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1.
BMC Cancer ; 23(1): 1097, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950153

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Immunotherapy targeting the programmed death protein 1(PD-1) and its ligand (PD-L1), is a promising treatment option for many cancers, but has exhibited poor therapeutic efficacy in CRC. This study aimed to identify and validate the prognostic value of immune-related genes and PD-1-associated genes for immunotherapy treatment of CRC. METHODS: An extensive analysis of prognostic immune-related DEGs and PD-1-related genes has highlighted CDKN2A as a vital overlapping gene. To further explore its expression in CRC and its prognostic value, we conducted qRT-PCR, Western blot experiments, and consulted various databases. Subsequently, we conducted gene expression analysis, survival and prognostic analysis, enrichment analysis, immune infiltration assessment, and TIDE analysis to assess the significance of CDKN2A. RESULTS: In CRC, CDKN2A was highly expressed compared to normal tissue. It was found that CDKN2A expression was related to clinicopathological features such as inflammation and tumor stage. Furthermore, a significant correlation was identified between CDKN2A and immune infiltration, specifically involving CD4 T cells, CD8 T cells, and macrophages. The analysis of the GSEA of CRC samples with high CDKN2A expression identified enrichment of genes involved in MYC target-v2 and metabolism pathways. Furthermore, UBE2I, CDK4, CDK6, TP53, and CCND1 were found to be significantly coexpressed with CDKN2A, suggesting a potential role that these gene play in CRC and immunotherapy. CONCLUSIONS: Our study revealed that high CDKN2A expression in CRC is a potentially valuable prognostic biomarker, which may guide PD-1-mediated immunotherapy.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Prognóstico , Linfócitos T CD8-Positivos , Imunoterapia , Inibidor p16 de Quinase Dependente de Ciclina/genética
2.
Med Sci Monit ; 28: e937880, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089755

RESUMO

BACKGROUND Anisometropic amblyopia results from the unequal ability to focus between the right and left eyes. Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) measures the proportion of oxygenated hemoglobin in specific areas. Diffusion kurtosis imaging (DKI) is a method of diffusion tensor imaging that estimates the skewed distribution of water diffusion probability. We aimed to evaluate and compare 11 adult patients with anisometropic amblyopia (AA) with 13 normally sighted healthy controls (HC) using BOLD-fMRI and DKI. MATERIAL AND METHODS Eleven adults with AA (age range 20-49; mean age 29.18±8.089) and 13 HC adults (age range 22-50; mean age 28.00±5.79) were recruited. DKI scanning used a single excitation echo-planar imaging sequence and a region of interest to obtain DKI parameters for optic radiation; the corpus callosum was manually placed, including mean kurtosis (MK), fractional anisotropic (FA), and mean diffusivity (MD) values; and BOLD data used a gradient-echo echo-planar imaging sequence. RESULTS The AA group had lower MK and FA of bilateral optic radiation than the HC group (P=0.008 and P=0.006, respectively) and higher MD than the HC group (P=0.005). The MK of the corpus callosum in the AA group was lower than that of HC group (P=0.012).Compared with the non-dominant eyes of the HC group, the amblyopic eyes in the AA group had less activation range and intensity in Brodmann areas 17, 18, and 19. CONCLUSIONS The combined use of DKI and BOLD-fMRI detected microstructural changes associated with local visual pathways and identified damage to the visual cortex in patients with amblyopia.


Assuntos
Ambliopia , Córtex Visual , Adulto , Ambliopia/diagnóstico por imagem , Anisotropia , Imagem de Tensor de Difusão/métodos , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Adulto Jovem
3.
Int J Clin Pract ; 2022: 7405448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052305

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.


Assuntos
COVID-19 , Gastroenteropatias , Bilirrubina , Biomarcadores , COVID-19/prevenção & controle , China/epidemiologia , Sistema Digestório , Gastroenteropatias/diagnóstico , Humanos , Interleucina-6 , SARS-CoV-2 , Vacinas de Produtos Inativados/uso terapêutico
4.
Fish Shellfish Immunol ; 111: 227, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33612357

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editors-in-Chief and first Author. The article duplicates significant parts of a paper that had already appeared in Fish & Shellfish Immunology, Volume 93 (2019) 726-731, https://doi.org/10.1016/j.fsi.2019.06.052. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. The article was published without the knowledge of the co-authors.

5.
Sensors (Basel) ; 21(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34372409

RESUMO

Considerable research and surveys indicate that skin lesions are an early symptom of skin cancer. Segmentation of skin lesions is still a hot research topic. Dermatological datasets in skin lesion segmentation tasks generated a large number of parameters when data augmented, limiting the application of smart assisted medicine in real life. Hence, this paper proposes an effective feedback attention network (FAC-Net). The network is equipped with the feedback fusion block (FFB) and the attention mechanism block (AMB), through the combination of these two modules, we can obtain richer and more specific feature mapping without data enhancement. Numerous experimental tests were given by us on public datasets (ISIC2018, ISBI2017, ISBI2016), and a good deal of metrics like the Jaccard index (JA) and Dice coefficient (DC) were used to evaluate the results of segmentation. On the ISIC2018 dataset, we obtained results for DC equal to 91.19% and JA equal to 83.99%, compared with the based network. The results of these two main metrics were improved by more than 1%. In addition, the metrics were also improved in the other two datasets. It can be demonstrated through experiments that without any enhancements of the datasets, our lightweight model can achieve better segmentation performance than most deep learning architectures.


Assuntos
Dermatopatias , Neoplasias Cutâneas , Retroalimentação , Humanos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Manejo de Espécimes
6.
Fish Shellfish Immunol ; 94: 697-704, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31561027

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editors-in-Chief and first Author. The article duplicates significant parts of a paper that had already appeared in Fish & Shellfish Immunology, Volume 93 (2019) 726-731, https://doi.org/10.1016/j.fsi.2019.06.052. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. The first author informed the journal that the article was published without the knowledge of the co-authors.


Assuntos
Aquicultura/métodos , Doenças dos Peixes/imunologia , Rhodobacter capsulatus/química , Tilápia/imunologia , Eliminação de Resíduos Líquidos/métodos , Aeromonas hydrophila/fisiologia , Animais , Resistência à Doença/genética , Regulação da Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , NF-kappa B/genética , Distribuição Aleatória , Transdução de Sinais/imunologia , Serina-Treonina Quinases TOR/genética , Águas Residuárias/microbiologia
7.
Fish Shellfish Immunol ; 93: 726-731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265912

RESUMO

Application of traditional bait in aquaculture caused environment pollution and disease frequent occurrence. Residual coconut could be re-utilized to culture Spinibarbus sinensis as dietary supplement. Therefore, a novel integrated system of the improvement of yield, antioxidant and nonspecific immunity of Spinibarbus sinensis by dietary residual coconut was proposed and investigated. Spinibarbus sinensis could grow well in all supplement residual coconut groups. Survival rate, yield, whole fish body composition under 15-45% groups were increased compared with control group (CK). Bioactive substances (polyphenols and vitamin) in residual coconut enhanced AKP, ACP, phagocytic, SOD, CAT activities through up-regulating AKP, ACP, SOD, CAT genes expression levels. Theoretical analysis showed bioactive substances regulated these genes expressions and enzyme activities as stimulus signal, component, active center. Moreover, residual coconut improved mTOR and NF-kB signaling pathway. Furthermore, residual coconut inhibited Aeromonas hydrophila that increased resistance to diseases. This technology completed the solid waste recovery and the Spinibarbus sinensis culture simultaneously.


Assuntos
Antioxidantes/metabolismo , Óleo de Coco/metabolismo , Cyprinidae/imunologia , Resistência à Doença/imunologia , Imunidade Inata/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Aquicultura/métodos , Óleo de Coco/administração & dosagem , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estudos de Viabilidade
8.
Bioprocess Biosyst Eng ; 42(8): 1375-1384, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172262

RESUMO

Simultaneous (SPW and propyzamide) wastewater treatment and the production of biochemicals by Rhodopseudomonas capsulata (R. capsulata) were investigated with supplement of soybean processing wastewater (SPW). Compared to control group, propyzamide was removed and biochemicals production were enhanced with the supplement of SPW. Propyzamide induced camH gene expression through activating MAPKKKs gene in MAPK signal transduction pathway. The induction of camH gene and CamH occurs after 1 day for R. capsulata. However, lack of organics in original wastewater did not maintain R. capsulata growth for over 1 day. The supplement of SPW provided sufficient carbon source for R. capsulata under three addition dosages. This new method resulted in the mixed (SPW and propyzamide) wastewater treatment and improvement of biochemicals simultaneously, as well as the realization of reutilization of wastewater and R. capsulata as sludge. Meanwhile, high-order nonlinear mathematical model of the relationship between propyzamide removal rate, Xt and Xt/r, was established.


Assuntos
Benzamidas , Glycine max/química , Rodopseudomonas/crescimento & desenvolvimento , Eliminação de Resíduos Líquidos , Águas Residuárias/microbiologia , Benzamidas/química , Benzamidas/metabolismo
9.
BMC Cancer ; 18(1): 730, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986697

RESUMO

BACKGROUND: Telomerase activity is required for both initiation and maintenance of tumorigenesis and over 90% cancers overexpress telomerase. Therefore, telomerase targeting has emerged as a potential strategy for cancer treatment. In agreement with this, several telomerase inhibitors are being tested for cancer treatment and have shown some promise. However, because of the variability in response between the cancer patients, it is important to identify biomarkers that allow for distinguishing cancers that are responsive to telomerase inhibition from the cancers that are not. Therefore, in this study we performed experiments to identify a biomarker that can be used to predict telomerase inhibition induced tumor growth inhibition. METHODS: In our study, we have performed transcriptome-wide gene expression analysis on multiple ovarian and colon cancer cell lines that were treated with telomerase inhibitor imetelstat and were responsive to telomerase inhibition-induced tumor growth attenuation. RESULTS: We demonstrate that telomerase inhibition by telomerase inhibitor imetelstat results in decreased expression of interleukin 8 (IL8) in all telomerase responsive cancer cell lines. This phenomenon is of general occurrence because we find that multiple ovarian and colon cell lines show decrease in IL8 mRNA and protein levels after telomerase inhibition. Additionally, we find loss of IL8 phenocopy Telomerase inhibition mediated growth inhibitory effect in cancer cells. CONCLUSION: Taken together, our results show that IL8 is a biomarker that predict telomerase inhibition mediated growth attenuation of cancer cells and its loss phenocopy telomerase inhibition. Therefore, IL8 expression can be utilized as a biomarker for telomerase targeted cancer therapies to potentially predict therapeutic response.


Assuntos
Interleucina-8/antagonistas & inibidores , Telomerase/antagonistas & inibidores , Biomarcadores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interleucina-8/análise , Interleucina-8/genética , Oligonucleotídeos/farmacologia , Transcriptoma
10.
Proc Natl Acad Sci U S A ; 111(30): E3062-71, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-25024194

RESUMO

Tumor suppressor p53 plays an important role in mediating growth inhibition upon telomere dysfunction. Here, we show that loss of the p53 target gene cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21(WAF1/CIP1)) increases apoptosis induction following telomerase inhibition in a variety of cancer cell lines and mouse xenografts. This effect is highly specific to p21, as loss of other checkpoint proteins and CDK inhibitors did not affect apoptosis. In telomerase, inhibited cell loss of p21 leads to E2F1- and p53-mediated transcriptional activation of p53-upregulated modulator of apoptosis, resulting in increased apoptosis. Combined genetic or pharmacological inhibition of telomerase and p21 synergistically suppresses tumor growth. Furthermore, we demonstrate that simultaneous inhibition of telomerase and p21 also suppresses growth of tumors containing mutant p53 following pharmacological restoration of p53 activity. Collectively, our results establish that inactivation of p21 leads to increased apoptosis upon telomerase inhibition and thus identify a genetic vulnerability that can be exploited to treat many human cancers containing either wild-type or mutant p53.


Assuntos
Apoptose , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Neoplasias Experimentais/metabolismo , Telomerase/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Camundongos , Camundongos Nus , Mutação , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Telomerase/genética , Telomerase/metabolismo , Proteína Supressora de Tumor p53/genética
13.
Lancet ; 381(9871): 1037-45, 2013 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-23352749

RESUMO

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/efeitos adversos , Anticorpos Antivirais/sangue , Formação de Anticorpos/efeitos dos fármacos , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Lactente , Masculino , Resultado do Tratamento , Vacinas Virais/imunologia
14.
Lancet ; 381(9882): 2024-32, 2013 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-23726161

RESUMO

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/efeitos adversos , Compostos de Alúmen , Anticorpos Antivirais/sangue , Pré-Escolar , Método Duplo-Cego , Infecções por Enterovirus/imunologia , Feminino , Humanos , Imunidade Ativa/fisiologia , Lactente , Estimativa de Kaplan-Meier , Masculino , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/efeitos adversos
15.
Front Oncol ; 14: 1330344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549940

RESUMO

Objective: This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients undergoing surgery for right-sided colon cancer (RCC). Methods: We collected 25,203 patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into 7:3 training and internal validation set. Utilizing the Cox proportional hazards regression model, we constructed a nomogram based on prognostic risk factors. Furthermore, for external validation, we retrospectively followed up with 228 patients from Jiaxing First Hospital and assessed and calibrated the nomogram using the C-index and calibration curves. Results: After identifying independent prognostic factors through univariate and multivariate analyses, a nomogram was developed. The c-index values of this nomogram differed as follows: 0.851 (95% CI: 0.845-0.857) in the training set, 0.860 (95% CI: 0.850-0.870) in the internal validation set, and 0.834 (95% CI: 0.780-0.888) in the external validation set, indicating the model's strong discriminative ability. Calibration curves for 1-year, 3-year, and 5-year overall survival (OS) probabilities exhibited a high level of consistency between predicted and actual survival rates. Furthermore, Decision Curve Analysis (DCA) demonstrated that the new model consistently outperformed the TNM staging system in terms of net benefit. Conclusion: We developed and validated a survival prediction model for patients with RCC. This novel nomogram outperforms the traditional TNM staging system and can guide clinical practitioners in making optimal clinical decisions.

16.
Gene ; 896: 148034, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38013129

RESUMO

BACKGROUND: By extracting and sequencing miRNAs from serum exosomes of patients with early-onset ocular myasthenia gravis (OMG), generalized myasthenia gravis (GMG) and healthy controls, we screened differentially expressed miRNAs and explored the possibility as potential biomarkers for early-onset OMG. METHODS: Peripheral blood samples were collected from patients with early-onset OMG, early-onset GMG, and age-matched healthy subjects, with 6 samples in each group. All these patients were diagnosed as MG for the first time and did not undergo any treatment. Exosomes miRNAs were extracted from the serum and performed deep sequencing; the differentially expressed miRNAs were compared and analyzed between OMG, GMG, and healthy control groups using edgeR. The differential expression standard was set to | log2FC |>1, p < 0.05. Target prediction of mRNAs were performed using miRTarBase, TargetScan, and miRDB databases, and a protein-protein interaction (PPI) network was constructed subsequently. The miRNAs with a significant difference were validated using RT-qPCR (10 early-onset OMG patients, 10 early-onset GMG patients and 10 age-sex-matched healthy subjects), and the value of the area under the ROC curve (AUC) was used to assess the diagnostic accuracy and evaluate clinical prognostic value. RESULTS: In total, one upregulated (miR-130a-3p) miRNA was obtained through the upregulated intersection between control vs OMG and OMG vs GMG; four downregulated (miR-4712-3p; miR-6752-5p; miR-320d; miR-3614-3p) miRNAs were obtained through the downregulated intersection between control vs OMG and OMG vs GMG. A total of 408 target genes were predicted for the five differentially expressed miRNAs. The mTOR signaling pathway and Rap1 signaling pathway were significantly enriched based on the enrichment results. RT-qPCR findings revealed that for the OMG, the expression of miR-320d, miR-4712-3p and miR-3614-3p was markedly up-/down-regulated as compared to GMG and healthy control group. The AUC for the three miRNAs between OMG and healthy control groups were 0.78, 0.79 and 0.79 respectively; the AUC between OMG and GMG was 0.84. CONCLUSIONS: The present study identified three novel miRNAs as candidate biomarkers for early-onset OMG patients and it was expected to provide a possibility and a new orientation for serum exosomal miRNAs as OMG diagnostic biomarkers.


Assuntos
Exossomos , MicroRNAs , Miastenia Gravis , Adulto , Humanos , MicroRNAs/genética , Exossomos/genética , Miastenia Gravis/diagnóstico , Miastenia Gravis/genética , Biomarcadores
17.
Sci Total Environ ; 917: 170317, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301787

RESUMO

Lead (Pb), a pervasive and ancient toxic heavy metal, continues to pose significant neurological health risks, particularly in regions such as Southeast Asia. While previous research has primarily focused on the adverse effects of acute, high-level lead exposure on neurological systems, studies on the impacts of chronic, low-level exposure are less extensive, especially regarding the precise mechanisms linking ferroptosis - a novel type of neuron cell death - with cognitive impairment. This study aims to explore the potential effects of chronic low-level lead exposure on cognitive function and hippocampal neuronal ferroptosis. This research represents the first comprehensive investigation into the impact of chronic low-level lead exposure on hippocampal neuronal ferroptosis, spanning clinical settings, bioinformatic analyses, and experimental validation. Our findings reveal significant alterations in the expression of genes associated with iron metabolism and Nrf2-dependent ferroptosis following lead exposure, as evidenced by comparing gene expression in the peripheral blood of lead-acid battery workers and workers without lead exposure. Furthermore, our in vitro and in vivo experimental results strongly suggest that lead exposure may precipitate cognitive dysfunction and induce hippocampal neuronal ferroptosis. In conclusion, our study indicates that chronic low-level lead exposure may activate microglia, leading to the promotion of ferroptosis in hippocampal neurons.


Assuntos
Ferroptose , Chumbo , Humanos , Chumbo/toxicidade , Cognição , Aprendizado de Máquina , Biologia Computacional , Hipocampo , Neurônios
18.
Medicine (Baltimore) ; 103(33): e39446, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151495

RESUMO

RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.


Assuntos
Anemia , Hipotireoidismo Congênito , Tiroxina , Talassemia alfa , Humanos , Feminino , Talassemia alfa/complicações , Talassemia alfa/diagnóstico , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/tratamento farmacológico , Pré-Escolar , Tiroxina/uso terapêutico , Anemia/etiologia , Anemia/tratamento farmacológico , Doenças Musculares/etiologia , Doenças Musculares/diagnóstico , Doenças Musculares/complicações
19.
Biomed Mater ; 19(1)2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37917998

RESUMO

Conjunctival reconstruction is an essential part of ocular surface restoration, especially in severe conjunctival disorders. Decellularized conjunctival tissues have been used in tissue engineering. In this study, we investigated the feasibility of constructing tissue-engineered conjunctiva using stem cell (human amniotic epithelial cells, hAECs), and cross-linked modified decellularized rabbit conjunctival stroma (DRCS-Asp-hEGF), and decellularized rabbit conjunctiva stroma (DRCS). With phospholipase A2 and sodium dodecyl, DRCS were nearly DNA-free, structurally intact and showed no cytotoxic effectsin vitro, as confirmed by DNA quantification, histology, and immunofluorescence. The results of Fourier transform infrared, Alcian blue staining and human epidermal growth factor (hEGF) release assays showed that DRCS-Asp-hEGF was successfully prepared via crosslinking with aspartic acid (Asp) and modified by hEGF at pH 7.7. The hAECs were positive for octamer-binding transcription factor-4 and ABCG2 cell markers. The hAECs were directly placed on the DRCS and DRCS-Asp-hEGF for five days respectively. Tissue-engineered conjunctiva was constructedin vitrofor five days, and the fluorescence staining results showed that hAECs grew in monolayers on DRCS-Asp-hEGF and DRCS. Flow cytometry results showed that compared with DRCS, the number of apoptotic cells stained in DRCS-Asp-hEGF was small, 86.70 ± 0.79% of the cells survived, and 87.59 ± 1.43% of the cells were in the G1 phase of DNA synthesis. Electron microscopy results showed that desmosome junction structures, which were similar to the native conjunctival tissue, were formed between cells and the matrix in the DRCS-Asp-hEGF.


Assuntos
Túnica Conjuntiva , Engenharia Tecidual , Animais , Coelhos , Humanos , Engenharia Tecidual/métodos , Células Epiteliais/metabolismo , Matriz Extracelular , DNA/metabolismo
20.
J Colloid Interface Sci ; 649: 148-158, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37348334

RESUMO

Herein, a ternary TiO2/MIL-88A(Fe)/g-C3N4 heterojunction is successfully constructed through a facile hydrothermal strategy for enhancing solar energy harvesting and efficiency of catalytic nitrogen reduction induced by enlarged light absorption range, increasing interfacial charge transfer ability and desirable stability. Under the simulated sunlight irradiation, the N2 fixation experiment shows that the yield of NH3 reaches 1084.31 µmol/(g·h) over the TiO2/MIL-88A(Fe)/g-C3N4 photocatalyst, and the yield is significantly enhanced, which is 33.68 and 13.94 times that is higher than the pure TiO2 and g-C3N4, respectively. In a mean time, the excellent performance of the photocatalytic N2 fixation over the ternary TiO2/MIL-88A(Fe)/g-C3N4 is verified based on density function theory calculation and the decisive step over the composite is investigated by calculating Gibbs free energies of nitrogen reduction paths. The performance enhancement mechanism of TiO2/MIL-88A(Fe)/g-C3N4 is speculated, which indicates that the hybridized three-component system presents a desirable Z-scheme band alignment, resulting in the improvement of separation and transfer efficiency of photoinduced charge carriers. The article shows a new and high-efficiency TiO2/MIL-88A(Fe)/g-C3N4 photocatalysis for excellent nitrogen reduction ability.

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