive impairment. Meanwhile, compared to drinking from a well, drinking from tap water was associated with a lower incidence of cognitive impairment.


Assuntos
Disfunção Cognitiva , Água , Idoso , Criança , China/epidemiologia , Disfunção Cognitiva/epidemiologia , Hábitos , Humanos , Incidência , Pessoa de Meia-Idade
17.
J Am Chem Soc ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284624

RESUMO

Emergent quantum phenomena in electronically coupled two-dimensional heterostructures are central to next-generation optical, electronic, and quantum information applications. Tailoring electronic band gaps in coupled heterostructures would permit control of such phenomena and is the subject of significant research interest. Two-dimensional polymers (2DPs) offer a compelling route to tailored band structures through the selection of molecular constituents. However, despite the promise of synthetic flexibility and electronic design, fabrication of 2DPs that form electronically coupled 2D heterostructures remains an outstanding challenge. Here, we report the rational design and optimized synthesis of electronically coupled semiconducting 2DP/2D transition metal dichalcogenide van der Waals heterostructures, demonstrate direct exfoliation of the highly crystalline and oriented 2DP films down to a few nanometers, and present the first thickness-dependent study of 2DP/MoS2 heterostructures. Control over the 2DP layers reveals enhancement of the 2DP photoluminescence by two orders of magnitude in ultrathin sheets and an unexpected thickness-dependent modulation of the ultrafast excited state dynamics in the 2DP/MoS2 heterostructure. These results provide fundamental insight into the electronic structure of 2DPs and present a route to tune emergent quantum phenomena in 2DP hybrid van der Waals heterostructures.

18.
Toxicol Lett ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33290829

RESUMO

Belinostat is a pan-histone deacetylase (HDAC) inhibitor which recently approved for the treatment of relapsed/refractory Peripheral T-cell lymphomas (PTCL). To assess drug-drug interactions (DDIs) potential of belinostat via inhibition of UDP-glucuronosyltransferases (UGTs), the effects of belinostat on UGTs activities were investigated using the non-selective probe substrate 4-methylumbelliferone (4-MU) and trifluoperazine (TFP) by UPLC-MS/MS. Belinostat exhibited a wide range of inhibition against UGTs activities, particularly a potent non-competitive inhibition against UGT1A3, and weak inhibition against UGT1A1, 1A7, 1A8, 2B4 and 2B7. Further, in vitro-in vivo extrapolation (IVIVE) approaches were used to predict the risk of DDI arising from inhibition of UGTs. Our data indicate that the intravenous infusion of belinostat at clinical available dose can contribute a significant increase to the AUC of co-administrated drugs primarily cleared by UGT1A3 or UGT1A1, which will result in potential DDIs. In contrast, oral administrated belinostat is unlikely to cause significant DDIs through inhibition of glucuronidation.

19.
J Exp Clin Cancer Res ; 39(1): 284, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317597

RESUMO

The enthusiasm for immune checkpoint inhibitors (ICIs), an efficient tumor treatment model different from traditional treatment, is based on their unprecedented antitumor effect, but the occurrence of immune-related adverse events (irAEs) is an obstacle to the prospect of ICI treatment. IrAEs are a discrete toxicity caused by the nonspecific activation of the immune system and can affect almost all tissues and organs. Currently, research on biomarkers mainly focuses on the gastrointestinal tract, endocrine system, skin and lung. Several potential hypotheses concentrate on the overactivation of the immune system, excessive release of inflammatory cytokines, elevated levels of pre-existing autoantibodies, and presence of common antigens between tumors and normal tissues. This review lists the current biomarkers that might predict irAEs and their possible mechanisms for both nonspecific and organ-specific biomarkers. However, the prediction of irAEs remains a major clinical challenge to screen and identify patients who are susceptible to irAEs and likely to benefit from ICIs.

20.
Crit Care ; 24(1): 700, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353548

RESUMO

BACKGROUND: Bedside lung ultrasound (LUS) has emerged as a useful and non-invasive tool to detect lung involvement and monitor changes in patients with coronavirus disease 2019 (COVID-19). However, the clinical significance of the LUS score in patients with COVID-19 remains unknown. We aimed to investigate the prognostic value of the LUS score in patients with COVID-19. METHOD: The LUS protocol consisted of 12 scanning zones and was performed in 280 consecutive patients with COVID-19. The LUS score based on B-lines, lung consolidation and pleural line abnormalities was evaluated. RESULTS: The median time from admission to LUS examinations was 7 days (interquartile range [IQR] 3-10). Patients in the highest LUS score group were more likely to have a lower lymphocyte percentage (LYM%); higher levels of D-dimer, C-reactive protein, hypersensitive troponin I and creatine kinase muscle-brain; more invasive mechanical ventilation therapy; higher incidence of ARDS; and higher mortality than patients in the lowest LUS score group. After a median follow-up of 14 days [IQR, 10-20 days], 37 patients developed ARDS, and 13 died. Patients with adverse outcomes presented a higher rate of bilateral involvement; more involved zones and B-lines, pleural line abnormalities and consolidation; and a higher LUS score than event-free survivors. The Cox models adding the LUS score as a continuous variable (hazard ratio [HR]: 1.05, 95% confidence intervals [CI] 1.02 ~ 1.08; P < 0.001; Akaike information criterion [AIC] = 272; C-index = 0.903) or as a categorical variable (HR 10.76, 95% CI 2.75 ~ 42.05; P = 0.001; AIC = 272; C-index = 0.902) were found to predict poor outcomes more accurately than the basic model (AIC = 286; C-index = 0.866). An LUS score cut-off > 12 predicted adverse outcomes with a specificity and sensitivity of 90.5% and 91.9%, respectively. CONCLUSIONS: The LUS score devised by our group performs well at predicting adverse outcomes in patients with COVID-19 and is important for risk stratification in COVID-19 patients.


Assuntos
/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Estudos Prospectivos , /virologia , Tempo para o Tratamento , Tomografia Computadorizada por Raios X
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