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1.
J Orthop Surg Res ; 16(1): 132, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579316

RESUMO

BACKGROUND: Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment. MATERIALS AND METHODS: The chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits. RESULTS: After chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress. CONCLUSION: In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.

2.
Hepatology ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33576035

RESUMO

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), especially the nonalcoholic steatohepatitis (NASH), have become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. However, there is no FDA-approved medication to treat this devastating disease. Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases. APPROACH & RESULTS: We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatment significantly and dose-dependently decreased the elevated levels of serum aminotransferases in mice with diet-induced NASH. Furthermore, cordycepin treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that a key mechanism linking the protective effects of cordycepin were AMPK phosphorylation-dependent, as indicated by the finding that treatment with the AMPK inhibitor Compound C abrogated cordycepin-induced hepatoprotection in hepatocytes and mice with NASH. CONCLUSION: Cordycepin exerts significant protective effects against hepatic steatosis, inflammation, liver injury, and fibrosis in mice under metabolic stress through activation of the AMPK signaling pathway. Cordycepin might be a novel AMPK activator that can be used for the treatment of NASH.

3.
Medicine (Baltimore) ; 100(5): e24625, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592915

RESUMO

RATIONALE: Primary breast angiosarcoma (PBA) is a rare and overly aggressive entity and account for less than 1% of all breast cancer cases. PBA had a high rate of delayed preoperative diagnosis due to absent distinctive radiographic characteristics. PATIENT CONCERNS: We report a case of a 47-year-old female patient who had a previous history of luminal cancer in the right breast with mastectomy; the patient complained of asymmetrically diffuse enlarged, accompanying with a painless mass in the left breast 12 years after the mastectomy of her right breast. DIAGNOSES: The tumor mimicked idiopathic granulomatous mastitis on magnetic resonance imaging (MRI) at the first presentation. Contrast-enhanced ultrasound (CEUS) was performed for further lesion characterization and showed heterogeneous rapid hyper enhanced. An ultrasound-guided core needle biopsy was performed, and the pathology report indicated a breast angiosarcoma. INTERVENTIONS: The patient underwent a nipple-sparing simple mastectomy with immediate reconstruction of the left breast. OUTCOMES: After 8 months later, the tumor recurred, CEUS and MRI examination suggested PBA recurrence, then re-excision with implant removal was performed, the patient had a lung metastasis 4 months later eventually died 22 months after diagnosis. LESSONS: It is not easy to diagnose PBA with the radiographic examination. This case's importance is by combining CEUS and MRI to reflect enhanced morphology and hemodynamic characteristics of PBA and help diagnose breast angiosarcomas.

4.
Theranostics ; 11(3): 1396-1411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391541

RESUMO

Rationale: circular RNAs (circRNAs) have been demonstrated to play a crucial role in cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. The aim of present study is to investigate the role of circular RNAs in KIAA1429-mediated HCC progression. Methods: RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined in vitro and in vivo. RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq. Results: Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells in vitro and in vivo, while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, and thus inhibited the expression of MMP1, ultimately contributing to inhibition of HCC progression. Conclusion: Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.

5.
Gene ; 773: 145384, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33383119

RESUMO

Porcine circovirus type 4 (PCV4), a novel circovirus, was identified in pigs with serious symptoms, including porcine dermatitis and nephropathy syndrome (PDNS)-like signs, in China in 2019. This study investigated the prevalence and genome diversity of PCV4 in pigs from Guangxi Province, China, between 2015 and 2019. Thirteen of 257 (5.1%) samples were positive for PCV4, 9 of these (69.2%) PCV4-positive samples were coinfected with PCV2 or PCV3, and one PCV4-positive sample was coinfected with both PCV2 and PCV3. Three complete PCV4 genomes shared 36.9-73.8% nucleotide similarity with other representative circovirus genomes. Phylogenetic analysis indicated that PCV4 was most closely related to bat-associated circovirus and mink circovirus. In summary, this is the first epidemiological investigation and evolutionary analysis of PCV4 in Guangxi Province, China, and the results provide insight into the molecular epidemiology of PCV4.


Assuntos
Infecções por Circoviridae/genética , Circovirus/genética , Filogenia , Doenças dos Suínos/genética , Animais , Proteínas do Capsídeo/genética , China/epidemiologia , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/patologia , Infecções por Circoviridae/veterinária , Circovirus/patogenicidade , Genoma Viral/genética , Humanos , Suínos/genética , Suínos/virologia , Doenças dos Suínos/epidemiologia , Proteínas Virais/genética
6.
Entropy (Basel) ; 22(4)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33286154

RESUMO

Shannon entropy is currently the most popular method for quantifying the disorder or information of a spatial data set such as a landscape pattern and a cartographic map. However, its drawback when applied to spatial data is also well documented; it is incapable of capturing configurational disorder. In addition, it has been recently criticized to be thermodynamically irrelevant. Therefore, Boltzmann entropy was revisited, and methods have been developed for its calculation with landscape patterns. The latest method was developed based on the Wasserstein metric. This method incorporates spatial repetitiveness, leading to a Wasserstein metric-based Boltzmann entropy that is capable of capturing the configurational disorder of a landscape mosaic. However, the numerical work required to calculate this entropy is beyond what can be practically achieved through hand calculation. This study developed a new software tool for conveniently calculating the Wasserstein metric-based Boltzmann entropy. The tool provides a user-friendly human-computer interface and many functions. These functions include multi-format data file import function, calculation function, and data clear or copy function. This study outlines several essential technical implementations of the tool and reports the evaluation of the software tool and a case study. Experimental results demonstrate that the software tool is both efficient and convenient.

7.
Front Cell Neurosci ; 14: 554613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262689

RESUMO

Progression of neuronal deterioration within specific brain regions is considered as one of the principal bases for the development of major depressive disorders. Therefore, protects and promotes the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of depression. Here, we report that the antioxidant, N-acetylcysteine (NAC), inhibited neuronal injury through its capacity to reduce oxidative stress and exerted antidepressant effects. Specifically, we show that antioxidant enzyme activity was significantly decreased in the hippocampal CA1 region of depressive rats, while treatment with NAC (300 mg/kg, i.p.) produced neuroprotective effects against mitochondrial oxidative stress injuries and oxidative DNA damage in CA1 neurons of these rats. Moreover, NAC treatment alleviated neuronal injury resulting from neuroinflammation and apoptosis in depressed rats, effects that were associated with reductions in dendritic spine atrophy, and synapse deficits. These effects appear to involve a down-regulation of p38 mitogen-activated protein kinase (MAPK)-JNK signaling along with an up-regulation of ERK signaling within the hippocampal CA1 region. Moreover, this NAC treatment significantly ameliorated depression-like behaviors as indicated by performance in the sucrose preference and forced swim tests (FST). Taken together, these results reveal the potential involvement of oxidative stress in the generation of depression. And, the antidepressant-like effects exerted by NAC may involve reductions in this oxidative stress that can result in neuronal deterioration. Such neuroprotective effects of NAC may indicate a potential therapeutic strategy for the treatment of stress-related depression.

8.
Animals (Basel) ; 10(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266170

RESUMO

The gut microbiota in sows is important for the health of the host, and potential benefits may also be transferred to piglets during pregnancy. Therefore, systematic studies investigating the changes in the gut microbiota of sows are needed to elucidate the microbial compositions and functions. This study was conducted at 12 time points to investigate the temporal variations in gut microbiota on Days 27, 46, 64, 81, 100, and 113 during gestation (G) and Days 3, 5, 7, 10, 14, and 21 during lactation (L). Results suggested that the gut microbiota changed across the perinatal period with microbial function and abundance varying between the prenatal and postnatal periods. The alpha diversity was higher in the postnatal period than in the prenatal period. Thirty-eight genera were distributed between the two periods with Methanobrevibacter, Desulfovibrio, Akkermansia, and Turicibacter being enriched in the prenatal period while Eubacterium, Actinobacillus, Paludibacter, Butyricimonas, Megasphaera, Succiniclasticum, Acidaminococcus, and Rummeliibacillus were enriched in the postnatal period. Analysis done at the different time points of the prenatal period suggested that Days 27 and 113 had more microbial biomarkers than other days. Bacteroidales, Bacteroidia, and Prevotella were enriched on the 27th day, while bacteria belonging to the Clostridium and Ruminococcaceae were enriched on the 113th day. On the other hand, Clostridiales, Ruminococcaceae, Clostridia, and unclassified Christensenellaceae were enriched three days after delivery. Predicted microbial KO functions were also more enriched on Day 27 of the gestation period and Day 3 of the lactation period. Random forest, a machine learning method, was used to identify the top five important genera of Megasphaera, Stenotrophomonas, Phyllobacterium, Catenibacterium, and Turicibacter, while the most important function was arginine and proline metabolism. These systematic results provide important information for the gut microbiota of sows.

9.
Aging (Albany NY) ; 12(21): 21518-21543, 2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-33216732

RESUMO

In this study, we used bioinformatics tools to analyze transcriptome data from cholangiocarcinoma (CCA) patients in multiple datasets (Sun Yat-sen University, TCGA and GSE32225 cohorts) to identify mechanisms that regulate tumor infiltration by immune cells and survival outcomes. We identified 96 differentially expressed genes (DEGs), including 13 upregulated and 83 downregulated genes, in CCA tissues as regulatory T cells were significantly higher and the proportions of activated natural killer cells and monocytes were significantly lower in CCA tissues than the precancerous tissues. The survival outcomes of CCA patients were associated with the TP53 gene mutation status, levels of Oncostatin M (OSM) expression, and the proportions of tumor-infiltrating immune cell types, including dendritic cells, monocytes, and T follicular helper cells. Functional enrichment analysis of the DEGs in the high OSM-expressing CCA tissues showed that pathways related to tumor progression and immune response were significantly upregulated. Our study demonstrates that OSM expression and TP53 mutation status regulate the tumor infiltration by immune cells and survival outcomes in CCA. OSM is thus a potential prognostic biomarker and therapeutic target in cholangiocarcinoma.

10.
Foods ; 9(10)2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096786

RESUMO

: The effects of ultrasound (US), thermosonication (TS), ultrasound combined with nisin (USN), TS combined with nisin (TSN), and conventional thermal sterilization (CTS) treatments on the inactivation of microorganisms in grape juice were evaluated. TS, TSN, and CTS treatments provided the desirable bactericidal and enzyme inactivation, and nisin had a synergistic lethal effect on aerobic bacteria in grape juice while not having any obvious effect on the mold and yeast. Compared with CTS, the sensory characteristics of grape juice treated with TS and TSN are closer to that of fresh juice, its microbial safety is ensured, and the physicochemical properties are basically unchanged. More importantly, the total phenolic content and antioxidant capacity of juice treated with TS and TSN were significantly increased, and the total anthocyanin and flavonoid contents were largely retained. Taken together, these findings suggest that TS and TSN has great potential application value and that it can ensure microbial safety and improve the quality of grape juice.

11.
Brief Bioinform ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073843

RESUMO

Single-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver-Beer tool combination and the Baynorm-Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.

12.
Aging (Albany NY) ; 12(20): 20235-20253, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122451

RESUMO

Rho guanine nucleotide exchange factor 11 (ARHGEF11) has been proved to promote tumor metastasis in glioblastoma and ovarian carcinoma. However, the role of ARHGEF11 in hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that ARHGEF11 was upregulated in HCC samples and highly metastatic hepatoma cell lines. Knockdown of ARHGEFF11 inhibited the cell proliferation and invasion in both HCCLM3 and SKHEP1 cell lines. Subsequent mechanistic investigation showed that downregulation of ARHGEF11 significantly attenuated ß-catenin nuclear translocation, thereafter repressed the expression of ZEB1 and cyclinD1, finally contributing to inhibition of epithelial-mesenchymal transition (EMT) and cell cycle arrest. Moreover, high levels of ARHGEF11 were found to be associated with shorter disease free and overall survival. A prognostic nomogram model that integrated ARHGEF11, tumor size and BCLC classification showed good performance in predicting clinical outcomes of HCC patients. Overall, this study demonstrated that ARHGEF11 could promote proliferation and metastasis of HCC via activating ß-catenin pathway, suggesting that ARHGEF11 might serve as a potential prognostic biomarker for HCC.

13.
Sensors (Basel) ; 20(21)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114381

RESUMO

Recently, the direction of arrival estimation with co-prime arrays has gradually been applied in underwater scenarios because of its significant advantages over traditional uniform linear arrays. Despite the advantages of co-prime arrays, the spatial spectra obtained directly from conventional beamforming can be degraded by grating lobes due to the sparse spatial sampling in passive sensing applications, which will seriously deteriorate the estimation performance. In this paper, capon beamforming is applied to a co-prime sensor array as a pretreatment before high-resolution direction of arrival (DOA) estimation methods. The amplitudes extracted from the beam-domain outputs of two subarrays and the phases extracted from the cross-spectrum of the spatial spectrum are exploited to suppress the spurious peaks in beam patterns and eliminate ambiguities. Consequently, interference can be further mitigated, and the performance of high-resolution DOA methods will be guaranteed. Simulations show that the method proposed can improve the reliability and accuracy of DOA estimation with great value in practice.

14.
J Pharm Biomed Anal ; 192: 113652, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33039912

RESUMO

Diabetic encephalopathy (DE) is a severe diabetic complication with cognitive dysfunction. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese formula, is effective for the treatment of diabetes mellitus and Alzheimer's disease in clinical practices, however, the therapeutic effects and the underlying mechanisms of HLJDD on DE is unclear yet. With this purpose, behavior test, brain histological and biochemical analysis were estimated to assess the beneficial effects of HLJDD on DE. Plasma samples were collected for metabolomics analysis based on UPLC-Q-Orbitrap HRMS/MS and chemometric analysis. As a result, morris water maze test revealed that HLJDD could effectively improve the learning and memory abilities in db/db mice. Brain histological and biochemical analysis indicated that HLJDD could protect against neurodegeneration and oxidative stress in db/db mice. Meanwhile, a total of 21 potential biomarkers with significant differences were identified between Model group and Control group using untargeted metabolomics strategy. Among them, 11 metabolites showed a trend towards the normal levels after HLJDD intervention. These metabolites principally involved in glycerophospholipid metabolism, fatty acid ß-oxidation, linoleic acid metabolism, glucose metabolism and glutathione metabolism based on the metabolic pathway analysis, which were regulated in DE model mice after HLJDD intervention. Generally, the results demonstrated that HLJDD had beneficial effects on DE, which could be mediated via ameliorating the metabolic disorders.

15.
Front Neurol ; 11: 1036, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041980

RESUMO

Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate the survival benefits of carmustine in glioma patients, especially those with GBM. Methods: Randomized controlled trials (RCTs) and cohort studies regarding carmustine for glioma treatment were searched in PubMed, the Cochrane Library, and Embase from January 1979 to March 2020. Quality assessment was conducted with Jadad and Newcastle-Ottawa scales (NOS). Statistical analysis was conducted by the Revman 5.3 software. Results: Twenty-two eligible RCTs and cohort studies involving 5,821 glioma patients were included. Overall, glioma patients receiving carmustine as an adjuvant therapy had better progression-free survival [PFS; hazard ratio (HR) = 0.85, 95% CI = 0.77-0.94, P = 0.002] and overall survival (OS; HR = 0.85, 95% CI = 0.79-0.92, P < 0.0001) than those without carmustine treatment. Subgroup analysis showed that the OS benefit was observed in GBM (HR = 0.84, 95% CI = 0.78-0.91, P < 0.00001) but not in anaplastic glioma patients (HR = 1.20, 95% CI = 0.70-2.07, P = 0.50). Additionally, both newly diagnosed and recurrent GBM patients who received carmustine treatment showed better OS (HR = 0.86, 95% CI = 0.79-0.95, P = 0.002; HR = 0.77, 95% CI = 0.67-0.89, P = 0.0002, respectively). Both carmustine implantation in resection cavity and intravenous administration significantly prolonged OS (HR = 0.84, 95% CI = 0.78-0.92, P < 0.0001; HR = 0.86, 95% CI = 0.75-0.99, P = 0.04, respectively). Moreover, GBM patients receiving a combined carmustine and temozolomide (TMZ) therapy had longer OS than those receiving TMZ alone (HR = 0.78, 95% CI = 0.63-0.97, P = 0.03). Conclusion: Carmustine implantation in resection cavity provides survival benefit for GBM patients, and it may be a promising supplement to standard therapeutic protocol by offering a bridge between surgical resection and onset of TMZ therapy.

16.
Nephrology (Carlton) ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058364

RESUMO

AIM: The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of parathyroid, and the management of uraemic secondary hyperparathyroidism (SHPT). METHODS: Calcium-mediated PTH suppression test was performed in dialysis with SHPT, who were candidates for parathyroidectomy from June 2017 to December 2019 in our hospital. The PTH inhibition rate (PTH-IR) was calculated, and the correlation between PTH-IR and clinical indicators was explored. RESULTS: Fifty-one subjects were included. PTH-IR was negatively correlated with baseline PTH (r = -0.35, P = .012), it was also correlated with dialysis years, coronary artery calcification score (CACS) and parathyroid mass (r = -0.397, P = .004; r = -0.327, P = .028; r = -0.363, P = .015), which were not found for baseline PTH. Forty-four patients underwent surgical treatment. According to the histological results, 26 patients presented with parathyroid non-nodular hyperplasia, and 18 patients presented with parathyroid nodular hyperplasia. The mass of parathyroid of patients with nodular hyperplasia was higher than that of patients with non-nodular hyperplasia (ρ = 0.01). The difference of the PTH-IR was not found between the two groups (ρ = 0.296). During the test, the highest serum calcium was 2.9 ± 0.4 mmol/L, which dropped to normal at the end of the test. CONCLUSION: Parathyroid hormone inhibition rate might be a useful indicator in evaluating the autonomic secretory function of parathyroid and the progression of SHPT on top of intact PTH. Calcium-mediated PTH suppression test was safe in uraemic SHPT patients, but need to monitor for transient hypercalcaemia.

17.
World J Emerg Med ; 11(4): 206-215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014216

RESUMO

BACKGROUND: To evaluate the accuracy of National Early Warning Score (NEWS) in predicting clinical outcomes (28-day mortality, intensive care unit [ICU] admission, and mechanical ventilation use) for septic patients with community-acquired pneumonia (CAP) compared with other commonly used severity scores (CURB65, Pneumonia Severity Index [PSI], Sequential Organ Failure Assessment [SOFA], quick SOFA [qSOFA], and Mortality in Emergency Department Sepsis [MEDS]) and admission lactate level. METHODS: Adult patients diagnosed with CAP admitted between January 2017 and May 2019 with admission SOFA ≥2 from baseline were enrolled. Demographic characteristics were collected. The primary outcome was the 28-day mortality after admission, and the secondary outcome included ICU admission and mechanical ventilation use. Outcome prediction value of parameters above was compared using receiver operating characteristics (ROC) curves. Cox regression analyses were carried out to determine the risk factors for the 28-day mortality. Kaplan-Meier survival curves were plotted and compared using optimal cut-off values of qSOFA and NEWS. RESULTS: Among the 340 enrolled patients, 90 patients were dead after a 28-day follow-up, 62 patients were admitted to ICU, and 84 patients underwent mechanical ventilation. Among single predictors, NEWS achieved the largest area under the receiver operating characteristic (AUROC) curve in predicting the 28-day mortality (0.861), ICU admission (0.895), and use of mechanical ventilation (0.873). NEWS+lactate, similar to MEDS+lactate, outperformed other combinations of severity score and admission lactate in predicting the 28-day mortality (AUROC 0.866) and ICU admission (AUROC 0.905), while NEWS+lactate did not outperform other combinations in predicting mechanical ventilation (AUROC 0.886). Admission lactate only improved the predicting performance of CURB65 and qSOFA in predicting the 28-day mortality and ICU admission. CONCLUSIONS: NEWS could be a valuable predictor in septic patients with CAP in emergency departments. Admission lactate did not predict well the outcomes or improve the severity scores. A qSOFA ≥2 and a NEWS ≥9 were strongly associated with the 28-day mortality, ICU admission, and mechanical ventilation of septic patients with CAP in the emergency departments.

18.
Future Oncol ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32892636

RESUMO

Aim: The purpose of this study was to assess the role of marital status in esophageal adenocarcinoma (EAC). Methods: We identified 8341 EAC patients based on the Surveillance, Epidemiology and End Results database during 2007-2015, of whom 7275 were male and 1066 were female. Temporal trends, competing risk analysis and propensity score matching were performed. Results: There was an upward trend for the rate of unmarried patients in both male and female populations (p < 0.05). Unmarried status represented an independent risk factor for higher cancer-specific death (CSD) in males (hazard ratio: 1.11; 95% CI: 1.04-1.18; p = 0.001) but not in females (hazard ratio: 0.96; 95% CI: 0.81-1.13; p = 0.610). Married EAC patients experienced lower CSD compared with their unmarried counterparts in the male cohort.

19.
Urol Int ; : 1-17, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957106

RESUMO

The problem of resistance to therapy in prostate cancer (PCa) is multifaceted. Key determinants of drug resistance include tumor burden and growth kinetics, tumor heterogeneity, physical barriers, immune system and microenvironment, undruggable cancer drivers, and consequences of therapeutic pressures. With regard to the fundamental importance of the androgen receptor (AR) in all stages of PCa from tumorigenesis to progression, AR is postulated to have a continued critical role in castration-resistant prostate cancer (CRPC). Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all AR-directed therapies. However, AR-targeting agents ultimately lead to AR aberrations that promote PCa progression and drug resistance. Among these AR aberrations, androgen receptor variant 7 (AR-V7) is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-AR therapies in CRPC. Meanwhile, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. In the present review of the current literature, we have summarized the origin, alternative splicing, expression induction, protein conformation, interaction with coregulators, relationship with AR-FL, transcriptional activity, and biological function of AR-V7 in PCa development and therapeutic resistance. We hope this review will help further understand the molecular origin, expression regulation, and role of AR-V7 in the progression of PCa and provide insight into the design of novel selective inhibitors of AR-V7 in PCa treatment.

20.
Foods ; 9(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927636

RESUMO

Physicochemical characteristics, nutritional and functional components, and the antioxidant capacity of 15 kinds of domestic and imported kiwifruit in China were studied. Kiwifruit was classified according to flesh color or species, and the differences were analyzed and compared. Results demonstrated Ruiyu had the highest sugar-acid ratio, and Hongshi No.2 was an excellent cultivar with strong antioxidant capacity. TPC (total polyphenol content) and AAC (ascorbic acid content) showed a significant positive correlation. TPC was the greatest antioxidant contributor in the DPPH and FRAP assays. The sugar-acid ratio and TFC (total flavonoids content) in red-fleshed kiwifruit were significantly higher than those in yellow-fleshed and green-fleshed ones. The composition of free amino acids had a tendency to distinguish A. deliciosa and A. chinensis, but this needs further verification. In addition, the contents of mineral elements, folic acid and L-5-methyltetrahydrofolate were also analyzed. Generally, kiwifruit contains comprehensive nutrients and has strong antioxidant capacity. Cultivar is one of the main factors affecting nutritional and functional properties and antioxidant capacity.

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