RESUMEN
To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.
Asunto(s)
Linfohistiocitosis Hemofagocítica , Linfoma , Microglobulina beta-2 , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/etiología , Microglobulina beta-2/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Pronóstico , Linfoma/sangre , Linfoma/diagnóstico , Linfoma/complicaciones , Linfoma/mortalidad , Anciano de 80 o más Años , Adulto Joven , Adolescente , Tasa de Supervivencia , Relevancia ClínicaRESUMEN
Atherosclerosis, a chronic inflammatory disease that often leads to myocardial infarction and stroke, is mainly caused by lipid accumulation. Eukaryotic initiation factor 6 (Eif6) is a rate-limiting factor in protein translation of transcription factors necessary for lipogenesis. To determine whether Eif6 affects atherosclerosis, Eif6+/- mice were crossed into Apoe-/- background. Apoe-/-/Eif6+/- mice on high fat diet showed significant reduction in atherosclerotic lesions and necrotic core content in aortic root sections in comparison with Apoe-/- mice. RNA-Seq was used to investigate the effect of Eif6 in aorta. Deficiency of Eif6 shows broad effect on cell metabolism. Expression of genes for fatty acid synthesis including Fatty acid synthase (Fasn), Elovl3, Elovl6 and Acaca are down-regulated in aortas. Importantly, Fasn is decreased in macrophages. Results suggest that Eif6 deficiency may decrease atherosclerosis through inhibition of Fasn and lipids metabolism in macrophages.
Asunto(s)
Aterosclerosis , Ratones , Animales , Ratones Noqueados para ApoE , Aterosclerosis/metabolismo , Macrófagos/metabolismo , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH. METHODS: Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin-eosin staining to determine the role of gut microbiota on AIH. RESULTS: Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner. CONCLUSION: Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH. Video Abstract.
Asunto(s)
Microbioma Gastrointestinal , Hepatitis Autoinmune , Animales , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/etiología , Humanos , Lactobacillus , Leucocitos Mononucleares , Ratones , Prednisona/farmacología , Prednisona/uso terapéutico , Células T Auxiliares FolicularesRESUMEN
In recent years, the safety problems and events of traditional Chinese medicine represented by liver injury have occurred frequently. In particular, Polygonum multiflorum has been widely used and considered as a "non-toxic" tonic traditional Chinese medicine for thousands of years. However, in recent years, frequent reports of liver injury events have attracted widespread attention at home and abroad, which has made unfavorable impacts on traditional Chinese medicine and its international development. Some scho-lars have found that susceptible genes of P. multiflorum on liver injury lay a scientific foundation for formulating rational comprehensive prevention and control measures for liver injury risk of P. multiflorum and its relevant preparations. But what are the risk signals of adverse reactions of P. multiflorum in clinical application? Spontaneous reporting system is an important way to monitor and find adverse drug reaction(ADR) signals after the drug is launched in the market. It can find the ADR signals in time and effectively, and then effectively prevent and avoid the occurrence of adverse drug events. At present, the data mining technique has gradually become the main method of ADR/adverse event(AE) report analysis and evaluation at home and abroad. Specifically, Bayesian confidence propagation neural network in Bayesian method is a commonly used risk signal early warning analysis method. In this paper, BCPNN method was used to excavate the risk signals of adverse reactions of Xinyuan Capsules, a traditional Chinese medicine preparation containing P. multiflorum, such as nausea, diarrhea, rash, dizziness, vomiting, abdominal pain, headache, liver cell damage, so as to provide evidence-based evidence for clinical safe and rational use of drugs.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Teorema de Bayes , Cápsulas , Humanos , Redes Neurales de la ComputaciónRESUMEN
PURPOSE: Excessive activation of PI3K/AKT/mTOR signaling pathway is one of the most common changes in human cancers, and single nucleotide polymorphisms (SNPs) existing in its functional region can affect the occurrence process of a variety of cancers. This study aimed to screen out the SNPs associated with susceptibility to gastric cancer in the PI3K/AKT/mT0R signaling pathway. METHODS: In this case-control study, the tagging SNPs in the promoter region5'-UTR, exon region or 3'-UTR of PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, AKT1, AKT2, AKT3 and mTOR genes were screened out. The relationship between the genetic variation of PI3K/AKT/mT0R signaling pathway genes and the susceptibility to gastric cancer in Chinese Han population was investigated by this casecontrol study. RESULTS: The results showed that the polymorphisms of the two loci, PIK3R3 rs7536272 (Additive model: OR=1.16, 95% CI=1.01-1.35) and mTOR rs2295080 (GG vs TT: OR=0.75, 95% CI=0.60-0.94; Additive model: OR=0.78, 95% CI=0.66- 0.93), were associated with the risk of gastric cancer in the studied population and there was a combined effect between the two loci (ptrend=0.005). CONCLUSIONS: In conclusion, the polymorphisms of the two loci, PIK3R3 rs7536272 and mTOR rs2295080, on the PI3K/AKT/mTOR signaling pathway genes are associated with genetic susceptibility to gastric cancer in Chinese population.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias Gástricas/genética , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Transducción de Señal , Neoplasias Gástricas/patologíaRESUMEN
In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.
Asunto(s)
Antineoplásicos/farmacología , Leucemia/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Polisacáridos/farmacología , Reishi/química , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Western Blotting , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Células HL-60 , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Leucemia/metabolismo , Leucemia/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación/efectos de los fármacos , Polisacáridos/aislamiento & purificación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Perforation of a gastric tube is a rare yet lethal complication after esophagectomy for esophageal cancer treatment. Currently, over-the-scope clip (OTSC) is an effective way to treat gastric tube perforation. Due to the lack of OTSCs, we invented an alternative method composed of a titanium clip and gastroscope. The aim of this study was to describe this novel endoscopic device in the treatment of gastric tube perforation. We used a titanium clip system to treat 4 male patients (range, 53 to 77 years with gastric tube perforation. After the location of the perforation was identified by gastroscope, a titanium endoscopic clip was used to close the perforation. Successful closure of the gastric tube perforation was achieved in three patients while in one patient this failed due to his refusal to undergo reoperation. No postoperative complication was found in the three patients whose perforations were closed and the patient who refused reoperation died due to the reoccurrence of his esophago-cardiac carcinoma. The endoscopic system composed of titanium clip and gastroscope proved to be an efficient and effective device in the treatment of the patients with gastric tube perforations.
Asunto(s)
Endoscopía/instrumentación , Perforación Intestinal/cirugía , Microcirugia/instrumentación , Titanio , Técnicas de Cierre de Heridas , Anciano , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Instrumentos QuirúrgicosRESUMEN
Autophagy is involved in the activation of hepatic stellate cells (HSCs), which is the key process of liver fibrosis. We reasoned that chloroquine, based on its ability to inhibit autophagy, might exert beneficial effects in liver fibrosis. Liver fibrosis in rats was induced by carbon tetrachloride (CCl4). Rats were divided into three groups, a normal control group (N group), model group (M group), and chloroquine group (CQ group). Liver fibrosis in the rats was evaluated by hematoxyline-eosin (H&E) and Masson staining. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) were determined using an automated biochemistry analyzer. Total hepatic hydroxyproline levels were determined with a kit. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) were detected by immunofluorescence staining, and the expressions of LC3-II and p62 were determined by Western blotting. Compared with N group, M group showed impaired liver function, liver fibrosis, increased hydroxyproline content, up-regulated expressions of α-SMA and TGF-ß1, which have been reported to be pro-fibrogenic genes in vivo, and increased autophagy flux as indicated by the accumulation of LC3-II and degradation of p62. These changes were attenuated by chloroquine treatment. Chloroquine exerts beneficial effects in CCl4-induced liver fibrosis. The mechanism of action includes inhibition of autophagy pathways and inhibition of activation of HSCs.
Asunto(s)
Cloroquina/uso terapéutico , Cirrosis Hepática Experimental/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Actinas/metabolismo , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Autofagia/efectos de los fármacos , Tetracloruro de Carbono , Cloroquina/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Hidroxiprolina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Sustancias Protectoras/farmacología , Ratas Sprague-DawleyRESUMEN
Uncertainty has been demonstrated to influence the perception of noxious stimuli, but little is known about the effects of prolonged uncertain contexts on the perception of painful and non-painful stimuli. To address this knowledge gap, the present study utilized a cue-based NPU-threat task, where uncertain and certain trials were separated into distinct blocks. The objective was to investigate the impact of uncertain contexts on the temporal dynamics of electroencephalogram (EEG) activity during the processing of painful and non-painful stimuli. The results revealed that the influence of uncertain contexts on neural responses extends beyond painful trials and is also evident in non-painful trials. In uncertain contexts, it has been observed that painful stimuli elicit larger P2 amplitudes and late beta band (13-30 Hz) event-related desynchronization (ERD) around 500-700 ms. However, in certain contexts, painful stimuli evoke stronger late gamma band (50-70 Hz) event-related synchronization (ERS) around 600-700 ms. For non-painful trials, in uncertain contexts, significantly higher amplitudes of the late positive potential (LPP) component and delta-theta band (2-7 Hz) ERS were observed compared to certain non-painful stimuli. These findings demonstrate that uncertain contexts exert a significant impact on the processing of both painful and non-painful stimuli, and this influence is mediated by distinct neural mechanisms.
Asunto(s)
Electroencefalografía , Dolor , Humanos , IncertidumbreRESUMEN
BACKGROUND/AIMS: The endoscopic features of small-bowel gastrointestinal stromal tumors (GISTs) are not well defined. The objective of this study was to describe the endoscopic features of GISTs of the small intestine detected via single-balloon enteroscopy (SBE). MATERIALS AND METHODS: Patients with surgically confirmed small intestinal GISTs from January 2014 to September 2022 were retrospectively analyzed. The hospital's electronic medical record system was used to retrieve the patients' data, including their demographics, clinical symptoms, hemoglobin on admission, endoscopic and computerized tomography findings, clinicopathological findings, and surgical management data. RESULTS: In total, 46 GIST patients (23 men and 23 women) with overt bleeding were included, with a mean age of 52 years (23-80 years). The typical duration of the symptoms was 48 hours. Four patients (8.70%) had lesions in the duodenum, 32 (69.56%) had lesions in the jejunum, 8 (17.39%) had lesions in the ileum, and 2 (4.35%) had lesions around the junction of the jejunum and ileum. Out of the 46 patients, 27 underwent SBE, and GISTs were visualized in 25, while the lesions could not be visualized in the remaining 2. Submucosal round (n = 13), submucosal sessile (n = 8), and invasive/penetrating (n = 4) were among the endoscopic tumor features. Twenty patients exhibited submucosal protuberant lesions, with ulceration, vascular nodules/congestion, or erosion on the surface, and 5 patients presented ulcerative infiltrative lesions. The multiple logistic regression analysis indicated that the invasive/penetrating characteristics of GISTs under SBE evaluation are significantly correlated with the risk level of GIST malignancy (P < .05). CONCLUSION: A variety of endoscopic characteristics could be observed during the preoperative SBE evaluation of small-intestine GISTs.
Asunto(s)
Tumores del Estroma Gastrointestinal , Intestino Delgado , Enteroscopia de Balón Individual , Humanos , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Anciano , Adulto , Anciano de 80 o más Años , Enteroscopia de Balón Individual/métodos , Intestino Delgado/patología , Intestino Delgado/diagnóstico por imagen , Adulto Joven , Hemorragia Gastrointestinal/etiología , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugía , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/cirugíaRESUMEN
OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.
Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Anciano , Fracturas Óseas/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Fijación Interna de Fracturas/métodosRESUMEN
BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.
Asunto(s)
Coenzima A Transferasas , Disfunción Cognitiva , Hipocampo , Neurogénesis , Hemorragia Subaracnoidea , Ácido 3-Hidroxibutírico , beta Catenina , Coenzima A Transferasas/genética , Coenzima A Transferasas/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/crecimiento & desarrollo , Proteínas Proto-Oncogénicas c-akt , Animales , RatonesRESUMEN
Heterogeneity of CD20 expression exists in chronic lymphocytic leukemia (CLL), therefore, we explored the prognostic significance of CD20 expression in Chinese patients with CLL. Multiparameter flow cytometry was used to detect the expression of CD20 in CD5(+) CD19(+) cells. In 172 CLL patients, the median expression percent of CD20 was 97.82% (range, 0-100), and the median mean fluorescence intensity (MFI) of CD20 in CLL cells was 731.45 (range, 0.00-9071.90). The percentage of CD20(+) cells in the patient group with mutated variable region of immunoglobulin genes (IGHV) was higher than in the non-mutant IGHV group (mean, 92.1% vs 80.4%, P < 0.001). There were no differences in the MFI of CD20(+) cells in all prognostic factor groups. Representation of the data using a receiver operating characteristic plot reflected separation between the two IGHV groups, with an area under the curve of 0.661 (95% confidence interval, 0.569-0.753). At the cut-off value of 60.3% for percentage of CD20, the sensitivity and specificity were 90.00% and 38.46%, respectively. Patients whose percentage of CD20 antigen was above 60.3% had longer treatment-free survival (hazard ratio, 0.452; 95% confidence interval, 0.232-0.884, P = 0.020). Percentage and MFI of CD20 were the variables not associated with treatment-free survival by multivariate Cox regression analysis (P < 0.05). High level of CD20 expression in de novo CLL appears to be associated with a good prognosis.
Asunto(s)
Antígenos CD20/biosíntesis , Biomarcadores de Tumor/biosíntesis , Leucemia Linfocítica Crónica de Células B/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/genética , Antígenos CD20/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROCRESUMEN
The Nightmare Disorder Index Questionnaire (NDI) was developed to measure the impact of nightmares. The purpose of this study was to investigate the psychometric properties of NDI among Chinese adolescents. This study investigated the validity and internal consistency of the Nightmare Disorder Index Chinese (NDI-CV) among 6014 Chinese adolescents who completed the NDI-CV, Nightmare Distress Questionnaire-Chinese Version (NDQ-CV), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Chinese Adolescent Daytime Sleepiness Scale (CADSS), Generalized Anxiety Disorder-7 Questionnaire (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). In addition, we investigated the test-retest reliability of the NDI-CV among 423 adolescents who completed a retest of the NDI-CV after a 2-week interval. Finally, NDI-CV demonstrated good psychometric properties in a sample of Chinese adolescents (Cronbach's α coefficient of 0.876), and the 95% confidence interval for the 2-week retest correlation coefficient was 0.675-0.977 (p < 0.001).
Asunto(s)
Sueños , Psicometría , Adolescente , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Pueblos del Este de AsiaRESUMEN
The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.
Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Receptor X de Pregnano/genética , Sorafenib/farmacología , Sorafenib/uso terapéutico , Factores de Transcripción/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Citocromo P-450 CYP3A/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Ciclo Celular/genéticaRESUMEN
BACKGROUND: Ketones are not only utilized to produce energy but also play a neuroprotective role in many neurodegenerative diseases. However, whether this process has an impact on secondary brain damage after traumatic brain injury (TBI) remains unknown. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme in the intra-neuronal utilization of ketones. In this study, we investigated whether reduced expression of OXCT1 after TBI could impact neuroprotective mechanisms and exacerbate neurological dysfunction. MATERIALS AND METHODS: Experimental TBI was induced by a modified version of the weight drop model, it is a model of severe head trauma. Expression of OXCT1 in the injured hippocampus of mice was measured at different time points using immunoblotting assays. The release of abnormal mitochondrial cytochrome c from neurons of the mouse injured lateral hippocampus was measured 1 week after TBI using immunoblotting assays. Neuronal death was assessed by Nissl staining and the level of reactive oxygen species (ROS) within the neurons of the injured lateral hippocampus was assessed by Dihydroethidium staining. RESULTS: OXCT1 was overexpressed in hippocampal neurons by injection of adeno-associated virus into the lateral ventricle. OXCT1 expression levels decreased significantly 1 week post-TBI. After comparing the data obtained from different groups of mice, OXCT1 was found to significantly increase the expression of SIRT3 and reduce the proportion of acetylated SOD2, thus decreasing the production of ROS in the injured hippocampal neurons, reducing neuronal death, and improving cognitive function. CONCLUSIONS: OXCT1 has a critical previously unappreciated protective role in neurological impairment following TBI via the SIR3-SOD2 pathway. These findings highlight the potential of OXCT1 as a simple treatment for patients with TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Fármacos Neuroprotectores , Sirtuina 3 , Animales , Ratones , Lesiones Encefálicas/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Cetonas , Fármacos Neuroprotectores/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Introduction: Endothelial nitric oxide synthase (eNOS) uncoupling plays a significant role in acute vasoconstriction during early brain injury (EBI) after subarachnoid hemorrhage (SAH). Astrocytes in the neurovascular unit extend their foot processes around endothelia. In our study, we tested the hypothesis that increased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression in astrocytes after SAH leads to eNOS uncoupling. Methods: We utilized laser speckle contrast imaging for monitoring cortical blood flow changes in mice, nitric oxide (NO) kits to measure the level of NO, and a co-culture system to study the effect of astrocytes on endothelial cells. Moreover, the protein levels were assessed by Western blot and immunofluorescence staining. We used CCK-8 to measure the viability of astrocytes and endothelial cells, and we used the H2O2 kit to measure the H2O2 released from astrocytes. We used GSK2795039 as an inhibitor of NOX2, whereas lentivirus and adeno-associated virus were used for dihydrofolate reductase (DHFR) knockdown in vivo and in vitro. Results: The expression of NOX2 and the release of H2O2 in astrocytes are increased, which was accompanied by a decrease in endothelial DHFR 12 h after SAH. Moreover, the eNOS monomer/dimer ratio increased, leading to a decrease in NO and acute cerebral ischemia. All of the above were significantly alleviated after the administration of GSK2795039. However, after knocking down DHFR both in vivo and in vitro, the protective effect of GSK2795039 was greatly reversed. Discussion: The increased level of NOX2 in astrocytes contributes to decreased DHFR in endothelial cells, thus aggravating eNOS uncoupling, which is an essential mechanism underlying acute vasoconstriction after SAH.
RESUMEN
OBJECTIVE: To investigate the efficacy of posterior axillary approach internal fixation for Ideberg â a andâ ¡ glenoid fractures. METHODS: From December 2018 to September 2021, 9 patients with lower part of glenoid fractures were treated by posterior axillary approach, including 3 males and 6 females, aged from 50 to 78 years old. All the fractures were closed fractures. According to Ideberg type of scapular glenoid fracture was type â a in 6 cases and type â ¡ in 3 cases. AP and lateral X-ray films of scapula were taken at 6, 12 weeks and 6 and 12 months postoperatively. Constant-Murley and disabilities of the arm shoulder and hand (DASH), and other complications were recorded at the latest follow-up. RESULTS: Nine patients were followed up, ranged from 6 to 15 months. And bone healing was achieved in all 9 patients at the final follow-up, the healing time 3 to 6 months, Constant-Murley score at the final follow-up ranged from 55 to 96, and DASH score ranged from 3.33 to 33.33. Both of them were better than preoperative. CONCLUSION: The posterior axillary approach internal fixation for Ideberg â a and Ideberg â ¡ Glenoid fractures scapular fracture is satisfactory and worthy of clinical application.
Asunto(s)
Fracturas Óseas , Fracturas Cerradas , Fracturas del Hombro , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fijación Interna de Fracturas , Hombro/cirugía , Escápula/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA). Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h. Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.
RESUMEN
A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. The MDM2 SNP309 genotypes in 173 CLL patients and 260 healthy controls were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, which was confirmed by direct DNA sequencing. Compared with the T/T genotype, the SNP309 G/G genotype instead of T/G heterozygote was associated with a significantly increased risk of CLL (OR = 2.84; 95% CI 1.61-5.03; p < 0.001). Age at onset of CLL was similar irrespective of MDM2 status. MDM2 mRNA expression within CLL of G/G genotype was significantly higher than that in T/G (p = 0.009) and T/T genotypes (p < 0.001). Excluding patients with p53 deletions or mutations enhanced the significance of the findings (G/G vs. T/T, p < 0.001; G/G vs. T/G p = 0.001), which prompted us to study the role of the polymorphism in p53 wild-type individuals. In the p53 wild-type groups, survival analysis showed that the patients with MDM2 SNP309 G/G and T/G genotypes both had significantly shorter treatment-free survival (TFS) than SNP309 T/T genotype. Notably, univariate and multivariate analyses showed that MDM2 SNP309 genotypes were associated with TFS. These data show that MDM2 309G polymorphisms contribute to the risk of developing CLL. The unfavorable MDM2 SNP309 G/G genotype was associated with an increase of MDM2 mRNA expression. MDM2 SNP309 was found to be associated with TFS in p53 wild-type Chinese CLL populations.