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OBJECTIVE: Perioperative anxiety and depression syndrome (PADS) is a common clinical concern among women with systemic tumors. Esketamine has been considered for its potential to alleviate anxiety and depressive symptoms. However, its specific application and effectiveness in PADS among women with systemic tumors remain unclear. This study aimed to analyze the utility of Machine Learning (ML) algorithms based on electroencephalogram (EEG) signals in evaluating perioperative anxiety and depression in women with systemic tumors treated with Esketamine, utilizing a large-scale medical data background. PATIENTS AND METHODS: A single-center, randomized, placebo-controlled (SC-RPC) trial design was adopted. A total of 112 female patients with systemic tumors and PADS who received Esketamine treatment were included as study participants. A moderate dose (0.7 mg/kg) of Esketamine was administered through intravenous infusion over a duration of 60 minutes. EEG signals were collected from all patients, and the EEG signal features of individuals with depression were compared to those without depression. In this study, a Support Vector Machine (SVM)-K-Nearest Neighbour (KNN) hybrid classifier was constructed based on SVM and KNN algorithms. Using the EEG signals, the classifier was utilized to assess the anxiety and depression status of the patients. The predictive performance of the classifier was evaluated using accuracy, sensitivity, and specificity measures. RESULTS: The C2 correntropy feature of the delta rhythm in the left-brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). Moreover, the C2 correntropy feature of the Alpha, Beta, and Gamma rhythms in the left-brain EEG signal was significantly lower in individuals with depression compared to those without depression (p<0.05). In the right brain EEG signal, the C2 correntropy feature of the delta rhythm was significantly higher in individuals with depression (p<0.05), while the C2 correntropy feature of the alpha and gamma rhythms was significantly lower in individuals with depression compared to those without depression (p<0.05). Additionally, the C1 correntropy feature of the Gamma rhythm in the right brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). The SVM classifier achieved accuracy, sensitivity, and specificity of 98.23%, 98.10%, and 98.56%, respectively, in recognizing the left-brain EEG signals, with a correlation coefficient of 0.95. In recognizing the right brain EEG signals, the SVM classifier achieved accuracy, sensitivity, and specificity of 98.74%, 98.43%, and 99.03%, respectively, with a correlation coefficient of 0.96. The improved SVM-KNN approach yielded an accuracy, recall, precision, F-score, area over the curve (AOC), and Receiver Operation Characteristics (ROC) of 0.829, 0.811, 0.791, 0.853, 0.787, and 0.877, respectively, in predicting anxiety. For predicting depression, the accuracy, recall, precision, F-score, AOC, and ROC were 0.869, 0.842, 0.831, 0.893, 0.827, and 0.917, respectively. CONCLUSIONS: Significant differences were observed in the brain EEG signals between individuals with depression and those without depression. The improved SVM-KNN algorithm developed in this study demonstrates good predictive capability for anxiety and depression.
Assuntos
Big Data , Ketamina , Neoplasias , Feminino , Humanos , Depressão/diagnóstico , Depressão/tratamento farmacológico , Ritmo Gama , Ansiedade/diagnóstico , Ansiedade/tratamento farmacológico , SíndromeRESUMO
OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasound-guided stellate ganglion block (SGB) with different volumes of 0.375% ropivacaine on sleep quality in patients with insomnia. PATIENTS AND METHODS: A total of 80 patients who were selected to undergo SGB for the treatment of insomnia were enrolled. The patients were divided into saline control group, and low-volume (4 mL), medium-volume (6 mL), and high-volume (8 mL) ropivacaine injection groups according to the random table method. The treatment included 7 blocks with once every three days. The left and right stellate ganglions are alternately blocked. The onset and maintenance time of Horner syndrome, the degree of carotid artery dilation and blood flow velocity before and 20 minutes after the first block, the occurrence of complications such as drug crossing of the midline of the artery and hoarse throat were recorded, and the improvement of sleep disorders was evaluated with the Pittsburgh Sleep Quality Index Scale. RESULTS: Horner syndrome occurred in 100% of all volumes of ropivacaine block. The ipsilateral internal carotid artery was dilated and was accompanied by increased blood flow. The degree of dilation and increase in blood flow were not affected by the volumes of drug injection. There were no serious complications in any group, but the incidences of hoarseness and dysphagia were higher in the medium- and high-volume groups than those in the low-volume group (all p < 0.05). Compared with the low- and medium-volume groups, the high-volume group had a faster onset of action, longer maintenance time, and the highest chance of the drug crossing the artery (all p < 0.05). Compared to those before the pre-block and in the control groups, insomnia was improved in all volume groups after the block with nonsignificant intergroup differences. CONCLUSIONS: 4 mL of 0.375% ropivacaine for ultrasound-guided SGB is sufficient to improve the sleep quality of insomnia patients, whose overall risk is lower than block with 6 mL or 8 mL of ropivacaine.
Assuntos
Bloqueio Nervoso Autônomo , Síndrome de Horner , Distúrbios do Início e da Manutenção do Sono , Humanos , Anestésicos Locais/uso terapêutico , Bloqueio Nervoso Autônomo/métodos , Ropivacaina/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Qualidade do Sono , Gânglio EstreladoRESUMO
BACKGROUND: Digital treatment adherence technologies (DATs) have been recommended by the Chinese National Tuberculosis Programme since 2015. However, until now the extent to which DATs have been adopted in China remain unclear. In this study, we aimed to understand the current status and future prospects of DAT use in China.METHODS: A cross-sectional study was undertaken to collect data from all 2,884 county-level TB-designated institutions across China using a quantitative questionnaire and extraction of information from the Chinese TB information management system. Data were collected between 1 July 2020 and 30 June 2021.RESULTS: All of the 2,884 county-level TB-designated institutions responded to the questionnaire. We found that the utilisation rate of DATs in China was 21.5% (n = 620). Among those using DATs, the uptake of DATs among TB patients was 31.0%. Lack of financial, policy and technology support were the main barriers to adoption and scale up DATs at the institution level.CONCLUSIONS: The use of DATs is in an early stage in China; however, the number of institutions who offer DATs have increased significantly after July 2020. To facilitate the use of DATs, the national TB programme should provide more financial, policy and technology support, and a national guideline is required.
Assuntos
Tuberculose , Humanos , Estudos Transversais , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Cooperação e Adesão ao Tratamento , China/epidemiologia , TecnologiaRESUMO
OBJECTIVE: The objective of this research was to explore the importance of N6-methyladenosine (m6A) methylation-associated genes concerning the clinical outcome of patients with renal cell carcinoma (RCC) by employing the Cancer Genome Atlas (TCGA) database along with various bioinformatics methodologies. MATERIALS AND METHODS: The transcriptome and clinical data of RCC patients were obtained from the TCGA database. We identified the differential expression of 13 genes and selected potential predictive genes for further analysis of their prognostic values. RESULTS: Ten genes (YTHDC2, FTO, YTHDF2, METTL3, KIAA1429, ZC3H13, METTL14, ALKBH5, WTAP, and RBM15) exhibited altered expression levels in RCC. Subgroup analysis based on m6A methylation-related gene expression levels revealed no significant differences in survival rates, but significant differences were observed in grade, T stage, and gender. Five potential predictors (FTO, RBM15, YTHDC2, ZC3H13b, and ALKBH5) demonstrated independent predictive value. Multivariate analysis selected two regulators (METTL14 and METTL3), and based on these, prognostic signals for RCC were constructed, independent of potential confounding factors. The model clearly distinguished between samples with good and poor prognoses. CONCLUSIONS: The expression levels of m6A methylation-related genes in RCC patients were found to differ and were associated with survival rates and prognosis. These findings suggest that m6A methylation-related genes could serve as prognostic indicators and promising therapeutic targets for RCC patients.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Neoplasias Renais/genética , Metilação , Metiltransferases/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genéticaRESUMO
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Oncologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
Tyrp1 gene, as a member of the tyrosinase family, has undergone a recent duplication event during fourth-round whole genome duplication in common carp. In this research, three Tyrp1 genes were identified in Oujiang-color common carp (Cyprinus carpio var. color). The similar expression patterns and close phylogenetic relationship indicated that Tyrp1c is homologous to Tyrp1b and possibly originated from the ancient Tyrp1b. The rates of synonymous and non-synonymous substitution (Ka /Ks ) in Tyrp1 across teleost phylogeny indicated that Tyrp1a is more likely to be in the process of purifying selection. The CRISPR/Cas9 system was used to disrupt the Tyrp1 genes in zebrafish and the WB (black patches on white skin) strain of Oujiang-color common carp. The Tyrp1 loss of function variants in zebrafish and WB carp showed severe melanin deficiency in the skin. Meanwhile, inactivation of a single Tyrp1 gene did not obstruct melanin synthesis, which proved that the functional redundancy of Tyrp1 genes existed in both zebrafish and Oujiang-color common carp. Among the mosaic individuals with Tyrp1 genes in disrupted-color common carp, various mutations in Tyrp1b gene induced gray or brown phenotypes, suggesting that it may be bifunctional in Oujiang-color common carp. In addition, the phenotype of WB variants was different from that of WW (whole white skin), suggesting that Tyrp1 genes were not the key factor that caused the difference between WB and WW.
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Carpas/genética , Glicoproteínas de Membrana/genética , Oxirredutases/genética , Pigmentos Biológicos/genética , Animais , Cor , Feminino , Duplicação Gênica , Masculino , Glicoproteínas de Membrana/metabolismo , Oxirredutases/metabolismoRESUMO
The aim of this study was to determine whether endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa cells in patients with polycystic ovary syndrome (PCOS). A total of 116 patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles at the Binzhou Medical University Hospital IVF Center between September 2019 and January 2020 were enrolled in the study. Apoptosis of the granulosa cells in each patient was analyzed using flow cytometry, and progesterone and estrogen levels in the cell-culture fluid were measured by enzyme-linked immunosorbent assay. The expressions of X-box-binding protein 1 (XBP1(s)), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), B-cell CLL/lymphoma 2 protein (Bcl-2), and Bcl-2 associated X protein (Bax) at the gene or protein level were analyzed using quantitative real-time polymerase chain reaction and Western blotting, respectively. In patients with PCOS, body mass index and basal serum concentrations of luteinizing hormone, testosterone (T), and anti-Mullerian hormone significantly increased (P < 0.05). The number of oocytes retrieed and the rate of clinical pregnancy after the first frozen embryo transfer also significantly increased (P < 0.05). Although apoptosis rate in the granulosa cells significantly increased in patients with PCOS, progesterone (P) and estrogen (E2) levels in the cell-culture fluid significantly decreased (P < 0.05). The apoptosis of granulosa cells was also found to affect blastocyst formation. Furthermore, the messenger ribonucleic acid (mRNA) expressions of XBP1(s), ATF6, CHOP, and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). The protein expressions of CHOP and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). After treatment of the granulosa cells with tauroursodeoxycholic acid, apoptosis rate and mRNA or protein expressions of XBP1(s), CHOP, and Bax significantly decreased, while the expression of Bcl-2 and levels of progesterone and estrogen significantly increased (P < 0.05). We conclude that ER stress could induce the apoptosis of granulosa cells in patients with PCOS. Cell apoptosis may decrease the number of blastocysts formed.
Assuntos
Síndrome do Ovário Policístico , Apoptose , Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Feminino , Células da Granulosa , Humanos , GravidezRESUMO
OBJECTIVE: The diagnosis and prognosis of nasopharyngeal cancer (NPC) are still difficult. To investigate the effect of long-chain non-coding RNA GNAS-AS1 (lncRNA GNAS-AS1) on proliferation, migration, and invasion of NPC, we carried out this research to illustrate the underlying mechanism. PATIENTS AND METHODS: Real-time quantitative PCR was used to detect the expression of GNAS-AS1 in nasopharyngeal carcinoma cells. The effect of transfection of si-GNAS-AS1 on the growth of nasopharyngeal carcinoma SUNE-1 cells was analyzed by CCK-8 assay and colony formation assay. The effect of GNAS-AS1 on the migration and invasion of SUNE-1 cells was detected by transwell assay and Matrigel assay. The expression of C-myc, CyclinD, and MMP2 was detected by Western blot. The expression of ß-catenin was detected by real-time quantitative PCR and Western blot. RESULTS: GNAS-AS1 was upregulated in NPC. GNAS-AS1 promoted cell proliferation, cell migration, and cell invasion in vitro. GNAS-AS1 exerted its function by regulating Wnt/ß-catenin pathway. GNAS-AS1 functioned as an oncogenic role via mediating ß-catenin expression. CONCLUSIONS: LncRNA GNAS-AS1 played an important role in the proliferation, migration, and invasion of NPC cells, suggesting that GNAS-AS1 may be an important gene related to the formation and progression of nasopharyngeal carcinoma. The completion of this study provides new potential therapeutic targets for nasopharyngeal carcinoma.
Assuntos
Movimento Celular , Cromograninas/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Linhagem Celular , Proliferação de Células , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante/genéticaRESUMO
OBJECTIVE: To investigate the role of the transcription factor Zinc finger 703 (ZNF703) in influencing the progression of glioma by regulating linc-UBC1 level. MATERIALS AND METHODS: Linc-UBC1 level in glioma with different staging and tumor sizes was determined. The potential influences of linc-UBC1 on viability, cell cycle progression, and invasiveness of glioma cells were evaluated. Through RNA binding protein immunoprecipitation (RIP) assay and Dual-Luciferase reporter gene assay, the interaction between ZNF703 and linc-UBC1 was assessed. The rescue experiments were conducted to identify the role of ZNF703 in regulating cellular performances of glioma by interacting with linc-UBC1. RESULTS: Linc-UBC1 was highly expressed in glioma. Its level was higher in glioma with larger tumor size or advanced staging. The knockdown of linc-UBC1 reduced viability, arrested cell cycle in the G0/G1 phase, and attenuated invasiveness of U87 and LN229 cells. The presence of the binding sites was observed in the promoter regions of ZNF703 and linc-UBC1. The overexpression of ZNF703 could alleviate the inhibited proliferative and invasive potentials in U87 and LN229 cells with the linc-UBC1 knockdown. CONCLUSIONS: The transcription factor ZNF703 promotes the proliferative and invasive potentials in glioma cells by regulating the transcriptional activity of linc-UBC1.
Assuntos
Proteínas de Transporte/metabolismo , Glioma/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Transporte/genética , Células Cultivadas , Glioma/patologia , Humanos , RNA Longo não Codificante/genética , Regulação para CimaRESUMO
OBJECTIVE: The aim of this study was to investigate the expression level of long non-coding RNA (lncRNA) CASC11 in esophageal carcinoma (ECa), and to further explore its relationship with clinical progression, pathological parameters, and prognosis of ECa patients. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the level of lncRNA CASC11 in 45 pairs of ECa tissues and adjacent normal tissues. The relationship between the lncRNA CASC11 level and clinical progression, pathological parameters, and prognosis of ECa patients was analyzed. Meanwhile, the level of lncRNA CASC11 in the ECa cell lines was verified by qPCR as well. In addition, lncRNA CASC11 knockdown model was constructed using lentiviral transfection in ECa cell lines. Subsequently, the cell counting kit-8 (CCK8), colony formation assay, and flow cytometry were used to explore the effect of lncRNA CASC11 on the biological functions of the ECa cells. Finally, the Western Blot and the recovery experiments were used to explore the potential mechanism. RESULTS: In this work, the qPCR results showed that the expression level of lncRNA CASC11 in the ECa tissues was remarkably higher than that of the adjacent normal tissues, and the difference was statistically significant (p<0.05). Compared with patients with a low level of lncRNA CASC11, the pathological stage of patients with high expression was significantly higher, while the overall survival rate was lower (p<0.05). Compared with negative control (NC) group, the proliferation ability of the cells in the lncRNA CASC11 knockdown group CASC11 significantly decreased, whereas cell apoptosis remarkably increased (p<0.05). The Western Blot results revealed that protein expression of KLF6 was remarkably up-regulated after lncRNA CASC11 knockdown. In addition, the recovery experiments found that lncRNA CASC11 and KLF6 had mutual regulation, thereby promoting the malignant progression of ECa. CONCLUSIONS: LncRNA CASC11 expression was remarkably up-regulated in ECa, which was associated with the pathological stage and poor prognosis of ECa. In addition, lncRNA CASC11 could promote the malignant progression of ECa by mutual regulation of KLF6.
Assuntos
Neoplasias Esofágicas/patologia , Fator 6 Semelhante a Kruppel/metabolismo , RNA Longo não Codificante/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Fator 6 Semelhante a Kruppel/antagonistas & inibidores , Fator 6 Semelhante a Kruppel/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismoRESUMO
BACKGROUND: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. PATIENTS AND METHODS: In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. RESULTS: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). CONCLUSIONS: Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01856478.
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Afatinib/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Afatinib/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Povo Asiático , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
OBJECTIVE: The aim of this study was to explore whether 22-oxacalcitriol could protect inflammatory response induced by ischemia-reperfusion injury (IRI) in rats, and to investigate its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley rats were randomly assigned into the sham group, the IRI group and the 22-oxacalcitriol group, with 8 rats in each group. Serum and heart samples of each rat were collected 10 days after the animal procedure. The serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in each rat were detected by relative commercial kits. Pathological lesions in rat myocardium were observed by hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis in rat heart was accessed by TUNEL staining. Meanwhile, the serum levels of tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), and KC-GRO were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Also, the protein expression levels of NF-κB, TNF-α, VCAM-1, ICAM-1, and MCP-1 in rat myocardium were detected by Western blot and immunohistochemistry. RESULTS: The serum levels of CK-MB and LDH in rats of the IRI group were significantly higher than those of the sham group. 22-oxacalcitriol treatment remarkably decreased the serum levels of CK-MB and LDH when compared with the IRI group. However, cardiomyocyte apoptosis of the 22-oxacalcitriol group was markedly less than the IRI group. The activities of SOD, GSH, CAT and T-AOC in the cardiac homogenate of the 22-oxacalcitriol group were significantly elevated than those of the IRI group. Meanwhile, malondialdehyde (MDA) and reactive oxygen species (ROS) levels were remarkably decreased by 22-oxacalcitriol treatment. Furthermore, the serum levels of TNF-α, IL-1ß, IL-6 and KC-GRO were significantly downregulated in the 22-oxacalcitriol group. Western blot results showed that the protein expression levels of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 in the 22-oxacalcitriol group were significantly lower than those of the IRI group. CONCLUSIONS: 22-oxacalcitriol inhibits the inflammatory response in the myocardium by suppressing NF-kB/TNF-α pathway, thereby protecting myocardial ischemia-reperfusion injury in rats.
Assuntos
Calcitriol/análogos & derivados , Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Cardiotônicos/uso terapêutico , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , NF-kappa B/sangue , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ratos , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: This study was designed to investigate whether microRNA-1297 can regulate the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) through WNT5A, thus influencing the progression of osteoporosis. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) assay was performed to analyze microRNA-1297 level and osteogenesis-related markers in osteoporosis patients and controls. The protein levels of the above markers and WNT5A were detected by Western blot. Alkaline phosphatase (ALP) activity assay and ALP staining were used to measure the degree of osteogenic differentiation under the control of microRNA-1297 and WNT5A, and ARS staining was used to detect the mineralization ability of hBMSC after overexpression of microRNA-1297. The binding sites of microRNA-1297 and WNT5A were determined by the dual luciferase-reporting assay. Besides, the activity of Wnt signal transduction pathway in different treatment groups was detected by TOP/FOP report. RESULTS: MicroRNA-1297 was highly expressed in osteoporotic patients, and its level decreased significantly with the increasing of osteogenic induction. Bioinformatics prediction suggested that microRNA-1297 can target WNT5A. In vitro experiments showed that overexpression of microRNA-1297 in hBMSC can reduce the level of WNT5A, while interference with microRNA-1297 can increase the level of WNT5A. Overexpression of microRNA-1297 and transfection of si-WNT5A significantly reduced the mRNA levels of RUNX2, OSX, ALP, OCN, OPN and COL1A1, thereby inhibiting osteogenic differentiation. Overexpression of microRNA-1297 could interfere with WNT signaling pathway regulation and regulate the osteogenic differentiation of hBMSCs. CONCLUSIONS: microRNA-1297 could regulate the osteogenesis of BMSCs by combining with WNT5A so as to accelerate the progression of osteoporosis.
Assuntos
Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Osteoporose/genética , Regulação para Cima , Proteína Wnt-5a/genética , Regiões 3' não Traduzidas , Diferenciação Celular , Células Cultivadas , Progressão da Doença , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Osteoporose/metabolismo , Proteína Wnt-5a/metabolismoRESUMO
OBJECTIVE: To explore the molecular mechanism of micro ribonucleic acid-34a (miR-34a) in promoting the apoptosis of myocardial cells in the rat model of myocardial infarction (MI). MATERIALS AND METHODS: Sprague-Dawley (SD) rats were ligated with a left anterior descending branch to construct the MI model. The rats were randomly divided into four groups: sham operation group (Sham group), MI group, MI + miR-34a inhibitor group (MI + miR-34a antagomir group) and MI + miR-34a inhibitor negative control group (MI + antagomir NC group). Echocardiography (ECG) and magnetic resonance imaging (MRI) were adopted to detect the ejection fraction [EF (%)] and fraction shortening [FS (%)] of SD rats. Polymerase chain reaction (PCR) and Western blotting were used to detect expression levels of the apoptotic marker Caspase-3 and genes in Wnt/ß-catenin signaling pathway. Hematoxylin and eosin (H&E) staining was applied to detect cardiac injury. In in vitro experiments, the rat-derived myocardial cell line H9C2 was selected to simulate myocardial ischemia and hypoxia at the time of MI with an anoxic and serum-free injury model. C59, the Wnt/ß-catenin signaling pathway inhibitor was applied in MI + miR-34a antagomir + C59 group, and the effect of miR-34a on the apoptosis of myocardial cells through regulating the Wnt/ß-catenin pathway was measured with Real-Time quantitative PCR (qPCR) and 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyltetrazolium bromide (MTT) cell activity detection kits, respectively. RESULTS: It was found that after miR-34a antagomir reversed FS (%) and EF (%) in MI rats, the messenger RNA (mRNA) and protein levels of Caspase-3 in Sham group and MI + miR-34a antagomir group were significantly lower than those in the MI group (p < 0.05), indicating that the addition of miR-34a antagomir inhibited myocardial cell apoptosis after infarction, while the mRNA and protein levels of Wnt/ß-catenin were both higher than those in the MI group. Besides, H&E staining proved that miR-34a reversed the myocardial injury after MI. Similarly, in vitro experiments showed that, compared with those in Hypoxia group, the level of Caspase-3 decreased in Hypoxia + miR-34a inhibitor group and Sham group, while the apoptosis level in Hypoxia + miR-34a inhibitor + C59 group increased (p < 0.05). The results of the MTT assay were consistent with those of PCR. MiR-34a affects myocardial cell apoptosis by regulating the activation and inactivation of the Wnt/ß-catenin signaling pathway.
Assuntos
MicroRNAs/genética , Infarto do Miocárdio/diagnóstico por imagem , Regulação para Cima , Via de Sinalização Wnt , Animais , Apoptose , Linhagem Celular , Modelos Animais de Doenças , Ecocardiografia , Imagem Cinética por Ressonância Magnética , Masculino , Infarto do Miocárdio/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Volume SistólicoAssuntos
Azatioprina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Eritema Nodoso/genética , Imunossupressores/efeitos adversos , Pirofosfatases/genética , Adulto , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Urticária Crônica/tratamento farmacológico , Eritema Nodoso/induzido quimicamente , Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Feminino , Humanos , Testes de Função Hepática , Polimorfismo de Nucleotídeo Único , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.
Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Stenotrophomonas maltophilia/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stenotrophomonas maltophilia/isolamento & purificação , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.
Assuntos
Neoplasias Bucais/diagnóstico por imagem , Espectrometria de Fluorescência/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Discriminante , Feminino , Flavina-Adenina Dinucleotídeo/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/diagnóstico por imagem , NAD/metabolismo , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: To evaluate the effect of dextrose contained in banked blood products on the changes of blood glucose levels in adult living donor liver transplantation patients retrospectively. METHODS: Four hundred seventy-seven patients were divided into a non-blood transfusion (BT) group (G1) and a BT group (G2). The changes in blood glucose levels during the operation were compared using a Mann-Whitney U test, and a P value less than .05 was regarded as significant. RESULTS: No significant changes were detected in blood glucose levels after anesthesia, during dissection phase, in the anhepatic phase, or after reperfusion between the groups. Estimated blood loss for G1 (n = 89) and G2 (n = 388) were 718 ± 514 and 5804 ± 877 mL respectively, G1 had no blood transfusion but G2 had received 4350 ± 6230 mL leukocyte-poor red blood cell transfusion, the pre- and end operation hemoglobin for G1 and G2 were 13.2 ± 2.0, 10.2 ± 1.9 and 10.1 ± 1.6, 10.2 ± 1.9 mg/dL respectively, indicating that they were not under or over transfused. CONCLUSION: When banked blood products are used to replace ongoing blood loss, the dextrose contained in citrate-phosphate-dextrose-adenine seems to have no effect on the changes in the blood glucose levels of the recipients.
Assuntos
Glicemia/análise , Transfusão de Sangue/estatística & dados numéricos , Hemostasia Cirúrgica/métodos , Transplante de Fígado/métodos , Adulto , Bancos de Sangue , Citratos/sangue , Feminino , Glucose , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
OBJECTIVES: The aims of this study were to compare the core temperature changes between pediatric patients lying on regular operating room linen drapes and a water-repellent sheepskin rug during living donor liver transplantation (LDLT) and to evaluate the effectiveness of using a water-repellent sheepskin rug in preventing profound hypothermia due to fluid overflow from the abdominal cavity during LDLT. PATIENTS AND METHODS: The operative records of pediatric patients who underwent LDLT from June 1994-September 2003 were reviewed retrospectively. The nasopharyngeal temperature (NT) changes during the LDLT procedure between patients lying on regular operating room drapes (GI) and water-repellent sheepskin rug (GII) were compared and analyzed using the Mann-Whitney U test. A P value <.05 was regarded as significant. RESULTS: Thirty-two patients were included in GI and 56 in GII. Profound hypothermia was not observed in any recipients lying on a water-repellent sheepskin rug (GII). The NT after induction and the following 4 hours into the LT procedure were significantly higher in GII than GI. CONCLUSION: Pediatric patients lying on water-repellent sheepskin preserved their core temperature better in comparison to patients lying on linen drapes. The use of a water-repellent sheepskin rug seems to be effective in preventing profound hypothermia related to physical contact with abdominal fluid overflow during the LDLT.