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Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase ß (IKKß), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKß reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKß/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.
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Apoptosis/efectos de los fármacos , Inflamación/metabolismo , MicroARNs/farmacología , Traumatismos de la Médula Espinal/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Quinasa I-kappa B/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Members of the mitochondrial transcription terminator factor (mTERF) family, originally identified in vertebrate mitochondria, are involved in the termination of organellular transcription. In plants, mTERF proteins are mainly localized in chloroplasts and mitochondria. In Arabidopsis (Arabidopsis thaliana), mTERF8/pTAC15 was identified in the plastid-encoded RNA polymerase (PEP) complex, the major RNA polymerase of chloroplasts. In this work, we demonstrate that mTERF8 is associated with the PEP complex. An mTERF8 knockout line displayed a wild-type-like phenotype under standard growth conditions, but showed impaired efficiency of photosystem II electron flow. Transcription of most chloroplast genes was not substantially affected in the mterf8 mutant; however, the level of the psbJ transcript from the psbEFLJ polycistron was increased. RNA blot analysis showed that a larger transcript accumulates in mterf8 than in the wild type. Thus, abnormal transcription and/or RNA processing occur for the psbEFLJ polycistron. Circular reverse transcription PCR and sequence analysis showed that the psbJ transcript terminates 95 nucleotides downstream of the translation stop codon in the wild type, whereas its termination is aberrant in mterf8 Both electrophoresis mobility shift assays and chloroplast chromatin immunoprecipitation analysis showed that mTERF8 specifically binds to the 3' terminal region of psbJ Transcription analysis using the in vitro T7 RNA polymerase system showed that mTERF8 terminates psbJ transcription. Together, these results suggest that mTERF8 is specifically involved in the transcription termination of the chloroplast gene psbJ.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Transcripción Genética/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Cloroplastos/genética , Inmunoprecipitación de Cromatina , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Unión ProteicaRESUMEN
BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.
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Trasplante de Células Madre Mesenquimatosas , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/inmunología , Bazo/inmunología , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Apoptosis , Creatina Quinasa/sangre , Modelos Animales de Enfermedad , Inmunoglobulina G/farmacología , Interleucina-10/sangre , L-Lactato Deshidrogenasa/sangre , Masculino , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/inmunología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , Necrosis , Fenotipo , Bazo/efectos de los fármacos , Bazo/metabolismo , Esplenectomía , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Factor de Crecimiento Transformador beta1/sangreRESUMEN
OBJECTIVES: To understand whether different anesthesia and analgesia methods affected the incidence of chronic postsurgical pain (CPSP) in patients who underwent uniportal video-assisted lung surgery and to explore the influence factors of CPSP. DESIGN: Retrospective study. SETTING AND PARTICIPANTS: A total of 120 patients, who underwent selective uniportal video-assisted lung surgery at Zhongshan Hospital from March to June 2018, were enrolled. INTERVENTIONS: The visual analog scale was used to assess the degree of pain on the first and second postoperative days. At the third and sixth months after surgery, the telephone follow-up was conducted for the survey of the numerical rating scale. The incidence of acute and chronic pain in different anesthesia methods was analyzed, and the relevant factors of CPSP were statistically analyzed. RESULTS: Among the 111 patients who completed follow-up, no significant difference was noted in the incidences of acute and chronic postsurgical pain between patients who received different anesthesia and analgesia methods (p > 0.05). The incidence of CPSP was 29.7% at 3 months after surgery and 9.0% at 6 months after surgery. The degree of pain within 48 hours after surgery was a risk factor for CPSP (odds ratio [OR]â¯=â¯2.39, p < 0.05). CONCLUSION: CPSP accounted for a specific proportion of patients after uniportal video-assisted lung surgery; however, it was significantly lower than that of patients with conventional thoracotomy. The incidence did not differ significantly among anesthesia and analgesia methods. Active and effective control of acute postsurgical pain might reduce the incidence of CPSP.
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Analgesia , Anestesia , Dolor Crónico , Dolor Crónico/diagnóstico , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Humanos , Pulmón , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Estudios RetrospectivosRESUMEN
Efficient air removal from a vascular access line is a key step to prevent air embolism. Existing devices, especially for rapid infusers, are far from optimum. In this study, we developed a novel device, vascular access line air removal device (VALARD), and compared its efficiency of air removal and pause time of forward bulk flow with a commonly used device, the Belmont pump. Part I experiment, saline was infused at a forward bulk flow rate of 250, 500, and 750 mL/min. Meanwhile, air was introduced into the infusion line at a rate of 5, 10, and 15 mL/min for each bulk flow rate. Air bubbles > 10 µL downstream from either the VALARD or the Belmont pump and the fraction of pause time of the forward bulk flow were determined. Part II experiment, 120 mL of air was rapidly introduced into the VALARD at a bulk flow rate of about 500 mL/min. Air bubbles > 10 µL downstream from the VALARD, fraction of pause time of the forward bulk flow, and the transit time of the 120 mL of air at the working chamber were recorded. The VALARD: no air bubbles > 10 µL were detected during any tested combination of air injection and bulk flow rates without pause of forward flow. The Belmont pump: air bubbles > 10 µL were detected in 60% of the tests with pause of the forward flow. The VALARD eliminates air efficiently without pause of the forward bulk flow. Further clinical trials are needed to compare the VALARD with other devices and to assess its efficiency, safety, and user friendliness.
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Embolia Aérea/prevención & control , Bombas de Infusión , Dispositivos de Acceso Vascular , Aire , Embolia Aérea/sangre , Diseño de Equipo , Humanos , Técnicas In Vitro , Infusiones Intravenosas/instrumentación , PresiónRESUMEN
Mounting evidence has been shown that integrin-mediated cellular adhesion confers resistance to chemotherapy of multiple myeloma. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this report, we demonstrated that RPMI 8,226 cells accumulated p27(Kip1) in the nucleus when they were adhered to fibronectin (FN). The adhesion-mediated p27(Kip1) nuclear recruitment was regulated via the down-regulation of Jab1, a negative regulator of cell cycle. Overexpression of Jab1 reversed the elevated p27(Kip1) in the nucleus, which needed phosphorylation of p27(Kip1) on Serine 10, whereas inhibition of Jab1 by siRNA further increased the elevated p27(Kip1). Furthermore, we found overexpression of Jab1 did not affect 8,226 cells adhesion to FN, but reversed doxorubicin or mitoxantrone-induced CAM-DR phenotype. In conclusion, our data suggest that Jab1 plays an important role in CAM-DR, which depends on pSer10-p27(Kip1)-mediated subcellular localization of p27(Kip1). The understanding of this novel molecular mechanism may prove valuable in designing new therapeutic approaches for CAM-DR in Multiple myeloma.
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Adhesión Celular , Núcleo Celular/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación hacia Abajo , Fibronectinas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Mieloma Múltiple/patología , Péptido Hidrolasas/metabolismo , Complejo del Señalosoma COP9 , Línea Celular Tumoral , Resistencia a Antineoplásicos , Humanos , Microscopía Fluorescente , Mieloma Múltiple/metabolismo , FosforilaciónRESUMEN
Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and the corresponding damage; however, very little work has been done to evaluate the relationship between Ln-induced liver injury and its gene expression profile in mice. In this study, liver injury and gene-expressed profiles in male mice induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive days were investigated. The results showed that cerium accumulation, liver inflammation, and hepatocyte necrosis were observed. CeCl3 exposure significantly decreased the counts of white blood cells, lymphocyte, and platelet, the reticulocyte count (Ret) and neutrophilic granulocyte percentages as well as A/G ratio, whereas markedly increased the activities of alkaline phosphatase, lactate dehydrogenase, and cholinesterase, and the concentrations of triglycerides and total cholesterol. Furthermore, microarray results of liver showed that the differential expression of 675 known function genes involved in immune/inflammation response, apoptosis, metabolic process, cell cycle, cell proliferation, cytoskeleton, oxidative stress, signal transduction, transcription, translation, and transportation in CeCl3 exposed livers, respectively. Specifically, the significant downregulation of Nt5e led to inflammation, overexpressed Cyp4a12a and great suppression of Cdkn1a resulted in hepatocyte apoptosis, marked elevation of Cel, and Cyp7b1 expression caused the metabolic disorders in mouse liver after long-term CeCl3 exposure. Therefore, these genes may be in great relation to liver damages induced by exposure to CeCl3 .
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Cerio/toxicidad , Contaminantes Ambientales/toxicidad , Hígado/efectos de los fármacos , Animales , Apoptosis/genética , Biomarcadores/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Inflamación/genética , Inflamación/inmunología , Inflamación/metabolismo , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Masculino , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , TranscriptomaRESUMEN
Sewage irrigation is a common alternative to make up for the shortage of agricultural irrigation in intensive agricultural areas. Abundant organic matter and nutrients in sewage can improve soil fertility and crop yield, but hazardous materials, such as heavy metals, will damage the soil environmental quality and threaten human health. To better understand the characteristics of heavy metal enrichment and potential health risk in a sewage irrigated soil-wheat system, a total of sixty-three pairs of topsoil and wheat grain samples were collected from the sewage irrigated area of Longkou City in Shandong Province. The contents of Cr, Cu, Ni, Pb, Zn, As, Cd, and Hg were determined to analyze heavy metal contamination and calculate bio-accumulation factor (BAF), estimated daily absorption (EDA), as well as hazard quotient (HQ). The results showed that the average contents of the eight heavy metals were 61.647, 30.439, 29.769, 36.538, 63.716, 8.058, 0.328, and 0.028 mg·kg-1, respectively, which all exceeded the background values of corresponding heavy metals in the eastern Shandong Province. Especially, the average content of Cd was higher than the current standard value of soil environmental quality of agricultural land soil pollution risk control, indicating the apparent soil contamination. However, the correlations between the heavy metal contents in soil and wheat grains were not significant, suggesting that it is difficult to conclude the enrichment degree of heavy metals in wheat grains merely by the heavy metal contents in soil. The results of BAF showed that the high enrichment capacity of wheat grain was primarily obtained with Zn, Hg, Cd, and Cu. According to the national food safety limit standard, the over-limit ratios of Ni (100%) and Pb (96.8%) in wheat grains were the most serious. As a result, under the current consumption of local wheat flour, the EDAs of Ni and Pb were high, accounting for 28.278% and 1.955% of the acceptable daily intakes (ADI) for adults and 131.980% and 9.124% of the ADIs for children. The results of the health risk assessment exhibited that As and Pb were the main sources causing health risks, accounting for approximately 80% of the total risk. Although the sums of the HQ of the eight heavy metals for adults and children were below 10, the total HQ of children was 1.245 times higher than that of adults. The food safety of children should receive more attention. When considering spatial characteristics, the health risk in the southern study area was higher than that in the northern part of the study area. The prevention and control of heavy metal contamination in the southern area should be strengthened in the future.
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Mercurio , Metales Pesados , Adulto , Niño , Humanos , Suelo , Triticum , Aguas del Alcantarillado , Cadmio , Harina , Plomo , Medición de Riesgo , Grano ComestibleRESUMEN
C-type lectin-like receptor 2 (CLEC-2) is a newly identified type II transmembrane protein belonging to the C-type lectin family molecules, which acts as a cell-surface receptor for snake venom toxin rhodocytin and tumor antigen podoplanin. We previously demonstrated that the full-length mouse CLEC-2 (mCLEC-2) can be cleaved into soluble form. Elevated levels of soluble forms of membrane proteins in circulating blood may reflect increased expression of membrane proteins and disease activities. In the present study, we clarified the domain and sites contributing to the production of soluble mCLEC-2. The shedding process can be positively regulated by protein kinase C (PKC). Moreover, we explored the possibility that human CLEC-2 (hCLEC-2) may also be proteolyticly cleaved and released as a soluble form. We have observed that the production of soluble hCLEC-2 could be induced by phorbol ester (PMA) in cells stably transfected with hCLEC-2 cDNA. Further studies may explore therapeutic and diagnostic applications of soluble hCLEC-2 in platelet-related diseases.
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Expresión Génica , Lectinas Tipo C/biosíntesis , Lectinas Tipo C/genética , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Secuencia de Aminoácidos , Animales , Células CHO , Línea Celular Tumoral , Cricetinae , Citometría de Flujo , Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Lectinas Tipo C/agonistas , Glicoproteínas de Membrana/agonistas , Datos de Secuencia Molecular , Mutación , Plásmidos , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Proteolisis , Transducción de Señal/genética , Solubilidad , Acetato de Tetradecanoilforbol/farmacología , TransfecciónRESUMEN
This paper is concerned with the cross-dimensional formation control of a second-order multi-dimensional heterogeneous multi-agent system. Agents are first separated into several groups according to their position/velocity vector dimensions. Then the cross-dimensional formation control problem is formulated such that agents in the same group form a time-varying formation in their own dimension and agents in different groups cooperatively move in multiple dimensions. This can make follower agents in different dimensions cooperatively track a leader. Moreover, a cross-dimensional formation protocol is designed based on full or partial information of neighboring agents. For higher-dimensional agents, full information of lower-dimensional neighbors is adopted. For lower-dimensional ones, only partial information of higher-dimensional neighbors is used. Furthermore, a necessary and sufficient condition for the second-order heterogeneous multi-agent system to achieve cross-dimensional formation is provided. Accordingly, a criterion for designing cross-dimensional formation protocol is further derived. Finally, under an undirected graph, a lower-dimensional protocol design criterion is obtained if there is no data exchange between lower- and higher-dimensional followers. The effectiveness of the obtained results is demonstrated through cross-dimensional target enclosing performance analysis for multiple robots and quadrotors.
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Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Although DLB is characterized by fluctuating cognitive impairment, some symptoms may appear before cognitive impairment, including rapid eye movement, sleep behavior disorder (RBD), psychiatric symptoms, autonomic symptoms, Parkinson's symptoms, etc. Therefore, DLB may be misdiagnosed as other diseases in its early stage. Objective: This study aimed to investigate the characteristics of initial symptoms of DLB, which could potentially offer essential clues for the earliest diagnosis of this disorder. Methods: A total of 239 patients with probable DLB who visited the cognitive impairment outpatient department of Tianjin Huanhu Hospital from September 2015 to March 2021 were consecutively enrolled. We retrospectively evaluated the initial symptoms of all included participants. The time of onset of initial symptoms was also assessed. Results: The most frequent initial symptom was memory loss (53.9%), followed by psychiatric symptoms (34.7%), RBD (20.9%), parkinsonism (15.1%), and autonomic symptoms (10.1%). Significant gender and age differences existed in the initial symptoms of patients with DLB. Conclusions: Our study elucidated the initial symptoms in patients with probable DLB. RBD was significantly more reported by men than by women, whereas women showed a higher incidence of visual and auditory hallucinations. A better understanding of the initial symptoms of DLB could lead to a more accurate diagnosis.
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Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyeloma activity by inhibiting histone deacetylases (HDACs). Amitriptyline markedly decreased cyclin D2 promoter-driven luciferase activity, reduced cyclin D2 expression, and arrested cells at the G(0)/G(1) phase of the cell cycle. Amitriptyline-induced apoptosis was confirmed by Annexin V staining, and cleavage of caspase-3 and poly(ADP-ribose) polymerase-1. D-Cyclin expression is reported to be epigenetically regulated by histone acetylation. Thus, we examined the effects of amitriptyline on histone 3 (H3) acetylation and demonstrated that amitriptyline increased acetylation of H3 and expression of p27 and p21. Further studies indicated that amitriptyline interfered with HDAC function by down-regulation of HDAC3, -6, -7, and -8, but not HDAC2, and by interacting with HDAC7. Molecular docking analysis and molecular dynamics simulations revealed that amitriptyline bound to HDAC7 and formed strong van der Waals interactions with five residues of HDAC7, including Phe162, His192, Phe221, Leu293, and His326, thus inhibiting HDAC activity. Therefore, we found that amitriptyline inhibited cyclin D2 transactivation and HDAC activity and could be a promising treatment for multiple myeloma.
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Amitriptilina/farmacología , Antidepresivos Tricíclicos/farmacología , Apoptosis/efectos de los fármacos , Ciclina D/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Mieloma Múltiple/metabolismo , Apoptosis/fisiología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Ciclina D/metabolismo , Histona Desacetilasas/metabolismo , Humanos , Mieloma Múltiple/enzimología , Mieloma Múltiple/patología , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/fisiologíaRESUMEN
This study was designed to investigate the distribution of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients, its clinical significance, and the expression profile of Th17 cell-associated cytokines. The percentage of Th17 cells detected by flow cytometry analysis (FACS) was significantly higher in 46 pancreatic tumor tissues (5.28 ± 1.65%) compared with corresponding adjacent normal tissues (2.57 ± 0.83%) (P = 0.031). In addition, the percentage of Th17 cells was significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.039). The percentage of Th17 cells in peripheral blood of 20 pancreatic cancer patients (3.99 ± 1.15%) was significantly higher than 15 healthy volunteers (1.98 ± 0.57%) (P = 0.027). Immunohistochemistry (IHC) was performed to detect IL-17(+) cells in 46 pancreatic tumor tissues, as well as expression of CD34 in 24 tumor tissues. IL-17 was shown to mainly locate in cytoplasm, and the frequency of IL-17(+) cells in tumor tissues (39/46) was higher than control (29/46). The presence of IL-17(+) cells in tumor tissues was associated with tumor, node, and metastasis (TNM) stage, and lymph node metastasis (P = 0.012 and P = 0.009) but not with patient sex, age, tumor size, and histological grade (P > 0.05). Interestingly, distribution of Th17 cells in tumor tissues was positively correlated with microvessel density (MVD) (r = 0.86, P = 0.018). Furthermore, the median survival time of patients with high and low level of IL-17(+) cells frequency was 14.5 and 18.5 months respectively (P = 0.023). The serum levels of Th17 cell-associated cytokines, IL-17 and IL-23 in 20 pancreatic patients detected by enzyme-linked immunosorbent assay (ELISA) were 69.2 ± 28.5 pg/mL and 266.5 ± 98.1 pg/mL, respectively, which were significantly higher than 15 healthy volunteers (P = 0.015 and P = 0.02). Moreover, levels of IL-17 and IL-23 were significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.04 and P = 0.036). This study suggests that increase in Th17 cells frequency and its related cytokines levels in pancreatic tumor tissues may indicate involvement in the invasion and metastasis of pancreatic cancer, which may thereby affect patient prognosis. Therefore, Th17 cells and related cytokines may be served as important immune indicators for predicting the prognosis of pancreatic cancer patients.
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Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/inmunología , Células Th17/citología , Microambiente Tumoral , Antígenos CD34/metabolismo , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: While the impact of Livin expression on patients with lung cancer was evaluated in previous studies, the results remained debatable. The relationship between Livin expression and clinicopathological features and prognosis in lung cancer was assessed in the present meta-analysis. METHODS: Web of Science, PubMed, Embase, Springer, Cochrane Library, China National Knowledge Internet database (CNKI), Wanfang database, Chinese VIP database and Chinese Biological Medical Database (CBM) were searched for relevant publications analyzing the role of Livin in prognosis and clinicopathological features of lung cancer before September 2020. The results were evaluated using pooled odds ratio (OR) and 95% confidence intervals (CIs) calculated by STATA 12.0 software. RESULTS: Twenty studies with a total of 1,395 patients were enrolled in this meta-analysis based on inclusion and exclusion criteria. Livin expression was significantly associated with smoking status (OR =2.51, 95% CI: 1.70-3.72, P<0.05), lung adenocarcinomas (LAC) (OR =2.16, 95% CI: 1.60-2.92, P<0.05), TNM stage (OR =2.49, 95% CI: 1.63-3.69, P<0.05) and poor differentiation (OR =2.04, 95% CI: 1.35-3.08, P<0.05). Livin expression was significantly related to metastasis (OR =4.22, 95% CI: 2.68-6.64, P<0.05) and lower 5-year overall survival (OR =4.23, 95% CI: 2.60-6.88, P<0.05) of patients with lung cancer. CONCLUSIONS: The results of our study manifested that Livin expression was significantly related to smoking status, LAC, high TNM stage, poor differentiation, metastasis and 5-year overall survival rate, which indicated that Livin may be a potential biomarker for prognosis of lung cancer.
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Despite efforts to abrogate the severe threat to life posed by the profound malignancy of mature natural killer/T-cell lymphoma (NKTCL), therapeutic advances still require further investigation of its inherent regulatory biochemical processes. Next-generation sequencing (NGS) is an increasingly developing gene detection technique, which has been widely used in lymphoma genetic research in recent years. Targeted therapy based on the above studies has also generated a series of advances, making genetic mutation a new research hotspot in lymphoma. Advances in NKTCL-related gene mutations are reviewed in this paper.
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Introduction: Numerous countries went into lockdown to contain the COVID-19 outbreak, which has impeded follow-up of chronic diseases, such as cognitive impairment (CI). Cognitive and neuropsychiatric changes during the COVID-19 pandemic are neglected in China, which is the world's whistleblower. To investigate the cognitive and neuropsychologic changes in CI, as well as the proportions of rapid cognitive decline (RCD) before and during the COVID-19 pandemic to provide clinical evidence for CI intervention during a public health emergency. Methods: We performed a descriptive and retrospective study based on medical records from the memory clinic of Tianjin Dementia Institute collected through face-to-face evaluations. Information of 205 patients with CI, including patients with mild cognitive impairment and dementia, of whom 131 with Alzheimer's disease (AD) were analyzed and compared to a control group before the COVID-19 pandemic. Results: Among the 205 CI patients, the scores on the Chinese Mini Mental State Examination (C-MMSE), the Montreal Cognitive Assessment (MoCA), activities of daily living (ADLs), and the global Neuropsychiatric Inventory (NPI) were significantly different at the baseline and follow-up evaluations (p < 0.05) after 14.07 (±2.87) months. The same findings were recorded among AD patients, and they exhibited more sleep disturbances at the follow-up than at baseline (32.8 vs. 20.6%, p = 0.035). When compared to the control group, slightly worse performance of cognitive, -1.00 (-4.00, 1.00) from the C-MMSE, -1.00 (-2.00, 0.00) on the MoCA, 1.00 (0.00, 9.00) on ADLs and neuropsychological 0.00 (-1.00, 3.50) on the global NPI profile, at the follow-up were presented, particularly for delusion, agitation, irritability, and appetite disturbances (p < 0.05). Twenty-five (19.1%) AD patients and 48 (36.6%) controls suffered RCD during the COVID-19 pandemic. Moreover, AD patients during the COVID-19 pandemic were 0.408 times (95% confidence interval: 0.232-0.716) less likely to suffer RCD than the control. Conclusion: Confinement might ease the cognitive and neuropsychiatric deterioration of AD patients compared to those not in crisis and help prevent RCD in AD patients.
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PURPOSE: To provide theoretical basis for clinical CAD/CAM restorations with a comparison of the fracture strength between two chairside CAD/CAM immediate restorative materials (IPS e.max CAD and Vita Enamic) with different occlusal thickness in vitro. METHODS: IPS e.max CAD and Vita Enamic full-crowns with occlusal thicknesses 1.5/2.0/2.5 mm were fabricated with CEREC and adhesively seated to dies customized by manufacturer (n=42). All specimens were stored in distilled water at 37 â for 24 h. Later, static fractural loading was performed. The fracture surface was observed through scanning electron microscope (SEM) and energy dispersive spectrum (EDS). The composites of two materials were detected by X-Ray diffraction (XRD) techniques. The results of fracture strength were analyzed by one-way ANOVA and t-test via SPSS 20.0 software package. RESULTS: With the increase of occlusal thickness, the fracture strength of IPS e.max CAD increased remarkably. However, the Vita Enamic's fracture strength remained the same with no significant difference. With the occlusal thickness increased from 1.5 to 2.0 mm, there was no significant difference in the fracture strength between IPS e.max CAD group and Vita Enamic group. As the thickness increased from 1.5 to 2.0 mm, the fracture strength of IPS e.max CAD group was significantly higher than that of Vita Enamic group. The results of SEM showed that the filler particles of IPS e.max CAD were smaller compared to that of Vita Enamic. Cone cracks were mainly found in the fracture surface of IPS e.max CAD, while radical cracks appeared in Vita Enamic. EDS showed the metal oxide and SiO2 in Vita Enmic was significantly higher than that in IPS e.max CAD. XRD showed that the primary crystal phase of IPS e.max CAD was lithium silicate, while Vita Enamic was amorphous. CONCLUSIONS: Both IPS e.max CAD and Vita Enamic can meet the standard of clinical application as the occlusal thickness reaches 1.5 mm. IPS e.max CAD showed better fracture resistance when the thickness was greater than 2.0 mm.
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Porcelana Dental , Resistencia Flexional , Cerámica , Diseño Asistido por Computadora , Ensayo de Materiales , Dióxido de Silicio , Propiedades de SuperficieRESUMEN
BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have revolutionized the therapeutic strategy for anemia in chronic kidney disease. However, some cases are resistant or hyporesponsive to ESAs. Roxadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Here, we describe a hemodialysis patient with refractory anemia who did not respond to traditional treatments and depended on blood transfusion for more than 1 year. After applying Roxadustat, the patient's anemia improved significantly. CASE SUMMARY: A 44-year-old man was diagnosed with uremia accompanied by severe anemia with a hemoglobin (Hb) level ranging from 30-40 g/L. His anemia did not improve after sufficient dialysis or high doses of active ESAs; other causes of anemia were excluded. The patient required approximately 600-1000 mL of red blood cell suspension every 15-30 d for more than 1 year. After accepting Roxadustat therapy, the patient's anemia symptoms improved significantly; his Hb level gradually increased to 50 g/L, and no further blood transfusions were administered. His Hb level reached 69 g/L by the 34th week. Although a Hb level of 60-70 g/L cannot be considered satisfactory, he no longer required blood transfusions and his quality of life was substantially improved. Roxadustat showed good efficacy and safety in this case. CONCLUSION: Roxadustat represents an innovative and effective agent for the clinical treatment of renal anemia caused by multiple complex factors.
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Background: While the lockdown strategies taken by many countries effectively limited the spread of COVID-19, those were thought to have a negative impact on older people. This study aimed to investigate the impact of lockdown on cognitive function and neuropsychiatric symptoms over a 1-year follow-up period in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Methods: We enrolled consecutive patients with MCI, probable AD or DLB who were receiving outpatient memory care before the COVID-19 pandemic and followed-up with them after 1 year by face-to-face during the COVID-19 pandemic to assess changes in physical activity, social contact, cognitive function and neuropsychiatric symptoms (NPS). Results: Total 105 probable AD, 50 MCI and 22 probable DLB patients were included and completed the 1-year follow-up between October 31 and November 30, 2020. Among the respondents, 42% of MCI, 54.3% of AD and 72.7% of DLB patients had a decline in MMSE scores and 54.4% of DLB patients had worsening Neuropsychiatric inventory (NPI) scores. Patients with DLB showed a more rapid decline of MMSE than those with AD. Diminished physical activity and social contact might have hastened the deterioration of cognition and the worsening of NPS. Conclusion: Social isolation and physical inactivity even after strict lockdown for at least 6 months were correlated with accelerated decline of cognitive function and NPS in patients with AD and DLB.
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BACKGROUND: Constipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations. OBJECTIVE: To assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes. METHODS: From May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures. RESULTS: The overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6-15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3-21.0), 19.1% (95% CI, 16.8-21.5), 14.4% (95% CI, 12.8-15.9), and 13.8% (95% CI, 13.0-14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02-1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09-1.54). CONCLUSION: The present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.