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1.
PLoS Pathog ; 19(10): e1011742, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37871014

RESUMO

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.


Assuntos
Proteínas Serina-Treonina Quinases , Viroses , Humanos , Animais , Camundongos , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fator Regulador 3 de Interferon/metabolismo , Processamento de Proteína Pós-Traducional , Citocinas/metabolismo , Imunidade Inata , Quinases da Família src/metabolismo
2.
BMC Infect Dis ; 24(1): 770, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090540

RESUMO

BACKGROUND: The GeneXpert MTB/RIF (Xpert) assay is a widely used technology for detecting Mycobacterium tuberculosis (MTB) in clinical samples. However, the study on the failure of the Xpert assay during routine implementation and its potential solutions is limited. METHODS: We retrospectively analyzed the records of unsuccessful tests in the Xpert and the GeneXpert MTB/RIF Ultra (Ultra) assays between April 2017 and April 2021 at the Shanghai Public Health Clinical Center. To further investigate the effect of prolonged preprocessing on clinical sputum, an additional 120 sputum samples were collected for Xpert testing after 15 min, 3 h, and 6 h preprocessing. The analysis was performed by SPSS version 19.0 software. RESULTS: A total of 11,314 test records were analyzed, of which 268 (2.37%) had unsuccessful test results. Among these, 221 (1.95%) were reported as "Error", 43 (0.38%) as "Invalid", and 4 (0.04%) as "No result". The most common clinical specimen for Xpert tests was sputum, accounting for 114 (2.17%) unsuccessful tests. The failure rate of urine specimens was lower than that of sputum (OR = 0.12, 95% CI: 0.02-0.88, χ2 = 6.22, p = 0.021). In contrast, the failure rate of stool specimens was approximately twice as high as that of sputum (OR = 1.93, 95% CI: 1.09-3.40, χ2 = 5.35, p = 0.014). In the prolonged preprocessing experiment, 102 cases (85%) yielded consistent results in Xpert tests. Furthermore, 7 cases (5.83%) detected an increase in MTB load, 8 cases (6.67%) detected a decrease in MTB load, and 3 cases (2.5%) yielded incongruent results in MTB and rifampicin resistance detection. CONCLUSIONS: The primary cause of unsuccessful tests in the Xpert assay was reported as "Error". Despite varying failure rates depending on the samples, the Xpert assay can be applied to extrapulmonary samples. For paucibacillary specimens, retesting the remaining preprocessed mixture should be carefully considered.


Assuntos
Mycobacterium tuberculosis , Escarro , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Estudos Retrospectivos , China , Manejo de Espécimes/métodos , Técnicas de Diagnóstico Molecular/métodos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Rifampina/farmacologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Masculino , Feminino
3.
Dig Dis Sci ; 69(7): 2462-2476, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38653944

RESUMO

OBJECTIVE: To explore the expression of the ten eleven translocation (TET) 2 protein in early esophageal squamous cell carcinoma (EESCC), precancerous lesions, and cell lines and to evaluate the effect of TET2 on the functional behavior of EC109 esophageal cancer cells. METHODS: Thirty-one samples of EESCC and precancerous lesions collected via endoscopic submucosal dissection at Taihe Hospital, Shiyan, from February 1, 2017, to February 1, 2019, were analyzed. The study involved evaluating TET2 expression levels in lesion tissue and adjacent normal epithelium, correlating these with clinical pathological features. Techniques including 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell scratch assays, flow cytometry for propidium iodide (PI) staining, Hoechst 333258/PI double staining, and nude mouse tumorigenesis experiments were employed to assess the effect of TET2 on the proliferation, migration, cell cycle, apoptosis, and tumorigenic ability of esophageal cancer cells. RESULTS: TET2 expression was notably reduced in early esophageal cancer tissue and correlated with tumor invasion depth (P < 0.05). Overexpression of TET2 enhanced the proliferation and migration of esophageal cancer cells, increased the cell population in the G0 phase, decreased it in the S phase, and intensified cell necrosis (P < 0.05). There was a partial increase in tumorigenic ability (P = 0.087). CONCLUSION: TET2 downregulation in ESCC potentially influences the necrosis, cell cycle, and tumorigenic ability of esophageal cancer cells, suggesting a role in the onset and progression of esophageal cancer.


Assuntos
Proteínas de Ligação a DNA , Dioxigenases , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas Proto-Oncogênicas , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Dioxigenases/genética , Dioxigenases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética
4.
Oral Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569076

RESUMO

OBJECTIVES: Salivary gland injury is one of the most common complications of radiotherapy in head-and-neck cancers. This study investigated the mechanism by which rapamycin prevents irradiation (IR)-induced injury in the parotid glands. MATERIALS AND METHODS: Miniature pigs either received (a) no treatment (NT), (b) IR in the right parotid gland for 5 consecutive days (IR), or intraperitoneal administration of rapamycin (Rap) 1 h prior to IR (IR + Rap). Tissues were collected at three distinct time points (24 h, 4 weeks, and 16 weeks) after IR. Histological analyses, western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to explore the mechanisms of IR-induced injury in the parotid gland. RESULTS: Rapamycin treatment maintained parotid salivary flow 16 weeks post-IR, preserved the number of acinar cells, and reduced parotid tissue fibrosis, as well as reduced apoptosis levels, decreased cleaved caspase-3 expression, and increased the Bcl-2/Bax ratio in the parotid glands. Autophagy marker LC3B was upregulated by rapamycin after IR, while P62 expression was downregulated. Rapamycin reduced the expression of pro-inflammatory factors and the mesenchymal tissue fibrosis following IR. CONCLUSIONS: Rapamycin maintains gland homeostasis after IR by decreasing apoptosis, reducing the expression of pro-inflammatory factors, and enhancing autophagy.

5.
BMC Musculoskelet Disord ; 25(1): 317, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654244

RESUMO

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , Osteoporose , Humanos , Densidade Óssea/genética , Osteoporose/genética , Osteoporose/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , Vértebras Lombares/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Fenótipo
6.
Int J Mol Sci ; 25(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39063074

RESUMO

Alpha-amylase (AMY) plays a significant role in regulating the growth, development, and postharvest quality formation in plants. Nevertheless, little is known about the genome-wide features, expression patterns, subcellular localization, and functional regulation of AMY genes (MaAMYs) in the common starchy banana (Musa acuminata). Twelve MaAMY proteins from the banana genome database were clustered into two groups and contained a conserved catalytic domain. These MaAMYs formed collinear pairs with the AMYs of maize and rice. Three tandem gene pairs were found within the MaAMYs and are indicative of putative gene duplication events. Cis-acting elements of the MaAMY promoters were found to be involved in phytohormone, development, and stress responses. Furthermore, MaAMY02, 08, 09, and 11 were actively expressed during fruit development and ripening. Specifically, MaAMY11 showed the highest expression level at the middle and later stages of banana ripening. Subcellular localization showed that MaAMY02 and 11 were predominately found in the chloroplast, whereas MaAMY08 and 09 were primarily localized in the cytoplasm. Notably, transient attenuation of MaAMY11 expression resulted in an obvious increase in the starch content of banana fruit, while a significant decrease in starch content was confirmed through the transient overexpression of MaAMY11. Together, these results reveal new insights into the structure, evolution, and expression patterns of the MaAMY family, affirming the functional role of MaAMY11 in the starch degradation of banana fruit.


Assuntos
Regulação da Expressão Gênica de Plantas , Musa , Filogenia , Proteínas de Plantas , alfa-Amilases , Musa/genética , Musa/enzimologia , Musa/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regiões Promotoras Genéticas , Amido/metabolismo , Oryza/genética , Oryza/enzimologia , Oryza/crescimento & desenvolvimento
7.
Int J Mol Sci ; 25(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38203486

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell-cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF.


Assuntos
Fibrose Pulmonar Idiopática , Ácido Láctico , Humanos , Comunicação Celular , Glicólise , Pulmão
8.
Zhonghua Nan Ke Xue ; 29(12): 980-985, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38639949

RESUMO

OBJECTIVE: To investigate the expression and significance of GDF3 in testicular cancer through bioinformatics analysis. METHODS: Using the TCGA and GTEx databases, differential expression analysis and pan-cancer analysis were performed to identify the target gene GDF3, and the clinical relevance of GDF3 in testicular cancer was analyzed using the UALCAN database. Based on the R packages "org.Hs.eg.db" and "clusterProfiler," gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the potential functions of GDF3 in testicular cancer. The correlation of GDF3 with immune chemokines and immune inhibitors in testicular cancer was investigated using the TISIDB database. RESULTS: The GDF3 was significantly upregulated in testicular cancer (P<0.001) and closely associated with clinical staging (P<0.05) and tumor subtypes (P<0.001). The immune-related analysis revealed that GDF3 was strongly correlated with immune chemokines CCL26 (rho=0.599, P<0.001), CCL7 (rho=0.525, P<0.001), immune inhibitor ADORA2A (rho=0.723, P<0.001), and PVRL2 (rho=0.585, P<0.001). CONCLUSION: The GDF3 is closely related to the occurrence, development, and immune microenvironment of testicular cancer.


Assuntos
Fator 3 de Diferenciação de Crescimento , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Quimiocinas , Biologia Computacional , Neoplasias Testiculares/genética , Microambiente Tumoral , Fator 3 de Diferenciação de Crescimento/genética
9.
Cancer Sci ; 113(1): 79-90, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34706132

RESUMO

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remains unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased their sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as an miRNA sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor. Rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown in LUAD cells resistant to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, which contributes further to the resistance of LUAD cells to osimertinib. In addition, this study provides a novel insight into the mechanisms underlying osimertinib resistance of LUAD.


Assuntos
Adenocarcinoma de Pulmão/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Circular/genética , Receptor IGF Tipo 1/genética , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Transplante de Neoplasias , Regulação para Cima
10.
Br J Clin Pharmacol ; 88(8): 3760-3770, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35304924

RESUMO

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Adolescente , Adulto , Androstanóis/efeitos adversos , Humanos , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio , Sugammadex/farmacologia , Adulto Jovem , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
11.
Angew Chem Int Ed Engl ; 61(2): e202110082, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34653302

RESUMO

Switching materials in channels of nonlinear optics (NLOs) are of particular interest in NLO material science. Numerous crystalline NLO switches based on structural phase transition have emerged, but most of them reveal a single-step switch between two different second-harmonic-generation (SHG) states, and only very rare cases involve three or more SHG states. Herein, we report a new organic-inorganic hybrid salt, (Me3 NNH2 )2 [CdI4 ], which is an unprecedented case of a reversible three-step NLO switch between SHG-silent, -medium, -low, and -high states, with high contrasts of 25.5/4.3/9.2 in a temperature range of 213-303 K. By using the combined techniques of variable-temperature X-ray single-crystal structural analyses, dielectric constants, solid-state 13 C nuclear magnetic resonance spectroscopy, and Hirshfeld surface analyses, we disclose that this four-state switchable SHG behavior is highly associated with the stepwise-changed molecular dynamics of the polar organic cations. This finding demonstrates well the complexity of molecular dynamics in simple hybrid salts and their potential in designing new advanced multistep switching materials.

12.
Cancer Cell Int ; 21(1): 381, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273970

RESUMO

BACKGROUND: Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis. METHODS: Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted. RESULTS: Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant. CONCLUSIONS: PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma.

13.
BMC Gastroenterol ; 21(1): 169, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849450

RESUMO

BACKGROUND: Surgical resection remains the best option for long-term survival in colorectal cancer (CRC); however, surgery can lead to tumor cell release into the circulation. Previous studies have also shown that surgery can affect cancer cell growth. The role of perioperative factors influencing long-term survival in patients presenting for CRC surgery remains to be investigated. METHODS: This retrospective single-center cohort study was conducted to collect the clinical data of patients who underwent elective laparoscopic resection for CRC from January 2014 to December 2015, namely clinical manifestations, pathological results, and perioperative characteristics. Survival was estimated using the Kaplan-Meier log-rank test. Univariable and multivariable Cox regression models were used to compare hazard ratios (HR) for death. RESULTS: A total of 234 patients were eligible for analysis. In the multivariable Cox model, tumor-node-metastasis (TNM) stage (stage IV: HR 30.63, 95% confidence interval (CI): 3.85-243.65; P = 0.001), lymphovascular invasion (yes: HR 2.07, 95% CI 1.09-3.92; P = 0.027), inhalational anesthesia with isoflurane (HR 1.96, 95% CI 1.19-3.21; P = 0.008), and Klintrup-Makinen (KM) inflammatory cell infiltration grade (low-grade inflammation: HR 2.03, 95% CI 1.20-3.43; P = 0.008) were independent risk factors affecting 5-year overall survival after laparoscopic resection for CRC. CONCLUSIONS: TNM stage, lymphovascular invasion, isoflurane, and KM grade were independent risk factors affecting CRC prognosis. Sevoflurane and high-grade inflammation may be associated with improved survival in CRC patients undergoing resection.


Assuntos
Neoplasias Colorretais , Estudos de Coortes , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Neurol Sci ; 42(8): 3121-3133, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34008041

RESUMO

Stellate ganglion block (SGB) has been applied in clinic for almost a century as a therapeutic procedure to alleviate pain-related syndromes and vascular deficits in the upper extremities. A great number of causative side effects and complications due to technological insufficiency and anatomical variations called for the popularity of ultrasound-guided SGB which has made tremendous contribution for clinical diagnosis and therapy, primarily in postoperative pain and cardiac and vascular disorders. This work was aimed at systematically summarizing the current clinical application of ultrasound-guided SGB and putting forward the potential prospective application in future. By searching ultrasound-guided SGB-related works on PubMed database, we mainly elucidated the analgesic effect of preoperative SGB in patients undergoing surgical procedures and substantial reduction in patients with ventricular arrhythmias. The volume of local anesthetics used in ultrasound-guided SGB has been diminished in the recent few years' investigations and successful operation of ultrasound-guided SGB could be achieved with minimal safe volume of local anesthetics. This invasive and safe procedure shows vast potential for future development in clinical treatment for autonomic nervous system and autoimmune disorders. We also put forward hypothesis that ultrasound-guided SGB could be applied combined with controlled hypotension to reduce the intraoperative complications in orthopedic surgery such as insufficiency of cerebral blood flow and reflexive tachycardia. Thus, it is of vital essence to improve the professional skills of physicians for the high rate of success and explore more effective measures which could enhance therapeutic effects when combined with ultrasound-guided SGB in alleviating misery of patients.


Assuntos
Dor Pós-Operatória , Gânglio Estrelado , Arritmias Cardíacas , Humanos , Dor Pós-Operatória/terapia , Estudos Prospectivos , Gânglio Estrelado/diagnóstico por imagem , Ultrassonografia de Intervenção
15.
Int J Mol Sci ; 22(24)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34948290

RESUMO

Salivary gland function is commonly and irreversibly damaged by radiation therapy for head and neck cancer. This damage greatly decreases the patient's quality of life and is difficult to remedy. Previously, we found that the transient activation of Hedgehog signaling alleviated salivary hypofunction after radiation in both mouse and pig models through the inhibition of radiation-induced cellular senescence that is mediated by resident macrophages in mouse submandibular glands. Here we report that in swine parotid glands sharing many features with humans, the Hedgehog receptor PTCH1 is mainly expressed in macrophages, and levels of PTCH1 and multiple macrophage markers are significantly decreased by radiation but recovered by transient Hedgehog activation. These parotid macrophages mainly express the M2 macrophage marker ARG1, while radiation promotes expression of pro-inflammatory cytokine that is reversed by transient Hedgehog activation. Hedgehog activation likely preserves parotid macrophages after radiation through inhibition of P53 signaling and consequent cellular senescence. Consistently, VEGF, an essential anti-senescence cytokine downstream of Hedgehog signaling, is significantly decreased by radiation but recovered by transient Hedgehog activation. These findings indicate that in the clinically-relevant swine model, transient Hedgehog activation restores the function of irradiated salivary glands through the recovery of resident macrophages and the consequent inhibition of cellular senescence and inflammation.


Assuntos
Senescência Celular/fisiologia , Proteínas Hedgehog/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Glândulas Salivares/metabolismo , Transdução de Sinais/fisiologia , Animais , Citocinas/metabolismo , Masculino , Glândula Parótida/metabolismo , Receptor Patched-1/metabolismo , Glândula Submandibular/metabolismo , Suínos , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Oral Dis ; 26(5): 920-929, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32034858

RESUMO

OBJECTIVES: Our aim was to verify the alleviation effect of sphingosine-1-phosphate (S1P) in a miniature pig model. MATERIAL AND METHODS: Thirty male miniature pigs were randomly separated into 10 groups in our experiment. We administered S1P through the parotid duct in a retrograde fashion 2 hr before irradiation (IR). The salivary flow rate and blood flow rate were tested 20 weeks after IR. The apoptotic level was checked at 12, 24 hr and 7 days post-IR. RESULTS: Twenty weeks after IR, the salivary flow rate of the IR-side parotid gland in IR + S1P group can be maintained at about 40% of the non-IR side, while only 20% was maintained in the IR group. The blood flow rate and microvascular density were significantly higher in the IR + S1P group than in the IR group. The apoptotic level and cleaved caspase-3 expression were downregulated in IR + S1P group, and the ratio of Bcl-2/Bax was increased. The blood flow rate and CD31 level were significantly restored at 12, 24 hr and 7 days post-IR. CONCLUSION: Sphingosine-1-phosphate may partially alleviate IR-induced parotid dysfunction by decreasing apoptosis of microvascular endothelial cells and maintaining the blood flow rate.


Assuntos
Células Endoteliais , Lisofosfolipídeos , Glândula Parótida , Lesões por Radiação , Esfingosina/análogos & derivados , Animais , Apoptose , Lisofosfolipídeos/farmacologia , Masculino , Glândula Parótida/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Esfingosina/farmacologia , Suínos , Porco Miniatura
17.
Pak J Pharm Sci ; 33(5(Special)): 2393-2398, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33832880

RESUMO

Non-steroidal anti-inflammatory drugs are commonly used anti-inflammatory analgesics in clinic. Indomethacin is a kind of NSAIDs and has anti-tumor effect. It can significantly change the growth cycle of cancer cells, inhibit their proliferation. In this paper, the antineoplastic effect of indomethacin and its pharmacokinetic effect were analysed. The result showed that indomethacin had more metabolic distribution in tumor tissues and reached its peak at 4 hours, after that, the clearance rate was slower than that in the blood, with the clearance rate slowest at 6-12 hours. At the same time, the expression of Bcl-2 protein in cancer cells was significantly reduced and weakened, while the expression of Bax protein did not change significantly. Pharmacodynamic studies have proved that IN (Indomethacin) has a strong anti-tumor effect. It can enter into tumor cells through cell membrane and nuclear membrane to have an anti-tumor effect.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Indometacina/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/sangue , Antineoplásicos/sangue , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Indometacina/sangue , Masculino , Taxa de Depuração Metabólica , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
18.
BMC Anesthesiol ; 19(1): 75, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092191

RESUMO

BACKGROUND: The video laryngoscope is recommended for intubating difficult airways. The present study aimed to determine whether the video laryngoscope can further improve intubation success rates compared with the direct laryngoscope in patients with non-difficult airways. METHODS: In total, 360 patients scheduled for elective abdominal surgeries were randomly assigned to undergo intubation using either a video laryngoscope (n = 179) or a direct laryngoscope (n = 181). The following parameters were measured: mouth opening; thyromental distance; sternomental distance; shape angle of the tracheal catheter; and glottic exposure grade. RESULTS: The percentage of patients with level I-II of total glottic exposure in the video laryngoscope group was 100% versus 63.5% in the direct laryngoscope group (P < 0.001). The one-attempt success rate of intubation was 96.1% using a video laryngoscope versus 90.1% using a direct laryngoscope (P = 0.024). The intubation success rate using a video laryngoscope was 100% versus 94.5% using a direct laryngoscope (P = 0.004). Immediate oropharyngeal injury occurred in 5.1% of patients intubated using a direct laryngoscope versus 1.1% using a video laryngoscope (P = 0.033). On postoperative day 1, obvious hoarseness was exhibited by 7.9% of patients intubated using a direct laryngoscope versus 2.8% using a video laryngoscope (P = 0.035). The grade of glottic exposure and catheter shape angle were independent risk factors for tracheal intubation failure. Thyromental distance, shape angle, glottic exposure time, and surgical position were independent risk factors for postoperative complications. Thyromental distance and glottic exposure time were independent risk factors for complications lasting > 2 days. CONCLUSIONS: Intubation using a video laryngoscope yielded significantly higher intubation success rates and significantly fewer postoperative complications than direct laryngoscopy in patients with non-difficult airways. TRIAL REGISTRATION: Chinese Clinical Trial Registry. No: ChiCTR-IOR-16009023 . Prospective registration.


Assuntos
Procedimentos Cirúrgicos Eletivos/métodos , Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Procedimentos Cirúrgicos Eletivos/instrumentação , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/normas , Laringoscópios/normas , Laringoscopia/instrumentação , Laringoscopia/normas , Masculino , Pessoa de Meia-Idade , Cirurgia Vídeoassistida/instrumentação , Cirurgia Vídeoassistida/normas
19.
Int Heart J ; 60(4): 998-1002, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31257334

RESUMO

Ventricular pseudoaneurysm (PSA) is a rare, yet life-threatening complication of myocardial infarction, cardiac surgery, and transcatheter valve replacement. Although conventional surgery is the preferred treatment strategy, transcatheter closure has emerged as an effective alternative in selected candidates. In this report, we describe successful transcatheter closure of two unique cases of ventricular pseudoaneurysm (PSA): first, a complex post-myocardial infarction left ventricular PSA (LVPSA) with multi-communications, and second, a case of post-traumatic right ventricular PSA (RVPSA) following blunt chest injury caused by domestic violence.


Assuntos
Falso Aneurisma/cirurgia , Cateterismo Cardíaco/métodos , Aneurisma Cardíaco/cirurgia , Ventrículos do Coração , Infarto do Miocárdio/complicações , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Idoso , Falso Aneurisma/diagnóstico , Falso Aneurisma/etiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Violência Doméstica , Ecocardiografia , Feminino , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/etiologia , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Traumatismos Torácicos/diagnóstico , Ferimentos não Penetrantes/diagnóstico
20.
Environ Monit Assess ; 191(6): 395, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123882

RESUMO

Trace element contamination caused by mining is a serious environmental problem. The potential effects of exploiting the Yunfu pyrite mine (southern China) on soil were investigated by determining trace elements in 56 surface soil samples from the vicinity of the Yunfu pyrite mine. The samples were acid dissolved and measured by an inductively coupled plasma mass spectrometry (ICP-MS). Principal component analysis and hierarchical cluster analysis were used to identify factors influencing the trace element contents and possible sources of the trace elements. The degree of trace element pollution was determined using the geological accumulation index Igeo. Monte Carlo simulations were used to assess the health risks posed. The results show that (1) six factors (parent material, mining activities, ore composition, rainfall, terrain, and other inputs) strongly affected the trace element contents of the soil samples. (2) There were three groups of trace elements, according to their possible sources. One group (Cs, Ga, Ge, Hf, Nb, Rb, Ta, Th, Ti, U, and Zr) mainly originated in parent rocks. Another group (Cr, Ni, Sr, and V) was mainly supplied by industrial plants and traffic emissions. The third group (Ba, Co, Cu, Mn, Pb, and Zn) was mainly supplied through pyrite ore exploitation processes. (3) Some samples were slightly to moderately polluted with Cs, Ga, Ge, Nb, Rb, Ta, and Ti. Most samples were moderately to highly polluted with Ba, Co, Cu, Mn, Pb, and Zn. (4) Trace elements in soil pose strong non-carcinogenic and carcinogenic health risks to people (particularly children) living near the Yunfu pyrite mine.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes do Solo/análise , Oligoelementos/análise , Criança , China , Humanos , Ferro , Mineração , Solo/química , Sulfetos
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