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1.
J Am Chem Soc ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607333

RESUMO

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

2.
Arthritis Res Ther ; 25(1): 198, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838717

RESUMO

BACKGROUND: The clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in assessing relapsing polychondritis (RP) with airway involvement remains controversial. This study aimed to investigate PET/CT features of RP with airway involvement and explore its clinical value in predicting disease pattern, severity and prognosis. METHODS: RP patients with airway involvement who underwent PET/CT from January 2010 to July 2022 were retrospectively reviewed. PET/CT features were analyzed both visually and semiquantitatively with the maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). Patterns of airway involvement on PET were summarized. Correlations of SUVmax and TLG of the airway were made with spirometric indicators and serological inflammatory markers (CRP and ESR). In addition, long-term follow-up was conducted through questionnaires in regard to symptom control, subjective feeling, pulmonary function, and quality of life. RESULTS: Fifty-two cases were finally included. 18F-FDG PET showed FDG-avid lesions with increased FDG uptake in the airway among 94.2% of the patients. Three patterns (focal, multifocal and diffuse patterns) were identified. TLG of the whole airway was lower in patients with previous therapy (p = 0.046). Bronchoscopy was more sensitive in detecting tracheal abnormalities (90.7% vs.53.5%, p = 0.039) but less sensitive for peripheral airway lesions (65.1% vs. 79.1%, p = 0.046) compared with PET. SUVmax and TLG of the airway positively correlated with spirometry indicators (FEV1%pred, FEV1/FVC, MEF 50%pred, etc.) and serological inflammatory markers. Five patients died during the follow-up, with two deaths related to airway problems. Higher FDG uptake predicted worse subjective feeling, but not with symptom control or pulmonary function. CONCLUSION: PET/CT is a valuable tool for RP with airway involvement, particularly in assessing peripheral airway lesions, and PET/CT related parameters are significantly associated with disease patterns, severity, and long-term outcomes.


Assuntos
Policondrite Recidivante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Policondrite Recidivante/diagnóstico por imagem , Estudos Retrospectivos , Qualidade de Vida , Prognóstico , Compostos Radiofarmacêuticos
3.
Fitoterapia ; 171: 105691, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37757922

RESUMO

Four undescribed neolignan glycosides, bletineosides A-D (1-4) were isolated from the pseudobulbs of Bletilla striata. Their structures with absolute configurations were elucidated on the basis of spectroscopic analyses, along with acidic hydrolysis reactions and ECD experiments. All isolates were evaluated for their neuroprotective activities against glutamate-induced PC12 cell injury. Compound 3 and 4 showed significantly neuroprotective effects at the concentration of 10 µM when compared with the model group. Compounds 1-4 represented the first examples of neolignan glycosides from the genus Bletilla. This study disclosed the potency of Bletilla striata as a new source of anti-neurodegenerative agents.


Assuntos
Lignanas , Orchidaceae , Estrutura Molecular , Glutamatos , Glicosídeos/farmacologia , Lignanas/farmacologia
4.
Eur J Pharmacol ; 950: 175746, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37105515

RESUMO

Dihydroartemisinin (DHA), an active antimalaria metabolite derived from artemisinin, has received increasing attention for its anticancer activities. However, little is known about the anticancer mechanisms of DHA, although the existing data define its antimalaria effects by producing excessive reactive oxygen species (ROS). In this study, we showed that DHA effectively suppresses in vitro and in vivo tumor growth of non-small cell lung cancer (NSCLC) without perceptible toxicity on heart, liver, spleen, lung, and kidney tissues. Of note, DHA inhibited the expression of B7-H3 rather than PD-L1, whereas overexpression of B7-H3 completely rescued DHA's inhibition on cell proliferation and migration of NSCLC A549 and HCC827 cells. B7-H3 overexpression also largely inhibited DHA's induction on the apoptosis of the two cell lines. Furthermore, DHA treatment led to increased infiltration of CD8+ T Lymphocytes in the xenografts as compared with that of negative controls. Taken together, our results suggest that B7-H3 but not PD-L1 is involved in the antitumor effects of DHA in NSCLC, which may be indicative of an effective B7-H3 blockade and further combination with anti-PD-L1/PD-1 immunotherapy.


Assuntos
Artemisininas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Animais
5.
Front Cell Infect Microbiol ; 12: 886359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782119

RESUMO

Background: Metagenomic next-generation sequencing (mNGS) has emerged as an effective method for the noninvasive and precise detection of infectious pathogens. However, data are lacking on whether mNGS analyses could be used for the diagnosis and treatment of infection during the perioperative period in patients undergoing liver transplantation (LT). Methods: From February 2018 to October 2018, we conducted an exploratory study using mNGS and traditional laboratory methods (TMs), including culture, serologic assays, and nucleic acid testing, for pathogen detection in 42 pairs of cadaveric liver donors and their corresponding recipients. Method performance in determining the presence of perioperative infection and guiding subsequent clinical decisions was compared between mNGS and TMs. Results: The percentage of liver donors with mNGS-positive pathogen results (64.3%, 27/42) was significantly higher than that using TMs (28.6%, 12/42; P<0.05). The percentage of co-infection detected by mNGS in liver donors was 23.8% (10/42) significantly higher than 0.0% (0/42) by TMs (P<0.01). Forty-three pathogens were detected using mNGS, while only 12 pathogens were identified using TMs. The results of the mNGS analyses were consistent with results of the TM analyses in 91.7% (11/12) of donor samples at the species level, while mNGS could be used to detect pathogens in 66.7% (20/30) of donors deemed pathogen-negative using TMs. Identical pathogens were detected in 6 cases of donors and recipients by mNGS, among which 4 cases were finally confirmed as donor-derived infections (DDIs). For TMs, identical pathogens were detected in only 2 cases. Furthermore, 8 recipients developed early symptoms of infection (<7 days) after LT; we adjusted the type of antibiotics and/or discontinued immunosuppressants according to the mNGS results. Of the 8 patients with infections, 7 recipients recovered, and 1 patient died of severe sepsis. Conclusions: Our preliminary results show that mNGS analyses can provide rapid and precise pathogen detection compared with TMs in a variety of clinical samples from patients undergoing LT. Combined with symptoms of clinical infection, mNGS showed superior advantages over TMs for the early identification and assistance in clinical decision-making for DDIs. mNGS results were critical for the management of perioperative infection in patients undergoing LT.


Assuntos
Transplante de Fígado , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenoma , Metagenômica , Doadores de Tecidos
6.
J Clin Pharm Ther ; 47(10): 1563-1569, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35670240

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR-GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30-day all-cause mortality. METHODS: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30-day all-cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. RESULTS AND DISCUSSION: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30-day all-cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016-1.423, p = 0.032) was an independent risk factor for 30-day all-cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019-0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. WHAT IS NEW AND CONCLUSIONS: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety.


Assuntos
Injúria Renal Aguda , Infecções por Bactérias Gram-Negativas , Hiperpigmentação , Transplante de Fígado , Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Hiperpigmentação/induzido quimicamente , Transplante de Fígado/efeitos adversos , Polimixina B/efeitos adversos
7.
World J Surg Oncol ; 20(1): 159, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35590371

RESUMO

BACKGROUND: Not all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility of EGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling and EGFR signaling. METHODS: We detected tumoral B7-H3 expression in the original biopsy from 56 treatment-naïve LUAD patients and analyzed the association between high/low B7-H3 expression with the clinical outcomes of first-line anti-EGFR therapy. The main criteria for the analysis of response were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS), and the secondary criterion was overall survival (OS). RESULTS: In the subgroups of B7-H3 high and low expression, the ORR were 16.0% (4/25) and 74.2% (23/31) (p<0.001), and the DCR were 36.0% (9/25) and 87.1% (27/31) (p<0.001), respectively. The PFS of B7-H3 high [median 8.7, 95% confidence interval (CI) 4.0-13.4] was significantly worse than that of B7-H3 low (median not reached) [HR 6.54 (95% CI 2.18-19.60), p=0.001]. The median OS was 15.9 (95% CI 10.0-21.8) months in the B7-H3 high cohort and 25.7 (95% CI 9.0-42.4) months in the B7-H3 low subjects [HR 2.08 (95% CI 1.07-4.02), p=0.03], respectively. Both the univariate and multivariate analyses identified B7-H3 as an independent factor associated with poor PFS (p=0.001, p=0.000) and OS (p=0.03, p=0.015). CONCLUSION: B7-H3 may serve as a potential biomarker to predict clinical outcomes in EGFR-mutated LUAD patients treated with first-line EGFR-TKIs.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição/genética
8.
Natl Sci Rev ; 8(11): nwab126, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34876995

RESUMO

Marmosets are highly social non-human primates that live in families. They exhibit rich vocalization, but the neural basis underlying this complex vocal communication is largely unknown. Here we report the existence of specific neuron populations in marmoset A1 that respond selectively to distinct simple or compound calls made by conspecific marmosets. These neurons were spatially dispersed within A1 but distinct from those responsive to pure tones. Call-selective responses were markedly diminished when individual domains of the call were deleted or the domain sequence was altered, indicating the importance of the global rather than local spectral-temporal properties of the sound. Compound call-selective responses also disappeared when the sequence of the two simple-call components was reversed or their interval was extended beyond 1 s. Light anesthesia largely abolished call-selective responses. Our findings demonstrate extensive inhibitory and facilitatory interactions among call-evoked responses, and provide the basis for further study of circuit mechanisms underlying vocal communication in awake non-human primates.

9.
Front Oncol ; 11: 704042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327143

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains one of the most intractable malignancies. The development of effective drug treatments for ICC is seriously hampered by the lack of reliable tumor models. At present, patient derived xenograft (PDX) models prove to accurately reflect the genetic and biological diversity required to decipher tumor biology and therapeutic vulnerabilities. This study was designed to investigate the establishment and potential application of PDX models for guiding personalized medicine and identifying potential biomarker for lenvatinib resistance. METHODS: We generated PDX models from 89 patients with ICC and compared the morphological and molecular similarities of parental tumors and passaged PDXs. The clinicopathologic features affecting PDX engraftment and the prognostic significance of PDX engraftment were analyzed. Drug treatment responses were analyzed in IMF-138, IMF-114 PDX models and corresponding patients. Finally, lenvatinib treatment response was examined in PDX models and potential drug resistance mechanism was revealed. RESULTS: Forty-nine PDX models were established (take rate: 55.1%). Successful PDX engraftment was associated with negative HbsAg (P = 0.031), presence of mVI (P = 0.001), poorer tumor differentiation (P = 0.023), multiple tumor number (P = 0.003), presence of lymph node metastasis (P = 0.001), and later TNM stage (P = 0.039). Moreover, patients with tumor engraftment had significantly shorter time to recurrence (TTR) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis indicated that PDX engraftment was an independent risk factor for shortened TTR (HR = 1.84; 95% CI, 1.05-3.23; P = 0.034) and OS (HR = 2.13; 95% CI, 1.11-4.11; P = 0.024). PDXs were histologically and genetically similar to their parental tumors. We also applied IMF-138 and IMF-114 PDX drug testing results to guide clinical treatment for patients with ICC and found similar treatment responses. PDX models also facilitated personalized medicine for patients with ICC based on drug screening results using whole exome sequencing data. Additionally, PDX models reflected the heterogeneous sensitivity to lenvatinib treatment and CDH1 might be vital to lenvatinib-resistance. CONCLUSION: PDX models provide a powerful platform for preclinical drug discovery, and potentially facilitate the implementation of personalized medicine and improvement of survival of ICC cancer patient.

10.
Clin Transl Med ; 10(8): e233, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33377659

RESUMO

RATIONALE: CD13 is a new marker for liver cancer stem cells (CSCs) that contributes to sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanism of CD13 in HCC sorafenib resistance remains enigmatic. METHODS: The expression of CD13 in HCC cell lines and tissues was assayed by RT-PCR, western-blot, and immunohistochemistry staining. Athymic BALB/c nu/nu mice model was used to study the in vivo functions of CD13. Clinical significance of CD13 was evaluated by Kaplan-Meier methods. Cellular proliferation rate was evaluated by cell counting kit-8 cell proliferation assay and colony formation assay. Tunel assay was used to detect cell death ratio. Transwell assay was used to evaluate the motility of cells. Immunoprecipitation (IP), liquid chromatography-mass spectrometry (LC-MS)/MS, and co-IP were applied to investigate potential protein interactions of CD13. RESULTS: In this research, we found that CD13 expression was higher in metastatic HCC samples, and its overexpression was predicted worse prognosis for patients after surgical resection. Functionally, CD13 promoted HCC proliferation, invasion, cell cycle progression as well as sorafenib resistance. Mechanistically, CD13 interacted with histone deacetylase5 (HDAC5) to promote its protein stability, thus resulting in HDAC5-mediated lysine-specific demethylase 1 (LSD1) deacetylation and protein stabilization. Consequently, LSD1 decreased the NF-κB catalytic unit p65 methylation that led to p65 protein stability. A CD13 inhibitor ubenimex in combination with sorafenib, suppressed the tumor growth and attenuated the resistance of HCC cells toward sorafenib in patient-derived xenograft models. CONCLUSIONS: CD13 promotes HCC progression and induces sorafenib resistance, mainly via interacting with HDAC5 to prevent the degradation of p65 and activate NF-kB signaling pathway. CD13 is a prognostic indicator for HCC patients underwent curative resection as well as a predictor of response to treatment with sorafenib. Our study establishes the new therapeutic potential of targeting CD13-HDAC5-LSD1-NF-κB in HCC.

11.
EBioMedicine ; 62: 103107, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33181461

RESUMO

BACKGROUND: High rates of recurrence after resection severely worsen hepatocellular carcinoma (HCC) prognosis. This study aims to explore whether circulating tumor cell (CTC) is helpful in determine the appropriate liver resection margins for HCC patients. METHODS: HCC patients who underwent liver resection were enrolled into training (n=117) or validation (n=192) cohorts, then classified as CTC-positive (CTC≥1) or CTC-negative (CTC=0). A standardized pathologic sampling method was used in the training cohort to quantify microvascular invasion (mVI) and the farthest mVI from the tumor (FMT). FINDINGS: CTC number positively correlated with mVI counts (r=0.655, P<0.001) and FMT (r=0.495, P<0.001). The CTC-positive group had higher mVI counts (P=0.032) and greater FMT P=0.008) than the CTC-negative group. In the CTC-positive group, surgical margins of >1 cm independently protected against early recurrence (training cohort, P=0.004; validation cohort, P=0.001) with lower early recurrence rates (training cohort, 20.0% vs. 65.1%, P=0.005; validation cohort, 36.4% vs. 65.1%, P=0.003) compared to surgical margins of ≤1 cm. No differences in postoperative liver function were observed between patients with margins >1 cm vs. ≤1 cm. Surgical margin size minimally impacted early postoperative HCC recurrence in CTC-negative patients when using 0.5 cm or 1 cm as the threshold. INTERPRETATIONS: Preoperative CTC status predicts mVI severity in HCC patients and is a potential factor for determining optimal surgical margin size to ensure disease eradication and conserve liver function. A surgical margin of >1 cm should be achieved for patients with positive CTC. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgement section.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Células Neoplásicas Circulantes/patologia , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Testes de Função Hepática , Masculino , Microvasos/patologia , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Período Pré-Operatório , Prognóstico , Resultado do Tratamento
12.
Clin Transl Med ; 10(3): e137, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32702202

RESUMO

BACKGROUND: High rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC. METHODS: The retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC-negative [CTC = 0], n = 123; CTC-positive [CTC ≥ 1], n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups. RESULTS: In the study cohort as a whole or in CTC-negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC-positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P < .001; TTR: 45.8 vs 9.8 months, P < .001). Adjuvant TACE significantly reduced early recurrence (≤2 years) (64.1% vs 31.7%, P < .001) in CTC-positive patients. Notably, adjuvant TACE influenced TTR and OS even in subgroups of CTC-positive patients with low risk of recurrence according to traditional evaluation. CONCLUSIONS: Preoperative CTC status could serve as an indicator for the administration of adjuvant TACE in HCC patients. Adjuvant TACE benefits CTC-positive HCC patients mainly by reducing early recurrence.

13.
Cancer Med ; 8(16): 6933-6944, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31566899

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS: A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS: After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS: Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/cirurgia , Carcinoma Hepatocelular/mortalidade , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Perfusão , Veia Porta , Pontuação de Propensão , Trombectomia
14.
Proc Natl Acad Sci U S A ; 116(8): 3239-3244, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30718428

RESUMO

Marmoset has emerged as a useful nonhuman primate species for studying brain structure and function. Previous studies on the mouse primary auditory cortex (A1) showed that neurons with preferential frequency-tuning responses are mixed within local cortical regions, despite a large-scale tonotopic organization. Here we found that frequency-tuning properties of marmoset A1 neurons are highly uniform within local cortical regions. We first defined the tonotopic map of A1 using intrinsic optical imaging and then used in vivo two-photon calcium imaging of large neuronal populations to examine the tonotopic preference at the single-cell level. We found that tuning preferences of layer 2/3 neurons were highly homogeneous over hundreds of micrometers in both horizontal and vertical directions. Thus, marmoset A1 neurons are distributed in a tonotopic manner at both macro- and microscopic levels. Such organization is likely to be important for the organization of auditory circuits in the primate brain.


Assuntos
Córtex Auditivo/fisiologia , Mapeamento Encefálico , Callithrix/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Animais , Vias Auditivas/fisiologia , Humanos
15.
J Acoust Soc Am ; 144(1): 478, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30075670

RESUMO

This paper investigates the methods to detect and classify marmoset vocalizations automatically using a large data set of marmoset vocalizations and deep learning techniques. For vocalization detection, neural networks-based methods, including deep neural network (DNN) and recurrent neural network with long short-term memory units, are designed and compared against a conventional rule-based detection method. For vocalization classification, three different classification algorithms are compared, including a support vector machine (SVM), DNN, and long short-term memory recurrent neural networks (LSTM-RNNs). A 1500-min audio data set containing recordings from four pairs of marmoset twins and manual annotations is employed for experiments. Two test sets are built according to whether the test samples are produced by the marmosets in the training set (test set I) or not (test set II). Experimental results show that the LSTM-RNN-based detection method outperformed others and achieved 0.92% and 1.67% frame error rate on these two test sets. Furthermore, the deep learning models obtained higher classification accuracy than the SVM model, which was 95.60% and 91.67% on the two test sets, respectively.


Assuntos
Algoritmos , Aprendizado Profundo , Memória de Longo Prazo/fisiologia , Redes Neurais de Computação , Animais , Callithrix/fisiologia , Máquina de Vetores de Suporte
17.
JPEN J Parenter Enteral Nutr ; 41(7): 1146-1154, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27208039

RESUMO

BACKGROUND: Early use of enteral nutrition (EN) is indicated following surgical resection of esophageal cancer. However, early EN support does not always meet the optimal calorie or protein requirements, and the benefits of supplementary parenteral nutrition (PN) remain unclear. We aimed to evaluate the efficacy and safety of early supplementary PN following esophagectomy. MATERIALS AND METHODS: We enrolled 80 consecutive patients who underwent esophagectomy. Resting energy expenditure and body composition measurements were performed in all patients preoperatively and postoperatively. EN was administered after surgery, followed by randomization to either EN+PN or EN alone. The amount of PN administered was calculated to meet the full calorie requirement, as measured by indirect calorimetry, and 1.5 g protein/kg fat-free mass (FFM) per day was added as determined by body composition measurement. The clinical characteristics were compared between the 2 groups. RESULTS: Patients in the EN+PN group but not in the EN group preserved body weight (0.18 ± 3.38 kg vs -2.15 ± 3.19 kg, P < .05) and FFM (1.46 ± 2.97 kg vs -2.08 ± 4.16 kg) relative to preoperative measurements. Length of hospital stay, postoperative morbidity rates, and standard blood biochemistry profiles were similar. However, scores for physical functioning (71.5 ± 24.3 vs 60.4 ± 27.4, P < .05) and energy/fatigue (62.9 ± 19.5 vs 54.2 ± 23.5, P < .05) were higher in the EN+PN group 90 days following surgery. CONCLUSION: Early use of supplemental PN to meet full calorie requirements of patients who underwent esophagectomy led to better quality of life 3 months after surgery. Moreover, increased calorie and protein supplies were associated with preservation of body weight and FFM.


Assuntos
Proteínas Alimentares/uso terapêutico , Ingestão de Energia , Nutrição Enteral , Neoplasias Esofágicas/cirurgia , Esofagectomia , Nutrição Parenteral , Desnutrição Proteico-Calórica/prevenção & controle , Atividades Cotidianas , Adulto , Idoso , Composição Corporal , Compartimentos de Líquidos Corporais , Peso Corporal , Proteínas Alimentares/administração & dosagem , Suplementos Nutricionais , Metabolismo Energético , Esofagectomia/efeitos adversos , Fadiga , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Necessidades Nutricionais , Complicações Pós-Operatórias , Desnutrição Proteico-Calórica/etiologia , Qualidade de Vida
18.
J Thorac Dis ; 7(7): 1158-64, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26380731

RESUMO

BACKGROUND: Venous thromboembolism (VTE) remained common complication following surgical resection of esophageal cancer. In this prospective randomized double-blind placebo-controlled trial (NCT01267305), we aim to compare the safety and efficacy between low molecular weight heparin (LMWH) once-daily (QD) and twice-daily (BID) for the prophylaxis of VTE following esophagectomy. METHODS: During August 2012 to July 2013, patients underwent esophagectomy were randomly assigned to nadroparin calcium QD (4,100 AxaIU qd + placebo qd, group QD), or nadroparin calcium BID (4,100 AxaIU q12h, group BID) in the prophylaxis of VTE. All patients received thrombelastography (TEG) before and 0/24/48/72 hours after operation. Daily vascular ultrasound of lower extremities was followed during the first 7 postoperative days to confirm the suspected deep venous thrombosis (DVT). Cumulatively postoperative chest drainage at 72 hours after the surgery was collected to identify the difference in volume and red blood cell (RBC) counts between the two groups. Any bleeding events and thromboembolic events were also documented. RESULTS: A total of 117 patients were enrolled in this study, and 111 eligible patients were randomly assigned (group QD: 55 patients; group BID: 56 patients). Patients' clinical features were close between the two groups. TEG analysis [R time, K time, alpha angel and maximum amplitude (MA)] before and instantly after operation showed nearly identical results. However, compared with group QD, all TEG measurements of 24/48/72 hours postoperatively showed significantly prolonged R time and K time, and decreased alpha angel in group BID. In ultrasound follow-ups, a total of four cases of DVT (four cases in group QD and no case in group BID) were found in this cohort (7.27% versus 0%, P=0.046), and one case of pulmonary embolism (PE) (in group QD) was observed. The incidence of VTE was lower in group BID (9.09% versus 0%, P=0.032). At 72 hours after surgery, the cumulative volume of chest drainage were close between these two groups (1,001.39±424.58 versus 1,133.61±513.93 mL, P=0.406). RBC counts in chest drainage were also identical between two groups [(2.56±1.98)×10(5) versus (2.71±4.67)×10(5), P=0.61]. No patient died due to VTE or bleeding events. CONCLUSIONS: For the prophylaxis of VTE, BID LMWH provided more potent efficacy and equal safety when compared to QD LMWH in patients undergoing selective esophagectomy. Further study based on larger population is required to confirm these findings.

19.
Toxicol Ind Health ; 31(7): 585-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23448861

RESUMO

INTRODUCTION: Acute inhalational exposure leads to rapidly progressive acute respiratory distress syndrome (ARDS). This report is the first one to present a patient with ARDS in relation to long-standing exposure to a high-concentration mixture of ethenone and crotonaldehyde. CASE REPORT: A male worker in a chemical plant was accidentally exposed to the mixture of high-concentrated ethenone and crotonaldehyde for 5 min in an open space and worked continuously in the polluted area for approximately 12 h. On admission, he was conscious with the following vital parameters: blood pressure, 151/91 mmHg; pulse rate, 107 beats/min; respiratory rate, 30 breaths/min; temperature, 37.6°C; oxygen saturation, 92% supported by mask saturation 10 L/min; arterial blood gases showed P/F oxygen ratio of less than 200. Physical examination disclosed decreased bilateral vesicular sounds. A chest computed tomography revealed bilateral nonsegmental ground-glass opacities. The patient was mechanically ventilated and treated with corticosteroid. The patient was discharged without any symptoms. CONCLUSION: Exposure to mixtures of ethenone and crotonaldehyde can cause severe pulmonary injury leading to delayed ARDS.


Assuntos
Aldeídos/efeitos adversos , Etilenos/efeitos adversos , Cetonas/efeitos adversos , Exposição Ocupacional/efeitos adversos , Síndrome do Desconforto Respiratório/induzido quimicamente , Corticosteroides/uso terapêutico , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Tomógrafos Computadorizados , Resultado do Tratamento
20.
PLoS One ; 8(3): e59115, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23527103

RESUMO

Arabinogalactan proteins (AGPs), are a group of highly glycosylated proteins that are found throughout the plant kingdom. To date, glycosyltransferases that glycosylate AGP backbone have remained largely unknown. In this study, a gene (GhGalT1) encoding a putative ß-1,3-galactosyltransferase (GalT) was identified in cotton. GhGalT1, belonging to CAZy GT31 family, is the type II membrane protein that contains an N-terminal transmembrane domain and a C-terminal galactosyltransferase functional domain. A subcellular localization assay demonstrated that GhGalT1 was localized in the Golgi apparatus. RT-PCR analysis revealed that GhGalT1 was expressed at relatively high levels in hypocotyls, roots, fibers and ovules. Overexpression of GhGalT1 in Arabidopsis promoted plant growth and metabolism. The transgenic seedlings had much longer primary roots, higher chlorophyll content, higher photosynthetic efficiency, the increased biomass, and the enhanced tolerance to exogenous D-arabinose and D-galactose. In addition, gas chromatography (GC) analysis of monosaccharide composition of cell wall fractions showed that pectin was changed in the transgenic plants, compared with that of wild type. Three genes (GAUT8, GAUT9 and xgd1) involved in pectin biosynthesis were dramatically up-regulated in the transgenic lines. These data suggested that GhGalT1 may be involved in regulation of pectin biosynthesis required for plant development.


Assuntos
Parede Celular/metabolismo , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Pectinas/biossíntese , Adaptação Biológica/genética , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Arabinose/metabolismo , Galactose/metabolismo , Galactosiltransferases/química , Espaço Intracelular , Dados de Sequência Molecular , Especificidade de Órgãos/genética , Filogenia , Plantas Geneticamente Modificadas , Transporte Proteico , Plântula/genética , Plântula/crescimento & desenvolvimento , Alinhamento de Sequência
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