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BACKGROUND: Laboratory biosafety should be a priority in all healthcare institutions. In traditional laboratory safety teaching students typically receive knowledge passively from their teachers without active involvement. The combination of experiential learning and mobile learning may provide students with greater engagement, retention, and application of knowledge. To address this issue, we developed and conducted a convergent mixed methods study to assess the feasibility and usability of a WeChat mini program (WMP) named WeMed for laboratory biosafety education for medical laboratory students at Guangzhou Medical University (GMU). METHODS: The study was conducted between November 2022 and October 2023 among second-year undergraduate students at GMU. It involved the concurrent collection, analysis, and interpretation of both qualitative and quantitative data to assess feasibility and usability. In the quantitative strand, two evaluations were conducted via online surveys from students (n = 67) after a four-week study period. The System Usability Scale (SUS) was used to evaluate usability, while self-developed questions were used to assess feasibility. Additionally, a knowledge test was administered 6 months after the program completion. In the qualitative strand, fourteen semi-structured interviews were conducted, whereby a reflexive thematic analysis was utilized to analyze the interview data. RESULTS: The overall SUS score is adequate (M = 68.17, SD = 14.39). The acceptability of the WeMed program is in the marginal high range. Most students agreed that WeMed was useful for learning biosafety knowledge and skills (13/14, 93%), while 79% (11/14) agreed it was easy to use and they intended to continue using it. After 6 months, a significant difference in the knowledge test scores was observed between the WeMed group (n = 67; 2nd year students) and the traditional training group (n = 90; 3rd year students). However, the results should be interpreted cautiously due to the absence of a pretest. CONCLUSION: The combination of experiential learning and mobile learning with WMP is a feasible tool for providing laboratory biosafety knowledge and skills. Ongoing improvements should be made in order to increase long-term acceptance.
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Estudantes de Medicina , Humanos , Contenção de Riscos Biológicos , Estudos de Viabilidade , Universidades , AprendizagemRESUMO
Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected phytochemicals and Trp metabolites on the ion transport and 5-HT metabolism and signaling in the ileum of mice in vitro using the Ussing chamber technique. During the in vitro incubation, vanillylmandelic acid (VMA) reduced (p < 0.05) the short-circuit current, and 100 µM chlorogenic acid (CGA) (p = 0.12) and perillic acid (PA) (p = 0.14) had a tendency to reduce the short-circuit current of the ileum. Compared with the control, PA and N-acetylserotonin treatment upregulated the expression of tryptophan hydroxylase 1 (Tph1), while 100 µM cinnamic acid, indolelactic acid (ILA), and 10 µM CGA or indoleacetaldehyde (IAld) treatments downregulated (p < 0.05) the mRNA levels of Tph1. In addition, 10 µM IAld or 100 µM ILA upregulated (p < 0.05) the expression of monoamine oxidase A (Maoa). However, 10 µM CGA or 100 µM PA downregulated (p < 0.05) Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p < 0.05) the expression of Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p < 0.05) the ratios of Htr1a/Htr7 and Htr4/Htr7. These findings may help to elucidate the effects of phytochemicals and Trp metabolites on the regulation of gut ion transport and 5-HT signaling-related gut homeostasis in health and disease.
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Cinamatos , Íleo , Serotonina , Transdução de Sinais , Triptofano , Animais , Serotonina/metabolismo , Camundongos , Íleo/metabolismo , Íleo/efeitos dos fármacos , Triptofano/metabolismo , Transdução de Sinais/efeitos dos fármacos , Cinamatos/farmacologia , Cinamatos/metabolismo , Transporte de Íons/efeitos dos fármacos , Masculino , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/genética , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismoRESUMO
As an important factor secreted by skeletal muscle, myonectin can regulate lipid metabolism and energy metabolism, but its role in the utilization of peripheral free fatty acids (FFAs) by porcine intramuscular fat cells remains to be further investigated. In this study, porcine intramuscular adipocytes were treated with recombinant myonectin and palmitic acid (PA), either alone or in combination, and then were examined for their uptake of exogenous FFAs, intracellular lipid synthesis and catabolism, and mitochondrial oxidation of fatty acids. The results showed that myonectin decreased the area of lipid droplets in intramuscular adipocytes (p < 0.05) and significantly increased (p < 0.05) the expression levels of hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). Moreover, myonectin can up-regulate the expression of p38 mitogen-activated protein kinase (p38 MAPK). Myonectin significantly promoted the uptake of peripheral FFAs (p < 0.01), improved (p < 0.05) the expression of fatty transport protein 1 (FATP1) and fatty acid binding protein 4 (FABP4) in intramuscular adipocytes. Myonectin also significantly increased (p < 0.05) the expression levels of fatty acid oxidation markers: transcription factor (TFAM), uncoupling protein-2 (UCP2) and oxidative respiratory chain marker protein complex I (NADH-CoQ) in mitochondria of intramuscular adipocytes. In summary, myonectin promoted the absorption, transport, and oxidative metabolism of exogenous FFAs in mitochondria, thereby inhibiting lipid deposition in porcine intramuscular adipocytes.
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Ácidos Graxos não Esterificados , Regulação da Expressão Gênica , Suínos , Animais , Ácidos Graxos não Esterificados/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Adipócitos/metabolismo , Diferenciação Celular , Músculo Esquelético/metabolismo , Ácidos Graxos/farmacologiaRESUMO
Gastric cancer (GC) is the most common cancer worldwide. Although advances in the treatments, the oncogenic mechanisms are still largely unknown. RNF168 (ring-finger nuclear factor 168) is an important regulator of DNA double-strand break (DSB) repair, and its defects have been involved in the pathogenesis of a number of human diseases including cancer. However, its effects on GC are still unclear. In the study, we demonstrated that RNF168 expression was remarkably down-regulated in human GC tissues, and its low expression showed worse overall survival rate in GC patients. Importantly, we here reported that RNF168 directly interacted with Ras homolog gene family member C (RHOC) and induced its ubiquitination to promote RHOC degradation. RHOC exhibited higher expression in human GC tissues, and its knockdown significantly restrained cell proliferation, migration and invasion in GC cell lines. Moreover, RHOC knockdown led to a significant reduction in GC tumor growth in a xenograft mouse model. Additionally, histone deacetylase 1 (HDAC1) was found to be markedly decreased in GC cells with RHOC knockdown. Intriguingly, RHOC suppression-ameliorated proliferative and migratory ability in GC cells were significantly diminished by HDAC1 over-expression. Our in vivo studies finally confirmed that RHOC inhibition dramatically reduced the lung metastasis in nude mice. Collectively, all our results demonstrated that RNF168 directly interacted with RHOC to induce its degradation via promoting its ubiquitination, contributing to the inhibition of cell proliferation and metastasis in GC through decreasing HDAC1. Thus, targeting RNF168/RHOC/HDAC1 axis might be promising to develop effective therapies for GC treatment.
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Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Histona Desacetilase 1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Gástricas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína de Ligação a GTP rhoC/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Regulação para Baixo , Técnicas de Silenciamento de Genes , Histona Desacetilase 1/genética , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína de Ligação a GTP rhoC/genéticaRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is often associated with multisystem damage. The gut is a pivotal organ that initiates the pathophysiological processes of multisystem diseases. Intermittent hypoxia resulting from OSA may impair the intestinal barrier prior to the induction of systemic inflammation. We hypothesize that the intestinal barrier markers D-lactic acid (D-LA) and intestinal fatty acid-binding protein (I-FABP) levels would be higher in patients with OSA. METHODS: Consecutive snoring and nonsnoring adults were included in this study and were grouped based on their apnea-hypopnea index (AHI) scores: the control group (AHI < 5) and the OSA group (AHI ≥ 5). Plasma D-LA and I-FABP levels were measured using colorimetry and ELISA, respectively. Other parameters, such as fasting levels of lipids, routine blood tests, and glucose were also assessed. RESULTS: Of 76 participants, patients in the OSA group accounted for 73% (55/76). Plasma D-LA and I-FABP levels were significantly higher in patients with OSA [7.90 (7.42) (IQR) vs. 0.88 (2.79) (IQR) mmol/L, p < 0.001 and 1851.99 ± 754.23 (SD) vs. 1131.98 ± 383.38 pg/mL, p < 0.001, respectively]. Increased glucose, triglycerides (TGs), leukocytes, neutrophils, and monocytes but decreased high density lipoprotein (HDL) were also found in patients with OSA. It was also observed that the increase in D-LA and I-FABP exhibited the strongest positive association with AHI (r = 0.443, p < 0.001; r = 0.645, p < 0.001), followed by the lowest SaO2 (p ≤ 0.001), BMI (p ≤ 0.017), glucose (p ≤ 0.011), and TGs (p ≤ 0.025). Moreover, multivariate regression analysis showed that D-LA (B = 0.823, p < 0.001) and I-FABP (B = 0.002, p = 0.017) were independently associated with OSA. CONCLUSIONS: The systemic expression of D-LA and I-FABP is dramatically higher in OSA patients, suggesting that hypoxia resulting from OSA might have the capacity to impair the intestinal barrier prior to the induction of multisystem dysfunction.
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Proteínas de Ligação a Ácido Graxo/sangue , Ácido Láctico/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangueRESUMO
This study is performed to examine the impacts of microRNA-218 (miR-218) on cardiac microvascular endothelial cells (CMECs) injury induced by coronary artery disease (CAD). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was applied for detecting miR-218 expression in serum of patients with CAD and healthy controls, and the correlation between miR-218 expression and the clinical indexes such as creatine kinase, creatine kinase-myocardial band, cardiac troponin I, and coronary Gensini score was analyzed. CMECs were coincubated with homocysteine for 24 hr for CMECs injury, and the cells were transfected with miR-218 mimics or miR-218 inhibitors. Besides, we used oxidized low density lipoprotein as an inducer to incubate with CMECs for 24 hr, and the model of CMECs injury was established to be transfected with miR-218 mimics. RT-qPCR and western blot analysis were used to detect miR-218 and HMGB1 expression in CMECs. A series of experiments were used to determine cell proliferation, apoptosis, migration, and angiogenesis ability of CMECs. Vascular endothelial growth factor expression and inflammatory factor contents were measured. The obtained results suggested that miR-218 expression in peripheral blood of patients with CAD descended substantially versus that of healthy controls. Low miR-218 expression was found in CAD-induced CMECs injury. Overexpressed miR-218 promoted the proliferation, migration, angiogenesis ability, induced apoptosis, and alleviated the inflammatory injury of CAD-induced CMECs. miR-218 may negatively regulate the expression of HMGB1 in CAD. This study demonstrates that upregulation of miR-218 reduces CMECs injury induced by CAD through the inhibition of HMGB1.
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Células Endoteliais/metabolismo , Proteína HMGB1/metabolismo , MicroRNAs/genética , Miocárdio/metabolismo , Apoptose/genética , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Proteína HMGB1/genética , Humanos , Neovascularização Patológica/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Ativação Transcricional , Regulação para CimaRESUMO
PURPOSE: To translate quality of life questionnaire of the European foundation for osteoporosis (QUALEFFO-31) into a simplified Chinese version, and test its reliability and validity in osteoporosis patients from mainland Chinese population. METHODS: Postmenopausal osteoporosis women with history of vertebral fracture were included as cases, and age-matched healthy female were included as controls. All subjects were from mainland China. The simplified Chinese version of QUALEFFO-31 and SF-36 were assigned to the two groups. Reliability was assessed using kappa statistics of agreement for each item and the intra-class correlation coefficient (ICC). The internal consistency was assessed with Cronbach's α. Pearson's correlation was used to assess convergent and discriminant validity. RESULTS: Overall, 66 cases and 66 age-matched controls were included. The ICC for the test-retest reliability ranged from 0.76 to 0.91. Cronbach's α for pain, physical function, and mental function domains were 0.94, 0.87, and 0.79, respectively. Convergent validity and discriminant validity showed that each correlation coefficient between score of each item with total score of related domain was higher than that with total score of unrelated domain. Pearson's correlation coefficients indicated significantly high correlations between corresponding domains of QUALEFFO-31 and SF-36. CONCLUSIONS: The simplified Chinese version of the QUALEFFO-31 is a reliable and valid outcome measure of functional status in patients with osteoporosis. This Chinese version of the QUALEFFO-31 can be utilized for future clinical studies in mainland China.
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Indicadores Básicos de Saúde , Osteoporose Pós-Menopausa/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Idoso , Estudos de Casos e Controles , China , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , TraduçõesRESUMO
BACKGROUND: Glycogen synthase kinase-3ß (GSK3ß) expression and activity are upregulated in pancreatic cancer tissues. In our previous study, we found that stromal cell-derived factor-1/ chemokine receptor C-X-C motif chemokine receptor 4 (SDF-1α/CXCR4) upregulated matrix metalloproteinase 2 (MMP-2) and promoted invasion in PANC1 and SW-1990 pancreatic cancer cells by activating p38 mitogen-activated protein kinase (p38 MAPK). Additionally, inhibition of GSK3ß reduced MMP-2 secretion. METHODS: To investigate the molecular mechanism of GSK3ß in pancreatic cancer tissues, we created stable PANC1 cells up-regulation of GSK3ß by transfecting GSK3ß overexpression plasmid, and down-regulation of GSK3ß using two different types of RNA interference. RESULTS: Western blotting showed that overexpression of GSK3ß up-regulated CXCR4 and MMP-2 expression; suppression of GSK3ß down-regulated CXCR4 and MMP-2 protein expression. Up-regulation of MMP2 induced by overexpression of GSK3ß was blocked by inhibition of CXCR4. Overexpression of GSK3ß promoted PANC1 cell invasion, and down-regulation of GSK3ß suppressed PANC1 cell invasion in the transwell invasion assays. However, inhibition of CXCR4 using shRNA attenuated the ability of GSK3ß to promote PANC1 cell invasion. CONCLUSIONS: This study demonstrated that GSK3ß promotes PANC1 cell invasion via the CXCR4/MMP-2 pathway.
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Islet-cell autoantigen 69 kDa (ICA69) plays an important role in many diseases and physiological activities by forming heteromeric complexes with protein interacts with C-kinase 1 (PICK1). PICK1 is critical for inflammatory pain hypersensitivity by regulating trafficking of AMPA receptor subunit GluA2 in spinal neurons. However, the role of ICA69 in inflammatory pain has not yet been investigated. Here we reported that expression of PICK1 in spinal cord was reduced largely in ICA69 knockout mice. The pain hypersensitivity was enhanced in the second phase 7 days after formalin administration. Meanwhile, increased Ser880 phosphorylation in GluA2 and decreased surface GluA2 were concordant with the pain. Furthermore, the number of activated microglia in spinal dorsal horn increased in line with pain hypersensitivity. Together, ICA69 deficiency promoted the internalization of GluA2 and FML-induced long-lasting pain hypersensitivity. In addition, microglia activation might be an important factor in the development of the pain hypersensitivity.
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Autoantígenos/metabolismo , Formaldeído/toxicidade , Membro Posterior/efeitos dos fármacos , Membro Posterior/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Animais , Formaldeído/administração & dosagem , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de TempoRESUMO
BACKGROUND: CXCR4 and glycogen synthase kinase-3ß (GSK3ß) promote proliferation and invasion of pancreatic cancer. Inhibition of CXCR4 suppresses GSK3ß expression. However, the molecular mechanism by which CXCR4 contributes to human pancreatic cancer metastasis is not completely understood. In this study, therefore, we analyzed the effect of CXCR4 on GSK3ß expression and its molecular mechanism. METHODS: PANC-1 and SW-1990 cells were used in this study. PANC-1 and SW-1990 cell lines which stably expressed upregulated or downregulated CXCR4 were used for further study. Western blotting was employed to detected the expression of CXCR4, GSK3ß and MMP-2. Cell invasion assay was used to detect the effect of the Akt pathway on CXCR4-induced GSK3ß expression. RESULTS: Overexpression of CXCR4 promoted GSK3ß expression and silencing of CXCR4 suppressed GSK3ß expression. Overexpression of CXCR4 activated cyclin D1 and p-Akt expression, but inhibited p21 expression. Silencing of CXCR4 had the reverse effect. CXCR4 promoted GSK3ß expression and PANC-1 invasion by Akt signaling. CXCR4 upregulated GSK3ß expression, at least in part, at the level of transcription. CONCLUSIONS: CXCR4 promotes GSK3ß expression via the Akt cell signaling pathway in pancreatic cancer cells.
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Adenocarcinoma/metabolismo , Quinase 3 da Glicogênio Sintase/biossíntese , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/biossíntese , Linhagem Celular Tumoral , Ciclina D1/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Glicogênio Sintase Quinase 3 beta , Humanos , Invasividade Neoplásica , Transdução de SinaisRESUMO
BACKGROUND: It has long been debated whether pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ) is the better choice for reconstruction after pancreaticoduodenectomy. The purpose of this study is to evaluate the two techniques. METHODS: Randomized controlled trials (RCTs) comparing PG with PJ published from January 1995 to January 2014 were searched electronically using PubMed, Medline, and Cochrane Library. Published data of these RCTs were analyzed using either fixed-effects model or random-effects model. RESULTS: Seven RCTs were included in this meta-analysis, with a total of 1121 patients (562 in PG, 559 in PJ). The incidence of postoperative pancreatic fistula and intra-abdominal fluid collection were significantly lower in PG than in PJ (respectively: odds ratio = 0.53 [0.37, 0.74], P < 0.001; odds ratio = 0.48 [0.30, 0.76], P < 0.01), no significant difference could be found for delayed gastric emptying, hemorrhage, morbidity, reoperation rate, and mortality. CONCLUSIONS: The evidence from RCTs suggests that PG technique is associated with a lower rate of postoperative pancreatic fistula and intra-abdominal fluid collection than PJ.
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Gastrostomia/mortalidade , Fístula Pancreática/mortalidade , Pancreaticojejunostomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Reoperação/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Lemon, as an important cash crop with rich nutritional value, holds significant cultivation importance and market demand worldwide. However, lemon diseases seriously impact the quality and yield of lemons, necessitating their early detection for effective control. This paper addresses this need by collecting a dataset of lemon diseases, consisting of 726 images captured under varying light levels, growth stages, shooting distances and disease conditions. Through cropping high-resolution images, the dataset is expanded to 2022 images, comprising 4441 healthy lemons and 718 diseased lemons, with approximately 1-6 targets per image. Then, we propose a novel model lemon surface disease YOLO (LSD-YOLO), which integrates Switchable Atrous Convolution (SAConv) and Convolutional Block Attention Module (CBAM), along with the design of C2f-SAC and the addition of a small-target detection layer to enhance the extraction of key features and the fusion of features at different scales. The experimental results demonstrate that the proposed LSD-YOLO achieves an accuracy of 90.62% on the collected datasets, with mAP@50-95 reaching 80.84%. Compared with the original YOLOv8n model, both mAP@50 and mAP@50-95 metrics are enhanced. Therefore, the LSD-YOLO model proposed in this study provides a more accurate recognition of healthy and diseased lemons, contributing effectively to solving the lemon disease detection problem.
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BACKGROUND AND AIMS: The cytotoxic T-lymphocyte antigen 4 (CTLA4) gene polymorphisms have been shown to be associated with the risk of primary biliary cirrhosis (PBC). The study aimed to confirm the associations of CTLA4 gene polymorphisms with risk of PBC and patients' quality of life in Chinese population. METHODS: A total of 312 female PBC patients from Chinese Han population were included as case, and 375 age-matched female healthy volunteers were included as control. Four single nucleotide polymorphisms (SNPs) including rs231775, rs3087243, rs231725, and rs5742909 were genotyped. The differences of genotype and allele distributions between PBC patients and healthy controls were assessed. The relationship between CTLA4 gene polymorphisms and healthy status of PBC patients were then investigated through comparisons of the domain scores of PBC-40 questionnaire between different genotype categories of each single nucleotide polymorphism. RESULTS: The frequencies of G allele at rs231775 and A allele at rs231725 were both significantly increased in PBC patients when compared with normal controls (P < 0.001, odds ratio = 1.44, 95% confidence interval = 1.24-1.67 for rs231775; P < 0.001, odds ratio = 1.29, 95% confidence interval = 1.12-1.48 for rs231725). Besides, patients carrying A allele of rs3087243 had significantly lower score of fatigue domain than those carrying G allele (2.5 ± 0.8 vs 3.9 ± 1.3, P < 0.001). CONCLUSIONS: This study revealed that CTLA4 gene polymorphism might be associated with susceptibility of PBC. G allele of rs231775 and A allele of rs231725 were significantly associated with the risk of PBC. In addition, patients carrying A allele of rs3087243 could have significantly better quality of life than those carrying G allele.
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Povo Asiático/genética , Antígeno CTLA-4/genética , Predisposição Genética para Doença/genética , Genótipo , Cirrose Hepática Biliar/genética , Estudos Multicêntricos como Assunto , Polimorfismo de Nucleotídeo Único/genética , Feminino , Frequência do Gene/genética , Humanos , Qualidade de Vida , Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The aim of this research is to investigate the feasibility of folate receptor-positive circulating tumor cells (FR+CTCs) as a biomarker for the diagnosis of malignant pulmonary nodules and the correlation between clinicopathological factors and FR+CTC levels. METHODS: Patients initially diagnosed with one or more pulmonary nodules from a computed tomography scan were prospectively included. Three milliliters of peripheral blood was collected from each participant for FR+CTC analysis prior to surgery. Clinical and pathological parameters and FR+CTC levels were compared between patients with lung cancer and benign diseases. RESULTS: Six hundred fifty-three patients had lung cancer and the other 124 had benign lung diseases based on pathological examinations of the resected specimens. The median FR+CTC value of the lung cancer group was 12.0 (95% CI 9.6-16.2) FU/3 mL and that of the benign group was 7.2 (95% CI 5.78-11.2) FU/3 mL. The difference was statistically significant (P < 0.0001). In a receiver operating characteristic analysis to distinguish the two groups, the area under curve of FR+CTC was 0.7457 (95% CI 0.6893-0.8021; P < 0.0001) using a cutoff of 8.65 FU/3 mL. The sensitivity was 86.37%, and the specificity was 74.19%. Combined with conventional serum tumor biomarkers, the area under curve was 0.922 (0.499-0.963). The sensitivity was 92.20%, and the specificity was 83.05%. FR+CTC levels were related to tumor staging (P4 < 0.001), the degree of tumor invasion both in single (P = 0.011) and multiple lesions (P = 0.022), pathological subtypes (P = 0.013), and maximum tumor diameter (P = 0.014). CONCLUSIONS: FR+CTC is an effective and reliable biomarker for the diagnosis of lung cancer. Further, FR+CTC level is correlated with tumor staging, degree of invasion, pathological subtypes, and tumor size.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais , Estadiamento de Neoplasias , Nódulos Pulmonares Múltiplos/patologia , Ácido FólicoRESUMO
Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect fecal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers-intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Plasma D-LA and I-FABP were significantly elevated in patients with OSA. The severity of OSA was related to differences in the structure and composition of the fecal microbiome. Enriched Fusobacterium, Megamonas, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the fecal microbiome, intestinal barrier biomarkers, and AHI. The study confirms that changes in the intestinal microbiota are associated with intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.
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Microbiota , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/diagnóstico , Polissonografia/métodos , BiomarcadoresRESUMO
Background soluble programmed death-ligand 1 (sPD-L1) expression in lung squamous cell carcinoma and lung adenocarcinoma is associated with disease progression, and sPD-L1 expression in small cell lung cancer (SCLC) may have similar manifestations and become a potential marker for treatment. The purpose of this study was to observe the changes of plasma sPD-L1 expression in SCLC patients. Methods. 90 patients diagnosed with SCLC from January 2019 to November 2020 were selected as the test group, including 72 males and 18 women, 58.7 ± 6.6 years; 30 healthy subjects were selected from the physical examination center, including 18 males, 12 females, and 60.3 ± 7.0 years. There were no statistical difference in sex and age factors between the trial and control groups (p > 0.05). Selected SCLC used chemotherapy regimen: cisplatin + etoposide (EP), carboplatin + etoposide (CE), and SCLC group were divided into three subgroups of disease progression group, partial remission group, and disease stability group according to the treatment effect. Comparison of the differences in sPD-L1 expression content between the experimental and control populations. Plasma sPD-L1 levels were dynamically monitored pre- and posttreatment in 90 patients with small-cell lung cancer and were associated with efficacy among subgroups. Meanwhile, the risk factors for patient sPD-L1 expression content were analyzed by logistic regression. Results. Plasma sPD-L1 levels were higher in the SCLC group than in the healthy people group (t = 7.40, p < 0.01). In the disease progression group of the SCLC group, sPD-L1 levels were decreased in the SCLC group, sPD-L1 in some remission group was increased after treatment, and sPD-L1 levels in the disease-stable group (p > 0.05). Multivariate logistic regression analysis showed that factors promoting increased sPD-L1 expression in SCLC patients included increased smoking, brain metastasis, and ProGRP expression (both p values < 0.05). Conclusion. (1) Higher peripheral sPD-L1 expression in SCLC patients than in healthy patients, and the expression levels were closely related to efficacy. (2) Dynamic changes in s PD-L1 were correlated with clinical efficacy. (3) The progression of sPD-L1 and ProGRP in SCLC patients showed the same extent during remission and stabilization, suggesting the effect of s PD-L1 in the evaluation of SCLC tumors and the reflection of the tumor marker ProGRP.
Assuntos
Antígeno B7-H1/sangue , Neoplasias Pulmonares/irrigação sanguínea , Carcinoma de Pequenas Células do Pulmão/sangue , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Biologia Computacional , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Solubilidade , Resultado do TratamentoRESUMO
Background: Skin cutaneous melanoma (SKCM) is the most frequently encountered tumor of the skin. Immunotherapy has opened a new horizon in melanoma treatment. We aimed to construct a CD8+ T cell-associated immune gene prognostic model (CDIGPM) for SKCM and unravel the immunologic features and the benefits of immunotherapy in CDIGPM-defined SKCM groups. Method: Single-cell SKCM transcriptomes were utilized in conjunction with immune genes for the screening of CD8+ T cell-associated immune genes (CDIGs) for succeeding assessment. Thereafter, through protein-protein interaction (PPI) networks analysis, univariate COX analysis, and multivariate Cox analysis, six genes (MX1, RSAD2, IRF2, GBP2, IFITM1, and OAS2) were identified to construct a CDIGPM. We detected cell proliferation of SKCM cells transfected with IRF2 siRNA. Then, we analyzed the immunologic features and the benefits of immunotherapy in CDIGPM-defined groups. Results: The overall survival (OS) was much better in low-CDIGPM group versus high CDIGPM group in TCGA dataset and GSE65904 dataset. On the whole, the results unfolded that a low CDIGPM showed relevance to immune response-correlated pathways, high expressions of CTLA4 and PD-L1, a high infiltration rate of CD8+ T cells, and more benefits from immunotherapy. Conclusion: CDIGPM is an good model to predict the prognosis, the potential immune escape from immunotherapy for SKCM, and define immunologic and molecular features.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/terapia , Melanoma/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/metabolismo , Linfócitos T CD8-Positivos , Prognóstico , Imunoterapia , Melanoma Maligno CutâneoRESUMO
Colorectal cancer (CRC) is one of the most common malignancies worldwide, leading to a large number of cancer-related mortalities. Aberrant CD8+â T cell infiltration plays a critical role in tumor progression and patient prognosis. This study aimed to identify a prognostic model for CRC based on CD8+â T cell-related genes. The infiltration levels of immune cells in CRC tissues were accessed by the ESTIMATE algorithm. Weighted gene co-expression network analysis (WGCNA) analysis was used to select CD8+â T cell-related genes. Prognostic genes were identified using Cox regression analysis and Kaplan-Meier curves. The least absolute shrinkage and selection operator (LASSO) algorithm was used to construct prognostic models. Gene set enrichment analysis (GSEA) was performed to annotate enriched gene sets. Single-cell RNA (scRNA) sequencing analysis was used to examine gene expression in different cell types. We found that the downregulated infiltration level of CD8+â T cells was an independent prognostic factor for CRC and selected a cluster of differentially expressed genes correlated with CD8+â T cell infiltration (CD8TDEGs). Subsequently, we identified 18 prognostic CD8TDEGs, according to which patients were reclassified into two clusters with distinct overall survival. Seven prognostic CD8TDEGs were selected to calculate the constructed prognostic model's risk scores. Interestingly, although CRC tissues with higher risk scores had higher infiltration levels of CD8+â T cells, the level of immune checkpoint genes was also high. Moreover, the scRNA-sequencing analysis showed that the expression levels of CD8TDEGs in the prognostic model varied among different types of cells. This study constructed a novel prognostic model for CRC and provided a foundation for targeting CD8+â T cell infiltration to improve the survival of CRC patients.
Assuntos
Neoplasias Colorretais , Análise de Célula Única , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/patologia , Humanos , Prognóstico , RNA/metabolismo , Estudos Retrospectivos , Análise de Sequência de RNARESUMO
BACKGROUND: Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in the carcinogenesis of many developing human tumors. However, the clinical significance and biological function of microRNA-3648 (miR-3648) in non-small cell lung cancer (NSCLC) have been largely undefined. METHODS: The expression of miR-3648 and the mRNA of adenomatous polyposis coli 2 (APC2) in NSCLC tissues and cell lines were analyzed using quantitative real-time RT-PCR. The prognostic value of miR-3648 and APC2 was examined using the Kaplan-Meier method and Cox regression analyses. Experiments using NSCLC cells were conducted to explore the influences of miR-3648 on tumor cell proliferation, migration and invasion. RESULT: Increased expression of miR-3648 was observed in NSCLC tissues and cell lines compared with the corresponding controls (all P<0.05). miR-3648 expression was associated with the differentiation, lymph node metastasis and TNM stage (all P<0.05) of NSCLC patients, and high expression of miR-3648 was associated with poor overall survival rate. NSCLC cell proliferation, migration and invasion were significantly enhanced by miR-3648 overexpression. The further luciferase reporter assay and expression results showed that the decreased APC2 might also be a prognostic biomarker, and served as a target of miR-3648 in NSCLC. CONCLUSION: The findings from the present study indicate that the overexpression of miR-3648 serves as a useful biomarker for the prediction of prognosis in NSCLC, and promotes tumor cell proliferation, migration and invasion. APC2, as another prognosis-related molecule, may be a target of miR-3648 in NSCLC.
Assuntos
Polipose Adenomatosa do Colo , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Polipose Adenomatosa do Colo/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , PrognósticoRESUMO
This experiment aimed to investigate the effects of fermented bamboo powder (FBP) on the growth performance, serum biochemical parameters, immunoglobulins and inflammatory cytokines, and fecal microbial composition of growing−finishing pigs. A total of 108 barrows (initial body weight, 56.30 ± 0.55 kg) were randomly allocated to three dietary treatments in a 75 d trial, including a control (CON) diet and two FBP supplementation diets. The CON diet was formulated to three-phase diets according to the body weight of pigs, and the FBP diets were formulated used 5.00% (FBP1) or 10.00% (FBP2) FBP to replace the wheat bran in the CON diet, respectively. The results showed that there were no influences on growth performances between the CON diet and FBP addition diets, whereas the 5% FBP addition decreased the feed:gain of pigs compared to the pigs fed the FBP2 diet from d 0−75 (p < 0.05). Meanwhile, the FBP addition increased the high-density lipoprotein cholesterol (HDLC) and immunoglobulin A (IgA) content in serum (linear, p < 0.05), and pigs fed the FBP1 diet had greater HDLC and IgA contents in serum than those in the pigs fed the CON diet (p < 0.05). Microbial analysis showed that the FBP addition diets decreased the abundance of Spirochaetes, and the FBP2 diet increased the abundance of Firmicutes more than the CON diet (p < 0.05). In addition, the pigs fed the FBP2 diet increased the abundance of uncultured_bacterium_f_Lachnospiraceae, Ruminococcaceae_UCG-005, Prevotellaceae_UCG-003, Lachnospiraceae_XPB1014_group, and Lactobacillus more than the CON group (p < 0.05). In conclusion, the FBP supplementation to the diet had no negative effects on the growth performance and exerted beneficial effects on promoting serum biochemical and immune indices, as well as modulating the fecal microbiota of pigs. Therefore, these results showed that the fermented bamboo powder could be one potential fiber-rich ingredient for growing−finishing pigs, and that the recommended addition proportion in the growing−finishing pigs' diet is 5%.