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AIMS AND OBJECTIVES: The main aim of this study is to synthesize the prevalent predictive models for pressure injuries in hospitalized patients, with the goal of identifying common predictive factors linked to pressure injuries in hospitalized patients. This endeavour holds the potential to provide clinical nurses with a valuable reference for providing targeted care to high-risk patients. BACKGROUND: Pressure injuries (PIs) are a frequently occurring health problem throughout the world. There are mounting studies about risk prediction model of PIs reported and published. However, the prediction performance of the models is still unclear. DESIGN: Systematic review and meta-analysis: The Cochrane Library, PubMed, Embase, CINAHL, Web of Science and Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang Database, Weipu Database and CBM (China Biology Medicine). METHODS: This systematic review was conducted following PRISMA recommendations. The databases of Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and CNKI, Weipu Database, Wanfang Database and CBM were searched for all studies published before September 2023. We included studies with cohort, case-control designs, reporting the development of risk model and have been validated externally and internally among the hospitalized patients. Two researchers selected the retrieved studies according to the inclusion and exclusion criteria, and critically evaluated the quality of studies based on the CHARMS checklist. The PRISMA guideline was used to report the systematic review and meta-analysis. RESULTS: Sixty-two studies were included, which contained 99 pressure injuries risk prediction models. The AUC (area under ROC curve) of modelling in 32 prediction models were reported ranged from .70 to .99, while the AUC of verification in 38 models were reported ranged from .70 to .98. Gender (OR = 1.41, CI: .99 ~ 1.31), age (WMD = 8.81, CI: 8.11 ~ 9.57), diabetes mellitus (OR = 1.64, CI: 1.36 ~ 1.99), mechanical ventilation (OR = 2.71, CI: 2.05 ~ 3.57), length of hospital stay (WMD = 7.65, CI: 7.24 ~ 8.05) were the most common predictors of pressure injuries. CONCLUSION: Studies of PIs risk prediction model in hospitalized patients had high research quality, and the risk prediction models also had good predictive performance. However, some of the included studies lacked of internal or external validation in modelling, which affected the stability and extendibility. The aged, male patient in ICU, albumin, haematocrit, low haemoglobin level, diabetes, mechanical ventilation and length of stay in hospital were high-risk factors for pressure injuries in hospitalized patients. In the future, it is recommended that clinical nurses, in practice, select predictive models with better performance to identify high-risk patients based on the actual situation and provide care targeting the high-risk factors to prevent the occurrence of diseases. RELEVANCE TO CLINICAL PRACTICE: The risk prediction model is an effective tool for identifying patients at the risk of developing PIs. With the help of risk prediction tool, nurses can identify the high-risk patients and common predictive factors, predict the probability of developing PIs, then provide specific preventive measures to improve the outcomes of these patients. REGISTRATION NUMBER (PROSPERO): CRD42023445258.
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Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, RAB31-induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31/AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.
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BACKGROUND/AIM: To investigate the treatment outcomes and determinants of prognosis in patients experiencing visual acuity (VA) deterioration due to inflammatory isolated sphenoid sinus disease (ISSD) who underwent endonasal endoscopic surgery (EES). PATIENTS AND METHODS: Thirteen patients with 14 lesions treated with EES between March 2010 and April 2022 were included. Evaluation included improvements in VA using the logarithm of the minimum angle of resolution (LogMAR) scale, resolution rates of associated symptoms, and identification of factors predicting VA recovery. A literature review was conducted to assess the outcomes for ISSD-related VA impairments. RESULTS: The most common etiology is mycetoma (n=5), followed by an equal representation of mucocele and sphenoiditis (n=4). The mean interval from symptom onset to intervention was 4.7 months, with an average follow-up duration of 14.4 months. Seven eyes exhibited preoperative VA of 2.1 LogMAR or worse, with diplopia/ptosis (n=8) and headache (n=5) being the predominant co-occurring symptoms. After surgery, all ancillary symptoms improved, with an overall VA recovery rate of 87.5% (improvement more than 0.2 logMAR units). Mucocele exhibited the best improvements, whereas sphenoiditis showed the least progress (p=0.021). Poor baseline VA (p=0.026) and combined diplopia/ptosis (p=0.029) were identified as negative prognostic factors for VA recovery. CONCLUSION: Our findings suggest a favorable prognosis for VA recovery following EES in patients with inflammatory ISSDs, with response variations based on disease entity. However, further research is needed to personalize therapeutic strategies for enhanced outcomes.
Subject(s)
Visual Acuity , Humans , Female , Male , Middle Aged , Adult , Aged , Treatment Outcome , Sphenoid Sinus/surgery , Sphenoid Sinusitis/complications , Sphenoid Sinusitis/surgery , Sphenoid Sinusitis/physiopathology , Endoscopy/methods , Prognosis , Young Adult , Inflammation , Vision Disorders/etiology , Vision Disorders/physiopathologyABSTRACT
Malic enzyme (ME) genes are key functional metabolic enzymes playing a crucial role in carcinogenesis. However, the detailed effects of ME gene expression on breast cancer progression remain unclear. Here, our results revealed ME1 expression was significantly upregulated in breast cancer, especially in patients with oestrogen receptor/progesterone receptor-negative and human epidermal growth factor receptor 2-positive breast cancer. Furthermore, upregulation of ME1 was significantly associated with more advanced pathological stages (p < 0.001), pT stage (p < 0.001) and tumour grade (p < 0.001). Kaplan-Meier analysis revealed ME1 upregulation was associated with poor disease-specific survival (DSS: p = 0.002) and disease-free survival (DFS: p = 0.003). Multivariate Cox regression analysis revealed ME1 upregulation was significantly correlated with poor DSS (adjusted hazard ratio [AHR] = 1.65; 95% CI: 1.08-2.52; p = 0.021) and DFS (AHR, 1.57; 95% CI: 1.03-2.41; p = 0.038). Stratification analysis indicated ME1 upregulation was significantly associated with poor DSS (p = 0.039) and DFS (p = 0.038) in patients with non-triple-negative breast cancer (TNBC). However, ME1 expression did not affect the DSS of patients with TNBC. Biological function analysis revealed ME1 knockdown could significantly suppress the growth of breast cancer cells and influence its migration ability. Furthermore, the infiltration of immune cells was significantly reduced when they were co-cultured with breast cancer cells with ME1 knockdown. In summary, ME1 plays an oncogenic role in the growth of breast cancer; it may serve as a potential biomarker of progression and constitute a therapeutic target in patients with breast cancer.
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Triple Negative Breast Neoplasms , Humans , Breast , Carcinogenesis , Coculture Techniques , Disease-Free SurvivalABSTRACT
BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is a frequent consequence of stroke, which affects the quality of life and prognosis of stroke survivors. Numerous studies have indicated that blood biomarkers may be the key determinants for predicting and diagnosing cognitive impairment, but the results remain varied. Therefore, this meta-analysis aims to summarize potential biomarkers associated with PSCI. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched for studies exploring blood biomarkers associated with PSCI from inception to 15 April 2022. RESULTS: 63 studies were selected from 4,047 references, which involves 95 blood biomarkers associated with the PSCI. We meta-analyzed 20 potential blood biomarker candidates, the results shown that the homocysteine (Hcy) (SMD = 0.35; 95 %CI: 0.20-0.49; P < 0.00001), c-reactive protein (CRP) (SMD = 0.49; 95 %CI: 0.20-0.78; P = 0.0008), uric acid (UA) (SMD = 0.41; 95 %CI: 0.06-0.76; P = 0.02), interleukin 6 (IL-6) (SMD = 0.92; 95 % CI: 0.27-1.57; P = 0.005), cystatin C (Cys-C) (SMD = 0.58; 95 %CI: 0.28-0.87; P = 0.0001), creatinine (SMD = 0.39; 95 %CI: 0.23-0.55; P < 0.00001) and tumor necrosis factor alpha (TNF-α) (SMD = 0.45; 95 %CI: 0.08-0.82; P = 0.02) levels were significantly higher in patients with PSCI than in the non-PSCI group. CONCLUSION: Based on our findings, we recommend that paramedics focus on the blood biomarkers levels of Hcy, CRP, UA, IL-6, Cys-C, creatinine and TNF-α in conjunction with neuroimaging and neuropsychological assessment to assess the risk of PSCI, which may help with early detection and timely preventive measures. At the same time, other potential blood biomarkers should be further validated in future studies.
Subject(s)
Biomarkers , Cognition , Cognitive Dysfunction , Predictive Value of Tests , Stroke , Humans , Biomarkers/blood , Cognitive Dysfunction/blood , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Stroke/blood , Stroke/diagnosis , Stroke/complications , Aged , Female , Male , Middle Aged , Prognosis , Risk Factors , Aged, 80 and overABSTRACT
OBJECTIVES: We previously identified certain peripheral biomarkers of bipolar II disorder (BD-II) including circulating miRNAs (miR-7-5p, miR-142-3p, miR-221-5p, and miR-370-3p) and proteins (Matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)). We try to explore the connection between these biomarkers. METHODS: We explored correlations between the peripheral levels of above circulating miRNAs and proteins in our previously collected BD-II (N = 96) patients and control (N = 115) groups. We further searched TargetScan and BioGrid websites to identify direct and indirect interactions between these protein-coding genes and circulating miRNAs. RESULTS: In the BD-II group, we identified significant correlations between the miR-221-5p and CA-1 (rho = -0.323, P = 0.001), FARSB (rho = 0.251, P = 0.014), MMP-9 (rho = 0.313, P = 0.002) and PCSK9 (rho = 0.252, P = 0.014). The miR-370-3p also significantly correlated with FARSB expression (rho = 0.330, P = 0.001) and PCSK9 expression (rho = 0.221, P = 0.031) in the BD-II group. Our findings were in line with the modulating axis identified from TargetScan and BioGrid, miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9, suggesting their association with BD-II. CONCLUSION: Our result supported that peripheral candidate miRNA and protein biomarkers may interact in BD-II. We concluded that miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9 axes might act a critical role in the pathomechanism of BD-II.
Subject(s)
Bipolar Disorder , Circulating MicroRNA , MicroRNAs , Humans , Proprotein Convertase 9/genetics , Matrix Metalloproteinase 9 , Bipolar Disorder/diagnosis , Bipolar Disorder/genetics , MicroRNAs/genetics , BiomarkersABSTRACT
Background/purpose: The serpin peptidase inhibitor, clade E, member 2 (SERPINE2), is upregulated in breast cancer, prostate cancer, and urothelial carcinoma; however, limited information exists regarding its expression in oral cancer. Therefore, this study aimed to analyze the association between SERPINE2 expression and oral squamous cell carcinoma (OSCC) outcomes. Materials and methods: SERPINE2 mRNA and protein expression in patients with head and neck squamous cell carcinoma and OSCC were investigated using online databases and tissue-array analysis. Its relationship with clinicopathological characteristics, OSCC prognosis and its biological function in OSCC cells were explored. Results: Analysis using online databases revealed higher SERPINE2 expression in tumor tissues and its role as a prognostic factor. High SERPINE2 protein levels were significantly correlated with adverse pathological parameters, including advanced clinical stage and tumor status (P < 0.001), lymph nodes (P = 0.014), and distant metastases (P = 0.013). High SERPINE2 expression was associated with worse overall survival (P < 0.001) and was identified as an independent prognostic factor for OSCC. In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines. Conclusion: This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.
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Callicarpa nudiflora (C. nudiflora) is widely used in the treatment of bleeding related diseases. However, its main material basis has not been fully defined which limits the in-depth study of screening out the material basis of hemostasis and coagulation from C. nudiflor. In this study, the method of spectrum-effect relationship was used to quickly screen the material basis of hemostasis and coagulation. The five compounds related to hemostasis and coagulation were screened as Alyssonoside (P24), Luteolin (P25), Quercetin (P26), Apigenin (P28), Isorhamnetin (P29). And the contribution of these five peaks to hemostasis and coagulation efficacy was P24 > P25 > P28 > P26 > P29.
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Immunotherapy has attracted widespread attention in cancer treatment and has achieved considerable success in the clinical treatment of some tumors, but it has a low response rate in most tumors. To achieve sufficient activation of the immune response, significant efforts using nanotechnology have been made to enhance cancer immune response. In recent years, the induction of various regulated cell death (RCD) has emerged as a potential antitumor immuno-strategy, including processes related to apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. In particular, damage-associated molecular patterns (DAMPs) released from the damaged membrane of dying cells act as in situ adjuvants to trigger antigen-specific immune responses by the exposure of an increased antigenicity. Thus, RCD-based immunotherapy offers a new approach for enhancing cancer treatment efficacy. Furthermore, incorporation with multimodal auxiliary therapies in cell death-based immunotherapy can trigger stronger immune responses, resulting in more efficient therapeutic outcome. This review discusses different RCD modalities and summarizes recent nanotechnology-mediated RCDs in cancer immunotherapy.
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Neoplasms , Regulated Cell Death , Humans , Nanomedicine , Apoptosis , Neoplasms/drug therapy , Immunotherapy/methodsABSTRACT
Genes of the homeobox (HOX) family encode transcription factors, which play a role in cancer progression. However, their role in gastric cancer has not been adequately evaluated. Herein, we evaluated the genetic changes and mRNA of target genes of the HOX family in gastric cancer patients using publicly available online datasets. We found that HOXC8 was amplified in gastric cancer tissues, and mRNA expression levels were significantly associated with tumor status (P=0.044) and poor overall survival (P<0.01). HOXC8 knockdown significantly reduced the viability of gastric cancer cell lines. HOXC8 modulated the expression of secreted phosphoprotein 1 (SPP1, osteopontin) and phosphorylation of AKT/ERK in gastric cancer cells. Survival analysis demonstrated a decrease in overall survival rates among the high HOXC8/high SPP1 expression group compared with the low HOXC8/low SPP1 expression group. In conclusion, HOXC8 may be an independent prognostic factor and serve as a useful predictive biomarker for gastric cancer.
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Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.
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Introduction: Objective: to determine the validity of the Global Leadership Initiative on Malnutrition (GLIM) against the Patient Generated-Subjective Global Assessment (PG-SGA) as a gold standard tool in malnutrition diagnosis, and to assess the impact of malnutrition diagnosed using GLIM and PG-SGA on the clinical outcomes of patients with esophageal squamous carcinoma (ESCC) resection. Methods: we prospectively analyzed 182 patients with ESCC who underwent radical esophagectomy. Preoperative malnutrition was diagnosed using GLIM and PG-SGA, and the postoperative clinical outcomes, including postoperative complications, postoperative chest tube indwelling time, length of stay and total hospitalization cost, were recorded. The association between the prevalence of malnutrition defined by the two tools and postoperative clinical outcomes was evaluated. Results: among the 182 ESCC patients, the incidence of malnutrition before surgery was 58.2 % and 48.4 % defined by PG-SGA and GLIM, respectively. GLIM and PG-SGA had good consistency in nutritional assessment of ESCC patients (k = 0.628, p < 0.001). Malnourished patients had higher TNM stages and older ages (all p < 0.05). Patients with malnutrition as assessed by PG-SGA and GLIM had a higher incidence of postoperative complications, a longer indwelling time of chest tube after esophagectomy, longer hospital length of stay, and higher hospitalization costs than patients with good nutrition (p < 0.001). Comparing the predictive efficiency of postoperative complications, the sensitivity of PG-SGA- and GLIM-defined malnutrition were 81.6 % and 79.6 %, the specificity were 50.4 % and 63.2 %, the Youden index were 0.320 and 0.428, and the Kappa value were 0.110 and 0.130, respectively. The areas under ROC curve of PG-SGA- and GLIM-defined malnutrition and postoperative complications were 0.660 and 0.714, respectively. Conclusions: this study indicates the effectiveness of malnutrition diagnosed according to GLIM and PG-SGA in predicting postoperative clinical outcomes among patients with ESCC. Compared with PG-SGA, GLIM criteria can better predict postoperative complications of ESCC. Follow-up analysis of postoperative long-term survival is needed to explore the association between different assessment tools and postoperative long-term clinical outcomes.
Introducción: Objetivo: determinar la validez de la iniciativa de Liderazgo Global sobre la Malnutrición (GLIM) frente a la Evaluación Global Subjetiva Generada por el Paciente (PG-SGA) como herramienta de referencia en el diagnóstico de la malnutrición y evaluar el impacto de la malnutrición diagnosticada usando GLIM y PG-SGA en los resultados clínicos de los pacientes con resección de carcinoma escamoso de esófago (CEE). Métodos: se analizaron prospectivamente 182 pacientes con CEE sometidos a esofagectomía radical. La desnutrición preoperatoria se diagnosticó utilizando GLIM y PG-SGA, y se registraron los resultados clínicos posoperatorios, incluyendo complicaciones posoperatorias, tiempo de permanencia del tubo torácico, posoperatorio, duración de la estancia y coste total de hospital. Se evaluó la asociación entre la prevalencia de desnutrición definida por las dos herramientas y los resultados clínicos postoperatorios. Resultados: entre 182 pacientes con CEE, la incidencia de desnutrición antes de la cirugía fue del 58,2 % y 48,4 % definida por PG-SGA y GLIM, respectivamente. GLIM y PG-SGA tuvieron buena consistencia en la evaluación nutricional de los pacientes con CEE (k = 0,628, p < 0,001). Los pacientes desnutridos presentaron estadios TNM más altos y edades mayores (todos p < 0,05). Los pacientes con desnutrición evaluada por PG-SGA y GLIM tuvieron una mayor incidencia de complicaciones posoperatorias, mayor tiempo de permanencia del tubo torácico después de la esofagectomía, mayor tiempo de hospitalización y mayores costos de hospitalización que los pacientes con buena nutrición (p < 0,001). Comparando la eficacia predictiva de las complicaciones posoperatorias, la sensibilidad de la desnutrición definida por PG-SGA y GPG fue del 81,6 % y 79,6 %; la especificidad, del 50,4 % y 63,2 %; el índice de Youden, del 0,320 y 0,428; y el valor de Kappa, de 0,110 y 0,130, respectivamente. Las áreas bajo la curva de ROC de la malnutrición definida por PG-SGA y GPG y las complicaciones postoperatorio fueron 0,660 y 0,714, respectivamente. Conclusiones: este estudio indica la eficacia de la desnutrición diagnosticada según GLIM y PG-SGA en la predicción de los resultados clínicos postoperatorios en pacientes con CEE. En comparación con PG-SGA, los criterios GLIM pueden predecir mejor las complicaciones posoperatorias del CEE. Es necesario realizar un análisis de seguimiento de la supervivencia posoperatoria a largo plazo para explorar la asociación entre las diferentes herramientas de evaluación y los resultados clínicos posoperatorios a largo plazo.
Subject(s)
Carcinoma, Squamous Cell , Malnutrition , Humans , Leadership , Postoperative Complications/epidemiology , Malnutrition/diagnosis , Malnutrition/epidemiology , Nutritional Status , Nutrition AssessmentABSTRACT
The glucose transporter family (GLUT) consists of fourteen members. It is responsible for glucose homeostasis and glucose transport from the extracellular space to the cell cytoplasm to further cascade catalysis. GLUT proteins are encoded by the solute carrier family 2 (SLC2) genes and are members of the major facilitator superfamily of membrane transporters. Moreover, different GLUTs also have their transporter kinetics and distribution, so each GLUT member has its uniqueness and importance to play essential roles in human physiology. Evidence from many studies in the field of diabetes showed that GLUT4 travels between the plasma membrane and intracellular vesicles (GLUT4-storage vesicles, GSVs) and that the PI3K/Akt pathway regulates this activity in an insulin-dependent manner or by the AMPK pathway in response to muscle contraction. Moreover, some published results also pointed out that GLUT4 mediates insulin-dependent glucose uptake. Thus, dysfunction of GLUT4 can induce insulin resistance, metabolic reprogramming in diverse chronic diseases, inflammation, and cancer. In addition to the relationship between GLUT4 and insulin response, recent studies also referred to the potential upstream transcription factors that can bind to the promoter region of GLUT4 to regulating downstream signals. Combined all of the evidence, we conclude that GLUT4 has shown valuable unknown functions and is of clinical significance in cancers, which deserves our in-depth discussion and design compounds by structure basis to achieve therapeutic effects. Thus, we intend to write up a most updated review manuscript to include the most recent and critical research findings elucidating how and why GLUT4 plays an essential role in carcinogenesis, which may have broad interests and impacts on this field.
Subject(s)
Insulin , Neoplasms , Humans , Cell Membrane/metabolism , Glucose/metabolism , Glucose Transport Proteins, Facilitative/metabolism , Glycolysis , Insulin/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein TransportABSTRACT
Lung cancer is one of the leading causes of cancer mortality worldwide. As it is often first diagnosed only when cancer metastasis has already occurred, the development of effective biomarkers for the risk prediction of cancer metastasis, followed by stringent monitoring and the early treatment of high-risk patients, is essential for improving patient survival. Cancer cells exhibit alterations in metabolic pathways that enable them to maintain rapid growth and proliferation, which are quite different from the metabolic pathways of normal cells. Fumarate hydratase (FH, fumarase) is a well-known tricarboxylic acid cycle enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. The current study sought to investigate the relationship between FH expression levels and the outcome of patients with lung cancer. FH was knocked down in lung cancer cells using shRNA or overexpressed using a vector, and the effect on migration ability was assessed. Furthermore, the role of AMP-activated protein kinase (AMPK) phosphorylation and disabled homolog 2 in the underlying mechanism was investigated using an AMPK inhibitor approach. The results showed that in lung cancer tissues, low FH expression was associated with lymph node metastasis, tumor histology and recurrence. In addition, patients with low FH expression exhibited a poor overall survival in comparison with patients having high FH expression. When FH was overexpressed in lung cancer cells, cell migration was reduced with no effect on cell proliferation. Furthermore, the level of phosphorylated (p-)AMPK, an energy sensor molecule, was upregulated when FH was knocked down in lung cancer cells, and the inhibition of p-AMPK led to an increase in the expression of disabled homolog 2, a tumor suppressor protein. These findings suggest that FH may serve as an effective biomarker for predicting the prognosis of lung cancer and as a therapeutic mediator.
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Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate.
Subject(s)
Circadian Clocks , Neoplasms , Humans , Neoplasms/diagnostic imaging , Neoplasms/genetics , Circadian Clocks/genetics , Signal Transduction/genetics , Cellular Reprogramming , HomeostasisABSTRACT
State of charge (SOC) of ultracapacitor plays an important role in the energy management optimization of hybrid energy storage system for electric vehicles. In addition to the perfection of the model and the SOC estimation algorithm, the parameter identification method and temperature factor should also be considered. In this paper, an ultracapacitor test platform is established, the characteristic parameters of ultracapacitor at full temperature range are obtained. This paper uses the forgetting factor recursive least squares algorithm (FFRLS) to identify the parameters of the second-order equivalent circuit model of ultracapacitor online. The extended Kalman filter (EKF) algorithm is used to estimate the SOC of ultracapacitor cell. The results show that: (1) FFRLS algorithm can identify R 0 , R 1 , R 2 , C 1 , and C 2 values of ultracapacitor at full temperature range. Under the hybrid pulse power characterization working condition, the average mean absolute error between the estimated voltage and the actual voltage is about 0.0132 V. (2) EKF algorithm has a good adaptability to estimate SOC of ultracapacitor under different temperatures and working conditions. The SOC estimation error under different working conditions is low. From the perspective of mean square error, the estimation error at -20 °C is the lowest. (3) FFRLS and EKF joint estimation algorithm with good robustness and reliability can be used to estimate the SOC of ultracapacitor under different temperatures and working conditions. This study can provide a useful guidance for the parameter identification and SOC estimation of ultracapacitor for electric vehicle at different temperatures.
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With the rapid development of computer technology, the loss of long-distance information in the transmission process is a prominent problem faced by English machine translation. The self-attention mechanism is combined with convolutional neural network (CNN) and long-term and short-term memory network (LSTM). An English intelligent translation model based on LSTM-SA is proposed, and the performance of this model is compared with other deep neural network models. The study adds SA to the LSTM neural network model and constructs the English translation model of LSTM-SA attention embedding. Compared with other deep learning algorithms such as 3RNN and GRU, the LSTM-SA neural network algorithm has faster convergence speed and lower loss value, and the loss value is finally stable at about 8.6. Under the three values of adaptability, the accuracy of LSTM-SA neural network structure is higher than that of LSTM, and when the adaptability is 1, the accuracy of LSTM-SA neural network improved the fastest, with an accuracy of nearly 20%. Compared with other deep learning algorithms, the LSTM-SA neural network algorithm has a better translation level map under the three hidden layers. The proposed LSTM-SA model can better carry out English intelligent translation, enhance the representation of source language context information, and improve the performance and quality of English machine translation model.
Subject(s)
Language , Neural Networks, Computer , Algorithms , Technology , TranslationsABSTRACT
Callicarpa nudiflora, belonging to the family Verbenaceaae, is wildly used as a traditional Chinese herbal medicine (Luo-hua-zi-zhu) for hemostasis, antibiosis and antiphlogosis in clinic. However, the underlying chemical basis of C. nudiflora for the significant effects remains obscure. Hence, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method was established for the characterization of multi-constituents in C. nudiflora. As a result, 57 chemical compounds were identified based on their retention times, accurate masses and MS/MS data, and 20 of them were uncovered for the first time in C. nudiflora. In addition, an optimized UHPLC fingerprint analysis, combined with chemometrics including similarity analysis, principal component analysis and partial least squares-discriminant analysis was developed for quality assessment and origin discrimination of C. nudiflora. Multivariate data analysis revealed the resemblances and differences of C. nudiflora related to regions, while partial least squares-discriminant analysis screened nine characteristic markers including luteoloside, acteoside, luteolin-4'-O-ß-D-glucopyranoside, pachypodol, isoquercitrin, nudifloside, 5,7,3',4'-tetrahydroxy-8-methoxy-6-C-ß-D-glucopyranosylflavone, 7α-acetoxysandaracopimaric acid and sandaracopimaric acid which contributed the most to the classification. This was the first report on the comprehensive profiling of chemical components in C. nudiflora, which helped to uncover the material basis of C. nudiflora and possess potential value for quality evaluation and clinical application purpose.