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1.
Cell Mol Life Sci ; 81(1): 143, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493426

RESUMO

Hippo-Yes-associated protein 1 (YAP1) plays an important role in gastric cancer (GC) progression; however, its regulatory network remains unclear. In this study, we identified Copine III (CPNE3) was identified as a novel direct target gene regulated by the YAP1/TEADs transcription factor complex. The downregulation of CPNE3 inhibited proliferation and invasion, and increased the chemosensitivity of GC cells, whereas the overexpression of CPNE3 had the opposite biological effects. Mechanistically, CPNE3 binds to the YAP1 protein in the cytoplasm, inhibiting YAP1 ubiquitination and degradation mediated by the E3 ubiquitination ligase ß-transducin repeat-containing protein (ß-TRCP). Thereby activating the transcription of YAP1 downstream target genes, which creates a positive feedback cycle to facilitate GC progression. Immunohistochemical analysis demonstrated significant upregulation of CPNE3 in GC tissues. Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Transdução de Sinais , Retroalimentação , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
2.
Cell Commun Signal ; 22(1): 168, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454413

RESUMO

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.


Assuntos
Neoplasias Colorretais , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral , Proteínas Nucleares , Proteínas Repressoras , Evasão Tumoral
3.
J Cardiothorac Surg ; 18(1): 246, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596679

RESUMO

BACKGROUND: In the present case, we applied postmortem computed tomography angiography (PMCTA) in a medical dispute involving sudden death after cardiovascular surgery. CASE PRESENTATION: A 39-year-old man underwent aortic arch replacement combined with stented elephant trunk implantation surgery under extracorporeal circulation. All vital signs were stable and he was arranged for discharge seven days after surgery. Several days later, the patient was sent back to the hospital for chest pain and poor appetite. Unfortunately, his condition worsened and he ultimately died. PMCT scanning detect pericardial effusion. Family members suspected that the surgical sutures were not dense enough, causing the patient's postoperative bleeding and resulting in cardiac tamponade and death. PMCTA was performed before autopsy, which showed pericardial effusion. However, postmortem angiography with simulated blood pressure showed no leakage of contrast agent, which guided the subsequent autopsy and histological examinations. CONCLUSIONS: While many previous postmortem imaging case reports have shown positive results that provided evidence of medical malpractice, the current case excludes the possibility of physician negligence and reasonably settles the medical dispute from another perspective. In short, the PMCTA approach we describe here was an effective tool that can be applied to certain medical-related forensic cases.


Assuntos
Dissecção Aórtica , Derrame Pericárdico , Masculino , Humanos , Adulto , Angiografia por Tomografia Computadorizada , Dissidências e Disputas , Angiografia , Dissecção Aórtica/cirurgia
4.
Front Immunol ; 14: 1058627, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923407

RESUMO

Background: Despite great success, immunotherapy still faces many challenges in practical applications. It was previously found that family with sequence similarity 110 member A (FAM110A) participate in the regulation of the cell cycle and plays an oncogenic role in pancreatic cancer. However, the prognostic value of FAM110A in pan-cancer and its involvement in immune response remain unclear. Methods: The Human Protein Atlas (HPA) database was used to detect the expression of FAM110A in human normal tissues, the Tumor Immune Estimation Resource (TIMER) and TIMER 2.0 databases were used to explore the association of FAM110A expression with immune checkpoint genes and immune infiltration, and the Gene Set Cancer Analysis (GSCA) database was used to explore the correlation between FAM110A expression and copy number variations (CNV) and methylation. The LinkedOmics database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Statistical analysis and visualization of data from the The Cancer Genome Atlas (TCGA) or the Genotype-Tissue Expression (GTEx) databases were performed using the R software (version 3.6.3). Clinical samples were validated using immunohistochemistry. Results: FAM110A expression was elevated in most tumor tissues compared with that in normal tissues. CNV and methylation were associated with abnormal FAM110A mRNA expression in tumor tissues. FAM110A affected prognosis and was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer, especially in liver hepatocellular carcinoma (LIHC). FAM110A-related genes were involved in multiple immune-related processes in LIHC. Conclusion: FAM110A participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in LIHC. FAM110A may serve as a prognostic and immunological biomarker for human cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores , Bases de Dados de Proteínas , Variações do Número de Cópias de DNA , Prognóstico
5.
Mol Cancer ; 22(1): 60, 2023 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-36966334

RESUMO

BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cell fate and angiogenesis, with dysregulation of the signaling axis driving tumorigenesis. Therefore, many studies have targeted FGF/FGFR signaling for cancer therapy and several FGFR inhibitors have promising results in different tumors but treatment efficiency may still be improved. The clinical use of immune checkpoint blockade (ICB) has resulted in sustained remission for patients. MAIN: Although there is limited data linking FGFR inhibitors and immunotherapy, preclinical research suggest that FGF/FGFR signaling is involved in regulating the tumor microenvironment (TME) including immune cells, vasculogenesis, and epithelial-mesenchymal transition (EMT). This raises the possibility that ICB in combination with FGFR-tyrosine kinase inhibitors (FGFR-TKIs) may be feasible for treatment option for patients with dysregulated FGF/FGFR signaling. CONCLUSION: Here, we review the role of FGF/FGFR signaling in TME regulation and the potential mechanisms of FGFR-TKI in combination with ICB. In addition, we review clinical data surrounding ICB alone or in combination with FGFR-TKI for the treatment of FGFR-dysregulated tumors, highlighting that FGFR inhibitors may sensitize the response to ICB by impacting various stages of the "cancer-immune cycle".


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/uso terapêutico , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo
6.
Chem Commun (Camb) ; 59(13): 1825-1828, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36722898

RESUMO

Herein, a new nickel-catalysed protocol for the preparation of di- and trisubstituted allenes has been successfully developed via the reactions of 1,3-enynes with alkyl N-hydroxyphthalimide esters. The new method based on a reductive radical-polar crossover (RPC) process features broad substrate scope, wide functional group tolerance, and a simple catalyst system. The late-stage allenylation of drugs has also been illustrated.

7.
Chinese Journal of School Health ; (12): 375-378, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965863

RESUMO

Objective@#To understand the influence of junior middle school students health literacy on knowledge, belief and behavior of COVID-19 in rural areas of Jiangxi Province, and to enhance junior middle school students ability to deal with public health emergencies.@*Methods@#Stratified cluster random sampling was used to investigate the health literacy, knowledge level and behavior of COVID-19 protection of 4 311 grade 7 to grade 8 students in rural areas of Jiangxi Province; Chi square test and Logistic regression analysis were used to analyze the correlation between junior high school students health literacy and COVID-19 protection knowledge, belief and behavior.@*Results@#The rate of health literacy of junior middle school students in rural areas was 18.21 %( n =785), the reported rate of intermediate level was high ( n =2 454, 56.92%), and the reported rate of junior high school students at a low level of health literacy was 24.87%( n =1 072). The rate of junior middle school students in rural areas with good COVID-19 protection knowledge was 63.49%, the rate of positive protection attitude was 74.25%, and the rate of good protection behavior was 85.36%; Rate of COVID-19 protection knowledge ( OR=4.85, 95%CI =3.80-6.18) and positive rate of protection attitude of high level health literacy ( OR=44.07, 95%CI =24.57-79.05), protective behavior possession rate ( OR=25.99, 95%CI = 19.67-34.35) were higher than those with low level of health literacy( P <0.01).@*Conclusion@#Health literacy is associated with COVID-19 protection knowledge, belief and behavior in rural junior high school students of Jiangxi Province, the findings provide direction for junior middle school students to improve their ability to deal with public health emergencies.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-960907

RESUMO

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets (TWPT) by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis (RA) and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts, the "efficacy-toxicity" association network of TWPT was constructed, and the key network targets were identified by calculating the topological values of the nodes, including the degree, closeness and betweenness. After that, the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes (58 up-regulated and 61 down-regulated) between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics, and 49 differentially expressed proteins (36 up-regulated and 13 down-regulated) were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition, the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine, and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore, the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically, the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance, especially playing an important role in neutrophil degranulation, complement cascade reaction, and immune-inflammatory response mediated by protein post-translational modification. Notably, the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation, such as RAS and mitogen-activated protein kinase (MAPK) signaling pathway, and in several liver functional processes, such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics, transcriptomics and proteomics, laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-960905

RESUMO

ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis (RA) due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method, with 51 cases in each group. All patients were treated with methotrexate tablets, while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score (DAS28), visual analogue scale (VAS) scores, morning stiffness time, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, vascular endothelial growth factor (VEGF), and serum amyloid A (SAA) of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP, ESR, RF, SAA, VEGF, and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment, the total effective rate in the observation group was 90.19% (46/51), which was higher than 74.51% (38/51) in the control group (χ2=4.320,P<0.05). DAS28, VAS score, and morning stiffness time in the observation group were improved compared with those in the control group (P<0.05). Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF, ESR, hs-CRP, SAA, and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP, ESR, RF, SAA, and VEGF in the observation group were all better than those of the control group, and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP, ESR, RF, SAA, and VEGF in the observation group was superior to that of the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than in the control group (χ2=4.057,P<0.05). ConclusionOn the basis of the treatment with methotrexate tablets, Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.

10.
Acta Pharmaceutica Sinica ; (12): 938-945, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978763

RESUMO

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

11.
Journal of Forensic Medicine ; (6): 66-71, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-984182

RESUMO

Bone development shows certain regularity with age. The regularity can be used to infer age and serve many fields such as justice, medicine, archaeology, etc. As a non-invasive evaluation method of the epiphyseal development stage, MRI is widely used in living age estimation. In recent years, the rapid development of machine learning has significantly improved the effectiveness and reliability of living age estimation, which is one of the main development directions of current research. This paper summarizes the analysis methods of age estimation by knee joint MRI, introduces the current research trends, and future application trend.


Assuntos
Epífises/diagnóstico por imagem , Determinação da Idade pelo Esqueleto/métodos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Articulação do Joelho/diagnóstico por imagem
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-984173

RESUMO

OBJECTIVES@#To explore the difference in CT values between pulmonary thromboembolism and postmortem clot in postmortem CT pulmonary angiography (CTPA) to further improve the application value of virtual autopsy.@*METHODS@#Postmortem CTPA data with the definite cause of death from 2016 to 2019 were collected and divided into pulmonary thromboembolism group (n=4), postmortem clot group (n=5), and control group (n=5). CT values of pulmonary trunk and left and right pulmonary artery contents in each group were measured and analyzed statistically.@*RESULTS@#The average CT value in the pulmonary thromboembolism group and postmortem clot group were (168.4±53.8) Hu and (282.7±78.0) Hu, respectively, which were lower than those of the control group (1 193.0±82.9) Hu (P<0.05). The average CT value of the postmortem clot group was higher than that of the pulmonary thromboembolism group (P<0.05).@*CONCLUSIONS@#CT value is reliable and feasible as a relatively objective quantitative index to distinguish pulmonary thromboembolism and postmortem clot in postmortem CTPA. At the same time, it can provide a scientific basis to a certain extent for ruling out pulmonary thromboembolism deaths.


Assuntos
Humanos , Autopsia , Trombose , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Angiografia , Cadáver
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009447

RESUMO

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in TranswellTM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. TranswellTM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.


Assuntos
Humanos , Artrite Reumatoide/genética , Interleucina-23 , Macrófagos , RNA Mensageiro , RNA Interferente Pequeno/genética , Proteína Smad7/genética , Fator de Crescimento Transformador beta1/genética , Proteína Smad3/genética , Inativação Gênica
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009200

RESUMO

OBJECTIVE@#To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy.@*METHODS@#Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR.@*RESULTS@#There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05).@*CONCLUSION@#Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.


Assuntos
Feminino , Humanos , Masculino , Proteína Beclina-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Mensageiro/metabolismo , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/metabolismo
15.
ACS Biomater Sci Eng ; 8(11): 4807-4818, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36222713

RESUMO

Multimodal neural interfaces include combined functions of electrical neuromodulation and synchronic monitoring of neurochemical and physiological signals in one device. The remarkable biocompatibility and electrochemical performance of polystyrene sulfonate-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) have made it the most recommended conductive polymer neural electrode material. However, PEDOT:PSS formed by electrochemical deposition, called PEDOT/PSS, often need multiple doping to improve structural instability in moisture, resolve the difficulties of functionalization, and overcome the poor cellular affinity. In this work, inspired by the catechol-derived adhesion and semiconductive properties of polydopamine melanin (PDAM), we used electrochemical oxidation polymerization to develop PDAM-doped PEDOT (PEDOT/PDAM) as a bioactive multimodal neural interface that permits robust electrochemical performance, structural stability, analyte-trapping capacity, and neural stem cell affinity. The use of potentiodynamic scans resolved the problem of copolymerizing 3,4-ethylenedioxythiophene (EDOT) and dopamine (DA), enabling the formation of PEDOT/PDAM self-assembled nanodomains with an ideal doping state associated with remarkable current storage and charge transfer capacity. Owing to the richness of hydrogen bond donors/acceptors provided by the hydroxyl groups of PDAM, PEDOT/PDAM presented better electrochemical and mechanical stability than PEDOT/PSS. It has also enabled high sensitivity and selectivity in the electrochemical detection of DA. Different from PEDOT/PSS, which inhibited the survival of human induced pluripotent stem cell-derived neural progenitor cells, PEDOT/PDAM maintained cell proliferation and even promoted cell differentiation into neuronal networks. Finally, PEDOT/PDAM was modified on a commercialized microelectrode array system, which resulted in the reduction of impedance by more than one order of magnitude; this significantly improved the resolution and reduced the noise of neuronal signal recording. With these advantages, PEDOT/PDAM is anticipated to be an efficient bioactive multimodal neural electrode material with potential application to brain-machine interfaces.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Melaninas , Polímeros/farmacologia , Neurônios/fisiologia
16.
Oncogene ; 41(18): 2555-2570, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35318441

RESUMO

The importance of the Hippo-Yes-associated protein 1 (YAP1) pathway in gastric carcinogenesis and metastasis has attracted considerable research attention; however, the regulatory network of YAP1 in gastric cancer (GC) is not completely understood. In this study, ubiquitin-specific peptidase 49 (USP49) was identified as a novel deubiquitinase of YAP1, knockdown of USP49 inhibited the proliferation, metastasis, chemoresistance, and peritoneal metastasis of GC cells. Overexpression of USP49 showed opposing biological effects. Moreover, USP49 was transcriptionally activated by the YAP1/TEAD4 complex, which formed a positive feedback loop with YAP1 to promote the malignant progression of GC cells. Finally, we collected tissue samples and clinical follow-up information from 482 GC patients. The results showed that USP49 expression was high in GC cells and positively correlated with the expression of YAP1 and its target genes, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61). Survival and Cox regression analysis showed that high USP49 expression was associated with poor prognosis and was an independent prognostic factor. Moreover, patients with high USP49 and YAP1 expression had extremely short overall survival. The findings of this study reveal that the aberrant activation of the USP49/YAP1 positive feedback loop plays a critical role in the malignant progression of GC, thus providing potential novel prognostic factors and therapeutic targets for GC.


Assuntos
Neoplasias Gástricas , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Musculares/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ubiquitina Tiolesterase/metabolismo , Proteínas de Sinalização YAP
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-934306

RESUMO

Objective:To compare and observe the curative effect of different body positions after pars plana vitrectomy (PPV) combined with inert gas filling for rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From October 2019 to September 2021, 192 eyes of 192 RRD patients who were diagnosed and received PPV combined with inert gas filling in Qingdao Eye Hospital of Shandong First Medical University were included in the study. Best corrected visual acuity (BCVA), intraocular pressure, ultra-wide-angle fundus photography, optical coherence tomography, and B-mode ultrasonography were performed in all affected eyes. The BCVA examination was performed using a standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. According to the post-operative position requirements, the affected eyes were divided into the face-down positioning group and the adjustable positioning group, with 97 eyes in 97 patients and 95 eyes in 95 patients, respectively. Age ( Z=0.804), course of disease ( Z=-0.490), eye type ( χ2=0.175), logMAR BCVA( Z=-0.895), intraocular pressure ( Z=0.178), lens status ( χ2=1.090), number of detached clocks ( Z=0.301) and macular involvement ( χ2=0.219), number of holes ( Z=-1.051) and number of lower holes ( χ2=0.619) were compared, there was no significant difference ( P>0.05). The gender composition ratio was compared, and the difference was statistically significant ( χ2=5.341, P<0.05). The follow-up time after surgery was more than 3 months. The retinal reattachment rate in one operation, the improvement of BCVA and the incidence of complications were observed. The independent sample Mann-Whitney test was used for the comparison of continuous variables between groups; the χ2 test was used for the comparison of categorical variables. Results:In the face-down positioning group and the adjustable positioning group, retinal reattachment in one operation was performed in 92 (94.8%, 92/97) and 89 (93.7%, 89/95) eyes, respectively; logMAR BCVA was 0.45±0.34, 0.41±0.21. There was no significant difference in the retinal reattachment rate in one operation ( χ2=0.120, P=0.729) and logMAR BCVA ( Z=-0.815, P=0.416) between the two groups. After surgery, the intraocular pressure increased in 11 (11.3%, 11/97) and 5 (5.3%, 5/95) eyes in the face-down positioning group and the adjustable positioning group, respectively; the secondary epimacular membrane was 2 (2.1%, 2/97), 3 (3.2%, 3/95) eyes. There was no significant difference in the incidence of elevated intraocular pressure and secondary epimacular membrane between the two groups after surgery ( χ2=2.320, 0.227; P=0.128, 0.634). Conclusion:It is safe and effective to adopt adjustable positioning after PPV combined with inert gas filling for RRD, which is equivalent to the effect of face-down positioning.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-958314

RESUMO

To investigate the clinical efficacy and safety of Wei nasal jet tube (WNJT) in painless gastroscopy in patients over age of 60, 80 patients aged 60 years or older scheduled for gastroscopy under propofol mono-sedation in Beijing Friendship Hospital were divided into WNJT group ( n=40) and nasal cannula group ( n=40) according to the random number table method from January to June 2021. The main observation indicator was the difference in the incidence of hypoxemia between the two groups, the secondary observation indicators included the lowest pulse blood oxygen saturation (SpO 2), interventions related to hypoxemia, adverse events such as body movement, cough, epistaxis, sore throat, and the satisfaction of physicians, anesthetists and patients. The results showed that the procedure time and total dosage of propofol were no significant differences between the two groups ( P>0.05). Compared with the nasal cannula group, the incidence of hypoxemia in the WNJT group was significantly lower [2.5% (1/40) VS 25.0% (10/40), χ2=8.538, P=0.003], the lowest SpO 2 was significantly higher (97.7%±2.5% VS 92.6%±5.8%, t=5.093, P<0.001), and the use of jaw lift was reduced [5.0% (2/40) VS 35.0% (14/40), χ2=11.250, P=0.001]. The adverse events were not significantly different between the two groups ( P>0.05), but no case of epistaxis and sore throat occurred in the nasal cannula group. The two groups were comparable in terms of the satisfaction of patients, anesthetists and physicians ( P>0.05). In conclusion, WNJT can be used safely during gastroscopy with propofol mono-sedation in patients over 60 years old, with less incidence of hypoxemia and the number of airway interventions. But violent operation should be avoided to reduce the incidence of epistaxis and sore throat.

19.
Journal of Forensic Medicine ; (6): 223-230, 2022.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-984113

RESUMO

OBJECTIVES@#To apply the convolutional neural network (CNN) Inception_v3 model in automatic identification of acceleration and deceleration injury based on CT images of brain, and to explore the application prospect of deep learning technology in forensic brain injury mechanism inference.@*METHODS@#CT images from 190 cases with acceleration and deceleration brain injury were selected as the experimental group, and CT images from 130 normal brain cases were used as the control group. The above-mentioned 320 imaging data were divided into training validation dataset and testing dataset according to random sampling method. The model classification performance was evaluated by the accuracy rate, precision rate, recall rate, F1-value and AUC value.@*RESULTS@#In the training process and validation process, the accuracy rate of the model to classify acceleration injury, deceleration injury and normal brain was 99.00% and 87.21%, which met the requirements. The optimized model was used to test the data of the testing dataset, the result showed that the accuracy rate of the model in the test set was 87.18%, and the precision rate, recall rate, F1-score and AUC of the model to recognize acceleration injury were 84.38%, 90.00%, 87.10% and 0.98, respectively, to recognize deceleration injury were 86.67%, 72.22%, 78.79% and 0.92, respectively, to recognize normal brain were 88.57%, 89.86%, 89.21% and 0.93, respectively.@*CONCLUSIONS@#Inception_v3 model has potential application value in distinguishing acceleration and deceleration injury based on brain CT images, and is expected to become an auxiliary tool to infer the mechanism of head injury.


Assuntos
Humanos , Encéfalo/diagnóstico por imagem , Lesões Encefálicas , Aprendizado Profundo , Redes Neurais de Computação
20.
Journal of Forensic Medicine ; (6): 217-222, 2022.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-984112

RESUMO

OBJECTIVES@#To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree.@*METHODS@#A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ2 test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected.@*RESULTS@#χ2 test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury (P<0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant (P<0.05).@*CONCLUSIONS@#EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.


Assuntos
Humanos , Contusão Encefálica , Lesões Encefálicas/diagnóstico por imagem , Hematoma Epidural Craniano , Hematoma Subdural/etiologia , Modelos Logísticos , Fraturas Cranianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico por imagem
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