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1.
Front Med (Lausanne) ; 8: 720119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631744

RESUMO

Background: Diagnosing chronic pulmonary aspergillosis is a major challenge in clinical practice. The development and validation of a novel, sensitive and specific assay for diagnosing chronic pulmonary aspergillosis is urgently needed. Methods: From April 2018 to June 2019, 53 patients with chronic pulmonary aspergillosis (CPA), 32 patients with community-acquired pneumonia (CAP) and 48 healthy controls were recruited from the First Affiliated Hospital of Guangzhou Medical University. Clinical characteristics and samples were collected at enrollment. All exhaled breath samples were analyzed offline using thermal desorption single-photon ionization time-of-flight mass spectrometry; to analyze the metabolic pathways of the characteristic volatile organic compounds, serum samples were subjected to ultrahigh-performance liquid chromatography. Results: We identified characteristic volatile organic compounds in patients with chronic pulmonary aspergillosis, which mainly consisted of phenol, neopentyl alcohol, toluene, limonene and ethylbenzene. These compounds were assessed using a logistic regression model. The sensitivity and specificity were 95.8 and 96.9% for discriminating patients in the CPA group from those in the CAP group and 95.8 and 97.9% for discriminating patients in the CPA group from healthy controls, respectively. The concentration of limonene (m/z 136) correlated significantly positively with anti-Aspergillus fumigatus IgG antibody titers (r = 0.420, P < 0.01). After antifungal treatment, serum IgG and the concentration of limonene (m/z 136) decreased in the subgroup of patients with chronic pulmonary aspergillosis. Conclusions: We identified VOCs that can be used as biomarkers for differential diagnosis and therapeutic response prediction in patients with chronic pulmonary aspergillosis.

2.
Front Microbiol ; 12: 751073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603275

RESUMO

Clinical value of metagenomic next-generation sequencing (mNGS) in pneumonia management is still controversial. A prospective study was conducted to evaluate the clinical impact of PneumoSeq in 57 immunocompetent (ICO) and 75 immunocompromised (ICH) pneumonia patients. The value of PneumoSeq for both etiological and clinical impact investigation in pneumonia was assessed. Among the 276 potential pathogens detected with PneumoSeq in our cohort, 251 (90.9%) were cross-validated. Clinical diagnoses of the causative pathogens were obtained for 97 patients, 90.7% of which were supported by PneumoSeq. Compared to conventional testing, PneumoSeq suggested potentially missed diagnoses in 16.7% of cases (22/132), involving 48 additional pathogenic microorganisms. In 58 (43.9%) cases, PneumoSeq data led to antimicrobial treatment de-escalation (n = 12 in ICO, n = 18 in ICH) and targeted treatment initiation (n = 7 in ICO, n = 21 in ICH). The PneumoSeq assay benefited the diagnosis and clinical management of both ICH and ICO pneumonia patients in real-world settings.

3.
Ann Clin Lab Sci ; 51(5): 698-704, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34686513

RESUMO

OBJECTIVE: Studies have confirmed that real-time PCR detection of Aspergillus DNA in bronchoalveolar lavage fluid (BALF) is more valuable than blood samples in the diagnosis of invasive pulmonary aspergillosis (IPA). The latest guidelines recommend the use of serum samples for Aspergillus antibody testing for chronic pulmonary aspergillosis (CPA). However, research on CPA diagnosed by real-time PCR testing of BALF has been limited. In this study, we assessed the clinical value of BALF GM and PCR detection in diagnosing CPA. METHODS: The diagnostic criteria of this study were based on the 2015 ESCMID/ERS guidelines for CPA. Seventy-nine patients with CPA and 74 non-CPA patients were enrolled. Aspergillus DNA in BALF was detected in the patients with CPA. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of BALF PCR in the CPA group were 87.18%, 89.80%, 87.18%, 89.80%, and 0.89 (95% CI 0.82-0.95), respectively (P<0.005). The sensitivity, specificity, PPV, and NPV of BALF Aspergillus galactomannan (GM) detection in the CPA group were 66.67%, 89.80%, 83.87%, and 77.19%, respectively, and the AUC was 0.94 (95% CI 0.89-0.99) (P<0.005). When combining BALF GM and BALF PCR detection, the sensitivity, specificity, PPV, and NPV were 92.31%, 89.80%, 87.80%, and 93.62%, respectively. CONCLUSION: The BALF PCR detection method has good diagnostic value for CPA and combining this method with BALF GM detection can improve diagnostic sensitivity and specificity.

4.
Front Cell Dev Biol ; 9: 728574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676211

RESUMO

Hepatocellular carcinoma (HCC) is one of the major cancer-related deaths worldwide. Genomic instability is correlated with the prognosis of cancers. A biomarker associated with genomic instability might be effective to predict the prognosis of HCC. In the present study, data of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were used. A total of 370 HCC patients from the TCGA database were randomly classified into a training set and a test set. A prognostic signature of the training set based on nine overall survival (OS)-related genomic instability-derived genes (SLCO2A1, RPS6KA2, EPHB6, SLC2A5, PDZD4, CST2, MARVELD1, MAGEA6, and SEMA6A) was constructed, which was validated in the test and TCGA and ICGC sets. This prognostic signature showed more accurate prediction for prognosis of HCC compared with tumor grade, pathological stage, and four published signatures. Cox multivariate analysis revealed that the risk score could be an independent prognostic factor of HCC. A nomogram that combines pathological stage and risk score performed well compared with an ideal model. Ultimately, paired differential expression profiles of genes in the prognostic signature were validated at mRNA and protein level using HCC and paratumor tissues obtained from our institute. Taken together, we constructed and validated a genomic instability-derived gene prognostic signature, which can help to predict the OS of HCC and help us to explore the potential therapeutic targets of HCC.

5.
Front Genet ; 12: 689801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497633

RESUMO

Dysregulation of autophagy-related genes (ARGs) is related to the prognosis of cancers. However, the aberrant expression of ARGs signature in the prognosis of hepatocellular carcinoma (HCC) remain unclear. Using The Cancer Genome Atlas and the International Cancer Genome Consortium database, 188 common autophagy-related gene pairs (ARGPs) were identified. Through univariate, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis, a prognostic signature of the training set was constructed on the basis of 6 ARGPs. Further analysis revealed that the ARGP based signature performed more accurately in overall survival (OS) prediction compared to other published gene signatures. In addition, a high risk of HCC was closely related to CTLA4 upregulation, LC3 downregulation, low-response to axitinib, rapamycin, temsirolimus, docetaxel, metformin, and high-response to bleomycin. Univariate Cox and multivariate Cox analysis revealed that the risk score was an independent prognostic factor for HCC. These results were internally validated in the test and TCGA sets and externally validated in the ICGC set. A nomogram, consisting of the risk score and the TNM stage, performed well when compared to an ideal nomogram. In conclusion, a 6-ARGP-based prognostic signature was identified and validated as an effective predictor of OS of patients with HCC. Furthermore, we recognized six small-molecule drugs, which may be potentially effective in treating HCC.

6.
Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526363

RESUMO

PURPOSE: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma(ICC). However, little is known about the intertumor heterogeneity(ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. EXPERIMENTAL DESIGN: We obtained 66 tumor samples from sixteen multifocal ICC patients and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA-sequencing, methylation-microarray and multiplex immunostaining. Patients were divided into high or low ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. RESULTS: Multifocal ICC presented considerable intertumor genomic, transcriptional and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions and upregulated IFN-signature expression in high immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA-methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. CONCLUSIONS: There is comprehensive heterogeneity in the genome, transcriptome and epigenome of multifocal ICC. Based on the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.

7.
Mol Cell ; 81(16): 3339-3355.e8, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352206

RESUMO

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.


Assuntos
Colangiocarcinoma/genética , Proteínas de Ligação ao GTP/genética , Metiltransferases/genética , Biossíntese de Proteínas , Animais , Carcinogênese/genética , Colangiocarcinoma/patologia , Progressão da Doença , Receptores ErbB/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Camundongos , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
8.
Front Cell Infect Microbiol ; 11: 701913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262882

RESUMO

Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.


Assuntos
Infecções por HIV , Talaromyces , Adulto , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Humanos , Micoses , Esfingolipídeos
9.
BMC Infect Dis ; 21(1): 587, 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34144700

RESUMO

BACKGROUND: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. METHODS: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. RESULTS: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. CONCLUSION: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.


Assuntos
Síndromes de Imunodeficiência/etiologia , Interferon gama/imunologia , Micoses/imunologia , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
10.
J Gastroenterol Hepatol ; 36(9): 2531-2539, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33948991

RESUMO

BACKGROUND AND AIM: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients who underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in a hepatitis B virus (HBV)-related HCC population. METHODS: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection and remote site infection were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rates with different durations of POA was investigated. RESULTS: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of surgical site infection and 2.0% (19/934) of remote site infection. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (odds ratio = 0.50, 95% confidence interval = 0.30 to 0.83; P = 0.008). Albumin-bilirubin score, Barcelona Clinic Liver Cancer (BCLC) stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection. CONCLUSIONS: Postoperative antibiotic is necessary for HBV-related HCC patients to prevent postoperative infection, especially for those with higher albumin-bilirubin score, at BCLC stage B-C, or who underwent major hepatectomy. For HBV-related HCC patients, postoperative second-generation cephalosporins, or ceftriaxone for 3 days after surgery might be proper.

11.
Sci China Life Sci ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33945070

RESUMO

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been reported. However, the clinical outcome and pathogenesis remain unclear. In this study, we recruited 43 laboratory-confirmed COVID-19 patients. We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients (P<0.05). The average viral shedding time in severe/critical patients was more than 50 days, and up to 100 days in some patients, after symptom onset. However, chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive, but specific antibodies appeared. Furthermore, the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred (P<0.01 and FDR<0.01) and increased when G227A occurred (P<0.05 and FDR<0.05). High IL1R1, IL1R2, and TNFRSF21 expression in the host positively correlated with viral shedding time (P<0.05 and false discovery rate <0.05). Prolonged viral RNA shedding often occurs but may not increase disease damage. Prolonged viral RNA shedding is associated with viral mutations and host factors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34052144

RESUMO

BACKGROUND: We presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. METHODS: Between February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples. RESULTS: Here, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p < 0.001) with pulmonary lesion size, while the BALF value showed no correlation (r: 0.253, p: 0.13). The positivity rate of BALF was higher than that of serum when the diameter of the pulmonary lesion was small (diameter less than 20 mm). Moreover, the serum cryptococcal GXM antigen levels showed an overall decreasing trend with the decrease in pulmonary lesion size after antifungal therapy in patient follow-up. CONCLUSIONS: The Chinese-made cryptococcal GXM antigen test has better sensitivity and specificity for diagnosing pulmonary cryptococcosis in the HIV-negative Chinese population, and it could be used to diagnose and to monitor this disease.

13.
Ann Transl Med ; 9(8): 621, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987319

RESUMO

Background: Since there are reports of cases of 2019-coronavirus disease (COVID-19) asymptomatic carriers in China recently and fever is one of the main symptoms, we aimed to distinguish COVID-19 cases from other febrile patients with clinical examinations in this study. Methods: A total of 134 suspected COVID-19 patients in the isolation ward of the First Affiliated Hospital of Guangzhou Medical University were recruited from January 23 to May 23, 2020. We analyze the pathogenic form and clinical characteristics. Results: Among them, pathogens were identified in only 84 patients (62.7%), including 23 (17.1%) with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 30 (22.3%) with other viruses, 31 (25.0%) with other pathogens and 3 (3.5%) with mixed infections. The commonly observed symptoms of COVID-19 patients were cough, fever, fatigue, and muscle aches, which were significantly different than the symptoms of nonviral infections (P<0.05) but from those of other viral infections (P>0.05). Furthermore, lactate dehydrogenase and the neutrophil/lymphocyte were found significantly high in COVID-19 patients compared to non-COVID-19 patients (P<0.05). The most common manifestations of COVID-19 patients were ground-glass opacities (100%) with or without lung consolidation, however, they also often showed involvement of several lobes of both lungs (P<0.05). Due to the clear differential diagnosis, the overall antibiotic use rate was 35.8% (31/87). Conclusions: When diagnosing COVID-19, infections with other pathogens should not be ignored. Successful pathogen identification will support accurate treatment.

14.
Front Oncol ; 11: 605296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777748

RESUMO

Objectives: Preoperative prediction of post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) is significant for developing appropriate treatment strategies. We aimed to establish a radiomics-based clinical model for preoperative prediction of PHLF in HCC patients using gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). Methods: A total of 144 HCC patients from two medical centers were included, with 111 patients as the training cohort and 33 patients as the test cohort, respectively. Radiomics features and clinical variables were selected to construct a radiomics model and a clinical model, respectively. A combined logistic regression model, the liver failure (LF) model that incorporated the developed radiomics signature and clinical risk factors was then constructed. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) with 95% confidence interval (CI). Results: The radiomics model showed a higher AUC than the clinical model in the training cohort and the test cohort for predicting PHLF in HCC patients. Moreover, the LF model had the highest AUCs in both cohorts [0.956 (95% CI: 0.955-0.962) and 0.844 (95% CI: 0.833-0.886), respectively], compared with the radiomics model and the clinical model. Conclusions: We evaluated quantitative radiomics features from MRI images and presented an externally validated radiomics-based clinical model, the LF model for the prediction of PHLF in HCC patients, which could assist clinicians in making treatment strategies before surgery.

15.
J Nanobiotechnology ; 19(1): 37, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541369

RESUMO

BACKGROUND: The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy. RESULTS: A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza-boron-dipyrromethene (aza-BODIPY) dyes with donor-acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity. CONCLUSIONS: Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.


Assuntos
Compostos de Boro/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/terapia , Terapia Fototérmica/métodos , Animais , Compostos de Boro/análise , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/análise , Corantes Fluorescentes/farmacocinética , Humanos , Raios Infravermelhos , Camundongos , Nanopartículas/análise , Neoplasias/diagnóstico por imagem , Nanomedicina Teranóstica , Termografia
16.
Int J Cancer ; 149(1): 127-138, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586134

RESUMO

The population of patients with huge hepatocellular carcinoma (H-HCC diameter > 10.0 cm) is an odd group that is not well adjudicated in the current staging systems, whose prognosis after curative resection varies. We aimed to develop novel models to predict the long-term outcomes of patients with H-HCC without portal vein tumor thrombus after hepatectomy. There were 1076 H-HCC patients enrolled who underwent curative liver resection in five institutions in China. In total, 670 patients were recruited from our center and randomly divided into the training cohort (n = 502) and internal validation (n = 168) cohorts. Additionally, 406 patients selected from other four centers as the external validation cohort. Novel models were constructed based on independent preoperative and postoperative predictors of postsurgical recurrence (PSR) and postsurgical mortality (PSM) determined in multivariable cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C index) and calibration curve and compared with five conventional HCC staging systems. PSR model and PSM model were constructed based on tumor number, microscopic vascular invasion, tumor differentiation, preoperative alpha-fetoprotein level, albumin-bilirubin grade, liver segment invasion, neutrophil-to-lymphocyte ratio or platelet-to-neutrophil ratio, and surgical margin or intraoperative blood transfusion. The C-indexes were 0.84 (95% CI, 0.78-0.90) and 0.85 (95% CI, 0.78-0.91) for the PSR and PSM models, respectively, which were substantially higher than those of the five conventional HCC staging systems (0.63-0.75 for PSR; 0.66-0.77 for PSM). The two novel models achieved more accurate prognostic predictions of PSR and PSM for H-HCC patients after curative liver resection.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/patologia , Modelos Estatísticos , Recidiva Local de Neoplasia/patologia , Nomogramas , Carcinoma Hepatocelular/cirurgia , China , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Emerg Microbes Infect ; 10(1): 450-460, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33620282

RESUMO

Recently, the prevalence trend of pulmonary fungal infection (PFI) has rapidly increased. Changes in the risk factors for, distributions of underlying diseases associated with and clinical characteristics of some individual PFIs have been reported in the past decade. However, data regarding PFIs remain uncertain. This study reports the epidemiological characteristics and trends of PFIs over time in recent years. We applied an automated natural language processing (NLP) system to extract clinically relevant information from the electronic health records (EHRs) of PFI patients at the First Affiliated Hospital of Guangzhou Medical University. Then, a trend analysis was performed. From January 1, 2013, to December 31, 2019, 40,504 inpatients and 219,414 outpatients with respiratory diseases were screened, in which 1368 inpatients and 1313 outpatients with PFI were identified. These patients were from throughout the country, but most patients were from southern China. Upward trends in PFIs were observed in both hospitalized patients and outpatients (P<0.05). The stratification by age showed that the incidence of hospitalized patients aged 14-30 years exhibited the most obvious upward trend, increasing from 9.5 per 1000 patients in 2013 to 88.3 per 1000 patients in 2019. Aspergillosis (56.69%) was the most common PFI, but notably, the incidence rates of Talaromyces marneffei, which used to be considered uncommon, exhibited the most rapid increases. In younger PFI patients, the incidence and trend of PFIs have increased. Infection by previously uncommon pathogens has also gradually increased. Increased attention should be paid to young PFI patients and uncommon PFI pathogen infections.


Assuntos
Aspergilose/epidemiologia , Hospitalização/estatística & dados numéricos , Pneumopatias Fúngicas/epidemiologia , Micoses/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Registros Eletrônicos de Saúde , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Processamento de Linguagem Natural , Fatores de Risco , Adulto Jovem
18.
Theranostics ; 11(5): 2137-2148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500716

RESUMO

Aggregation induced emission (AIE)-active bright two-photon fluorescent probes with second near-infrared (NIR-II) light excitability can be used for efficient brain bioimaging studies, wherein the fabrication of water-dispersible nanoparticles by encapsulating the hydrophobic probes with amphiphilic polymer holds the key to ensuring biocompatibility and in vivo adaptability. However, barely any study has evaluated the structural requirements that can substantially affect the water-dispersible nanoparticle formation ability of an organic AIE-active dye with amphiphilic polymers. The present study systematically assessed the structural dependency of a well-known acrylonitrile based AIE system/fluorogenic core upon the formation of water-dispersible nanoparticles and elucidated how the structural modifications can impact the in vivo two-photon imaging. Methods: A total of four acrylonitrile-based aggregation induced emission (AIE)-active two-photon (TP) fluorescent probes (AIETP, AIETP C1, AIETP C2 and AIETP C3) have been judiciously designed and synthesized with structural variations to realize how the structural alterations could substantially influence the water-dispersible nanoparticle formation ability (with amphiphilic polymers) and photo-stability to impact the in vivo imaging. Results: It has been found that the incorporation of the phenyl-thiazole unit in AIETP, AIETP C2 and AIETP C3 facilitated the formation of water-dispersible nanoparticles (NPs) with amphiphilic polymers (Pluronic F127) whereas the presence of only phenyl moiety instead in AIETP C1 could not meet the suitable condition to form the NPs with good aqueous dispersibility. Rationally designed AIETP NPs that exhibited higher brightness, improved photostability and good two-photon absorption cross section was successfully employed for in vivo brain vasculature imaging. Conclusions: Robust noninvasive 2D and 3D two-photon (NIR-II light, 1040 nm) brain vasculature imaging with beneficial attributes such as outstanding penetration depth (800 µm) and exceptional spatial resolution (1.92 µm), were achieved by utilizing AIETP NPs in this study.


Assuntos
Encéfalo/irrigação sanguínea , Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica/métodos , Fótons , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Apoptose , Encéfalo/patologia , Proliferação de Células , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poloxâmero/química , Polímeros/química
19.
Phytochemistry ; 181: 112587, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33246306

RESUMO

Acidic compounds were enriched from a water decoction of Portulaca oleracea using 717 anion exchange resin column chromatography. A total of 22 compounds including 9 catecholamine derivatives, of which six were rare sulfonic acid derivatives, and 9 nitro derivatives, were further isolated through various column chromatographic methods, and their structures were elucidated by interpreting their spectroscopic data and ECD calculations. Among them, 16 compounds were isolated from P. oleracea for the first time, 8 of which were undescribed compounds and four compounds were natural products. Pharmacological screening indicated that cis-3-(3-nitro-4-hydroxyphenyl)-methyl acrylate exhibited anti-inflammatory activity, measured as inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophage cells, with an EC50 value of 18.0 µM, The compounds showed only weak anti-microbial activity with (2R)-(+)-2-chloro-3-(3-nitro-4-hydroxyphenyl)-propionic acid methyl ester inhibiting Candida albicans with a MIC of 256 µg/mL, and 3-methoxy-4,5-dinitrophenol inhibiting Shigella sonnei with a MIC of 512 µg/mL.


Assuntos
Alcaloides , Portulaca , Animais , Anti-Inflamatórios/farmacologia , Camundongos , Nitrocompostos , Extratos Vegetais , Células RAW 264.7
20.
Ann Transl Med ; 8(21): 1402, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33313147

RESUMO

Background: The role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatocellular carcinoma (HCC) remains controversial. Methods: The records of 23 consecutive patients with hepatitis B virus (HBV)-related HCC who underwent ALPPS at our center between November 2013 and June 2018 were retrospectively reviewed. Oncological results were compared between patients who received ALPPS and those that received transarterial chemoembolization (TACE) using propensity score matching (PSM) analysis. Results: In patients with a single tumor (n=12) the median tumor diameter was 13.0 (range: 5.1-20.0) cm, whereas in patients with multiple tumors (n=11) the median total tumor diameter was 6.3 (range: 2.3-26.0) cm. After the stage-1 ALPPS, the median future liver remnant (FLR) increased by 50.0%. The stage-2 ALPPS was completed in 20 patients (87.0%) after a median of 12 days. The 90-day mortality rate was 13% (3/23). The overall survival (OS) rates at 1-, 2-, and 5-year were 61.1%, 34.9%, and 8.7%, respectively, whereas the disease-free survival (DFS) rates at 1-, 2-, and 5-year were 27.8%, 27.8%, and 0.0%, respectively. PSM analysis showed no difference in OS between patients who underwent ALPPS and those that received TACE [P=0.178, Barcelona Clinic Liver Cancer (BCLC) stage A-C patients; P=0.241, BCLC stage B and C patients]. Conclusions: ALPPS is a safe and effective treatment option for unresectable HBV-related HCC. However, for HBV-related intermediate and advanced HCC patients, ALPPS may not be superior to TACE.

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