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PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.
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Laparoscopía , Neoplasias Hepáticas , Humanos , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hepatectomía/métodos , Laparoscopía/métodosRESUMEN
Soil microorganisms play important roles in vegetation establishment and soil biogeochemical cycling. Ammodendron bifolium is a dominant sand-fixing and endangered plant in Takeermohuer Desert, and bacterial community associated with this plant rhizosphere is still unclear. In this study, we studied the composition and diversity of bacterial community from A. bifolium rhizosphere and bulk soil at different soil depths (i.e., 0-40 cm, 40-80 cm, 80-120 cm) using traditional bacterial isolation and high-throughput sequencing approaches, and preliminarily analyzed the edaphic factors influencing the structure of bacterial communities. Results showed that Takeermohuer Desert with high salinity has been an oligotrophic environment, while the rhizosphere exhibited eutrophication resulting from high content SOM (soil organic matter) and SAN (soil alkaline nitrogen) compared with bulk soil. The dominant bacterial groups in the desert were Actinobacteria (39.8%), Proteobacteria (17.4%), Acidobacteria (10.2%), Bacteroidetes (6.3%), Firmicutes (6.3%), Chloroflexi (5.6%), and Planctomycetes (5.0%) at the phyla level. However, the relative abundances of Proteobacteria (20.2%) and Planctomycetes (6.1%) were higher in eutrophic rhizosphere, and Firmicutes (9.8%) and Chloroflexi (6.9%) relatively higher in barren bulk soil. A large number of Actinobacteria were detected in all soil samples, of which the most abundant genus was Streptomyces (5.4%) and Actinomadura (8.2%) in the bulk soil and rhizosphere, respectively. The Chao1 and PD indexes in rhizosphere were significantly higher than those in bulk soil at the same soil depth, and tended to decrease with increasing soil depth. Co-occurrence network analyses showed that the keystone species in Takeermohuer Desert were Actinobacteria, Acidobacteria, Proteobacteria, and Chlorofexi. Furthermore, the major environmental factors affecting rhizosphere bacterial community were EC (electrical conductivity), SOM, STN (soil total nitrogen), SAN, and SAK (soil available potassium), while bulk soil were distance and C/N (STC/STN). We concluded that A. bifolium rhizosphere bacterial community is different from non-rhizosphere in composition, distribution, and environmental influencing factors, which will have important significances for understanding their ecological functions and maintaining biodiversity.
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Fabaceae , Rizosfera , Bacterias , Proteobacteria , Acidobacteria , Suelo/química , Nitrógeno , Microbiología del SueloRESUMEN
Soil microorganisms play important roles in vegetation establishment and soil biogeochemical cycling. Ammodendron bifolium is a dominant sand-fixing (i.e., stabilizing sand dunes) and endangered plant in the Takeermohuer Desert, and the bacterial community associated with this plant rhizosphere is still unclear. In this study, we investigated the composition and diversity of the bacterial community from the A. bifolium rhizosphere and bulk soil at different soil depths (i.e., 0-40 cm, 40-80 cm, 80-120 cm) using culture and high-throughput sequencing methods. We preliminarily analyzed the edaphic factors influencing the structure of bacterial communities. The results showed that the high-salinity Takeermohuer Desert has an oligotrophic environment, while the A. bifolium rhizosphere exhibited a relatively nutrient-rich environment due to higher contents of soil organic matter (SOM) and soil alkaline nitrogen (SAN) than bulk soil. The dominant bacterial groups in the desert were Actinobacteria (39.8%), Proteobacteria (17.4%), Acidobacteria (10.2%), Bacteroidetes (6.3%), Firmicutes (6.3%), Chloroflexi (5.6%), and Planctomycetes (5.0%) at the phylum level. However, the relative abundances of Proteobacteria (20.2%) and Planctomycetes (6.1%) were higher in the rhizosphere, and those of Firmicutes (9.8%) and Chloroflexi (6.9%) were relatively higher in barren bulk soil. A large number of Actinobacteria were detected in all soil samples, of which the most abundant genera were Streptomyces (5.4%) and Actinomadura (8.2%) in the bulk soil and rhizosphere, respectively. The Chao1 and PD_whole_tree indices in the rhizosphere soil were significantly higher than those in the bulk soil at the same soil depth and tended to decrease with increasing soil depth. Co-occurrence network analyses showed that the keystone species in the Takeermohuer Desert were the phyla Actinobacteria, Acidobacteria, Proteobacteria, and Chloroflexi. Furthermore, the major edaphic factors affecting the rhizosphere bacterial community were electrical conductivity (EC), SOM, soil total nitrogen (STN), SAN, and soil available potassium (SAK), while the major edaphic factors affecting the bacterial community in bulk soil were distance and ratio of carbon to nitrogen (C/N). We concluded that the A. bifolium rhizosphere bacterial community is different from that of the nonrhizosphere in composition, structure, diversity, and driving factors, which may improve our understanding of the relationship between plant and bacterial communities and lay a theoretical foundation for A. bifolium species conservation in desert ecosystems.
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Ecosistema , Fabaceae , Rizosfera , Bacterias/genética , Proteobacteria , Acidobacteria , Suelo/química , Plantas , Nitrógeno , Microbiología del SueloRESUMEN
It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson's disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Proteínas de Unión al ADN/genética , Neuronas Dopaminérgicas/metabolismo , Enfermedad de Parkinson/genética , Proteínas Proto-Oncogénicas/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animales , Metilación de ADN/genética , Dioxigenasas , Modelos Animales de Enfermedad , Epigénesis Genética , Humanos , Masculino , Mesencéfalo/lesiones , Mesencéfalo/metabolismo , Ratones , Enfermedad de Parkinson/patologíaRESUMEN
BACKGROUND: With the growing awareness of restless legs syndrome (RLS), sensory disorders similar to RLS but initially confined to the arms, abdomen, and perineum have been reported. One of them is restless abdomen, which refers to a restless sensation in abdomen. Our study is designed to evaluate the clinical phenotype of restless abdomen and investigate its relationship with RLS. METHODS: We enrolled 10 patients with restless abdomen according to RLS diagnostic criteria, excluding the requiring of leg involvement. Laboratory examinations were performed to exclude mimics and notable comorbidities. RESULTS: All 10 patients had RLS like symptoms in the abdomen and otherwise satisfied all other RLS diagnostic criteria, and responded to dopaminergic therapy. CONCLUSIONS: Neurologists and gastroenterologists should be aware that RLS-related restlessness can occur in extra-leg anatomy in the absence of episodes of worsening or augmentation of restlessness.
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Abdomen/fisiopatología , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/fisiopatología , Síndrome de las Piernas Inquietas/diagnóstico , Síndrome de las Piernas Inquietas/fisiopatología , Adolescente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/complicaciones , Fenotipo , Síndrome de las Piernas Inquietas/complicaciones , Estudios Retrospectivos , Adulto JovenRESUMEN
Amyloid-ß (Aß)-induced mitochondrial dysfunction has been recognized as a prominent, early event in Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuro-protective effects, but its preventive effects on Aß-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two quercetin (either 20 or 40 mg kg(-1) day(-1)) groups, or an Aricept (2 mg kg(-1) day(-1)) group. After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg kg(-1) day(-1)), including lessening learning and memory deficits, reducing scattered senile plaques, and ameliorating mitochondrial dysfunction, as evidenced by restoration of mitochondrial membrane potential, reactive oxygen species and ATP levels in mitochondria isolated from the hippocampus compared to control. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated (40 mg kg(-1) day(-1)) group. These findings suggest that a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms by which quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológico , Modelos Animales de Enfermedad , Mitocondrias/efectos de los fármacos , Quercetina/administración & dosificación , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Antioxidantes/administración & dosificación , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Esquema de Medicación , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias/fisiología , Distribución Aleatoria , Resultado del TratamientoRESUMEN
BACKGROUND: The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC). AIM: To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC. METHODS: A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis. RESULTS: Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues. CONCLUSION: These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
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Amyloid-ß (Aß) is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the mitochondrial voltage-dependent anion channel 1 (VDAC1), which is involved in the release of apoptotic proteins with possible relevance in Alzheimer's disease (AD) neuropathology, plays an important role in maintaining mitochondrial function and integrity. However, the application of therapeutic drugs, especially natural products in (AD) therapy via VDAC1-regulated mitochondrial apoptotic pathway has not aroused extensive attention. In the present study, we investigated neuroprotective effects of hesperidin, a bioactive flavonoid compound, on Aß25-35-induced neurotoxicity in PC12 cells and also examined the potential cellular signalling mechanism. Our results showed that treatment with hesperidin significantly inhibited Aß25-35-induced apoptosis by reversing Aß-induced mitochondrial dysfunction, including the mitochondrial permeability transition pore opening, intracellular free calcium increase and reactive oxygen species production. Further study indicated that hesperidin can decrease the level ofVDAC1 phosphorylation through inhibiting the activity of the glycogen synthase kinase-3b and increase the level of hexokinaseI in mitochondria, preventing release of cytochrome c from mitochondria [corrected]. Furthermore, hesperidin inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9 and caspase-3. These results demonstrate that hesperidin can protect Aß-induced neurotoxicity via VDAC1-regulated mitochondrial apoptotic pathway, and they raise the possibility that hesperidin could be developed into a clinically valuable treatment for AD and other neuronal degenerative diseases associated with mitochondrial dysfunction.
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Péptidos beta-Amiloides/metabolismo , Apoptosis/efectos de los fármacos , Hesperidina/farmacología , Mitocondrias/efectos de los fármacos , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Animales , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Células PC12 , Fosforilación , RatasRESUMEN
A novel switchable sensor was developed for the determination of phosphate based on Ce(3+) induced aggregation and phosphate triggered disaggregation of cysteine (Cys)-capped CdS quantum dots (QDs) and silver nanoparticles (AgNPs). The rare earth metal Ce(3+) could aggregate a mixture of QDs and AgNPs, which induced electron or energy transfer between CdS QDs and AgNPs and serious fluorescence quenching. However, phosphate dissociated the formed aggregation of CdS QDs and AgNPs, restoring the enhanced fluorescence of Cys-capped CdS triggered by AgNPs. Although, CdS QDs alone could also be used to detect phosphate through the aggregation-disaggregation mechanism adjusted by Ce(3+) and phosphate. It was found that the distance-dependent interaction between AgNPs and CdS QDs driven by Ce(3+) and phosphate could lead to enhanced quenching or enhancement of the fluorescence of Cys-capped CdS to form a more sensitive detection system for phosphate. The developed method was applied in the detection of phosphate in real water samples with acceptable and satisfactory results.
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Nanopartículas del Metal/química , Fosfatos/análisis , Puntos Cuánticos , Plata , Compuestos de Cadmio , Cerio , Cisteína/química , Espectrometría de Fluorescencia/métodos , SulfurosRESUMEN
Optic neuritis is an inflammatory disease of the optic nerve with an abrupt loss of vision. The mechanism of the disease is not completely clear. Autophagy is an important metabolic pathway of eukaryotic cells involved degrading and recycling damaged organelles and proteins to maintain intracellular homeostasis. It is involved in the pathogenesis of various diseases. In this article, the probable effects of autophagy in the mechanism of optic neuritis is reviewed.
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Autofagia , Neuritis Óptica , Animales , HumanosRESUMEN
Background: Laparoscopic isolated caudate lobectomy is still a challenging procedure for hepatobiliary surgeons because of its deep location and narrow operating space. Hilar exposure and adequate operation space play an important role during laparoscopic caudate lobectomy. Very few references are available on this technique, and in this study, we present a new suspension technique to assist laparoscopic caudate lobectomy. Materials and Methods: The data of patients with caudate hepatic tumors who underwent laparoscopic isolated caudate lobectomy with or without the double suspension technique at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Results: A total of 25 patients underwent laparoscopic isolated caudate lobectomy at Eastern Hepatobiliary Surgery Hospital between June 2016 and March 2022. Eight patients had perioperative complications, and no patient died within 30 days after surgery. There were no significant differences between the two groups in terms of conversion rate (8.3% versus 7.7%; P = .954), complication rate (25.0% versus 38.5%; P = .480), length of stay (8.0 [6.0-11.0] days versus 9.0 [6.0-19.0] days; P = .098), and postoperative liver function changes. Patients who underwent resection in the suspension group had shorter operation time (154.9 ± 44.3 minutes versus 224 ± 86.3 minutes; P = .018), inferior vena cava dissection time (30.1 ± 5.4 minutes versus 44.8 ± 7.4 minutes; P < .001), and less bleeding (125.0 [20-800.0] mL versus 350 [80-850.0] mL, P = .011). Conclusions: This double suspension technique is a safe and feasible method to assist laparoscopic caudate lobectomy. It provides clear exposure and adequate surgical space, thereby shortening the operation time and reducing intraoperative blood loss.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Estudios RetrospectivosRESUMEN
Deleted in liver cancer 1 (DLC1), a tumor suppressor gene identified in a primary human hepatocellular carcinoma, encodes a Rho GTPase-activating protein (RhoGAP). Although DLC1 expression has been studied at the transcriptional level, little is known about its regulation at the protein level. Here we show that DLC1 is an unstable protein that is degraded by the 26S proteasome in human hepatocellular carcinoma Hep3B cells. In addition, five putative PEST motifs were identified in the N-terminus of DLC1. Unexpectedly, the N-terminus of DLC1 appeared to be stable. Furthermore, deletion of any one of the five PEST motifs except PEST2 decreased the stability of the N-terminus of DLC1, which suggests that the PEST motifs may play an unrevealed role in maintaining the stability of DLC1. These data indicated that the intracellular stability of DLC1 is regulated by the 26S proteasome via its PEST motifs.
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Carcinoma Hepatocelular/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Neoplasias Hepáticas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Secuencias de Aminoácidos/genética , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Proteínas Activadoras de GTPasa/genética , Humanos , Ratones , Datos de Secuencia Molecular , Inhibidores de Proteasoma , Estabilidad Proteica , Ratas , Eliminación de Secuencia , Proteínas Supresoras de Tumor/genéticaRESUMEN
A novel colorimetric thiourea (TU) sensor was developed utilizing citrate modified silver nanoparticles (AgNPs). The introduction of TU reduced the overall surface charges of the AgNPs, resulting in aggregation of AgNPs and a colorimetric response correlating with the concentration of TU. The detection of TU could be realized within 2 min, with an ultralow detection limit of 0.8 nM by the absorption method. In addition, the AgNPs sensor also showed good selectivity in the presence of potential interfering compounds. Since common steps such as modification and separation could be successfully avoided, the sensor developed here could provide a simple, cost-effective yet rapid and sensitive measurement tool for TU detection, and may provide new opportunities in the development of sensors for food safety and environmental monitoring in the future.
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OBJECTIVE: To investigate bone health conditions in 1637 aged women. METHODS: From May 2004 to October 2008, Bone mineral density (BMD) of 1637 women at age of more than 60 years old were measured by Hologic DephiA dual energy X-ray absorptiometry (DXEA) in Huadong hospital affiliated to Fudan University. All data were compared and analyzed among each group which will be divided by every ten years. Those women were divided into groups on 10 years range. BMD of lumbar vertebral and hip bone, fracture incidence and bone turnover marker were compared and analyzed. RESULTS: (1) BMD: at age of ≥90, 80-89, 70-79, 60-69, BMD of the lumbar vertebral 2-4 (L2-4) values were (0.96±0.18), (0.90±0.20), (0.81±0.16), (0.83±0.14) g/cm2, respectively. There were significantly increased BMD of lumbar of women at the age of 80-89 and ≥90 year-old compared with those of 60-69 year-old (P<0.05). At age of ≥90, 80-89, 70-79, 60-69 BMD of femur neck, Total, Torch, Ward's trianger were (0.60±0.11), (0.65±0.11), (0.47±0.09), (0.37±0.09) g/cm2; at age of 80-89 BMD of FN, Total, Torch, Ward's trianger were (0.57±0.10), (0.68±0.13), (0.48±0.11), (0.35±0.10) g/cm2; at age of 70-79 BMD of FN, Total, Torch, Ward's trianger were (0.57±0.10), (0.69±0.12), (0.49±0.10), (0.36±0.11) g/cm2; at age of 60-69 BMD of FN, Total, Torch, Ward's trianger were (0.63±0.10), (0.76±0.12), (0.54±0.10), (0.45±0.15) g/cm2; There were significantly decreased in BMD of hip at the age of 70-79, 80-89, ≥90 year-old compared with those of 60-69 year-old (P<0.05). (2) Fracture incidence:one time fracture incidence at age of 60-69, 70-79, 80-89, ≥90 were 34.8% (242/695), 45.0% (296/658), 51.3% (137/267), 5/17. There were increasing trend of fracture in aged women. (3) Bone turnover marker of bone Gla protein (BGP) N-mid (N-midBGP) in serum and C-terminal telopeptide of type I collagen/Cr (CTX/Cr) in urine values were (17±5) µg/L, (106±56) µg/mmol at age of more than 90 years, (17±7) µg/L, (128±99) µg/mmol at age of 80-89 years, (21±14) µg/L, (182±173) µg/mmol at age of 70-79 years, (25±13) µg/L, (190±168) µg/mmol at age of 60-69 years. There were significant decreased trends of N-midBGP at age of 70-79, 80-89 compared with that of 60-year (P<0.05). There were significant decreased trends of CTX/Cr 80-89 compared with that of 60-year (P<0.05). CONCLUSIONS: There were significant decreased bone metabolism in aged women. The risk of hip fracture is significantly increased in aged women. Diagnosis of osteoporosis based on BMD of hip in aged women is more reliable.
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Anciano , Envejecimiento/fisiología , Densidad Ósea/fisiología , Estado de Salud , Osteoporosis/prevención & control , Absorciometría de Fotón , Factores de Edad , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/orina , Huesos/metabolismo , Huesos/fisiopatología , Colágeno Tipo I/orina , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Humanos , Persona de Mediana Edad , Osteocalcina/sangre , Osteoporosis/epidemiología , Péptidos/orinaRESUMEN
Background: Our previous studies have reported that polycomb chromobox 4 (CBX4) has a potential promoting hepatocellular carcinoma (HCC) angiogenesis and tumor progression. However, it is unclear whether genetic single-nucleotide polymorphisms (SNPs) in this gene are associated with HCC prognosis. Methods: We conducted a hospital-based two-phase study, including 598 patients with pathologically diagnosed HCC for the SNPs screening phase and 328 HCC patients for clinic significance validating phase, to elucidate the association between SNPs of CBX4 and the survival of HCC. The genotypes of CBX4 were tested using the SNaPshot method and the effects of CBX4 SNPs on HCC prognosis were analyzed using Kaplan-Meier survival model and Cox regression model. Results: A total of 33 SNPs were selected and genotyped in this study. We found the rs77447679 SNP was significantly related to survival in individuals with HCC. Specifically, survival was noticeably decreased in HCC patients who have mutant homozygote AA of this SNP (rs77447679-AA) compared with these with wild type (rs77447679-CC). An additive effect of rs77447679 polymorphism and aflatoxin B1 exposure level was also observed in the survival analyses of HCC cases. Furthermore, this SNP was positively correlated not only with tumor size, grade, stage, and microvessel density (correlation coefficient r = 0.17, 0.23, 0.23, and 0.42, respectively), but also with increasing CBX4 expression (r = 0.57). Interestingly, the mutant genotypes of rs77447679 can significantly improve the therapeutic response of HCC cases on post-operative adjuvant transarterial chemoembolization (pa-TACE), but wild type not. Conclusions: These data suggest that genetic polymorphisms in the CBX4 may be a prognostic biomarker for HCC, and the rs77447679 SNP is such a potential candidate.
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Carcinoma Hepatocelular , Ligasas/genética , Neoplasias Hepáticas , Proteínas del Grupo Polycomb , Carcinoma Hepatocelular/genética , Quimioembolización Terapéutica , Humanos , Neoplasias Hepáticas/genética , Proteínas del Grupo Polycomb/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Background: Essential tremor (ET) is manifested as an isolated syndrome of bilateral upper limb action tremor. Parkinson's disease (PD) is the second most common neurodegenerative disease, with typical motor symptoms of bradykinesia, rigidity, and resting tremor. ET-PD describes the new-onset of PD in ET patients. Recently, numerous studies on epidemiology, genetics, pathology, clinical features, and neuroimaging studies are challenging the idea that ET is an isolated disease, suggesting that patients with ET have the tendency to develop PD. Methods: In this review article, we collected recent findings that reveal prodromal markers of PD in patients with ET. Results: Substantia nigra hyperechogenicity serves as a prodromal marker for predicting the development of PD in patients with ET and provides a reference for therapeutic strategies. Additional potential markers include other neuroimaging, clinical features, heart rate, and genetics, whereas others lack sufficient evidence. Conclusion: In consideration of the limited research of PD in patients with ET, we are still far from revealing the prodromal markers. However, from the existing follow-up studies on ET patients, Substantia nigra hyperechogenicity may enable further exploration of the relationship between ET and PD and the search for pathogenesis-based therapies.
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Although the advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the survival of patients with chronic myeloid leukaemia (CML), acquired drug resistance and TKI-insensitive leukaemic stem cells (LSCs) remain major obstacles to a CML cure. In recent years, the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers, including CML, and in turn may be exploited for therapeutic purposes. Here, we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide (AICAR) and decitabine could effectively increase the ATP content and mitochondrial biogenesis. In addition, these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation. Moreover, we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity of K562 cells to imatinib, as evidenced by a combination treatment assay. Altogether, our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.
Asunto(s)
Aminoimidazol Carboxamida/análogos & derivados , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Ribonucleótidos/farmacología , Aminoimidazol Carboxamida/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Decitabina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Humanos , Mesilato de Imatinib/farmacología , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Mitocondrias/genética , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Objective: Iron deficiency anemia (IDA) is a well-known cause of secondary restless legs syndrome (RLS). Iron deficiency without anemia (IDNA) is insidious, and its association with RLS is less evaluated. We investigate prevalence and features of IDNA in a consecutive cohort of patients with RLS. Methods: We included sequential primary RLS patients and RLS patients with IDA. We also recruited age- and gender-matched healthy controls. RLS mimics and other comorbidities were carefully excluded. Results: One-hundred and ninety-six RLS patients without anemia, 26 RLS patients with IDA, and 63 controls were included. 42.3% of RLS patients without anemia had iron deficiency. Women were much more susceptible for IDNA with a relative risk of 5.51 (p < 0.0001). Women with IDNA and RLS had younger age both at interview and at RLS onset compared to women with RLS without iron deficiency (NID) (P < 0.01). IDNA RLS patients showed a tendency to higher risk of severe/very severe tiredness or sleepiness during the day as compared to NID RLS patients. Furthermore, IDNA RLS patients had longer duration of RLS (P < 0.01 in men, P < 0.05 in women) and younger age at onset (only in men, P < 0.05) compared to IDA RLS patients. Conclusion: IDNA is frequent in RLS and iron deficiency may be severe despite a normal hemoglobin level. Women are at much higher risk for IDNA, and IDNA in women presents some specific clinical features. Features of IDNA RLS are different from IDA RLS. Regular screening of peripheral iron parameters even in patients with normal blood counts is recommended for timely optimal management.
RESUMEN
BACKGROUND: Brain iron disequilibrium and dopaminergic dysfunction are key pathophysiological features of Restless Legs Syndrome (RLS). Rep1 polymorphism in the promotor region of SNCA is associated with risk of Parkinson's disease, however its association with RLS and iron status is unclear. OBJECTIVE: To investigate SNCA-Rep1 polymorphism in RLS and its phenotypes. METHODS: We recruited RLS patients as well as age and gender matched healthy controls. Demographic information and clinical features of RLS were recorded. Laboratory examinations were performed to exclude possible secondary causes. RESULTS: 215 RLS patients and 369 healthy controls were included. We found that the Rep1 allele 0 homozygosity significantly decreased RLS risk (OR: 0.345; P < 0.0001, and remained significant after the Bonferroni correction). Phenotypic analysis demonstrated that longer Rep1 alleles were associated with increased susceptibility to iron deficiency (53.0% vs 36.1%, P = 0.017), however had no phenotypic significant effects on age, gender, onset age, duration, RLS family history, severity, laterality, extra body involvement and seasonal fluctuation. Multivariate logistic regression analyses confirmed long Rep1 allele was associated with higher risk of iron deficiency in RLS after adjusting for potential confounding factors. In detail, Rep1 allele 2 homozygosity was prone to a higher risk of peripheral iron deficiency in RLS (OR: 4.550, P = 0.006, remained significant after the Bonferroni correction). CONCLUSION: The SNCA-Rep1 variability modified RLS risk and influenced peripheral iron deficiency in this group of Chinese RLS patients. Rep1 allele 0 homozygosity decreased the risk of RLS, while homozygous allele 2 increased the risk of nonanemic iron deficiency in RLS.