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1.
Asian J Androl ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376191

RESUMO

ABSTRACT: This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.

3.
Asian J Androl ; 25(1): 126-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35488668

RESUMO

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem , Biópsia , Nomogramas , Estudos Retrospectivos
4.
Curr Med Sci ; 42(5): 1000-1006, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36178578

RESUMO

OBJECTIVE: Ubiquitin-specific protease 4 (USP4) facilitates the development of transforming growth factor-beta 1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in various cancer cells. Moreover, EMT of renal tubular epithelial cells (RTECs) is required for the progression of renal interstitial fibrosis. However, the role of USP4 in EMT of RTECs remains unknown. The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism. METHODS: In established unilateral ureteral obstruction (UUO) rats and NRK-52E cells, immunohistochemistry and Western blot assays were performed. RESULTS: USP4 expression was increased significantly with obstruction time. In NRK-52E cells stimulated by TGF-ß1, USP4 expression was increased in a time-dependent manner. In addition, USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively. Meanwhile, USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin (α-SMA) expression, indicating that USP4 may promote EMT. After treatment with USP4 siRNA and TGF-ß1 for 24 h, the expression of TGF-ß1 receptor type I (TßRI) was decreased. CONCLUSION: USP4 promotes the EMT of RTECs through upregulating TßRI, thereby facilitating renal interstitial fibrosis. These findings may provide a potential target of USP4 in the treatment of renal fibrosis.


Assuntos
Transição Epitelial-Mesenquimal , Nefropatias , Animais , Ratos , Actinas/genética , Actinas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Fibrose , Nefropatias/genética , RNA Interferente Pequeno/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4744-4754, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164882

RESUMO

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1ß, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1ß, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lß, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.


Assuntos
Sepse , Receptor 4 Toll-Like , Animais , Anti-Inflamatórios/uso terapêutico , Proteína C-Reativa , Caspase 3/metabolismo , Interleucina-10 , Interleucina-6/metabolismo , Lactato Desidrogenases/metabolismo , Mieloblastina/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Farmacologia em Rede , Pró-Calcitonina/metabolismo , Pró-Calcitonina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
6.
Front Cardiovasc Med ; 9: 926218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990968

RESUMO

Introduction: Cancer and cardiovascular disease remain leading causes of death and disability worldwide, which places a heavy burden on public health systems and causes widespread suffering. Because these entities have highly overlapping risk factors, including hyperlipidemia, hypertension, diabetes, obesity, smoking and other lifestyle factors, many studies have reported that they have similar etiological mechanisms. Accumulating evidence indicates that there is an increased risk of cardiovascular disease among cancer survivors compared with the general population. However, whether cancer is associated with an increased risk of cardiovascular disease remains controversial. Methods and analysis: We will conduct and report the meta-analysis strictly based on the Cochrane Handbook for Systematic Reviews and the Meta-analysis of Observational Studies in Epidemiology guidelines combined with the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISM-P). This meta-analysis was registered with PROSPERO (registration number CRD42022307056). We will search for studies published from database inception to December 1, 2021, regardless of language or date, in three electronic databases (PubMed, EMBASE, and Cochrane Library) to identify and appraise cohort studies examining the relationship between cancer and subsequent cardiovascular disease risk. The literature screening, inclusion and data extraction will be conducted independently by two investigators using pre-designed standardized data extraction forms. A senior investigator will be consulted in cases of disagreement. We will assess risk of bias in the included cohort studies using the Newcastle-Ottawa Scale (NOS). Quantitative synthesis will be conducted using a random-effects model. To explore potential sources of heterogeneity, we will carry out multiple sensitivity analysis, meta-regression and subgroup analysis according to baseline characteristics. Publication bias will be evaluated through visual inspection of funnel plot asymmetry as well as by Begg's rank correlation test and Egger's weighted linear regression test.

7.
JAMA Netw Open ; 5(6): e2215217, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35657627

RESUMO

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.


Assuntos
Dexmedetomidina , Transplante de Rim , Adulto , Morte , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/prevenção & controle , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Masculino , Diálise Renal/efeitos adversos , Solução Salina
8.
Front Oncol ; 12: 871827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574321

RESUMO

Background: The paramount issue regarding multiple lung cancer (MLC) is whether it represents multiple primary lung cancer (MPLC) or intrapulmonary metastasis (IPM), as this directly affects both accurate staging and subsequent clinical management. As a classic method, histology has been widely utilized in clinical practice. However, studies examining the clinical value of histology in MLC have yielded inconsistent results; thus, this remains to be evaluated. Here, we performed a meta-analysis to assess the differential diagnostic value of histology in MPLC and IPM and to provide evidence-based medicine for clinical work. Methods: PubMed, Embase, and Web of Science databases were searched to collect relevant literature according to PRISMA, and inclusion and exclusion criteria were set up to screen and assess the literature. The data required for reconstructing a 2 × 2 contingency table were extracted directly or calculated indirectly from the included studies, and statistical analysis was carried out by using Stata 15, Meta-DiSc 1.4, and Review Manager 5.4 software. Results: A total of 34 studies including 1,075 pairs of tumors were included in this meta-analysis. Among these studies, 11 were about the M-M standard and the pooled sensitivity and specificity were 0.78 (95% CI: 0.71-0.84) and 0.47 (95% CI: 0.38-0.55), respectively; 20 studies were about CHA and the pooled sensitivity and specificity were 0.76 (95% CI: 0.72-0.80) and 0.74 (95% CI: 0.68-0.79), respectively; and 3 studies were about the "CHA & Lepidic" criteria and the pooled sensitivity and specificity were 0.96 (95% CI: 0.85-0.99) and 0.47 (95% CI: 0.21-0.73), respectively. The combined pooled sensitivity, specificity, PLR, NLR, DOR, and the area under the SROC curve of the 34 studies were 0.80 (95% CI: 0.73-0.86), 0.64 (95% CI: 0.51-0.76), 2.25 (95% CI: 1.59-3.17), 0.31 (95% CI: 0.23-0.43), 7.22 (95% CI: 4.06-12.81), and 0.81 (95% CI: 0.77-0.84), respectively. Conclusion: The current evidence indicated that histology had a moderate differential diagnostic value between MPLC and IPM. Among the three subgroups, the "CHA & Lepidic" criteria showed the highest sensitivity and CHA showed the highest specificity. Further research is necessary to validate these findings and to improve clinical credibility. Systematic Review Registration: PROSPERO, identifier CRD42022298180.

9.
J Integr Med ; 20(3): 274-280, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35181255

RESUMO

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION: This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.


Assuntos
Abietanos , Lesão Pulmonar Aguda , Ativação de Macrófagos , Animais , Camundongos , Abietanos/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Síndrome da Liberação de Citocina , Citocinas , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Macrófagos
10.
Nat Commun ; 12(1): 7085, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873166

RESUMO

Antibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW·NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics.


Assuntos
Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Vias Biossintéticas , Simulação de Dinâmica Molecular , Tetra-Hidroisoquinolinas/metabolismo , Antibacterianos/biossíntese , Antibacterianos/química , Bactérias/genética , Proteínas de Bactérias/genética , Biocatálise , Cromatografia Líquida de Alta Pressão , Resistência Microbiana a Medicamentos/genética , Humanos , Isoquinolinas/química , Isoquinolinas/metabolismo , Espectrometria de Massas/métodos , Estrutura Molecular , NADP/química , NADP/metabolismo , Naftiridinas/química , Naftiridinas/metabolismo , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Tetra-Hidroisoquinolinas/química
11.
J Card Surg ; 36(9): 3452-3455, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216385

RESUMO

BACKGROUND: Cardiac angiosarcoma is a rare but highly malignant cardiac tumor. It is characterized by poor prognosis, and current treatment approaches are not effective. CASE PRESENTATION: A 37-year-old female with 35 weeks pregnancy experienced chest tightness and shortness of breath for 1 month. She was diagnosed with primary cardiac angiosarcoma. Delivery of fetus was performed early to treat the mother. The patient underwent resection of the tumor then she was treated with chemotherapy. However, the tumor recurred 11 months after surgery. CONCLUSION: Angiosarcoma is a highly malignant tumor explaining recurrence of the tumor recurred after surgery. Cardiac angiosarcoma should be treated through a comprehensive treatment plan, comprising surgery, radiotherapy, and chemotherapy approaches.


Assuntos
Neoplasias Cardíacas , Hemangiossarcoma , Neoplasias do Timo , Adulto , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/cirurgia , Humanos , Recidiva Local de Neoplasia , Gravidez , Gestantes
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 306-310, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829707

RESUMO

OBJECTIVE: To assess the clinical effectiveness of boundary recognition of upper abdomen organs on CT images based on neural network model and the combination of different slices. METHODS: A total of 2 000 patients who underwent upper abdomen enhanced CT scans from March 2018 to March 2019 were included in the study. The quality of the CT images met the requirements for clinical diagnosis. Eight boundary layers (the upper and lower edge of liver, the upper and lower edge of spleen, the lower edge of left kidney, the lower edge of right kidney, the lower edge of the stomach and the lower edge of the gallbladder) of the main organs in the upper abdomen were labeled. The model training (training set, verification set and test set) based on different neural network methods and combinations of different slices were then performed to assess the accuracy of boundary recognition. Furthermore, clinical data from 50 cases were used as test group for assessing the accuracy and clinical effectiveness of this model. RESULTS: The fusion model created by integrating the two models according to different weight ratios yielded the highest accuracy, and then followed the EfficientNet-b3 model, with the Xception model showing the lowest accuracy. In each model, the boundary recognition accuracy of 5-slice image is higher than that of 3-silce image, and that of 1-slice image is the lowest. The recognition accuracy of fusion model of the 5-continuous-slice image for upper edge of liver, lower edge of liver, upper edge of spleen, lower edge of spleen, lower edge of left kidney, lower edge of right kidney, lower edge of stomach and lower edge of gallbladder was 91%, 87%, 92%, 85%, 92%, 95%, 76% and 74%, respectively. The fusion model was checked with the effectiveness data of 50 cases, yielding 88%, 86%, 88%, 80%, 82%, 80%, 69%, and 65% accuracy for 8-slice image, respectively, and the accuracy of meeting clinical application requirement was as high as 98%, 98%, 95%, 98%, 99%, 98%, 80% and 77%, respectively. CONCLUSION: By increasing boundary change logics in the continuous slices, the fusion model integrating different weight proportions demonstrates the highest accuracy for identifying the boundary of upper abdominal organs on CT images, achieving high examination effectiveness in clinical practice.


Assuntos
Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Abdome/diagnóstico por imagem , Humanos , Baço/diagnóstico por imagem , Resultado do Tratamento
13.
Hum Immunol ; 82(6): 429-437, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33875296

RESUMO

T cells in renal cell carcinoma (RCC) patients display multiple features of impairment and exhaustion. Here, we hypothesize that Astragalus membranaceus, a herbal medicine commonly used to accompany chemotherapy, might have adjuvating effects on T cells from RCC patients. To investigate this, circulating T cells from healthy individuals and RCC patients were cocultured ex vivo with aqueous extract from Astragalus. Functional characteristics of T cells in the absence and presence of Astragalus extract were then compared. We first identified a downregulation of IL-21 expression in RCC patients in association with a functional dysregulation of CXCR5+ Tfh-like cells. Astragalus extract could significantly increase IL-21 expression in a dose-dependent manner. This Astragalus-mediated effect depended on the presence of antigen-presenting cells (APCs), as purified CXCR5+ Tfh-like cells presented little IL-21 upregulation following Astragalus stimulation. APCs primed by Astragalus extract also promoted IL-21 expression from Tfh-like cells. Interestingly, Astragalus-stimulated Tfh-like cells presented enhanced helper function and resulted in higher humoral responses and better CD8 T cell survival. This effect was dependent on the presence of IL-21. Overall, these data indicated that Astragalus could enhance IL-21 production and effector function from CXCR5+ Tfh-like cells in a manner that depended on the presence of APCs.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Renais/terapia , Centro Germinativo/imunologia , Interleucinas/metabolismo , Neoplasias Renais/terapia , Receptores CXCR5/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Astragalus propinquus/imunologia , Carcinoma de Células Renais/imunologia , Medicamentos de Ervas Chinesas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Humoral , Neoplasias Renais/imunologia , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade
14.
Langmuir ; 37(12): 3731-3739, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33730854

RESUMO

Molecular dynamics simulations were conducted to systematically investigate how to maintain and enhance nanofilm pure evaporation on nanopillar surfaces. First, the dynamics of the evaporation meniscus and the onset and evolution of nanobubbles on nanopillar surfaces were characterized. The meniscus can be pinned at the top surface of the nanopillars during evaporation for perfectly wetting fluid. The curvature of the meniscus close to nanopillars varies dramatically. Nanobubbles do not originate from the solid surface, where there is an ultrathin nonevaporation film due to strong solid-fluid interaction, but originate and evolve from the corner of nanopillars, where there is a quick increase in potential energy of the fluid. Second, according to a parametric study, the smaller pitch between nanopillars (P) and larger diameter of nanopillars (D) are found to enhance evaporation but also raise the possibility of boiling, whereas the smaller height of nanopillars (H) is found to enhance evaporation and suppress boiling. Finally, it is revealed that the nanofilm thickness should be maintained beyond a threshold, which is 20 Å in this work, to avoid the suppression effect of disjoining pressure on evaporation. Moreover, it is revealed that whether the evaporative heat transfer is enhanced on the nanopillar surface compared with the smooth surface is also affected by the nanofilm thickness. The value of nanofilm thickness should be determined by the competition between the suppression effect on evaporation due to the decrease in the volume of supplied fluid and the existence of capillary pressure and the enhancement effect on evaporation due to the increase in the heating area. Our work serves as the guidelines to achieve stable and efficient nanofilm pure evaporative heat transfer on nanopillar surfaces.

15.
Ann Transl Med ; 8(16): 1010, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953810

RESUMO

BACKGROUND: Our study aims to summarize the data of radiation doses collected from consecutive CT examinations by using the Radiometrics software and contributing to the establishment of the region's diagnostic reference levels (DRLs). METHODS: The radiation doses in 158,463 CT examinations performed on 106,275 adults between April 2017 and April 2019 were retrospectively analyzed. The median value and interquartile range (IQR) of volumetric CT dose index (CTDIvol), dose-length product (DLP), effective dose (ED), and size-specific dose estimate (SSDE) were calculated according to the scanning region. RESULTS: The median CTDIvol (mGy) for each scanning region was 42.3 (head), 6.2 (chest), and 9.0 (abdomen). The median DLPs (mGy.cm) for single-phase, multi-phase, and all examinations were as follows: 607, 794, and 641 for the head; 220, 393, and 237 for the chest; 298, 1,141, and 570 for the abdomen. The median EDs (mSv) for single-phase, multi-phase, and all examinations are as follows: 1.6, 2.6, and 1.8 for the head; 5.1, 8.1, and 5.3 for the chest; 5.8, 20.3, and 10.4 for the abdomen. CONCLUSIONS: Our study's results could provide a basis for the evaluation of CT scanning radiation dosage and supply evidence for the establishment of local DRLs in China's Sichuan Province.

16.
Langmuir ; 36(9): 2375-2382, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32011891

RESUMO

Molecular dynamics simulations were conducted to investigate the generation and evolution of nanobubbles on heated gold-like nanoparticles (GNPs). The effects of surface wettability (ß) and heating intensity (Q) of the GNPs are studied. We found that nanobubbles are generated faster on the superhydrophobic GNP than on the superhydrophilic GNP where nanobubble formation appears after a delay. In the case of the superhydrophilic GNP, the nanobubble is observed to grow explosively because it is initially generated at a distance from the GNP surface instead of on its surface. In the case of the superhydrophobic GNP, the faster generation of the nanobubble is promoted by the larger temperature difference between the GNP and the surrounding fluid and an ultrathin low-density layer that exists before the GNP is heated. For a given ß, faster generation and growth of nanobubbles are observed with increasing Q. Furthermore, the maximum radius of the nanobubble is found to be dependent on ß and not Q. The mechanism is elaborated based on the thermal resistance analysis at the melting point of GNPs. Additionally, it was found that there exists a threshold Q for nanobubble generation and the threshold value for the case of the superhydrophobic GNP is lower than that for the case of the superhydrophilic GNP. The present results have demonstrated that the superhydrophobic GNP is favorable for fast and energy-saving nanobubble generation. Our work provides further understanding in the generation and evolution of nanobubbles and potentially offers a new insight for nanobubble manipulation.

17.
Langmuir ; 36(1): 456-464, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31840509

RESUMO

In this work, we use molecular dynamics (MD) simulations to investigate the dependences of formation and transition of surface condensation mode on wettability (ß) and vapor-to-surface temperature difference (ΔT). We build a map of different surface condensation modes against ß and ΔT based on plenty of MD simulation results and reveal five formation mechanisms and two transition mechanisms. At low ß and ΔT, the high free energy barrier (ΔG*) prevents any surface clusters from surviving, therefore no-condensation (NC) is observed. The formation of dropwise condensation (DWC) could evolve from either nucleation or film rupture. Similarly, the formation of filmwise condensation (FWC) could evolve from either nucleation or the adsorption-induced film. The transition between NC and DWC is determined by ΔG* according to classical nucleation theory. The transition between DWC and FWC depends on the stability of condensate film; there emerges the competition between the trend that the uneven condensate film contracts and ruptures to droplets favored by lower ß and the trend that the uneven condensate film continues growing promoted by higher ΔT. We finally present a schematic overview of all of the mechanisms revealed for a better understanding of the physical phenomenon of the surface condensation mode.

18.
Chin Med J (Engl) ; 132(22): 2684-2689, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725446

RESUMO

BACKGROUND: Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients. METHODS: A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and number of metastatic lesions (r = 0.296, P < 0.001). Compared with the non-metastatic and LVD groups, the HVD group showed the highest PSA (104.98 ng/mL, median) and fibrinogen levels (3.39 g/L, median), as well as the largest proportion of Gleason score >7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001). CONCLUSIONS: Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.


Assuntos
Neoplasias Ósseas/sangue , Neoplasias Ósseas/secundário , Fibrinogênio/metabolismo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/complicações , Idoso , Neoplasias Ósseas/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos
19.
Am J Transl Res ; 11(6): 3461-3471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312358

RESUMO

Prostate cancer is the second most common malignancy among men and causes a myriad of health problem for males that are diagnosed with the cancer. Although the 5-year relative survival rate of prostate cancer patients has been significantly increased due to prostate-specific antigen testing and treatment advances, patients that develop metastatic castrate-resistant prostate cancer continue to have poor survival rates. Thus, it is critical to discover new therapeutics to treat prostate cancer. Diosgenin is a steroidal saponin from Trigonella foenum graecum, which has been previously identified to exert anti-tumor properties. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 ligase that degrades multiple different proteins, and plays an oncogenic role in human cancer. In this study, we explore the molecular mechanism by which diosgenin mediates anti-tumor effects in prostate cancer cells. We found that diosgenin treatment led to cell growth inhibition, apoptosis and cell cycle arrest. Notably, we found that diosgenin inhibited the expression of NEDD4 in prostate cancer cells. Furthermore, overexpression of NEDD4 overcame the diosgenin-mediated anti-tumor activity, while downregulation of NEDD4 promoted the diosgenin-induced anti-cancer function in prostate cancer cells. Our findings indicate that diosgenin is a potential new inhibitor of NEDD4 in prostate cancer cells.

20.
J Cell Biochem ; 120(6): 10821-10829, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30672010

RESUMO

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Carga Tumoral , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Vimentina/genética , Vimentina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
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