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Objective: To investigate the status quo of the quality of life of schizophrenia patients in a city in Sichuan Province and to explore, thereof, the urban-rural differences in the factors influencing their quality of life. Methods: A total of 824 schizophrenia patients were selected for the study through multistage stratified cluster random sampling method. All the subjects were selected from a pool of patients covered by the Sichuan Provincial Information System for the Comprehensive Management of Severe Mental Disorders. Questionnaire surveys were conducted with the Schizophrenia Quality of Life Scale (SQLS), the Social Support Rating Scale (SSRS), the general circumstance questionnaire, and the lifestyle questionnaire. In addition, univariate and multiple linear regression models were used to analyze the influencing factors of quality of life among schizophrenia patients living in urban areas and those in rural areas. Results: Rural patients had poorer quality of life than urban patients did in all measurement domains ( P<0.05). Marital status, vocational skills, physical exercise, and social support were influencing factors of the quality of life among urban patients ( P<0.05). Age, marital status, annual household income, vocational skills, participation in community rehabilitation activities, and the time required to walk to the nearest medical institution were influencing factors of the quality of life among rural patients ( P<0.05). Conclusion: Targeted measures for the enhancement of the quality of life of schizophrenia patients should be formulated on the basis of urban and rural characteristics in terms of economic support, vocational skills training, input in mental health services, community rehabilitation services, and social support.
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Calidad de Vida , Esquizofrenia , Humanos , Encuestas y Cuestionarios , Población Urbana , Población Rural , ChinaRESUMEN
Objective: To prospectively explore the risk factors of suicide in patients with schizophrenia. Methods: Data on schizophrenia patients in Sichuan Province between 2006 and 2018 were obtained from the National Severe Mental Disorders Information System, and the Cox proportional hazards regression model was used to explore for risk factors for suicide in schizophrenia patients. Result: A total of 170006 patients with schizophrenia were included in the study. At the end of the follow-up period, 160570 patients were alive and 9436 died from various causes, 929 of which being suicide deaths, resulting in a suicide rate of 223.61/100, 000 person-years. The Cox proportional hazards regression model suggested that risk factors for suicide in patients with schizophrenia included poverty ( HR=1.20, 95% CI: 1.02-1.41), higher education level (primary school [ HR=1.32, 95% CI: 1.09-1.60], middle school [ HR=1.40, 95% CI: 1.14-1.73], high school and above [ HR=1.93, 95% CI: 1.49-2.52]) in comparison with illiteracy and semi-literacy, suicide attempts ( HR=2.70, 95% CI: 1.70-4.29), strict medication compliance ( HR=1.91, 95% CI: 1.66-2.20), history of antipsychotic drug therapy ( HR=1.42, 95% CI: 1.06-1.90), younger age group of patients of 46-60 ( HR=1.95, 95% CI: 1.60-2.39), 31-45 ( HR=3.61, 95% CI: 2.92-4.47), and 15-30 ( HR=12.37, 95% CI: 9.69-15.78) compared with the 61-90 age group, and doing agriculture jobs ( HR=1.36, 95% CI: 1.13-1.65). Conclusion: Young and middle-aged schizophrenia patients with higher education levels, especially those with a history of suicide attempts, are at high risk for suicide. Focused interventions should be directed at high-risk groups to reduce suicide deaths in patients with schizophrenia.
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Esquizofrenia , Persona de Mediana Edad , Humanos , Esquizofrenia/epidemiología , Intento de Suicidio , Factores de Riesgo , China/epidemiologíaRESUMEN
Carcinogenesis is a very complex process involving a series of changes of tumor-related genes. Therefore, genes differentially expressed in tumors have received significant attention. Among them is the tumor differentially expressed (TDE) protein family, which shows no homologue to any other protein families and is unique to eukaryotes. The members of the TDE (also known as Serinc) family are highly conserved, showing approximately 30-80% homologue of their amino acid sequences. Previous reports have shown that both human and mice TDE/Serinc proteins are always upregulated in carcinomatous tissues. However, their precise physiological roles remain unclear. The human TDE2/Serinc1 gene was cloned by our laboratory during the screening for differentially expressed genes in hepatocarcinoma. In the present study, we knocked down the expression of TDE2 with specific siRNA fragments in two human hepatocarcinoma cell lines, and this caused cell cycle arrest at G2. Cell cycle progression is monitored and regulated by several factors. p21, the cdk inhibitor, is a key player and could be transcriptionally activated by many factors including sterol regulatory element-binding proteins (SREBPs). Previous research demonstrated that rat TDE2 could facilitate the cellular sphingolipids biosynthesis in both yeast and mammalian cells. Therefore, we further analyzed the effect of TDE2 knockdown on p21 and SREBP, and found that endogenous p21 expression was upregulated, as was that of SREBPs (-1a and 2). In conclusion, our preliminary results indicated that TDE2 may have an effect on tumor cell growth by influencing the expression of SREBP and p21.
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Carcinoma Hepatocelular/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias Hepáticas/metabolismo , Proteínas de la Membrana/genética , ARN Interferente Pequeño/genética , Activación Transcripcional , Línea Celular Tumoral , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular , Técnicas de Silenciamiento del Gen , Humanos , Proteínas de la Membrana/metabolismo , Regiones Promotoras Genéticas , Elementos de Respuesta , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Transcripción GenéticaRESUMEN
Dicarbonyl/l-xylulose reductase (DCXR), mainly catalysing the reduction of α-dicarbonyl compounds and l-xylulose, belongs to the short-chain dehydrogenase/reductase superfamily. Its enzyme activity can be inhibited by short-chain fatty acids. In this study, a novel DCXR inhibitor named (-)-epigallocatechin-3-gallate (EGCG) was reported. First, we overexpressed recombinant human DCXR in Escherichia coli, purified the enzyme by affinity chromatography and measured its activity. The inhibition effects of EGCG and its analogues on DCXR were determined subsequently, and EGCG showed the strongest inhibition with 50% inhibition concentration value of 78.8 µM. The surface plasmon resonance analysis also indicated that the equilibrium dissociation constant (KD) reached to 7.11 × 10(-8) M, which implied a high affinity between EGCG and DCXR. From enzyme kinetic analysis, EGCG acted as a mixed inhibitor against its forward and reverse substrates and the coenzyme, reduced nicotinamide adenine dinucleotide phosphate (NADPH). However, the inhibition is pH dependent. The molecular docking finally showed that EGCG formed several hydrogen bonds with the Thr190 residue of DCXR, and the model was further verified by site-directed mutagenesis. Therefore, EGCG is a potential inhibitor to human DCXR.
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Catequina/análogos & derivados , Inhibidores Enzimáticos/química , NADP/química , Deshidrogenasas del Alcohol de Azúcar/antagonistas & inhibidores , Deshidrogenasas del Alcohol de Azúcar/química , Dominio Catalítico , Catequina/química , Escherichia coli , Expresión Génica , Humanos , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , NADP/genética , NADP/metabolismo , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deshidrogenasas del Alcohol de Azúcar/genética , Deshidrogenasas del Alcohol de Azúcar/metabolismo , Resonancia por Plasmón de SuperficieRESUMEN
AIM: To investigate the association between TP53 Arg72Pro polymorphism and esophageal cancer (EC) risk using meta-analysis. METHODS: All eligible studies published before March 1, 2010 were selected by searching PubMed using keywords "p53" or "TP53", "polymorphism" or "variation", "esophageal" and "cancer" or "carcinoma". Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for EC risk associated with TP53 Arg72Pro polymorphism using fixed- and random-effects models. RESULTS: Nine case-control studies involving 5545 subjects were included in this meta-analysis. Significantly reduced risk of EC was associated with TP53 genotypes for Arg/Arg + Arg/Pro vs Pro/Pro (OR = 0.73, 95% CI: 0.57-0.94, P = 0.014). Subgroup analyses according to the source of controls and the specimens used for determining TP53 Arg72Pro genotypes or sample size showed that significantly reduced risk was observed only in studies which have population-based controls (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.66, P < 0.001), and use white blood cells or normal tissue to assess TP53 genotypes of cases (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.65, P < 0.001) or include at least 200 subjects (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.65, P < 0.001). Analysis restricted to well-designed studies also supported the significantly decreased risk of EC (Arg/Arg vs Pro/Pro: OR = 0.54, 95% CI: 0.46-0.64, P < 0.001). CONCLUSION: TP53 Arg72 carriers are significantly associated with decreased EC risk. Nevertheless, more well-designed studies are needed to confirm our findings.
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Neoplasias Esofágicas/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína p53 Supresora de Tumor/genética , Estudios de Casos y Controles , Bases de Datos Factuales , Genotipo , Humanos , Oportunidad Relativa , Factores de RiesgoRESUMEN
Lysozyme plays an important role in human innate immunity by causing bacterial cell lysis. We describe for the first time, the actual performance of human lysozyme g-like 2 (HLysG2), a mammalian g-type lysozyme. RT-PCR revealed that the HLysG2 gene was transcribed in eye and testis tissues. A spot was detected from human tears using 2D gel electrophoresis and was identified as HLysG2 using MALDI-TOF/TOF MS and a MASCOT search with a matching score of 140 and 27% sequence coverage of the whole amino acid sequence. To gain insight into the in vitro antimicrobial activities of HLysG2, the mature peptide-coding region was cloned into Pichia pastoris for heterogeneous expression. Recombinant HLysG2, had an optimal at pH 6.0 and 30 °C, reached the peak activity of 1.2 × 10(4)U/mg at the sodium ion concentration of 75 mM and showed a higher salt tolerance than human c-type lysozyme (HLysC). Recombinant HlysG2 inhibited Gram-positive bacterial growth and did not inhibit Gram-negative bacterial and Candida albicans growth. Results indicated that HLysG2 is a potent antibacterial protein that may play a role in the innate immunity of the human eye.
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Ojo/enzimología , Muramidasa/metabolismo , Testículo/enzimología , Secuencia de Aminoácidos , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Electroforesis en Gel de Poliacrilamida , Perfilación de la Expresión Génica , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Muramidasa/química , Muramidasa/genética , Muramidasa/aislamiento & purificación , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Lágrimas/efectos de los fármacos , Lágrimas/enzimología , TemperaturaRESUMEN
The 2 microm circle plasmid in Saccharomyces cerevisiae is a model for a stable, high-copy-number, extrachromosomal "selfish" DNA element. By combining a partitioning system and an amplification system, the plasmid ensures its stable propagation and copy number maintenance, even though it does not provide any selective advantage to its host. Recent evidence suggests that the partitioning system couples plasmid segregation to chromosome segregation. We now demonstrate an unexpected and unconventional role for the mitotic spindle in the plasmid-partitioning pathway. The spindle specifies the nuclear address of the 2 microm circle and promotes recruitment of the cohesin complex to the plasmid-partitioning locus STB. Only the nuclear microtubules, and not the cytoplasmic ones, are required for loading cohesin at STB. In cells recovering from nocodazole-induced spindle depolymerization and G(2)/M arrest, cohesin-STB association can be established coincident with spindle restoration. This postreplication recruitment of cohesin is not functional in equipartitioning. However, normally acquired cohesin can be inactivated after replication without causing plasmid missegregation. In the mtw1-1 mutant yeast strain, the plasmid cosegregates with the spindle and the spindle-associated chromosomes; by contrast, a substantial number of the chromosomes are not associated with the spindle. These results are consistent with a model in which the spindle promotes plasmid segregation in a chromosome-linked fashion.
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Segregación Cromosómica/fisiología , Proteínas Nucleares/metabolismo , Plásmidos/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/genética , Huso Acromático/fisiología , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proteínas Cromosómicas no Histona , Segregación Cromosómica/efectos de los fármacos , Cromosomas Fúngicos/efectos de los fármacos , Cromosomas Fúngicos/genética , Cromosomas Fúngicos/metabolismo , Citoplasma/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas Fúngicas/metabolismo , Cinetocoros , Microtúbulos/metabolismo , Mutación/genética , Nocodazol/farmacología , Fosfoproteínas/metabolismo , Plásmidos/genética , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transactivadores/metabolismo , Tubulina (Proteína)/genética , CohesinasRESUMEN
The 2 microm circle is a highly persistent "selfish" DNA element resident in the Saccharomyces cerevisiae nucleus whose stability approaches that of the chromosomes. The plasmid partitioning system, consisting of two plasmid-encoded proteins, Rep1p and Rep2p, and a cis-acting locus, STB, apparently feeds into the chromosome segregation pathway. The Rep proteins assist the recruitment of the yeast cohesin complex to STB during the S phase, presumably to apportion the replicated plasmid molecules equally to daughter cells. The DNA-protein and protein-protein interactions of the partitioning system, as well as the chromatin organization at STB, are important for cohesin recruitment. Rep1p variants that are incompetent in binding to Rep2p, STB, or both fail to assist the assembly of the cohesin complex at STB and are nonfunctional in plasmid maintenance. Preventing the cohesin-STB association without impeding Rep1p-Rep2p-STB interactions also causes plasmid missegregation. During the yeast cell cycle, the Rep1p and Rep2p proteins are expelled from STB during a short interval between the late G(1) and early S phases. This dissociation and reassociation event ensures that cohesin loading at STB is replication dependent and is coordinated with chromosomal cohesin recruitment. In an rsc2 Delta yeast strain lacking a specific chromatin remodeling complex and exhibiting a high degree of plasmid loss, neither Rep1p nor the cohesin complex can be recruited to STB. The phenotypes of the Rep1p mutations and of the rsc2 Delta mutant are consistent with the role of cohesin in plasmid partitioning being analogous to that in chromosome partitioning.
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Cromatina/genética , Cromatina/metabolismo , Proteínas Nucleares/metabolismo , Plásmidos/genética , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , ADN de Hongos/genética , ADN de Hongos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Fúngicas , Genes Fúngicos , Modelos Biológicos , Mutación , Fosfoproteínas , Saccharomyces cerevisiae/citología , Transactivadores/genética , Transactivadores/metabolismo , CohesinasRESUMEN
The yeast 2 micron plasmid achieves high fidelity segregation by coupling its partitioning pathway to that of the chromosomes. Mutations affecting distinct steps of chromosome segregation cause the plasmid to missegregate in tandem with the chromosomes. In the absence of the plasmid stability system, consisting of the Rep1 and Rep2 proteins and the STB DNA, plasmid and chromosome segregations are uncoupled. The Rep proteins, acting in concert, recruit the yeast cohesin complex to the STB locus. The periodicity of cohesin association and dissociation is nearly identical for the plasmid and the chromosomes. The timely disassembly of cohesin is a prerequisite for plasmid segregation. Cohesin-mediated pairing and unpairing likely provides a counting mechanism for evenly partitioning plasmids either in association with or independently of the chromosomes.