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1.
EMBO J ; 41(24): e111021, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-35993232

RESUMO

Individual cells within de novo polarising tubes and cavities must integrate their forming apical domains into a centralised apical membrane initiation site (AMIS). This is necessary to enable organised lumen formation within multi-cellular tissue. Despite the well-documented importance of cell division in localising the AMIS, we have found a division-independent mechanism of AMIS localisation that relies instead on Cadherin-mediated cell-cell adhesion. Our study of de novo polarising mouse embryonic stem cells (mESCs) cultured in 3D suggests that cell-cell adhesion localises apical proteins such as PAR-6 to a centralised AMIS. Unexpectedly, we also found that mESC clusters lacking functional E-cadherin still formed a lumen-like cavity in the absence of AMIS localisation but did so at a later stage of development via a "closure" mechanism, instead of via hollowing. This work suggests that there are two, interrelated mechanisms of apical polarity localisation: cell adhesion and cell division. Alignment of these mechanisms in space allows for redundancy in the system and ensures the development of a coherent epithelial structure within a growing organ.


Assuntos
Caderinas , Polaridade Celular , Animais , Camundongos , Caderinas/genética , Caderinas/metabolismo , Membrana Celular/metabolismo , Adesão Celular , Células Epiteliais/metabolismo
2.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517697

RESUMO

Non-coding variants associated with complex traits can alter the motifs of transcription factor (TF)-deoxyribonucleic acid binding. Although many computational models have been developed to predict the effects of non-coding variants on TF binding, their predictive power lacks systematic evaluation. Here we have evaluated 14 different models built on position weight matrices (PWMs), support vector machines, ordinary least squares and deep neural networks (DNNs), using large-scale in vitro (i.e. SNP-SELEX) and in vivo (i.e. allele-specific binding, ASB) TF binding data. Our results show that the accuracy of each model in predicting SNP effects in vitro significantly exceeds that achieved in vivo. For in vitro variant impact prediction, kmer/gkm-based machine learning methods (deltaSVM_HT-SELEX, QBiC-Pred) trained on in vitro datasets exhibit the best performance. For in vivo ASB variant prediction, DNN-based multitask models (DeepSEA, Sei, Enformer) trained on the ChIP-seq dataset exhibit relatively superior performance. Among the PWM-based methods, tRap demonstrates better performance in both in vitro and in vivo evaluations. In addition, we find that TF classes such as basic leucine zipper factors could be predicted more accurately, whereas those such as C2H2 zinc finger factors are predicted less accurately, aligning with the evolutionary conservation of these TF classes. We also underscore the significance of non-sequence factors such as cis-regulatory element type, TF expression, interactions and post-translational modifications in influencing the in vivo predictive performance of TFs. Our research provides valuable insights into selecting prioritization methods for non-coding variants and further optimizing such models.


Assuntos
Polimorfismo de Nucleotídeo Único , Fatores de Transcrição , Sítios de Ligação/genética , Ligação Proteica/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , DNA/genética
3.
J Am Chem Soc ; 146(4): 2711-2717, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38237137

RESUMO

The coconversion of two kinds of waste materials, plastics and CO2, into a single value-added product is an innovative and challenging endeavor that simultaneously achieves the upcycling of plastic waste and reduces CO2 emissions. Herein, we report a one-pot, two-step catalytic process for transforming polyesters, such as poly(glycolic acid), carbonate, and water, into sodium formate with a high yield of 79%, using a commercial Pd/C catalyst. This process involves the aqueous-phase reforming of polyester with water at 250-270 °C and the hydrogenation of NaHCO3 at 150 °C, utilizing H2 generated during the reforming process. Notably, no external H2 or other reactive reagents are required. This strategy can be applied for the coconversion of poly(ethylene terephthalate) (PET), poly(butylene-adipate-co-terephthalate) (PBAT), and commercial biodegradable plastic bags with Na2CO3 obtained from CO2 capture via a NaOH solution, opening up a new path for "turning trash into treasure".

4.
Chemistry ; : e202401960, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777797

RESUMO

Cation order, which can be controlled by synthesis conditions and stoichiometry, plays an important role in properties of perovskite materials. Here we show that aliovalent doping by Sb5+ in Sm2MnMn(Mn4-xSbx)O12 quadruple perovskite solid solutions can control cation orders in both A and B sites. Samples with 0.4≤x≤2 were synthesized by a high-pressure, high-temperature method at 6 GPa and 1770 K. Three regions with different cation orders were found at 0.5≤x≤1.0, x=1.5-1.6, and x=1.8. The 0.5≤x≤1.0 compositions have a B-site-disordered and A-site columnar-ordered structure with space group P42/nmc; the x=1.5 and 1.6 samples have a B-site rock-salt-ordered and A-site columnar-ordered structure with space group P42/n; the x=1.8 sample has a B-site rock-salt-ordered and A-site-disordered structure with space group P21/n. All the samples show one ferrimagnetic transition: TC increases from 35 K to 73 K for 0.5≤x≤1.0, TC=81 K for x=1.5 and 1.6, and TC=53 K for x=1.8.

5.
J Cell Sci ; 134(17)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34368835

RESUMO

Epithelia migrate as physically coherent populations of cells. Previous studies have revealed that mechanical stress accumulates in these cellular layers as they move. These stresses are characteristically tensile in nature and have often been inferred to arise when moving cells pull upon the cell-cell adhesions that hold them together. We now report that epithelial tension at adherens junctions between migrating cells also increases due to an increase in RhoA-mediated junctional contractility. We found that active RhoA levels were stimulated by p114 RhoGEF (also known as ARHGEF18) at the junctions between migrating MCF-7 monolayers, and this was accompanied by increased levels of actomyosin and mechanical tension. Applying a strategy to restore active RhoA specifically at adherens junctions by manipulating its scaffold, anillin, we found that this junctional RhoA signal was necessary to stabilize junctional E-cadherin (CDH1) during epithelial migration and promoted orderly collective movement. We suggest that stabilization of E-cadherin by RhoA serves to increase cell-cell adhesion to protect against the mechanical stresses of migration. This article has an associated First Person interview with the first author of the paper.


Assuntos
Junções Aderentes , Proteína rhoA de Ligação ao GTP , Citoesqueleto de Actina/metabolismo , Actomiosina/metabolismo , Junções Aderentes/metabolismo , Caderinas/genética , Caderinas/metabolismo , Células Epiteliais/metabolismo , Humanos , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Transdução de Sinais , Proteína rhoA de Ligação ao GTP/metabolismo
6.
BMC Infect Dis ; 23(1): 472, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461013

RESUMO

BACKGROUND: Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients. METHODS: This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS: A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3-4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04-18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11-6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21-5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22-4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03-6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit. CONCLUSIONS: Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.


Assuntos
Infecção Hospitalar , Neoplasias Pulmonares , Humanos , Mortalidade Hospitalar , Nomogramas , Estudos Retrospectivos , Prognóstico
7.
BMC Anesthesiol ; 23(1): 397, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049713

RESUMO

BACKGROUND AND OBJECTIVE: The effectiveness of goal-directed fluid therapy (GDFT) in promoting postoperative recovery remains unclear, the aim of this study was to evaluate the effect of GDFT on length of hospital stay and postoperative recovery of GI function in patients undergoing major abdominal oncologic surgery. METHODS: In this randomized, double- blinded, controlled trial, adult patients scheduled for elective major abdominal surgery with general anesthesia, were randomly divided into the GDFT protocol (group G) or conventional fluid therapy group (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP) and central venous pressure (CVP) whereas those in group G received GDFT protocol associated with the SVV less than 12% and the cardiac index (CI) was controlled at a minimum of 2.5 L/min/m2. The primary outcomes were the length of hospital stay and postoperative GI function. RESULTS: One hundred patients completed the study protocol. The length of hospital stay was significantly shorter in group G compared with group C [9.0 ± 5.8 days versus 12.0 ± 4.6 days, P = 0.001]. Postoperative gastrointestinal dysfunction (POGD) occurred in two of 50 patients (4%) in group G and 16 of 50 patients (32%) in the control group (P < 0.001). GDFT significantly also shorten time to first flatus by 11 h (P = 0.009) and time to first tolerate oral diet by 2 days (P < 0.001). CONCLUSIONS: Guided by SVV and CI, the application of GDFT has the potential to expedite postoperative recovery of GI function and reduce hospitalization duration after major abdominal surgery. TRIAL REGISTRATION: This study was registered on www. CLINICALTRIALS: gov on 07/05/2019 with registration number: NCT03940144.


Assuntos
Abdome , Objetivos , Adulto , Humanos , Tempo de Internação , Volume Sistólico , Abdome/cirurgia , Hidratação/métodos , Complicações Pós-Operatórias/epidemiologia
8.
Perfusion ; 38(3): 557-566, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35102779

RESUMO

BACKGROUND: Atherosclerosis (AS), one of the leading causes of deaths and disabilities, is a kind of vascular disease of lipid disorders and chronic inflammation. Guanxinping (GXP) has been administrated in the treatment of AS for nearly 20 years with satisfying clinical response. This study aimed to explore its underlying mechanisms of anti-atherosclerotic effect in AS. METHODS: Male ApoE-/- mice were randomized into five groups and fed with either standard diet (control group, CON) or high-fat diet (HFD) for 12 weeks. HFD mice were further divided randomly and either fed continually with HFD as a model group, or atorvastatin (ATO), or low-dose GXP (LGXP), or high-dose GXP (HGXP). After 12 weeks, the body weight, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were detected. Moreover, serum inflammation cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) concentrations were measured. The structure of aortic tissues was examined by hematoxylin-eosin staining. The mRNA expression of TNF-α, IL-6, and IL-1ß were assessed by qPCR. The protein expressions of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1ß, p38MAPK, ERK1/2, JNK, IκB-α, and NF-κBp65 in the aorta were also detected. RESULTS: GXP treatment reduced serum TG, TC, and LDL-c levels in ApoE-/- mice. Moreover, GXP reduced lipid accumulation in the aorta of ApoE-/- mice, induced by HFD. Furthermore, GXP ameliorated the aorta morphological damage and reduced the serum TNF-α, IL-6, and IL-1ß levels. GXP also attenuated the protein expression of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1ß, p38MAPK, ERK1/2, JNK, and NF-κBp65, whereas it increased the IκBα level in aortic tissues of ApoE-/- mice. CONCLUSIONS: Our results show that GXP could ameliorate atherosclerosis, which is mediated by inhibition of the MAPK/NF-κB signaling pathway in ApoE-/- mice. This study provides evidence that GXP might be a promising drug for the treatment of AS.


Assuntos
Aterosclerose , NF-kappa B , Masculino , Camundongos , Animais , NF-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/farmacologia , Molécula 1 de Adesão Intercelular/uso terapêutico , Sistema de Sinalização das MAP Quinases , Interleucina-6 , Fator de Necrose Tumoral alfa , LDL-Colesterol/metabolismo , LDL-Colesterol/farmacologia , LDL-Colesterol/uso terapêutico , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/farmacologia , Molécula 1 de Adesão de Célula Vascular/uso terapêutico , Aterosclerose/genética , Transdução de Sinais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/farmacologia , Camundongos Endogâmicos C57BL
9.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686364

RESUMO

Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors. Kidney diseases and cancers commonly exhibit characteristic pathological features, such as the involvement of inflammatory cells and persistent chronic inflammation. Remarkably, CDK4/6 inhibitors have demonstrated impressive efficacy in treating non-cancerous conditions, including certain kidney diseases. Current studies have identified the renoprotective effect of CDK4/6 inhibitors, presenting a novel idea and potential direction for treating kidney diseases in the future. In this review, we briefly reviewed the cell cycle in mammals and the role of CDK4/6 in regulating it. We then provided an introduction to CDK4/6 inhibitors and their use in cancer treatment. Additionally, we emphasized the importance of these inhibitors in the treatment of kidney diseases. Collectively, growing evidence demonstrates that targeting CDK4 and CDK6 through CDK4/6 inhibitors might have therapeutic benefits in various cancers and kidney diseases and should be further explored in the future.


Assuntos
Antineoplásicos , Nefropatias , Neoplasias , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapias em Estudo , Divisão Celular , Inflamação , Nefropatias/tratamento farmacológico , Mamíferos , Neoplasias/tratamento farmacológico
10.
Angew Chem Int Ed Engl ; 62(48): e202310920, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-37842955

RESUMO

Spatiotemporal manipulation of biological processes in living animals using noninvasive, remote-controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT-NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT-NIR system was demonstrated through the NIR-triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer-aided screening, CAT-NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue-penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote-controlled rescue of drug molecules. Given its broad adaptability, this CAT-NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.


Assuntos
Pró-Fármacos , Camundongos , Animais , Pró-Fármacos/química , Raios Infravermelhos , Proteínas
11.
Int J Med Sci ; 19(4): 711-728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35582412

RESUMO

Background: Lipid metabolism plays a pivotal role in cancer progression and metastasis. This study aimed to investigate the prognostic value of lipid metabolism-related genes (LMRGs) in early-stage lung adenocarcinoma (LUAD) and develop a lipid metabolism-related gene prognostic index (LMRGPI) to predict their overall survival (OS) and treatment response. Methods: A total of 774 early-stage LUAD patients were identified from The Cancer Genome Atlas (TCGA, 403 patients) database and Gene Expression Omnibus (GEO, 371 patients) database. The non-negative Matrix Factorization (NMF) algorithm was used to identify different population subtypes based on LMRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to develop the LMRGPI, with receiver operating characteristic (ROC) curves and concordance index being used to evaluate its performance. The characteristics of mutation landscape, enriched pathways, tumor microenvironment (TME), and treatment response between different LMRGPI groups were also investigated. Results: We identified two population subtypes based on LMRGs in the TCGA-LUAD cohort, with distinct prognosis, TME, and immune status being observed. LMRGPI was developed based on the expression levels of six LMRGs, including ANGPTL4, NPAS2, SLCO1B3, ACOXL, ALOX15, and B3GALNT1. Higher LMRGPI was correlated with poor OS both in TCGA and GSE68465 cohorts. Two nomograms were established to predict the survival probability of early-stage LUAD, with higher consistencies being observed between the predicted and actual OS. Higher LMRGPI was significantly correlated with more frequent TP53 mutation, higher tumor mutation burden (TMB), and up-regulation of CD274. Besides, patients with higher LMRGPI presented unremarkable responses for gefitinib, erlotinib, cisplatin, and vinorelbine, while they tend to have a favorable response for immune checkpoint inhibitors (ICIs). The opposite results were observed in the low-LMRGPI group. Conclusions: We comprehensively investigated the prognostic value of LMRGs in early-stage LUAD. Given its good prognostic ability, LMRGPI could serve as a promising biomarker to predict the OS and treatment response of these patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Perfilação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Microambiente Tumoral/genética
12.
Cancer Control ; 28: 10732748211051228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34632799

RESUMO

INTRODUCTION: Combined small cell lung cancer (C-SCLC) represents a rare subtype of all small cell lung cancer cases, with limited studies investigated its prognostic factors. The aim of this study was to construct a novel nomogram to predict the overall survival (OS) of patients with C-SCLC. METHODS: In this retrospective study, a total of 588 C-SCLC patients were selected from the Surveillance, Epidemiology, and End Results database. The univariate and multivariate Cox analyses were performed to identify optimal prognostic variables and construct the nomogram, with concordance index (C-index), receiver operating characteristic curves, and calibration curves being used to evaluate its discrimination and calibration abilities. Furthermore, decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) were also adopted to assess its clinical utility and predictive ability compared with the classic TNM staging system. RESULTS: Seven independent predictive factors were identified to construct the nomogram, including T stage, N stage, M stage, brain metastasis, liver metastasis, surgery, and chemotherapy. We observed a higher C-index in both the training (.751) and validation cohorts (.736). The nomogram has higher area under the curve in predicting 6-, 12-, 18-, 24-, and 36-month survival probability of patients with C-SCLC. Meanwhile, the calibration curves also revealed high consistencies between the actual and predicted OS. DCA revealed that the nomogram could provide greater clinical net benefits to these patients. We found that the NRI for 6- and 12-month OS were .196 and .225, and the IDI for 6- and 12-month OS were .217 and .156 in the training group, suggesting that the nomogram can predict a more accurate survival probability. Similar results were also observed in the validation cohort. CONCLUSION: We developed and verified a novel nomogram that can help clinicians recognize high-risk patients with C-SCLC and predict their OS.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Nomogramas , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Curva ROC , Estudos Retrospectivos , Programa de SEER , Carcinoma de Pequenas Células do Pulmão/terapia
13.
Cancer Control ; 28: 10732748211050581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34654345

RESUMO

OBJECTIVES: Numerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg's and Egger's tests were also conducted. RESULTS: Sixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC. CONCLUSION: Dynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.


Assuntos
Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia
14.
Int J Med Sci ; 18(1): 226-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390791

RESUMO

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Microambiente Tumoral/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Modelos Genéticos , Modelos Imunológicos , Mutação , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Microambiente Tumoral/genética , Macrófagos Associados a Tumor/imunologia
15.
BMC Public Health ; 21(1): 1533, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380456

RESUMO

BACKGROUND: Cardiovascular disease (CVD), one of the most common comorbidities of coronavirus disease 2019 (COVID-19), has been suspected to be associated with adverse outcomes in COVID-19 patients, but their correlation remains controversial. METHOD: This is a quantitative meta-analysis on the basis of adjusted effect estimates. PubMed, Web of Science, MedRxiv, Scopus, Elsevier ScienceDirect, Cochrane Library and EMBASE were searched comprehensively to obtain a complete data source up to January 7, 2021. Pooled effects (hazard ratio (HR), odds ratio (OR)) and the 95% confidence intervals (CIs) were estimated to evaluate the risk of the adverse outcomes in COVID-19 patients with CVD. Heterogeneity was assessed by Cochran's Q-statistic, I2test, and meta-regression. In addition, we also provided the prediction interval, which was helpful for assessing whether the variation across studies was clinically significant. The robustness of the results was evaluated by sensitivity analysis. Publication bias was assessed by Begg's test, Egger's test, and trim-and-fill method. RESULT: Our results revealed that COVID-19 patients with pre-existing CVD tended more to adverse outcomes on the basis of 203 eligible studies with 24,032,712 cases (pooled ORs = 1.41, 95% CIs: 1.32-1.51, prediction interval: 0.84-2.39; pooled HRs = 1.34, 95% CIs: 1.23-1.46, prediction interval: 0.82-2.21). Further subgroup analyses stratified by age, the proportion of males, study design, disease types, sample size, region and disease outcomes also showed that pre-existing CVD was significantly associated with adverse outcomes among COVID-19 patients. CONCLUSION: Our findings demonstrated that pre-existing CVD was an independent risk factor associated with adverse outcomes among COVID-19 patients.


Assuntos
COVID-19 , Doenças Cardiovasculares , Doenças Cardiovasculares/epidemiologia , Comorbidade , Humanos , Masculino , Fatores de Risco , SARS-CoV-2
16.
BMC Anesthesiol ; 21(1): 304, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34856931

RESUMO

BACKGROUND: Postoperative pulmonary embolism (PE) is a serious thrombotic complication in the patients with otolaryngologic cancers. We investigated the risk factors associated with postoperative PE after radical resection of head and neck cancers. METHODS: A total of 3512 patients underwent head and neck cancers radical resection from 2013 to 2019. A one-to-three control group without postoperative PE was selected matched by age, gender, and type of cancer. Univariate analyses were performed for the perioperative patient data including hemodynamic management factors. Conditional logistic regression was used to analyze the factors and their odds ratios. RESULTS: Postoperative PE was prevalent in 0.85% (95%CI = 0.56-1.14). Univariate analyses showed that a high ASA grade, high BMI, and smoking history may be related to postoperative PE. There was significantly difference in operation time between the two groups, especially for> 4 h [22(78.6%) vs 43(51.2%), P = .011]. The urine output was lower [1.37(0.73-2.21) ml·kg- 1·h- 1 vs 2.14(1.32-3.46) ml·kg- 1·h- 1, P = .006] and the incidence of oliguria was significantly increased (14.3% vs 1.2%, P = .004) in the PE group. Multivariable conditional logistic regression showed postoperative PE were associated with the cumulative duration for intraoperative hypotension (OR = 2.330, 95%CI = 1.428-3.801, P = .001), oliguria (OR = 14.844, 95%CI = 1.089-202.249, P = .043), and operation time > 4 h (OR = 4.801, 95%CI = 1.054-21.866, P = .043). CONCLUSIONS: The intraoperative hypotension, oliguria, and operation time > 4 h are risk factors associated with postoperative PE after radical resection of head and neck cancers. Improving intraoperative hemodynamics management to ensure adequate blood pressure and urine output may reduce the occurrence of such complications.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Hipotensão/epidemiologia , Complicações Intraoperatórias/epidemiologia , Oligúria/epidemiologia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Embolia Pulmonar/epidemiologia , Pequim/epidemiologia , Estudos de Casos e Controles , Causalidade , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Org Biomol Chem ; 18(19): 3707-3716, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32356531

RESUMO

Mild [2 + 2] photodimerization of enone substrates was induced by donor-acceptor fluorophores. Enone substrates were activated efficiently for anti-head to head dimerizations with a high yield (up to 83%) and high selectivity. The adjustable excited state potential also allows donor-acceptor fluorophores to be used for isomerization of the above substrates, confirming the potential of donor-acceptor fluorophores as energy transfer photocatalysts.

18.
BMC Infect Dis ; 20(1): 452, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600270

RESUMO

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Neoplasias/microbiologia , Idoso , Antibacterianos/farmacologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
19.
J Stroke Cerebrovasc Dis ; 29(11): 105283, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066922

RESUMO

OBJECTIVE: The aim of this study was to address the association between cerebrovascular disease and adverse outcomes in coronavirus disease 2019 (COVID-19) patients by using a quantitative meta-analysis based on adjusted effect estimates. METHOD: A systematic search was performed in PubMed, Web of Science, and EMBASE up to August 10th, 2020. The adjusted effect estimates were extracted and pooled to evaluate the risk of the unfavorable outcomes in COVID-19 patients with cerebrovascular disease. Subgroup analysis and meta-regression were also carried out. RESULTS: There were 12 studies with 10,304 patients included in our meta-analysis. A significant trend was observed when evaluating the association between cerebrovascular disease and adverse outcomes (pooled effect = 2.05, 95% confidence interval (CI): 1.34-3.16). In addition, the pooled effects showed that patients with a history of cerebrovascular disease had more likelihood to progress fatal outcomes than patients without a history of cerebrovascular disease (pooled effect = 1.78, 95% CI: 1.04-3.07). CONCLUSION: This study for the first time indicated that cerebrovascular disease was an independent risk factor for predicting the adverse outcomes, particularly fatal outcomes, in COVID-19 patients on the basis of adjusted effect estimates. Well-designed studies with larger sample size are needed for further verification.


Assuntos
Transtornos Cerebrovasculares/terapia , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Adulto , Idoso , COVID-19 , Causas de Morte , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/mortalidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Int J Urol ; 26(6): 624-629, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30861595

RESUMO

OBJECTIVES: To develop a predictive model for the oncological outcomes of clear cell renal cell carcinoma in a Chinese population. METHODS: A retrospective study of 1108 patients with clear cell renal cell carcinoma who underwent nephrectomy or partial nephrectomy between January 2006 and December 2013 was carried out. Recurrence-free survival was calculated using Kaplan-Meier analysis. Differences between the groups were compared using the log-rank test. Cox proportional hazard regression was used to test associations between features and outcomes. The discriminative ability of the models was validated using Harrell's concordance index and bootstrapping. RESULTS: Overall, 942 patients who met the inclusion criteria had been followed. The median follow-up period was 72 months (range 1-143 months). Multivariate analysis showed that age, Eastern Cooperative Oncology Group performance status, preoperative platelet count, neutrophil-to-lymphocyte ratio, tumor size, 2010 tumor stage (pT3 and pT4) and Fuhrman nuclear grade were independent risk factors affecting recurrence-free survival in clear cell renal cell carcinoma patients (P < 0.05). These factors were assigned to develop a new model. The patients were divided into three groups based on the risk of recurrence. The difference among the prognoses of patients in the three groups was statistically significant (P < 0.05). The concordance index for our new model and that for Leibovich's 2018 model were 0.791 and 0.750, respectively. CONCLUSIONS: In the present study, the new model has a higher concordance index than does Leibovich's 2018 model of clear cell renal cell carcinoma in the Asian population, with no added pain for patients. This new model might be an appropriate risk stratification tool for clinical work.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/cirurgia , China/epidemiologia , Feminino , Humanos , Neoplasias Renais/cirurgia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Nefrectomia/estatística & dados numéricos , Contagem de Plaquetas , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
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