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AIMS: To detect the acute myocardial injury in fulminant myocarditis (FM) survivors after extracorporeal membrane oxygenation (ECMO) and to demonstrate its significant differences from non-FM patients by cardiac magnetic resonance (CMR). MATERIALS AND METHODS: This retrospective study enrolled 59 patients with acute myocarditis (AM), including 35 non-FM patients, 24 FM patients, and 54 controls. The peak value of cardiac troponin T (cTnT) was recorded. Tissue parameters, including native T1, extracellular volume (ECV), late gadolinium-enhancement (LGE)%, and T2 by CMR were assessed. RESULTS: The mean age was 35 ± 14 years, and 45.8% of the population were males in the AM group. Patients had higher levels of peak cTnT, peak NT-proBNP and peak C-reactive protein in the FM group (all p<0.05). Comparing with non-FM, the values of T1-based imaging parameters were significantly higher in the FM group (all p<0.05). In contrast, no difference was observed among the two groups in terms of T2 value (p=0.707). The septal area was more frequently involved in FM survivors after ECMO treatment, both in T1 and T2-based images. In addition, the cubic relationship was the relative best fit of LGE% against logcTnT and indicated that cTnT value exceeding 300ng/L exhibited a rapid upward trend of LGE%. CONCLUSION: Comparing to non-FM, higher myocardial necrosis and fibrosis but similar edema determined by T1 and T2 based imaging was found in FM survivors after ECMO treatment. Furthermore, the inter-ventricular septal area was more frequently involved by acute myocardial injury in FM survivors after ECMO treatment. In addition, LGE% showed an overall increasing trend with cTnT values elevating with rapidly increasing with cTnT exceeding 300 ng/L.
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Oxigenação por Membrana Extracorpórea , Imageamento por Ressonância Magnética , Miocardite , Humanos , Masculino , Oxigenação por Membrana Extracorpórea/métodos , Miocardite/diagnóstico por imagem , Miocardite/terapia , Adulto , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Sobreviventes , Pessoa de Meia-Idade , Doença Aguda , Meios de Contraste , Miocárdio/patologiaRESUMO
A total of 82 patients with temporal lobe epilepsy (TLE) and temporal plus epilepsy (TPE)admitted in Xuanwu Hospital from January 1, 2019, to January 1, 2021 were restrospectively analyzed, including 41 males and 41 females, aged 2 to 52 (24±10) years. The patients were randomly divided into the training set (58 cases) and test set (24 cases) by Python. FreeSurfer software was used to segment the cortex of the affected hemisphere, defining 33 regions of interest (ROIs), and radiomics features were extracted by Python. After selecting features using the filter-based feature selection method, a radiomics model was constructed with a logistic regression classifier, and radiomics scores were calculated. Combining clinical characteristics with radiomics scores, a nomogram model was constructed using R software, the predictive accuracy of the model was assessed with the concordance index (C-index), and the model's goodness-of-fit was tested with the Hosmer-Lemeshow method. The results showed statistically significant differences between TLE and TPE patients in disease duration, intracranial electrode implantation, and hippocampal sclerosis (both P<0.05). The accuracy of the radiomics model in the training set and the test set was 91.4% and 87.5%, respectively. The nomogram model uses C-index to predict accuracy. Hosmer-Lemeshow method was used to test the goodness of fit, with AUCs of 0.95 (95%CI: 0.853-0.991) in the training set and 0.84 (95%CI: 0.676-0.999) in the test set. The study indicates that the radiomics nomogram model based on MPRAGE sequences can effectively differentiate TLE from TPE, providing reference for the development of personalized treatment plans in clinical practice.
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Epilepsia do Lobo Temporal , Epilepsia , Feminino , Masculino , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Nomogramas , Radiômica , Área Sob a Curva , Estudos RetrospectivosRESUMO
Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
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Neoplasias Encefálicas , Robótica , Masculino , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Imagem de Tensor de Difusão , Estudos Retrospectivos , Biópsia , Software , Técnicas EstereotáxicasRESUMO
Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.
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Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Lesões Pré-Cancerosas , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Colonoscopia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/terapia , Lesões Pré-Cancerosas/patologia , Doenças Inflamatórias Intestinais/patologia , HiperplasiaRESUMO
OBJECTIVE: To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells. METHODS: The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation. RESULTS: The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05). CONCLUSION: Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
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MicroRNAs , Animais , Linhagem Celular Tumoral , Flavonóis/farmacologia , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor IGF Tipo 1 , TrastuzumabRESUMO
OBJECTIVE: To investigate the protective effect of ulinastatin combined with dexmedetomidine against ischemiareperfusion injury (IRI) of the liver in patients undergoing laparoscopic hepatectomy (LH) for liver cancer with cirrhosis. METHODS: Eighty patients with liver cancer and cirrhosis undergoing elective LH were randomized into ulinastatin (administered immediately before hepatectomy) group, dexmedetomidine (administered before anesthesia induction) group, ulinastatin plus dexmedetomidine group, and saline group (groups U, D, UD, and C, respectively). Venous blood samples were collected before the operation (T0) and at 30 min (T1), 24 h (T2), 3 days (T3), and 5 days (T4) after the operation. Serum levels of α-GST, MDA, TNF-α and IL-6 were analyzed at T0-T2. Serum levels of ALT, AST, BUN and Cr were measured at T0 and T2-T4, and the incidence of liver dysfunction, complications and postoperative hospital stay of the patients were recorded. RESULTS: At T1, serum α-GST, MDA, TNF-α and IL-6 levels increased significantly in groups U, D and UD compared with those in group C, and were significantly higher in groups U and D than in group UD (all P < 0.05). At T2, the levels of MDA, TNF-α and IL-6 were significantly decreased in groups U, D and UD compared with those in group C, and were significantly higher in groups U and D than in group UD (all P < 0.05). At T2-T4, the levels of ALT and AST were significantly lower in groups U, D and UD than in group C, and were higher in groups U and D than in group UD (all P < 0.05). The patients in group UD had significantly shortened postoperative hospital stay as compared with those in group C (P < 0.05). The incidences of complications or postoperative renal or liver insufficiency did not differ significantly among the 4 groups. However, there was no significant difference in the incidence of renal function, liver insufficiency and complications among the four groups (all P > 0.05). CONCLUSION: In patients undergoing LH for liver cancer with cirrhosis, ulinastatin combined with dexmedetomidine provides enhanced protection against hepatic IRI possibly through a synergistic effect against oxidative stress and inflammatory response, thereby reducing perioperative liver injury and accelerating postoperative recovery.
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Dexmedetomidina , Laparoscopia , Neoplasias Hepáticas , Traumatismo por Reperfusão , Humanos , Hepatectomia/efeitos adversos , Fator de Necrose Tumoral alfa , Dexmedetomidina/uso terapêutico , Interleucina-6 , Traumatismo por Reperfusão/prevenção & controle , Neoplasias Hepáticas/cirurgia , Cirrose Hepática/complicações , Laparoscopia/efeitos adversosRESUMO
OBJECTIVE: To explore the preoperative radiomics features (RFs) and construct a nomogram for predicting postoperative recurrence of stage â -â ¢ clear cell renal carcinoma (ccRCC). METHODS: The clinicopathological data and preoperative enhanced CT images collected from 256 patients with ccRCC were used as the training dataset (175 patients) and test dataset (81 patients). The enhanced CT images of the tumor were segmented using ITK-SNAP software, and the RFs were extracted using the PyRadiomics computing platform. In the training dataset, the RFs were screened based on Lasso-CV algorithm, and the Rad_score was calculated. The Clinic factors were screened by univariate and multivariate logistic regression analysis of the clinical and pathological factors and CT characteristics. The Rad_score, ClinicãRad_score + Clinic nomograms were constructed and verified using the test dataset. The performance, discrimination power and calibration of the nomograms were compared, and their clinical value was evaluated using decision curve analysis. RESULTS: Six RFs were retained to calculate the Rad_score. The Clinic factors included Rad_score, KPS score, platelet, calcification and TNM clinical stage. In terms of discrimination, the Rad_score + Clinic nomogram showed better performance (AUC=0.84 for training set; AUC=0.85 for test set) than the Rad_score nomogram (AUC=0.78 for training set, P=0.029; AUC=0.77 for Test set, P=0.025) and Clinic nomogram (AUC=0.77 for training set, P=0.014; AUC=0.77 for test set, P=0.011). In terms of calibration, the P value for goodness of fit test of the Rad_score+Clinic nomogram was 0.065 for the training set and 0.628 for the test set. Decision curve analysis showed a greater clinical value of the Rad_score+Clinic nomogram with Rad_score than the Clinic nomogram without Rad_score. CONCLUSION: The nomogram based on preoperative CT RFs has a high value for predicting postoperative recurrence of stage â -â ¢ ccRCC to facilitate individualized treatment of RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nomogramas , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Objective: To investigate the correlations of laminin subunit gamma 3 (LAMC3) expression with prognosis of ovarian cancer (OC). Methods: LAMC3 protein expression was measured using immunohistochemical streptavidin-peroxidase-biotin connection method (IHC). Gene expression and related clinical data in the cancer genome atlas (TCGA) cohort and clinical proteomic tumor analysis consortium (CPTAC) were applied to analyse the correlation between gene and protein expressions and clinical outcomes. Correlations between LAMC3 and clinicopathological factors were evaluated using the Pearson χ2 test (2-sided). The probability of survival and significance was calculated using the Kaplan-Meier plot. The functional clustering of biological pathways enriched from co-expressed genes of LAMC3 was used to explore the possible mechanisms that LAMC3 might contribute to poor prognosis. Results: Based on the IHC results of 216 OC tissues or ovaries (including 208 tumors and 8 normal tissues) and 51 OC tissues (including 24 chemotherapy-resistant and 27 sensitive tissues), and the protein expression data from CPTAC (including 100 primary tumors and 25 normal tissues), the results showed that the protein expression of LAMC3 was significantly decreased in OC tissues compared with normal, decreased in advanced-stage tissues compared with early-stage tissues, and decreased in drug-resistant tissues compared with sensitive tissues (all P<0.05). Furthermore, low expression of LAMC3 protein was significantly associated with poor disease-free survival (DFS) and overall survival (OS) in 51 OC tissues (P<0.01), consistent with the results that the low levels of LAMC3 mRNA predicted short DFS and OS in 489 OC tissues of the TCGA cohort (P<0.05). The results suggested that low expression of LAMC3 might be the adverse factors for OC development, such as drug resistance and advanced tumors, and might be a risk indicator for prognosis. Moreover, functional clustering of biological pathways enriched from the co-expressed genes of LAMC3 in TCGA ovarian cohort indicated that LAMC3 potentially involved in regulation of OC via oncogene-pathways such as Ras associated protein 1 (Rap1), mitogen-activated protein kinase (MAPK), Ras and cell adhesion-related pathways such as extra cellular matrix (ECM)-receptor interaction and focal adhesion. It indicated that LAMC3 might contribute to short survival and tumor progression by regulation of the above pathways. Conclusion: Low expression of LAMC3 is related to poor prognosis and malignant progression in OC, and thus it is expected to be a new prognostic marker and therapeutic target for clinical treatment.
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Neoplasias Ovarianas , Proteômica , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Feminino , Humanos , Laminina , Neoplasias Ovarianas/genética , PrognósticoRESUMO
Objective: To investigate the clinical characteristics of R403C variant in DNM1L gene caused encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (EMPF1). Methods: The clinical data of three patients, who carried R403C variant in the DNM1L gene, diagnosed at Xiangya Hospital from February 2018 to February 2020 were retrospectively summarized. Literature reviewing was performed by taking "DNM1L" or "encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1" as keywords for searching in online Mendelian inheritance in man (OMIM), PubMed, China national knowledge infrastructure (CNKI), and Wanfang data knowledge service platform up to July 2020. And the clinical manifestation, laboratory examination, imaging, treatment, and prognosis were reviewed. Results: Case 1, a 7-year-old boy, developed seizures after a 9-day course of cough without fever. The seizures manifested as generalized tonic-clonic seizures (GTCS) and soon converted to focal status epilepticus (EPC) or focal myoclonus, which were resistant to multi-anti-epileptic drugs combined with sedative drugs. The boy died at the 2nd week after seizure onset. Case 2, also a 7-year-old boy, developed seizures after a 10-day history of amygdalitis. The seizures manifested as focal to generalized tonic-clonic seizure and then converted to EPC or focal myoclonus. And all seizures showed poor responses to multi-anti-epileptic drugs combined with sedative drugs, ketogenic diet, and methylprednisolone treatment. The boy died after 1 month's treatment. Case 3, a 3-year and 5-month old girl, had seizures onset after a 2-week course of viral pneumonia. The seizures onset manifested as focal clonic seizure and converted to EPC, shortly. She was resistant to multi-anti-epiletic drugs combined with sedative drugs and ketogenic treatment. The girl died 3 months afte seizure onset. All of their images showed multifocal T1 low, T2, fluid attenuated inversion recovery, and diffusion-weighted imaging high signal lesions among the brain, and diffuse brain atrophy in case 3. The blood metabolic and cerebrospinal-fluid immunological assays were normal. Genetic analysis suggested a de novo, heterozygous, NM_012062.4: c.1207C>T, p.R403C variant in the DNM1L gene. According to their clinical manifestations, all of them were diagnosed with EMPF1. Literature review included 11 patients carrying this variant in the world. Summarizing the 14 cases, 8 cases had an infectious history before seizure onset, 8 cases had mild or moderate development delay. All of 14 cases had seizures, and the forms mainly included EPC (n=9), focal myoclonus (n=6), GTCS (n=5) and focal clonic seizures (n=4). All of them were refractory, and no effective anti-epileptic drugs were recommended. Early-stage cranial magnetic resonance imaging results showed multiple intracranial focal lesions (n=10), including thalamus (n=7), hippocampus (n=5), basal ganglia (n=4), frontal lobe (n=3), and temporal lobe (n=2). As the disease progressed, the brain manifested as diffused progressive atrophy (n=10). Five of the 14 cases died at reported age. Conclusions: R403C variant in the DNM1L gene can cause mitochondrial fission dysfunction. Patients carrying this variant may manifest as refractory status epilepticus with or without mild-infection indction, development regression and brain atrophy.
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Encefalopatias , Dinâmica Mitocondrial , Encefalopatias/genética , Criança , China , Dinaminas , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Convulsões/genéticaRESUMO
Objective: To compare the clinical characteristics and prognosis of critical patients with COVID-19 and novel influenza A (H1N1) virus pneumonia (influenza pneumonia) applied with extracorporeal membrane oxygenation (ECMO). Methods: A total of 24 patients with influenza pneumonia treated with ECMO in respiratory intensive-care unit (ICU) of Beijing Chaoyang Hospital from March 2016 to December 2019 and 12 patients with COVID-19 hospitalized from February 1, 2020 to March 31, 2020 in 5 government designated infectious hospitals of Beijing and Hebei Province that applied with ECMO were enrolled. The demographic data, clinical manifestations, and ECMO related information were described and analyzed and all numerical variables are described as M (P25, P75). Results: The age of COVID-19 patients was 77 (66, 79) years old, which was older than influenza pneumonia patients [46 (32, 62) years old], P<0.05; acute lung injury score and respiratory ECMO survival prediction (RESP) score before ECMO application were 3.3 (3.0, 3.5) and 1 (0, 2), respectively, which were lower than influenza pneumonia patients [3.8 (3.5, 4.0) and 4 (2, 6), respectively], all P values<0.05. Thrombotic complications, bleeding complications, and ventilator-associated pneumonia occurred in ECMO applied COVID-19 patients were 4, 10 and 5 cases, respectively, which were more than that among influenza pneumonia patients (1, 9, and 2 cases, respectively), all P values<0.05. The length of ICU stay of COVID-19 patients was 31 (28, 75) d, which was longer than that of influenza pneumonia patients [27 (18, 39) d], P<0.05. The cases with successful decannulation of ECMO among COVID-19 and influenza pneumonia patients were 6 and 14 cases, respectively and mortality during ICU stay were 8 cases and 11 cases, respectively, and the difference were not statistically significant (all P values>0.05). Conclusion: COVID-19 patients applied with ECMO have more ECMO-related complications and a longer stay in the ICU than patients with influenza pneumonia.
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COVID-19 , Oxigenação por Membrana Extracorpórea , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia , Síndrome do Desconforto Respiratório , Idoso , Humanos , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of malignant epithelial tumors of the oral and maxillofacial region. OSCC has high rate of metastasis and poor prognosis. Tobacco and/or alcohol consumption and human papillomavirus infection are relatively exact susceptibility factors for OSCC, but the specific process of oral mucosal carcinogenesis and progression is very complicated. microRNA-302b (miR-302b) could regulate various characteristics of many tumor cells, such as proliferation and apoptosis, but its role and mechanism in OSCC have not been reported. This research aims to study the effect of miR-302b on the invasion and migration ability of OSCC and the mechanism by which it functions as well as to identify new prognostic indicators and therapeutic targets for OSCC patients. Functional studies showed that the miR-302b level was negatively correlated with the invasion and migration ability of OSCC. The studies also showed that the overexpression of miR-302b could attenuate the invasion and migration ability of OSCC cells and reduce lymphangiogenesis and the lung metastasis rate of OSCC cells in a mouse model. Mechanistic studies were performed by quantitative polymerase chain reactions, luciferase assays, and RNA pull-down experiments. The results verified that frizzled class receptor 6 (FZD6) is a target gene of miR-302b in OSCC that could promote cell invasion and migration. Clinical studies demonstrate that the protein expression level of FZD6 was higher in OSCC and metastatic lymph nodes than in normal oral mucosa epithelium. Taken together, these data showed that miR-302b could inhibit the invasion and migration ability of OSCC cells by targeting and downregulating FZD6, thereby inhibiting OSCC metastasis. As a new target gene of miR-302b, FZD6 has the potential to become a prognostic and therapeutic target for OSCC patients.
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Receptores Frizzled/genética , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , MicroRNAs/genética , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
OBJECTIVE: This study was designed to investigate the expression of syndecan-1 (Sdc-1), protein kinase C (PKC) and vascular endothelial growth factor (VEGF) in rats with acute kidney injury, as well as the association between Sdc-1 and indicators [such as serum creatinine (Scr) and blood urea nitrogen (BUN)] related to renal function. MATERIALS AND METHODS: A total of 120 clean grade 2-week-old SD rats were selected and randomized into experimental group and control group (n=60). At 12 h (T1), 24 h (T2), 36 h (T3), 48 h (T4) after the model was established, 3 mL blood from abdominal aorta was taken, and Sdc-1, PKC, VEGF, serum creatinine (Scr), urea nitrogen (BUN) and other indicators were detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The expression levels of Sdc-1, PKC and VEGF in the experimental group were increasing from T1 to T4, with statistically significant difference between every two time points (p<0.05); the expression levels of Scr and BUN in the experimental group was increasing from T1 to T4, with statistically significant difference between every two time points (p<0.05). The level of Sdc-1 in the serum of rats in the experimental group was positively correlated with Scr (r=0.668, p<0.001), negatively correlated with BUN (r=0.722, p<0.001), and positively correlated with BUN (r=0.722, p<0.001); PKC level was positively correlated with Scr (r=0.589, p<0.001), BUN (r=0.788, p<0.001), and VEGF level was positively correlated with Scr (r=0.666, p<0.001), BUN (r=0.784, p<0.001). CONCLUSIONS: As the concentration of syndecan-1 increases gradually, renal dysfunction aggravates accordingly, so syndecan-1 can be used as a marker of acute kidney injury and can be used to judge the degree of kidney injury at an early stage.
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Injúria Renal Aguda/metabolismo , Rim/metabolismo , Proteína Quinase C/biossíntese , Sindecana-1/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Injúria Renal Aguda/patologia , Animais , Modelos Animais de Doenças , Rim/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Objective: To establish the mice colorectal cancer (CRC) model induced by AOM/DSS with the intervention of high fat diet and probiotics, and to explore the potential mechanism of probiotics intervention in regulating intestinal flora disturbance and antitumor efficiency. Methods: Forty 8-week-old male C57BL/6J mice were randomly divided into 4 groups with 10 mice in each group: HFD group, HDF with probiotics intervention (HFD+P) group, normal diet (ND) group, normal diet with probiotics intervention (ND+P) group. The probiotic groups were administered with probiotics preparation by gavage. During the experiment, AOM/DSS was used to induce mouse colorectal cancer model. The mouse body weight was regularly recorded and the body status was evaluated weekly. High-throughput 16S rDNA sequencing was used to analyze the changes of fecal flora in bacterial structure before and after cancer induction. At the end of the experiment, intestinal tissues of mice were collected and the epididymis adipose mass (EAM) and tumor burden were recorded. The Alpha diversity index was used to analyze the abundance and diversity of the intestinal flora (higher chaol index means higher abundance of bacteria and greater Simpson index means lower diversity in flora structure). The Beta diversity index was used to analyze the significance of the difference in the distribution of intestinal flora among the four groups (When R>0, the difference in the distribution of bacteria among the groups is greater than the difference within the group). Results: After 15 weeks of experiment, the body weight of mice in HFD group, HFD+P group, ND group and ND+P group was (33.70±0.52) g, (28.70±0.32) g, (25.90±0.34) g and (25.60±0.40) g, whose difference was statistically significant (F=700.89, P<0.01). The body weight of HFD group was higher than that of ND group and HFD+P group while the body weight of HFD+P group was still higher than that of ND group, and the differences were statistically significant (all P<0.017). The average EAM of HFD group, HFD+P group, ND group and ND+P group was (1.36±0.15) g, (0.67±0.08) g, (0.58±0.10) g and (0.54±0.05) g, whose difference was statistically significant (F=114.03, P<0.01). Pairwise comparisons showed that EAM in HFD group was higher than that in ND group and HFD+P group respectively, with statistically significant difference (both P<0.01), while average EAM of HFD+P group was similar to ND group (P=0.09). Under the diet intervention, the Chao1 index of HFD group, HFD+P group, ND group and ND+P group was 217.62, 235.32, 301.51 and 305.71 respectively, and the Simpson index was 0.93, 0.89, 0.91 and 0.90. At the same time, the Anosim analysis of Beta diversity analysis showed that the difference in the flora distribution among four groups was greater than the difference with in each group with statistically significant difference (R=0.655, P=0.001). Species abundance analysis revealed that, compared with ND group, at phylum level, HFD group had a higher proportion of Bacteroides phylum and Firmicutes phylum in the intestinal flora and lower proportion of Verrucomicrobia; at genus level, the proportion of Bacteroides and Oscillibacter in HFD group was higher while the proportion of Akkermansia and Alloprevotella was lower. After the intervention of probiotics, the flora mentioned above was improved significantly except for Alloprevotella. The average number of tumor in HFD group, HFD+P group, ND group and ND+P group was 4.63±1.19, 2.33±0.52, 2.56±0.73 and 2.38±0.52 with statistically significant difference (F=14.92, P<0.01). Conclusion: Probiotics therapy can reduce obesity and flora imbalance caused by HFD and reduce the incidence of CRC by regulating intestinal flora disturbance.
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Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/terapia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Probióticos/uso terapêutico , Animais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This abstract has been retracted at the request of the authors. After submitting this abstract the authors realized that the core concept, the encoder-decoder design, was also being used by other investigators at their institution for similar radiation therapy applications. As a result the abstract had not been discussed with, nor approved by, all the relevant investigators before submission. International Journal of Radiation Oncology, Biology, Physics, 108, (2020) S128-S128, https://doi.org/10.1016/j.ijrobp.2020.07.854.
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Curcumin is a polyphenol derived from curcumin longa that exhibits anticancer and anti-inflammatory properties. The consumption of foods at supernutritional levels to obtain health benefits may paradoxically result in negative health outcomes. In the present study, multiple targeting characteristics of curcumin were analyzed using our gene expression screening system, which utilized the gene expression signatures of curcumin from human hepatocellular carcinoma and colorectal cancer cells to query gene expression databases and effectively identify the molecular actions of curcumin. In agreement with prediction, curcumin inhibited NF-κB and Aurora-A, and induced G2/M arrest and apoptosis. Curcumin-suppressed NF-κB was identified through inhibition of PLCG1, PIK3R1, and MALT1 in the CD4-T-cell-receptor-signaling NF-κB cascade pathway. The results suggest that our novel gene expression screening platform is an effective method of rapidly identifying unknown biological functions and side effects of compounds with potential nutraceutical benefits.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Curcumina/farmacologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Transcriptoma/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Bases de Dados Genéticas , Células HT29 , Células Hep G2 , Humanos , Mediadores da Inflamação/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Objective: To summarize the clinical features and gene variation characteristics of a child with Okur-Chung syndrome caused by CSNK2A1 gene variation. Methods: The medical records of one patient who was diagnosed with Okur-Chung syndrome in Department of Pediatrics, Xiangya Hospital of Central South University in July 2018 were analyzed. Using "CSNK2A1" gene as the keyword, relevant information about CSNK2A1 gene was searched at CNKI, Wangfang Data, OMIM, PubMed, ClinVar, Decipher (until August 2018). The characteristics of CSNK2A1 gene variation and the clinical phenotype of children with Okur-Chung syndrome were summarized. Results: The boy, 1 year and 8 months old, was sent to hospital at the age of 1 year and 6 months because of delayed growth for more than 1 year. He was susceptible to cough while eating or drinking. He was also suffering from constipation and poor sleep. Physical examination showed that his body weight was 10.2 kg, microcephalus, broad nasal bridge, micrognathia and hypotonia were observed. Whole exome-sequencing test identified a de novo heterozygous variation c.524A>G (p.D175G) in CSNK2A1 gene. This was the first case report of CSNK2A1 gene variation in the mainland of China. So far, a total of 52 cases were reported worldwide (52 single nucleotide variants), including 35 cases in 7 articles, 9 cases in Decipher database and 14 cases in ClinVar database, 6 of which were also reported in PubMed. In previously reported 52 cases, there were 48 missense variants, whereas, splice and frameshift variations were found in 3 cases and 1 case, respectively. Among the variation sites, p.K198R was the most common sites (12 cases), followed by p.R47 (6 cases), p.R80H (4 cases) and p.S51 (4 cases). Among these 52 cases, only 27 cases have been elaborately described in other studies, so the clinical characteristics were summarized in 28 cases eventually (including 27 cases in the articles and this patient), 27 of whom presented severe intellectual disability or global development delay, 1 case with mild language development delay, and 19 had hypotonia; 8 had autism spectrum disorders, 5 had attention deficit hyperactivity disorder, and 9 had sleep problems. 20 had dysmorphic facial features, 10 of them had microcephalus. 16 had failure to thrive or short stature, 12 had gastrointestinal or oromotor problem, 5 had immunological problem, and 4 had skin abnormalities. Conclusions: The main clinical feature of patients with CSNK2A1 gene variations is intellectual disability with multiple systems involved, such as microcephalus, abnormal facial shape and hypotonia. The variation of CSNK2A1 gene is the cause of Okur-Chung syndrome. Missense variation is the main cause, and P. K198R is the hotspot variation.
Assuntos
Deficiência Intelectual , Hipotonia Muscular , Mutação/genética , Caseína Quinase II/genética , China , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Síndrome , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial. OBJECTIVES: To compare the efficacy and safety of TCI vs. TCS for OLP. METHODS: The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events. RESULTS: Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3-8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus-TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. CONCLUSIONS: The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short-term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short-term and long-term efficacy and safety of TCI compared with TCS.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Líquen Plano Bucal/tratamento farmacológico , Mucosa Bucal/efeitos dos fármacos , Administração Tópica , Inibidores de Calcineurina/efeitos adversos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Humanos , Líquen Plano Bucal/patologia , Mucosa Bucal/patologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/análogos & derivados , Resultado do TratamentoRESUMO
Since the publication of this paper, the authors have noticed that the article contains an error in Figure 3e (TSN, 50 nM). As a result of the misfiling of the data, the incorrect image was inadvertently inserted in Figure 3e during figure preparation. The corrected image is shown in this correction.