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BACKGROUND: Radiomics may provide more objective and accurate predictions for extrahepatic cholangiocarcinoma (ECC). In this study, we developed radiomics models based on magnetic resonance imaging (MRI) and machine learning to preoperatively predict differentiation degree (DD) and lymph node metastasis (LNM) of ECC. METHODS: A group of 100 patients diagnosed with ECC was included. The ECC status of all patients was confirmed by pathology. A total of 1200 radiomics features were extracted from axial T1 weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and apparent diffusion coefficient (ADC) images. A systematical framework considering combinations of five feature selection methods and ten machine learning classification algorithms (classifiers) was developed and investigated. The predictive capabilities for DD and LNM were evaluated in terms of area under precision recall curve (AUPRC), area under the receiver operating characteristic (ROC) curve (AUC), negative predictive value (NPV), accuracy (ACC), sensitivity, and specificity. The prediction performance among models was statistically compared using DeLong test. RESULTS: For DD prediction, the feature selection method joint mutual information (JMI) and Bagging Classifier achieved the best performance (AUPRC = 0.65, AUC = 0.90 (95% CI 0.75-1.00), ACC = 0.85 (95% CI 0.69-1.00), sensitivity = 0.75 (95% CI 0.30-0.95), and specificity = 0.88 (95% CI 0.64-0.97)), and the radiomics signature was composed of 5 selected features. For LNM prediction, the feature selection method minimum redundancy maximum relevance and classifier eXtreme Gradient Boosting achieved the best performance (AUPRC = 0.95, AUC = 0.98 (95% CI 0.94-1.00), ACC = 0.90 (95% CI 0.77-1.00), sensitivity = 0.75 (95% CI 0.30-0.95), and specificity = 0.94 (95% CI 0.72-0.99)), and the radiomics signature was composed of 30 selected features. However, these two chosen models were not significantly different to other models of higher AUC values in DeLong test, though they were significantly different to most of all models. CONCLUSION: MRI radiomics analysis based on machine learning demonstrated good predictive accuracies for DD and LNM of ECC. This shed new light on the noninvasive diagnosis of ECC.
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Adenocarcinoma/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Área Bajo la Curva , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Colangiocarcinoma/secundario , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
As a modern dosage form drug with rapid effect, traditional Chinese medicine (TCM) injection has been more and more used in clinical practice. Meanwhile the safety of TCM injection has attracted more and more attention. The retrospective analysis on 74 cases of adverse reaction of TCM injections collected from 2007 to 2016 in the Third Affiliated Hospital of Beijing University of Chinese Medicine showed that the proportion of men and women with adverse reactions was 0.54:1; the average age was 62.5 years old; 21 kinds of TCM injections were involved. Among them, the most reported were blood-regulating agents. The top four kinds of TCM injections with highest adverse drug reactions (ADRs) were Tanreqing injection, Danhong Injection, Shuxuening Injection and Xuesaitong for injection. The top three clinical manifestations of adverse reactions were lesions of skin and its appendages, damage of circulatory system and damage of nervous system. The potential causes of the adverse reactions of TCM injections were analyzed, and it was believed that individual difference, medicine, pharmaceutical excipients, solvent and TCM syndrome differentiation may be the main five causes for the adverse reactions of TCM injections. In order to reduce the adverse reactions of TCM injections, it is suggested that the clinical pharmacists should participate in the application management of TCM injections in the hospital; the production enterprises shall strengthen the whole life cycle management of the drugs; and at the same time, the drug control and administration authorities should improve the drug management methods constantly and encourage the development of TCM injections to the high quality level.
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Medicamentos Herbarios Chinos/efectos adversos , Medicina Tradicional China/efectos adversos , Femenino , Humanos , Inyecciones/efectos adversos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism. Mutation c.1180delG was demonstrated to be de novo mutation. 26.3 % (5/19) patients carried the deletion c.1415_16delAG, which may be the mutational hot spot in South China population. In addition, 73.7 % (14/19) patients were type of childhood cerebral adrenoleukodystrophy, 26.3 %(5/19) were in Addison only. Half of the childhood cerebral adrenoleukodystrophy patients had the adrenocortical insufficiency preceded the onset of neurological symptoms. Furthermore, 5 of 19 cases underwent hematopoietic stem cell transplantation. Our data showed that hematopoietic stem cell transplantation performed at an advanced stage of the cerebral X- linked adrenoleukodystrophy would accelerate the progression of the disease. Good clinical outcome achieved when hematopoietic stem cell transplantation performed at the very early stage of the disease.
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Transportadoras de Casetes de Unión a ATP/genética , Adrenoleucodistrofia , Pueblo Asiatico/genética , Encéfalo/patología , Trasplante de Células Madre Hematopoyéticas , Mutación , Neuroimagen , Miembro 1 de la Subfamilia D de Transportador de Casetes de Unión al ATP , Insuficiencia Suprarrenal/etiología , Insuficiencia Suprarrenal/genética , Hormona Adrenocorticotrópica/sangre , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/patología , Adrenoleucodistrofia/terapia , Adulto , Preescolar , China , Progresión de la Enfermedad , Ácidos Grasos/metabolismo , Femenino , Eliminación de Gen , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/genética , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.
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Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 µg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).
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Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.
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OBJECTIVE: Glycogen storage disease type Ib (GSDIb) is caused by a deficiency of glucose-6-phosphate translocase (G6PT) activity due to SLC37A4 gene mutations. Most GSDIb patients have recurrent infections and inflammatory bowel disease, with poor prognosis. Detection of SLC37A4 gene mutations is of great significance for the diagnosis, subtyping and outcome prediction of GSD patients. This study aims to analyze SLC37A4 gene mutations in Chinese GSDIb patients and to investigate the relationship between its genotypes and clinical manifestations. METHODS: All exons and their flanking introns of SLC37A4 gene in 28 Chinese children with a primary diagnosis of GSDIb were screened by PCR combined with direct DNA sequencing to detect SLC37A4 gene mutations. RESULTS: Five SLC37A4 gene mutations were detected in 7 (25%) of the 28 children, i.e., p.Gly149Glu (9/13, 69%), p.Gly115Arg (1/13, 8%), p.Pro191Leu (1/13, 8%), c.959-960 insT (1/13, 8%) and c.870+5G>A (1/13, 8%). CONCLUSIONS: In this study, c.959-960 insT is a novel mutation and p.Gly149Glu is the most common mutation. p.Gly149Glu may be associated with severe infections in children with GSDIb.
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Antiportadores/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Proteínas de Transporte de Monosacáridos/genética , Mutación , Preescolar , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Humanos , Lactante , Masculino , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To explore the expression of Exosome Component 4ï¼EXOSC4ï¼ in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.
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Complejo Multienzimático de Ribonucleasas del Exosoma , Linfoma de Células B Grandes Difuso , Humanos , Relevancia Clínica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Pronóstico , Estudios Retrospectivos , Complejo Multienzimático de Ribonucleasas del Exosoma/genéticaRESUMEN
OBJECTIVE: To explore the incidence of various types of mucopolysaccharidosis (MPS) and their clinical characteristics. METHODS: A total of 75 children highly suspected as having MPS underwent quantitative and electrophoretic analysis of urinary glycosaminoglycans (GAGs) and enzymatic analysis of seven types of MPS from January 2009 to December 2011. Fluorescence assay was used to measure the activities of α-L-iduronidase, iduronate-2-sulfatase, α-N-acetylglucosaminidase, galactosamine-6-sulfatase, ß-galactosidase, arylsulfatase B and ß-glucuronidase in the white blood cells. RESULTS: A total of 52 cases were confirmed with MPS based on clinical, radiological, and enzymatic examinations. The 52 cases, with a mean age of 4.0 ± 2.2 years, included 5 cases of MPS I (10%), 20 cases of MPS II (38%), 20 cases of MPS IVA (38%), 6 cases of MPS VI (12%) and 1 case of MPS VII (2%). No MPS IV B cases or MPS IIIB cases were found. Compared with healthy children of the same age, the GAG/Cr ratio was significantly elevated in 50 confirmed cases of MPS (two MPS IVA cases having no increased ratio). All children with increased urinary GAGs had a confirmed diagnosis of MPS. The age of onset was between 1 and 2 years after birth in most cases, and often complicated by hernia and valvular heart disease. Children with MPS I, MPS II, and MPS VI presented with ugly and unsmooth face, short stature, joint stiffness, and limitation of motion, while children with MPS IVA presented with short stature, skeletal dysplasia, and joint laxity. CONCLUSIONS: Type IVA and type II are the most common in MPS cases, followed by type VI and type I. MPS children are characterized by special appearances including ugly and unsmooth facial appearance, short stature and skeletal dysplasia. Quantitative analysis of urinary GAG, as a simple, rapid, and reliable method, is recommended for screening of MPS.
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Mucopolisacaridosis/diagnóstico , Acetilglucosaminidasa/sangre , Niño , Preescolar , Creatinina/orina , Femenino , Glucuronidasa/sangre , Glicosaminoglicanos/orina , Humanos , Iduronidasa/sangre , Lactante , Imagen por Resonancia Magnética , Masculino , Mucopolisacaridosis/enzimología , Mucopolisacaridosis/patología , beta-Galactosidasa/sangreRESUMEN
OBJECTIVE: To investigate the release of exosome (Exo) from leukocyte-depleted red cell suspension (LDRCS) at different storage time and its regulation on proliferation of hematological tumor cells and possible mechanism. METHODS: The Exo (RBC-Exo) in LDRCS at different storage time was obtained by ultracentrifugation, and the morphology and immunological marker of RBC-Exo were detected by transmission electron microscopy and Western blot, respectively. The particle size distribution of RBC-Exo in LDRCS at different storage time was detected by Dynamic Light Scattering. CCK-8 assay was used to explore the effect of RBC-Exo on hematological tumor cell proliferation. Western blot was used to detect the expression of proliferation-related proteins in hematological tumor cells after co-culture with RBC-Exo. RESULTS: RBC-Exo was isolated, which was characterized by cup-like shape, particle size distribution ranged from 20 to 200 nm, CD63/TSG101 enriched, Calnexin negative, CD235a positive and CD41 negative. The particle size distribution of RBC-Exo from LDRCS between middle was not significantly different and late stored stage. But the particle size distribution of RBC-Exo at middle-late stored stage(>14 d) was larger than that at early stored stage (≤14 days). Compared with the control group, RBC-Exo could significantly promote the proliferation of HBL1, U2932 and Jurkat cells. Compared with the control group, the cycle-related protein P21 was significantly down-regulated in HBL1, U2932 and Jurkat cells after co-culture with RBC-Exo for 3 days, while the anti-apoptotic protein BCL-2 was not changed significantly. CONCLUSION: The morphology of RBC-Exo from LDRCS at middle-late stored stage was different from that at early stored stage. RBC-Exo could promote the proliferation of hematological tumor cells, possibly by regulating the expression of cycle-associated protein P21.
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Exosomas , Neoplasias Hematológicas , Proliferación Celular , Eritrocitos , Exosomas/metabolismo , Neoplasias Hematológicas/metabolismo , Humanos , LeucocitosRESUMEN
The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.
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Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/inervación , Proteínas de Transferencia de Fosfolípidos/metabolismo , Sistema Nervioso Simpático/fisiología , Termogénesis , Proteína Desacopladora 1/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Animales , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Metabolismo Energético , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Oxidación-Reducción , Proteínas de Transferencia de Fosfolípidos/deficiencia , Proteínas de Transferencia de Fosfolípidos/genética , Fosforilación , Transducción de Señal , Proteína Desacopladora 1/deficiencia , Proteína Desacopladora 1/genéticaRESUMEN
The asymmetric domino Michael-S(N)2 reaction of various 1,3-dicarbonyl compounds to α-bromonitroalkenes is described for the first time, employing readily available cinchona-derived bifunctional thioureas as organocatalysts. The novel transformations were highly regio-, chemo-, diastereo-, and enantioselective, which simultaneously gave the chiral tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and tetrasubstituted 2,3-dihydrofurans with two vicinal chiral carbon centers.
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Efficient kinetic resolution of racemic 3-nitro-2H-chromenes by bifunctional thiourea afforded optically active (R)-3-nitro-2H-chromene derivatives with moderate to good enantioselectivities, which simultaneously gave the multifunctional 3,4-diphenyl-3a-nitrobenzopyrano-[3,4-c]-pyrrolidine-1,1-dicarboxylate derivatives with four vicinal chiral carbon centers.
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Benzopiranos/química , Tiourea/química , Benzopiranos/síntesis química , Catálisis , Cristalografía por Rayos X , Cinética , Modelos Moleculares , Estructura Molecular , Estereoisomerismo , Tiourea/análogos & derivadosRESUMEN
OBJECTIVE: To investigate the expression of ribonucleotide reductase M2 (RRM2) in patients with multiple myeloma and its mechanism of inhibiting human multiple myeloma cell proliferation. METHODS: Thirty-Six patients with multiple myeloma in our hospital from July 2016 to September 2018 were selected as MM group, at the same time simple iron deficiency anemia patients were taken as the control group. RT-qPCR and Western blot techniques were used to determine the mRNA and protein expression of RRM2 in bone marrow mononuclear cells, respectively. siRNAs oligos targeting RRM2 was transfected into RPMI8226 cells to establish the RRM2 silence model. CCK-8 and flow cytometry were used to analyze the cell proliferation and the cell cycle, and Western blot was used to detect the expression of cell cycle related proteins. RESULTS: The expression level of RRM2 mRNA and the expression level of RRM2 protein in multiple myeloma group were significantly higher than those in control group (Pï¼0.05). Further analysis indicated that the level of RRM2 expression closely correlated with ISS staging, bone destruction and extramedullary infiltration (Pï¼0.05). Transfection with siRNAs targeting RRM2 could significantly down regulate the RRM2 expression. And the RRM2 down regulation inhibited the cell proliferation and arrested the cell cycle at S stage (Pï¼0.05). Further study indicated that RRM2 silencing influenced cell cycle-related proteins expression. CONCLUSION: RRM2 overexpressies in bone marrow mononuclear cells of MM patients, moreover significantly relates with the degree of malignancy. The silencing RRM2 in multiple myeloma cells can inhibit cell proliferation through arresting cell cycle at S phase. RRM2 may be a marker to predict the prognosis of patients with multiple myeloma and novel target for new drug development.
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Mieloma Múltiple , Línea Celular Tumoral , Proliferación Celular , Humanos , Ribonucleósido Difosfato ReductasaRESUMEN
To determine the cortical mechanism that underlies the cognitive impairment and motor disability in hereditary spastic paraplegia (HSP), nine HSP patients from a Chinese family were examined using clinical evaluation, cognitive screening, and genetic testing. Controls were matched healthy subjects. White-matter fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD; tract-based spatial statistics), cortical thickness (FreeSurfer), and subcortical gray matter (FIRST) based on T1-weighted MRI and diffusion tensor imaging were analyzed. A novel mutation in the SPAST gene (NM_014946.3, c.1321+2T>C) was detected. Patients had motor disability and low Montreal Cognitive Assessment (MoCA) scores. Patients showed significantly decreased total gray- and white-matter volumes, corpus callosum volume, cortical thickness, and subcortical gray-matter volume as well as significantly lower FA and AD values and significantly higher MD and RD values in the corpus callosum and corticospinal tract. Cortical thickness, subcortical gray-matter volume, and MoCA score were negatively correlated with disease duration. Cortical thickness in the right inferior frontal cortex was negatively correlated with Spastic Paraplegia Rating Scale score. Cortical thickness and right hippocampus volume were positively correlated with the MoCA score and subscores. In conclusion, brain damage is not restricted to the white matter in SPG4-HSP patients, and widespread gray-matter damage may account for the disease progression, cognitive impairment, and disease severity in SPG4-HSP.
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BACKGROUND: Hyperphosphatemia is a common complication of late-stage chronic kidney disease (CKD). Nicotinamide (NAM) has been reported as an adjunctive therapy for hyperphosphatasemia, but the effect of NAM on fibroblast growth factor 23 (FGF23) and Klotho has rarely been reported. METHODS: We randomly assigned 98 patients who underwent regular hemodialysis to received NAM (0.5-1.5 g per day, or 1-3 tablets per day) or placebo (1-3 tablets per day) as an add-on therapy of calcium-based phosphorus binders in a 1:1 ratio. All enrollments were followed-up for 52 weeks. We investigated the serum phosphorus as the primary outcome and serum FGF23 and Klotho as the secondary outcomes. Abdominal aortic calcification (AAC), which had a good correlation with coronary calcification was also compared between the two groups. RESULTS: In total, 37 patients in the placebo group and 35 patients in the NAM group completed the 52-week follow-up. Compared with the placebo group, the NAM group showed a significant decrease of serum phosphorus at the 8th, 12th, 20th, 44th, and 52nd week. There was a declining trend of FGF23 and Klotho in both the placebo and NAM groups. Linear mixed models (LMMs) for overall comparisons by repeated measures of analysis of variance (ANOVA) revealed a significant decrease of FGF23 and slower declining rate of Klotho in the NAM group. No significant difference of AAC was detected between the two groups (P=0.805). CONCLUSIONS: NAM can not only further decrease the phosphorus level but also reduce the FGF23 level and slow down the descending rate of Klotho in chronic hemodialysis patients.
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Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease and associated with a wide spectrum of hepatic disorders ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). NASH is projected to become the most common indication for liver transplantation, and the annual incidence rate of NASH-related HCC is 5.29 cases per 1000 person-years. Owing to the epidemics of NAFLD and the unclear mechanism of NAFLD progression, it is important to elucidate the underlying NAFLD mechanisms in detail. NASH is mainly caused by the development of NAFL Therefore, it is also of great significance to understand the mechanism of progression from NAFL to NASH. Gene expression chip data for NAFLD and NASH were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between NAFLD and normal controls (called DEGs for NAFLD), as well as between NASH and normal tissue (called DEGs for NASH-Normal), and between NASH and NAFL tissue (called DEGs for NASH-NAFL). For DEGs for the NAFLD group, key genes were identified by studying the form of intersection. Potential functions of DEGs for NASH were then analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction network (PPI) was constructed using the STRING database. A total of 249 DEGs and one key gene for NAFLD were identified. For NASH-Normal, 514 DEGs and 11 hub genes were identified, three of which were closely related to the survival analysis of HCC, and potentially closely related to progression from NASH to HCC. One key gene for NASH-NAFL (AKR1B10) was identified. These genes appear to mediate the molecular mechanism underlying NAFLD and may be promising biomarkers for the presence of NASH.
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Aldo-Ceto Reductasas/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Aldo-Ceto Reductasas/metabolismo , Biomarcadores/metabolismo , Carcinoma Hepatocelular/genética , Biología Computacional , Conjuntos de Datos como Asunto , Diagnóstico Diferencial , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Mapas de Interacción de Proteínas/genéticaRESUMEN
Cervical cancer is the second most common gynecological malignancy, and it remains a leading cause of tumor-related death among female in the world. Long non-coding RNAs (lncRNAs) have been indicated to play essential roles in tumorigenesis, and the lncRNA colorectal neoplasia differentially expressed (CRNDE) is increased in several tumors. Nevertheless, little is known about the effects of lncRNA CRNDE on human cervical cancer. The aim of the study was to explore the clinical significance of lncRNA CRNDE expression in human cervical cancer. Our results indicated that CRNDE expression was increased in cervical cancer tissues and several cervical cancer cell lines. Through loss-of-function and gain-of-function approaches, we found that CRNDE knockdown markedly reduced cervical cancer cell proliferation, while CRNDE overexpression significantly promoted cervical cancer cell growth. Consistently, CRNDE decreasing obviously inhibited tumorigenicity of cervical cancer cells in vivo, whereas CRNDE increasing markedly promoted cervical cancer progression. Mechanistically, we verified that CRNDE bond to p53 upregulated modulator of apoptosis (PUMA), and PUMA was required for CRNDE to enhance cervical cancer cell growth. Our study demonstrated that CRNDE, combined with PUMA, could be utilized as factor for the clinical diagnosis and prognosis of cervical cancer, and might be potential target for developing effective therapeutic strategy to prevent cervical cancer progression.
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Proteínas Reguladoras de la Apoptosis/genética , Progresión de la Enfermedad , Proteínas Proto-Oncogénicas/genética , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , ARN Largo no Codificante/genéticaRESUMEN
OBJECTIVE: To explore the effectiveness of the fallopian tubes embolization for the hydrosalpinx before in vitro fertilization and embryo transfer (IVF-ET). METHODS: The fallopian tubes embolization was performed on 46 hydrosalpinx patients. First, the hysterosalpingography was performed to show the positions and shape of the hydrosalpinx. Then the hydrops was drawn into the celiac cavity in order to be absorbed after performing fallopian tube recanalization. Finally, transvaginal therapy was performed, putting the embolization microcoils into the fallopian tube through a micro-catheter One month after the fallopian tubes embolization, hysterosalpingography was conducted to check for the effectiveness of the embolization. After 3 months, all the 46 patients received the treatment of IVF-ET. RESULTS: The interventional treatment of 82 fallopian tubes obtained one time success among 46 cases of fallopian tubes embolization. Among them, obvious results were achieved in 72 fallopian tubes, taking up 88% of the total; effective results were seen in 10 fallopian tubes, accounting for 12% of the total. No one was invalid. In the same period, compared with the 91 cases of non-hydrosalpinx as the control group, the embolization group of patients achieved a higher fertilization rate (69%), and clinical pregnancy rate (41%), compared with the control group (63% and 39% respectively), but without a significant difference ( P>0.05). However, the ectopic pregnancy rate (0) and the abortion rate (8%) were significantly lower than the control group (8%, 16% respectively; P<0.05). CONCLUSIONS: Fallopian tubes embolization used in hydrosalpinx treatment before IVF-ET is an innovative approach, simple, safe, economical, with no negative impact on ovarian function. It can significantly increase the clinical pregnancy rate and prevent the occurrence of tubal pregnancy. It is a feasible and effective method.
Asunto(s)
Embolización Terapéutica , Enfermedades de las Trompas Uterinas/terapia , Fertilización In Vitro , Infertilidad Femenina/terapia , Adulto , Transferencia de Embrión , Enfermedades de las Trompas Uterinas/complicaciones , Trompas Uterinas/patología , Trompas Uterinas/cirugía , Femenino , Humanos , Histerosalpingografía , Infertilidad Femenina/etiología , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: To explore the effect of storage time on arginase level and possible source of arginase in apheresis leukocyte-reduced platelets(ALR-Plt). METHODS: The arginase level and myeloperoxidase(MPO) levels in ALR-Plt and control plasma were detected by ELISA. The relationship between arginase level and MPO level in ALR-Plt was analyzed by correlation analysis. RESULTS: There was no significant difference of arginase level between ALR-Plt stored less than 3 days and control plasma. However, arginase level in ALR-Plt stored over 3 days was significantly higher than that in ALR-Plt stored less than 3 days and control plasma(P<0.05). There was no significant difference of MPO level in ALR-Plt stored for different times, but the MPO level in ALR-Plt stored for different time was lower than that in control plasma. Correlation analysis showed that arginase level positively correlated with MPO level in ALR-Plt of different storage time (r=0.58). CONCLUSION: The arginase level in ALR-Plt stored over 3 days increase significantly. The main possible source of arginase in ALR-Plt is the residual white blood cells, especially neutrophils.