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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(1): 100-104, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33565410

RESUMO

OBJECTIVE: To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis. METHODS: Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio (OR) = 0.92, 95% confidence interval (95%CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95%CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95%CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95%CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. CONCLUSIONS: Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.


Assuntos
Deambulação Precoce , Respiração Artificial , China , Humanos , Unidades de Terapia Intensiva , Alta do Paciente
2.
Photodiagnosis Photodyn Ther ; : 102223, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609758

RESUMO

The photodamage induced by PDT drugs usually occurs at the site where the photosensitizers accumulate in the tumor cells, thus the modulation of intrinsic apoptosis by mitochondria-targeting PDT drugs might be a promising way to enhance the therapeutic efficacy of PDT drugs against tumor cells. Novel triphenylphosphonium-functionalized nanocomposites employed as carriers of a photoactive platinum diimine complex have been fabricated and characterized. Upon irradiation, the IC50 value of photosensitizer-loaded triphenylphosphonium-functionalized nanocomposites was found to be 17.4 or 14.4 times lower than that of the photosensitizer studied alone against HCT116 cells or A549 cells, respectively. The results suggested that the triphenylphosphonium- functionalized nanocomposites as drug delivery vehicles could significantly enhance the photodynamic therapy efficacy of the photosensitizer.

3.
Commun Biol ; 4(1): 240, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603076

RESUMO

SARS-CoV-2 is the cause of COVID-19. It infects multiple organs including the respiratory tract and gut. Dynamic changes of regional microbiomes in infected adults are largely unknown. Here, we performed longitudinal analyses of throat and anal swabs from 35 COVID-19 and 19 healthy adult controls, as well as 10 non-COVID-19 patients with other diseases, by 16 S rRNA gene sequencing. The results showed a partitioning of the patients into 3-4 categories based on microbial community types (I-IV) in both sites. The bacterial diversity was lower in COVID-19 patients than healthy controls and decreased gradually from community type I to III/IV. Although the dynamic change of microbiome was complex during COVID-19, a synchronous restoration of both the upper respiratory and gut microbiomes from early dysbiosis towards late more diverse status was observed in 6/8 mild COVID-19 adult patients. These findings reveal previously unknown interactions between upper respiratory and gut microbiomes during COVID-19.

4.
Int J Cancer ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586179

RESUMO

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 x 1 day, every three weeks) cisplatin administration at the beginning of the week to optimize radiosensitization--a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 x2 days, every three weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 12/10/2001-December 23, 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, KPS, HPV status, and creatinine (baseline, peak, and post-treatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from RT start. Median follow up was 8.0 years (1.8 months - 17.0 years). DOW, dosing schedule, and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity, or TCD compared to bolus-HD cisplatin. Our data suggest there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates. This article is protected by copyright. All rights reserved.

5.
Radiother Oncol ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33587971

RESUMO

PURPOSE: To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. MATERIALS AND METHODS: 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to ≥40 Gy in 5-6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n=187) and the remaining 17% (n=43) and 10% (n=27) had low-risk and high-risk disease, respectively. RESULTS: The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n=9/24), 21.4% (n=6/28), 19.4% (n=6/31), and 10.9% (n=19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and ≥40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29-77% compared to negative biopsy: 7%, 95% CI: 3-14%; p<0.001). CONCLUSION: Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35-37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients.

6.
J Natl Cancer Inst ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33429428

RESUMO

BACKGROUND: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. METHODS: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. RESULTS: Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). CONCLUSIONS: Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

7.
Genome Biol ; 22(1): 4, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397441

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity. RESULTS: We conduct exome sequencing and RNA sequencing for synchronous surgically resected primary tumors and the paired hepatic metastases from 17 hepatic oligometastatic pancreatic ductal adenocarcinoma and validate our findings in specimens from 35 of such cases. The comprehensive analysis of somatic mutations, copy number alterations, and gene expressions show high similarity between primary tumors and hepatic metastases. However, hepatic metastases also show unique characteristics, such as a higher degree of 3p21.1 loss, stronger abilities of proliferation, downregulation of epithelial to mesenchymal transition activity, and metabolic rewiring. More interesting, altered tumor microenvironments are observed in hepatic metastases, especially a higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increases in primary tumors and hepatic metastases, C1q is mainly produced by M2 macrophage, and C1q promotes migration and invasion of PDAC cells. CONCLUSION: Taken together, we find potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understanding of molecular mechanisms driving PDAC metastasis.

8.
Int J Biol Sci ; 17(1): 107-118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390837

RESUMO

Aerobic glycolysis, also known as the Warburg effect, is emerged as a hallmark of most cancer cells. Increased aerobic glycolysis is closely associated with tumor aggressiveness and predicts a poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is characterized by prominent genomic aberrations and increased glycolytic phenotype. However, the detailed molecular events implicated in aerobic glycolysis of PDAC are not well understood. In this study, we performed a comprehensive molecular characterization using multidimensional ''omic'' data from The Cancer Genome Atlas (TCGA). Detailed analysis of 89 informative PDAC tumors identified substantial copy number variations (MYC, GATA6, FGFR1, IDO1, and SMAD4) and mutations (KRAS, SMAD4, and RNF43) related to aerobic glycolysis. Moreover, integrated analysis of transcriptional profiles revealed many differentially expressed long non-coding RNAs involved in PDAC aerobic glycolysis. Loss-of-function studies showed that LINC01559 and UNC5B-AS1 knockdown significantly inhibited the glycolytic capacity of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate. Moreover, genetic silencing of LINC01559 and UNC5B-AS1 suppressed tumor growth and resulted in alterations in several signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, and transcriptional misregulation in cancer. Notably, high expression of LINC01559 and UNC5B-AS1 predicted poor patient prognosis and correlated with the maximum standard uptakevalue (SUVmax) in PDAC patients who received preoperative 18F-FDG PET/CT. Taken together, our results decipher the glycolysis-associated copy number variations, mutations, and lncRNA landscapes in PDAC. These findings improve our knowledge of the molecular mechanism of PDAC aerobic glycolysis and may have practical implications for precision cancer therapy.

9.
Nat Commun ; 12(1): 174, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420030

RESUMO

The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.


Assuntos
Imunossupressores/farmacologia , Neoplasias Hepáticas/imunologia , Neutrófilos/metabolismo , Neoplasias Pancreáticas/imunologia , Microambiente Tumoral/imunologia , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Pâncreas/imunologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Receptores Purinérgicos P2X/genética , Receptores Purinérgicos P2X/imunologia , Receptores Purinérgicos P2X/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-33422612

RESUMO

PURPOSE: This prospective phase 3 randomized trial was designed to test whether ultra high single-dose radiation therapy (24 Gy SDRT) improves local control of oligometastatic lesions compared to a standard hypofractionated stereotactic body radiation therapy regimen (3 × 9 Gy SBRT). The secondary endpoint was to assess the associated toxicity and the impact of ablation on clinical patterns of metastatic progression. METHODS AND MATERIALS: Between November 2010 and September 2015, 117 patients with 154 oligometastatic lesions (≤5/patient) were randomized in a 1:1 ratio to receive 24 Gy SDRT or 3 × 9 Gy SBRT. Local control within the irradiated field and the state of metastatic spread were assessed by periodic whole-body positron emission tomography/computed tomography and/or magnetic resonance imaging. Median follow-up was 52 months. RESULTS: A total of 59 patients with 77 lesions were randomized to 24 Gy SDRT and 58 patients with 77 lesions to 3 × 9 Gy SBRT. The cumulative incidence of local recurrence for SDRT-treated lesions was 2.7% (95% confidence interval [CI], 0%-6.5%) and 5.8% (95% CI, 0.2%-11.5%) at years 2 and 3, respectively, compared with 9.1% (95% CI, 2.6%-15.6%) and 22% (95% CI, 11.9%-32.1%) for SBRT-treated lesions (P = .0048). The 2- and 3-year cumulative incidences of distant metastatic progression in the SDRT patients were 5.3% (95% CI, 0%-11.1%), compared with 10.7% (95% CI, 2.5%-18.8%) and 22.5% (95% CI, 11.1%-33.9%), respectively, for the SBRT patients (P = .010). No differences in toxicity were observed. CONCLUSIONS: The study confirms SDRT as a superior ablative treatment, indicating that effective ablation of oligometastatic lesions is associated with significant mitigation of distant metastatic progression.

11.
Mol Diagn Ther ; 25(1): 29-40, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433895

RESUMO

The ubiquitin proteasome system (UPS) is a highly conserved way to regulate protein turnover in cells. The UPS hydrolyzes and destroys variant or misfolded proteins and finely regulates proteins involved in differentiation, apoptosis, and other biological processes. This system is a key regulatory factor in the proliferation, differentiation, and collagen secretion of skin fibroblasts. E3 ubiquitin protein ligases Parkin and NEDD4 regulate multiple signaling pathways in keloid. Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) binding with deubiquitinase USP10 can induce p53 destabilization and promote keloid-derived fibroblast proliferation. The UPS participates in the occurrence and development of hypertrophic scars by regulating the transforming growth factor (TGF)-ß/Smad signaling pathway. An initial study suggests that TNFα-induced protein 3 (TNFAIP3) polymorphisms may be significantly associated with scleroderma susceptibility in individuals of Caucasian descent. Sumoylation and multiple ubiquitin ligases, including Smurfs, UFD2, and KLHL42, play vital roles in scleroderma by targeting the TGF-ß/Smad signaling pathway. In the future, drugs targeting E3 ligases and deubiquitinating enzymes have great potential for the treatment of skin fibrosis.

12.
Int J Radiat Oncol Biol Phys ; 109(4): 1007-1018, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33371964

RESUMO

PURPOSE: Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy. METHODS AND MATERIALS: Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology. RESULTS: A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P <.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P <.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P < .001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P <.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer. CONCLUSION: Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.

13.
Ecotoxicol Environ Saf ; 207: 111501, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254389

RESUMO

Deltamethrin (DLM) is widely used in agriculture and the prevention of human insect-borne diseases. However, the molecular mechanism of DLM induced liver injury remains unclear to date. This study investigated the potential molecular mechanism that DLM induced liver fibrosis in quails. Japanese quails received resveratrol (500 mg/kg) daily with or without DLM (45 mg/kg) exposure for 12 weeks. Histopathology, transmission electron microscopy, biochemical indexes, TUNEL, quantitative real-time PCR, and western blot analysis were performed. DLM exposure induced hepatic steatosis, oxidative stress, inflammation, and apoptosis. Most importantly, the Nrf2/TGF-ß1/Smad3 signaling pathway played an important role on DLM-induced liver fibrosis in quails. Interestingly, the addition of resveratrol, an Nrf2 activator, alleviates oxidative stress and inflammation response by activating Nrf2, thereby inhibits the liver fibrosis induced by DLM in quails. Collectively, these findings demonstrate that chronic exposure to DLM induces oxidative stress via the Nrf2 expression inhibition and apoptosis, and then results in liver fibrosis in quails by the activation of NF-κB/TNF-α and TGF-ß1/Smad3 signaling pathway.


Assuntos
Inseticidas/toxicidade , Cirrose Hepática/induzido quimicamente , Nitrilos/toxicidade , Substâncias Protetoras/farmacologia , Piretrinas/toxicidade , Codorniz/fisiologia , Resveratrol/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Fator 2 Relacionado a NF-E2 , NF-kappa B/metabolismo , Estresse Oxidativo , Codorniz/metabolismo , Transdução de Sinais , Proteína Smad3 , Fator de Crescimento Transformador beta1/metabolismo
14.
Environ Pollut ; 267: 115564, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254669

RESUMO

Dibutyl phthalate (DBP), an important plastic contaminant in the environment, is known to cause organ toxicity. Although current research has shown that DBP-induced organ toxicity is associated with oxidative stress, the toxic effect of DBP on the lungs have not been fully elucidated. Therefore, we investigated the potential mechanism by which DBP induces pulmonary toxicity using a model of DBP-induced allergic airway inflammation in rats. The results showed that chronic exposure to DBP induced histopathological damage, inflammation, oxidative stress, apoptosis, and increased the protein levels of thymic stromal lymphopoietin (TSLP) and its downstream protein Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Moreover, DBP exposure inhibited nuclear factor-erythroid-2-related factor 2 (Nrf2) and levels of its target genes NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Additionally, using in vitro experiments, we found that DBP induced oxidative stress, reduced cell viability, and inhibited the Nrf2/HO-1/NQO1 pathway in mouse alveolar type II epithelial cell line. Overall, these data demonstrate that DBP induces allergic airway inflammation in rats via inhibition of the Nrf2/TSLP/JAK1 pathway.

15.
Immun Inflamm Dis ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33277966

RESUMO

BACKGROUND: Altered lipid metabolism is involved in the development of many tumors. However, the role of dissimilar lipid metabolism in head and neck squamous cell carcinoma (HNSCC) is not fully established. AIMS: Here, we sought to determine the prognostic value of lipid metabolism-related genes in HNSCC. METHODS: RNA-seq data and clinical features of 545 HNSCC cases were obtained from The Cancer Genome Atlas database. A regulatory network of transcription factors-lipid metabolism genes and a risk prognostic model of lipid metabolism-related genes was developed using bioinformatics and Cox regression modeling. We used tumor immune estimation resource to analyze immune cell infiltration in patients with HNSCC based on the prognostic index (PI) of lipid metabolism-related genes. RESULTS: A total of 136 differentially expressed lipid metabolism genes were identified. Of these, 23 are related to prognosis. In addition to predicting HNSCC prognosis, 11 lipid metabolism-related genes (ARSI, CYP27B1, CYP2D6, DGKG, DHCR7, LPIN1, PHYH, PIP5K1B, PLA2G2D, RDH16, and TRIB3) also affect HNSCC clinical features (stage, gender, and pathological stage). The PI of lipid metabolism-related genes embodied the state of HNSCC tumor immune microenvironment.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33283127

RESUMO

Background: Accurate preoperative planning for total hip arthroplasty (THA) relies on conventional anteroposterior radiographs. The difficulty of determining the magnification factor of radiographs is a major limitation. Despite the use of markers for calibration, identifying the plane of the hip joint is a major challenge. The aim of this study was to evaluate the accuracy of a novel method for image calibration and preoperative planning in THA involving the use of a biplanar radiographic (EOS imaging) system and a self-designed coin device. Methods: Biplanar radiographs (with the self-designed coin device) and a conventional anteroposterior radiograph (with a coin) were made for 26 patients after primary THA. The agreement between the actual and calculated diameters for each method was assessed using the concordance correlation coefficient (CCC) and Bland-Altman plots. In addition, 15 patients undergoing primary THA were prospectively enrolled to evaluate the EOS imaging-based method (EOS method), with biplanar radiographs made with use of the coin device. The accuracy of the preoperative predicted size of the implants was evaluated. Results: Both the EOS and conventional anteroposterior radiograph-based methods were reliable in repeated measurements of the diameter of the artificial femoral head in the reproducibility study, with the average CCCs for both methods >0.990. The agreement between the actual and EOS-based calculated diameters of the artificial femoral head was excellent, with a CCC of >0.990, while the agreement was poor between the actual and anteroposterior radiograph-based calculated diameters, with a CCC of <0.75. The EOS method exhibited a lower absolute difference (0.09 ± 0.07 mm) between the actual and calculated diameters compared with conventional anteroposterior radiography (1.26 ± 0.86 mm) (p < 0.001). EOS-based preoperative plans also exhibited excellent performance on the accuracy of the planning of the cups and stems; only 1 patient (6.7%) had a final implanted cup that differed by 1 size from the predicted size. Two patients (13.3%) had final implanted stems that differed by 1 size from the predicted size, and for 1 patient (6.7%), the stem size was off by ≥2 sizes. Conclusions: We describe a novel and easy-to-use method for the accurate calibration of radiographs and preoperative planning for THA. The EOS method evaluated in this study is an alternative method for preoperative planning in clinical practice.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33259132

RESUMO

Alpinetin (ALP) has been reported to act as an anticancer agent. This study was carried out to elucidate the effect of ALP on high-fat diet (HFD)-induced aggressive cancer progression. C57BL/6 mice were fed with a control diet (CD) or HFD and administered with ALP. Following six weeks of feeding, mice were inoculated subcutaneously with Lewis lung carcinoma cells (LLC) to develop transplanted lung tumour. ALP suppressed cell proliferation which drives HFD-induced lung cancer progression. ALP inhibited lipid accumulation in tumour and tumour cells cultured in vitro. qPCR and ELISA analysis of tumour tissues revealed ALP restrained macrophages accumulation, M2s polarization and chemokine secretion. Further, in macrophages cultured in tumour cells conditioned medium (CM), ALP was confirmed to decrease M2s markers expression and chemokine production under high fat. These results demonstrate that ALP suppresses HFD-promoted harmful changes in tumour microenvironments which are crucial in curbing pulmonary tumour aggravation.

18.
Adv Radiat Oncol ; 5(6): 1213-1224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33305082

RESUMO

Purpose: The Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial reported overall survival benefits for prostate-directed radiation therapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiation therapy (ORT) improves androgen deprivation therapy (ADT)-free and progression-free survivals. Comprehensive PDRT + ORT to all detectable metastases may offer benefit for de novo oligometastatic prostate cancer (DNOPC) and is under prospective study; given few available benchmarks, we reviewed our institutional experience. Methods and Materials: Forty-seven patients with DNOPC with predominantly M1b disease received neoadjuvant, concurrent, and adjuvant ADT plus PDRT + ORT to 1 to 6 oligometastases. Gross pelvic (N1) nodes were not considered oligometastases unless focally targeted without broader nodal coverage. Outcomes were analyzed from radiation therapy (RT) start using Kaplan-Meier, competing risks, and Cox regression. Median follow-up was 27 (95% confidence interval, 16-42) months. Results: At 1- and 2-years post-RT, cumulative incidence of distant metastatic progression (DMP) was 21% and 32%, whereas overall survival was 90% and 87%, respectively. Neuroendocrine/intraductal histology, prostate-specific antigen (PSA) < 20, and detectable PSA after PDRT + ORT were associated with increased DMP risk; number and location of oligometastases were not. Local failure was rare, with 3 prostate recurrences and progression of 10 treated oligometastases during follow-up. After neoadjuvant ADT, 9 (19%) patients had undetectable PSA (<0.05 ng/mL), which increased to 32 (68%) after PDRT + ORT. Overall 2-year incidence of biochemical recurrence (BCR) and development of castrate resistance were 23% and 36%, respectively. Undetectable PSA post-RT was associated with lower risk of BCR (hazard ratio, 0.19; P = .004) and DMP (hazard ratio, 0.26; P = .025). Overall, 23 (49%) patients were trialed off ADT; 16 (70%) had testosterone recovery (>150 ng/dL) and, of these, 5 had subsequent PSA rise and restarted ADT 2 to 21 months postrecovery. The remaining 11 were maintained off ADT without BCR. Median noncastrate duration was 8 months; 7 patients had normalized testosterone for >1 year. Conclusions: A comprehensive, radiotherapeutic-based treatment strategy has favorable clinical outcomes and can produce prolonged noncastrate remissions in a subset with DNOPC.

19.
Viral Immunol ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33370550

RESUMO

Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 µg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3+/CD4+ T cells and CD3+/CD8+ T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.

20.
J Int Med Res ; 48(12): 300060520976492, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33349096

RESUMO

OBJECTIVES: Adenomyosis is a common and refractory disease in gynecology. Preserving the uterus during treatment for adenomyosis remains a problem. High-intensity focused ultrasound (HIFU) is widely used in treatment of solid tumors. This study aimed to analyze patients with adenomyosis who were treated by HIFU and to preliminarily examine the characteristics of patients who are more suitable for HIFU to treat adenomyosis with reliable efficacy. METHODS: Over 2 years, 67 women who were diagnosed with adenomyosis and treated with HIFU at our gynecology department were included in this study. We investigated outcomes of their symptoms (dysmenorrhea and hypermenorrhea) and the volume of their uterine lesions. We also compared the patients' clinical profiles. RESULTS: The women had a mean follow-up duration of 11.6 ± 0.46 months. In the numerical rating scale, used to assess the degree of dysmenorrhea, the score was significantly lower (mean difference: -1.94, 95% confidence interval: -2.704 to -1.176) 3 months after HIFU treatment compared with before treatment, then it remained stable for 3 to 12 months. Hypermenorrhea was reduced to a certain degree, with a mean difference of -0.54 (-1.01-0.02). CONCLUSIONS: HIFU is a new noninvasive treatment method for adenomyosis that may help relieve dysmenorrhea.

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