RESUMEN
CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both cultured cells and animal models. However, delivering large dCas9 fusion proteins to target cells and tissues is an obstacle to the widespread adoption of these tools for in vivo studies. Here, we describe the generation and characterization of two conditional transgenic mouse lines for epigenome editing, Rosa26:LSL-dCas9-p300 for gene activation and Rosa26:LSL-dCas9-KRAB for gene repression. By targeting the guide RNAs to transcriptional start sites or distal enhancer elements, we demonstrate regulation of target genes and corresponding changes to epigenetic states and downstream phenotypes in the brain and liver in vivo, and in T cells and fibroblasts ex vivo. These mouse lines are convenient and valuable tools for facile, temporally controlled, and tissue-restricted epigenome editing and manipulation of gene expression in vivo.
Asunto(s)
Sistemas CRISPR-Cas , Epigénesis Genética , Epigenoma , Edición Génica/métodos , Regulación de la Expresión Génica , Animales , Encéfalo/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Hígado/metabolismo , Masculino , Ratones , Ratones Transgénicos , Linfocitos T/metabolismoRESUMEN
OBJECTIVE: This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy. METHODS: This study reviewed the clinical characteristics and dose-volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child-Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated. RESULTS: Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child-Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child-Pugh ≥ 2). Pre-treatment Child-Pugh, body mass index and dose-volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose-volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683-0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635-0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child-Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719-0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657-0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1-2 and hepatic fibrosis require lower V15 dose limits. CONCLUSIONS: Risk assessment model constructed from Pre-treatment Child-Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nomogramas , Traumatismos por Radiación , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Masculino , Femenino , Estudios Retrospectivos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Persona de Mediana Edad , Anciano , Traumatismos por Radiación/etiología , Adulto , Anciano de 80 o más Años , Hígado/efectos de la radiaciónRESUMEN
Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.
RESUMEN
BACKGROUND: The post-insertion maintenance of central venous catheters(CVCs)is a common, vital procedure undertaken by nurses. Existing literature lacks a comprehensive review of evidence adoption for CVCs post-insertion maintenance specifically within the oncology context. This investigation assessed evidence-based practice by oncology nurses in the care of CVCs, elucidating facilitators and obstacles to this adoption process. METHODS: This was a sequential explanatory mixed methods study, executed from May 2022 to April 2023, adhering to the GRAMMS checklist. The study commenced with a cross-sectional study through clinical observation that scrutinized the adoption of scientific evidence for CVC maintenance, analyzing 1314 records from five hospitals in China. Subsequently, a semi-structured, in-depth interview with nurses based on the i-PARIHS framework was conducted to ascertain facilitators and barriers to evidence adoption for CVCs post-insertion maintenance. Fifteen nurses were recruited through purposive sampling. Descriptive statistics were used to summarize quantitative data, while content analysis was used to analyze qualitative data. RESULTS: An overall compliance rate of 90.0% was observed; however, two domains exhibited a lower adoption rate of less than 80%, namely disinfection of infusion connector and disinfection of skin and catheter. Three barriers and two facilitators were discerned from the interviews. Barriers encompassed (1) difficulty in accessing the evidence, (2) lack of involvement from nurse specialists, and (3) challenges from internal and external environments. Facilitators comprised (1) the positive attitudes of specialist nurses toward evidence application, and (2) the formation of a team specializing in intravenous therapy within hospitals. CONCLUSION: There exists a significant opportunity to improve the adoption of evidence-based practices for CVC maintenance. Considering the identified barriers and facilitators, targeted interventions should be conceived and implemented at the organizational level to augment oncology evidence-based practice, especially the clinical evidence pertinent to infection control protocols. TRIAL REGISTRATION: This investigation was sanctioned by the Medical Ethics Committee of Henan Cancer Hospital (Number 2023-KY-0014).
RESUMEN
Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining brain homeostasis. However, in neurodegenerative conditions, microglial cells undergo metabolic reprogramming in response to pathological stimuli, including Aß plaques, Tau tangles, and α-synuclein aggregates. This metabolic shift is characterized by a transition from oxidative phosphorylation (OXPHOS) to glycolysis, increased glucose uptake, enhanced production of lactate, lipids, and succinate, and upregulation of glycolytic enzymes. These metabolic adaptations result in altered microglial functions, such as amplified inflammatory responses and diminished phagocytic capacity, which exacerbate neurodegeneration. This review highlights recent advances in understanding the molecular mechanisms underlying microglial metabolic reprogramming in neurodegenerative diseases and discusses potential therapeutic strategies targeting microglial metabolism to mitigate neuroinflammation and promote brain health. Microglial Metabolic Reprogramming in Neurodegenerative Diseases This graphical abstract illustrates the metabolic shift in microglial cells in response to pathological stimuli and highlights potential therapeutic strategies targeting microglial metabolism for improved brain health.
Asunto(s)
Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/metabolismo , Microglía/metabolismo , Encéfalo/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: Sexual violence is far more prevalent in most societies than is usually suspected in daily life. However, no study has systematically summarized the global prevalence rate and the major outcomes of sexual violence against women. METHODS: We directed a wide-raging search in the PubMed, Embase, and Web of Science, catalogs since the beginning to December 2022 for relevant reports about the incidence of sexual fighting touching females. The occurrence frequency was assessed with a random-effects model. The heterogeneity was estimated with I 2 values. Differences by research features were assessed over subgroup evaluation and meta-regression. RESULTS: A total of 32 cross-sectional studies were included (a total of 19,125 participants). The pooled sexual violence rate was 0.29 (95% CI = 0.25-0.34). Subgroup analyses found that there was a higher rate of sexual violence against women in 2010-2019 period (0.33, 95% CI = 0.27-0.37), developing countries (0.32, 95% CI = 0.28-0.37), and interview (0.39, 95% CI = 0.29-0.49). The analysis found that more than half of women (0.56, 95% CI = 0.37-0.75) had post-traumatic stress disorder (PTSD) after experiencing sexual violence, and only a third of women considered seeking support (0.34, 95% CI = 0.13-0.55). CONCLUSIONS: Nearly one out of every three (29%) women around the world has been a victim of sexual violence in their life. This current study investigated the status and characteristics of sexual violence against women, which could provide an important reference for police and emergency health services management.
Asunto(s)
Delitos Sexuales , Trastornos por Estrés Postraumático , Femenino , Humanos , Masculino , Prevalencia , Conducta Sexual , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
A fluorescent and colorimetric poly (acrylamide)-based copolymer probe P(AAm-co-RBNCH) has been designed via free radical polymerization of a commercial acrylamide monomer with a rhodamine-functionalized monomer RBNCH. Metal ion selectivity of RBNCH was investigated by fluorescence and colorimetric spectrophotometry. Upon addition of Fe3+, a visual color change from colorless to red and a large fluorescence enhancement were observed for the ring-opening of the rhodamine spirolactam mechanism. The monomer gives a sensitive method for quantitatively detecting Fe3+ in the linear range of 100-200 µM, with a limit of detection as low as 27 nM and exhibiting high selectivity for Fe3+ over 12 other metal ions. The hydrogel sensor was characterized by FTIR, and the effects of RBNCH amount on gel content and swelling properties were explored. According to the recipe of 1.0 mol% RBNCH to the total monomers, the fabricated hydrogel sensor displayed a good swelling property and reversibility performance and has potential for application in the imaging of Fe3+ level in industrial wastewater.
RESUMEN
Baiyangdian Lake is a typical and largest multi-habitat lake in the North plain of China. To understand the generation and transmission of antibiotics resistance genes (ARGs) in multi-habitat lakes, the contents of nutrients (TC, TOC, TN, TP and TS), heavy metals (Zn, Cr, Ni, Cu, Pb, As, Cd and Hg), 22 antibiotics, 16S-rRNA(16S), Class I integron (intI1) and 20 ARGs were determined. Samples were taken from the Fuhe river, river estuaries, reed marshes, living area, fish ponds and open water of Baiyangdian Lake. The results showed that quinolones were the main pollutants in six habitats, and the content range was ND-104.94 ng/g. Thereinto, aac (6') -IB, blaTEM-1, ermF, qnrA, qnrD, tetG, sul1, sul2 and tetM were detected in all the analyzed samples. The absolute abundance of sul1 was the highest (5.25 × 105 copies/g-6.21 × 107 copies/g) in most of the samples. In these different habitats, the abundance of antibiotics and ARGs in river estuary was the highest, and that in reed marshes was the lowest. There was a significant positive correlation between the abundance of heavy metals (Cu, Pb, Zn, Ni, Cd, Hg) and the absolute abundance of 11 ARGs (P < 0.01). Redundancy analysis showed that Cu, Zn, intI1, TP and macrolides were the important factors affecting the distribution of ARGs. Our finding provides a more likely driving and influencing factor for the transmission of ARGs in lakes with complex and diverse habitats.
Asunto(s)
Mercurio , Metales Pesados , Animales , Antibacterianos/farmacología , Antibacterianos/análisis , Lagos , Cadmio/análisis , Plomo/análisis , Farmacorresistencia Microbiana/genética , Metales Pesados/análisis , Mercurio/análisis , Ecosistema , China , Sedimentos Geológicos , Monitoreo del AmbienteRESUMEN
Computed tomography (CT)-assessed body composition is considered a novel prognostic factor for cancer patients. Owing to the need for new prognostic markers for hepatocellular carcinoma (HCC) patients undergoing radiotherapy, we investigated the impact of body composition on outcomes in this patient population. We retrospectively evaluated 109 HCC patients receiving radiotherapy. The skeletal muscle index, subcutaneous adipose tissue index (SATI), and visceral adipose tissue index within 1 mo, before radiotherapy were assessed based on a single CT image slice at the level of the third lumbar (L3) vertebra. The impact of body composition parameters on progression-free survival (PFS) and overall survival (OS) was assessed. Overall, 62 (56.9%) patients died, and 47 (43.1%) patients experienced recurrence during a median follow-up period of 20.5 mo. Multivariate analysis revealed that SATI was an independent prognostic factor for both PFS (hazard ratio [HR] 0.542, P = 0.025) and OS (HR 0.385, P = 0.005). Patients with high SATI (n = 43) had significantly better PFS (P = 0.0093) and OS (P = 0.032) than those with low SATI (n = 66). CT-assessed SATI is an independent prognostic factor in HCC patients receiving radiotherapy. Further validation is warranted to determine whether this finding can be translated into other study populations.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Composición Corporal , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/radioterapia , Músculo Esquelético/patología , Pronóstico , Estudios RetrospectivosRESUMEN
A covalent organic framework (COF) was used as the support of the catalyst in this work in order to obtain an environmentally friendly catalyst with high catalytic performance, selectivity and stability for 4-nitrophenol hydrogenation. Pd tiny particles are fixed in the cavity of COF to obtain Pd/COF catalysts, which has a quite narrow particle size distribution (5.09 ± 1.30 nm). As-prepared Pd/COF catalysts (Pd loading-2.11 wt%) shows excellent catalytic performance (conversion - 99.3%, selectivity >99.0% and turnover frequency (TOF)-989.4 h-1) for 4-nitrophenol hydrogenation under relatively mild reaction conditions of reaction temperature-40 °C and reaction pressure-3.0 MPa H2, and Pd/COF catalysts have high stability. Pd/COF catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscope energy-dispersive X-ray spectroscopy (SEM-EDS), transmission electron microscope (TEM), high resolution TEM (HRTEM), Brunauer-Emmett-Teller (BET), scanning TEM energy-dispersive X-ray spectroscopy (STEM-EDS) elemental analysis techniques to prove that the Pd nanoparticles are highly dispersed on the COF. Pd/COF catalysts have good stability and reusability hence with certain industrial application value.
RESUMEN
BACKGROUND: Occupational stress among general practitioners (GPs) is a public health concern. This study aimed to investigate the prevalence and factors associated with occupational stress among GPs in China. METHODS: A cross-sectional design was used. Data were collected from 3,236 GPs in eastern, central, and western China (response rate, 99.75%) between October 2017 and February 2018 using a structured self-administered questionnaire. An ordinal logistic regression model was used to identify the factors associated with occupational stress among GPs. RESULTS: Among these respondents, 313 (9.67%), 1,028 (31.77%), and 1,895 (58.56%) of GPs had a low, medium, and high level of occupational stress, respectively. GPs from central China, with temporary work contracts, without management responsibility, receiving a moderate level of income, and with moderate occupational development opportunities had a lower level of occupational stress. GPs with greater than 40 working hours per week and those who worked overtime occasionally or frequently had a higher level of occupational stress. CONCLUSIONS: The prevalence of occupational stress among GPs is high in China. Substantial regional variation in determinants of occupational stress among GPs was observed. These findings should inform the design of policies to reduce the occupational stress of GPs.
Asunto(s)
Médicos Generales , Estrés Laboral , China/epidemiología , Estudios Transversales , Humanos , Estrés Laboral/epidemiología , Encuestas y CuestionariosRESUMEN
Due to the complex composition of ion-adsorbed type rare earth ore leaching solution, there are challenges in the process of rare earth (RE) separation, such as large RE loss rate, low product purity, radioactive residue and so on. In this article, 8-hydroxyquinoline modified silica gel (HQ-SiO2) and 2,2'-(1,4-phenylenebis(oxy)) dioctanoic acid (PPBOA) were used to form an efficient process for impurities removal and RE enrichment. Solid phase extraction successfully intercepted 96.7% of the radioactive element thorium. The concentration of aluminium was reduced to 2.14 ppm by frank chromatography. Rare earth elements were enriched from 336.35 mg/L to 237.75 g/L by extraction-precipitation, that is, the enrichment multiple reached more than 700 and the proportion of RE was increased from 21.85% to 96.62%. The loss rate of RE was controlled below 1.59%. Moreover, the magnesium salt leaching solution could be recycled for the leaching of RE ores. Although some liquid waste need to be treated in the processes of HQ-SiO2 production and regeneration, the integrated process helps to decrease volatile organic solvent, acid-base consumption, wastewater and waste residue. It is an environment-friendly RE enrichment and impurity removal process, which shows application potential in the production field of ion-adsorbed type rare earth mineral products.
Asunto(s)
Magnesio , Metales de Tierras Raras , Metales de Tierras Raras/análisis , Minerales , Reciclaje/métodos , Dióxido de SilicioRESUMEN
The aim of this study was to identify novel genetic variants affecting tacrolimus trough blood concentrations. We analyzed the association between 58 single nucleotide polymorphisms (SNPs) across the CYP3A gene cluster and the log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in 819 renal transplant recipients (Discovery cohort). Multivariate linear regression was used to test for associations between tacrolimus log (C0/D) and clinical factors. Luciferase reporter gene assays were used to evaluate the functions of select SNPs. Associations of putative functional SNPs with log (C0/D) were further tested in 631 renal transplant recipients (Replication cohort). Nine SNPs were significantly associated with tacrolimus log (C0/D) after adjustment for CYP3A5*3 and clinical factors. Dual luciferase reporter assays indicated that the rs4646450 G allele and rs3823812 T allele were significantly associated with increased normalized luciferase activity ratios (p < 0.01). Moreover, CYP3A7*2 was associated with higher TAC log(C0/D) in the group of CYP3A5 expressers. Age, serum creatinine and hematocrit were significantly associated with tacrolimus log (C0/D). CYP3A7*2, rs4646450, and rs3823812 are proposed as functional SNPs affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients. Clinical factors also significantly affect tacrolimus metabolism.
Asunto(s)
Citocromo P-450 CYP3A/genética , Inmunosupresores/farmacocinética , Trasplante de Riñón , Tacrolimus/farmacocinética , Adulto , Envejecimiento/metabolismo , Pueblo Asiatico , Estudios de Cohortes , Creatinina/sangre , Femenino , Variación Genética , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptores de TrasplantesRESUMEN
Cyanidin-3-glucoside (C3G) is a natural pigment, found in many colorful fruits and vegetables. It has many health benefits, including anti-inflammation, cancer prevention, and anti-diabetes. Although C3G is assumed to be an antioxidant, it has been reported to affect cell-matrix adhesions. However, the underlying molecular mechanism is unknown. Here, we show that the expression of talin1, a key regulator of integrins and cell adhesions, negatively correlated with the survival rate of colon cancer patients and that depletion of talin1 inhibited 3D spheroid growth in colon cancer cells. Interestingly, C3G bound to talin and promoted the interaction of talin with ß1A-integrin. Molecular docking analysis shows that C3G binds to the interface of the talin-ß-integrin complex, acting as an allosteric regulator and altering the interaction between talin and integrin. Moreover, C3G promoted colon cancer cell attachment to fibronectin. While C3G had no significant effect on colon cancer cell proliferation, it significantly inhibited 3D spheroid growth in fibrin gel assays. Since C3G has no or very low toxicity, it could be potentially used for colon cancer prevention or therapy.
Asunto(s)
Antocianinas/farmacocinética , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon , Glucósidos/farmacocinética , Proteínas de Neoplasias , Talina , Animales , Células CHO , Técnicas de Cultivo de Célula , Neoplasias del Colon/química , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Cricetinae , Cricetulus , Células HCT116 , Humanos , Simulación de Dinámica Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Talina/química , Talina/metabolismoRESUMEN
Organic polymeric flocculants are commonly used in improving dredged sludge dewaterability, but less attention has been paid to residual water quality. In this paper, the effects of cationic etherified starch (CS) and poly-dimethyl diallyl ammonium chloride (PDDA) on dredged sludge dewatering efficiency and residual water quality of Baiyangdian lake were comprehensively investigated and evaluated by analytic hierarchy process (AHP). The results indicated that PDDA had stronger electrical effect and flocculation performance compared with CS, resulting in more efficient dewatering performance. PDDA can reduce the pollutants of discharged residual water, while CS significantly promoted the increase of NH4+-N and NO3--N in the residual water. The increase of NH4+-N in the residual water of CS was due to the release of dredged sludge, while the increase of NO3--N was introduced by CS leaching. AHP showed that PDDA performed better in flocculation treatment of dredged sludge than other organic polymers. This work provides a method for optimization of flocculation treatment for dredged sludge dewaterability.
Asunto(s)
Polímeros , Aguas del Alcantarillado , Proceso de Jerarquía Analítica , Floculación , Eliminación de Residuos Líquidos , AguaRESUMEN
Human metapneumovirus (HMPV) is a leading cause of lower respiratory tract infection (LRTI) in pediatric and geriatric populations. We recently found that two PDZ-binding motifs of the M2-2 protein, 29-DEMI-32 and 39-KEALSDGI-46, play a significant role in mediating HMPV immune evasion in airway epithelial cells (AECs). However, their role in the overall pulmonary responses to HMPV infection has not been investigated. In this study, we found that two recombinant HMPVs (rHMPV) lacking the individual M2-2 PDZ-binding motif are attenuated in mouse lungs. Mice infected with mutants produce more cytokines/chemokines in bronchoalveolar lavage (BAL) fluid compared to mice infected with wild-type rHMPV. In addition, both mutants are able to enhance the pulmonary recruitment of dendritic cells (DCs) and T cells and induce effective protections against the HMPV challenge. The DC maturation is also significantly improved by the motif mutation. Taken together, our data provide proof-of-principle for two live-attenuated M2-2 mutants to be promising HMPV vaccine candidates that are effective in inducing higher pulmonary innate immunity and generating protection against HMPV infection.
RESUMEN
Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclin-dependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKIγ90 at S453, and that Cdk5-mediated PIPKIγ90 phosphorylation is essential for cell invasion. Moreover, Cdk5-mediated phosphorylation down-regulates the activity of PIPKIγ90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKIγ activity with the chemical inhibitor UNC3230 suppresses fibronectin secretion in a dose-dependent manner, whereas depletion of Cdk5 enhances fibronectin secretion. With total internal reflection fluorescence microscopy, we found that secreted fibronectin appears as round dots, which colocalize with Tks5 and CD9 but not with Zyxin. These data suggest that Cdk5-mediated PIPKIγ90 phosphorylation regulates cell invasion by controlling PIPKIγ90 activity and fibronectin secretion.-Li, L., Kolodziej, T., Jafari, N., Chen, J., Zhu, H., Rajfur, Z., Huang, C. Cdk5-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase type I γ 90 activity and cell invasion.
Asunto(s)
Neoplasias de la Mama/patología , Quinasa 5 Dependiente de la Ciclina/metabolismo , Fibronectinas/metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Quinasa 5 Dependiente de la Ciclina/genética , Femenino , Fibronectinas/genética , Humanos , Invasividad Neoplásica , Fosforilación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Transducción de Señal , Células Tumorales CultivadasRESUMEN
BACKGROUND: Studies on professional identity and related factors among Chinese general practitioners (GPs) are unavailable. The objective of this study was to investigate the professional identity level of GPs in China and explore factors associated with GPs' perceptions of their professional identity. METHODS: A multistage stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs working in community health service institutions (CHIs) in China between October, 2017 and February, 2018. Professional identity was measured by the 13 items scale. Descriptive statistics were calculated and groups' differences were estimated using nonparametric tests. Multiple linear stepwise regression analysis was used to analyze factors associated with professional identity among GPs. RESULTS: Based on a total score of 65 on the professional identity scale, the average score for GPs' professional identity was 51.23 (SD = 6.56). Multiple linear stepwise regression analysis showed that GPs who practiced in Central China, with an administrative responsibility, at a moderate or higher income level, who frequently worked overtime, had more occupational development opportunities, with a higher level of job satisfaction and older GPs had higher levels of professional identity. CONCLUSIONS: Professional identity level among GPs in China is high. Region, administrative responsibility, income level, working overtime, occupational development opportunities, age, and job satisfaction were significant predictors of professional identity.
Asunto(s)
Actitud del Personal de Salud , Médicos Generales , Identificación Social , China , Estudios Transversales , Femenino , Médicos Generales/estadística & datos numéricos , Humanos , Renta , Satisfacción en el Trabajo , Modelos Lineales , Masculino , Rol ProfesionalRESUMEN
Studies on turnover intention among Chinese general practitioners (GPs) at the national level are limited. This study aimed to assess intention to leave and its associated factors among a nationally representative sample of GPs. The participants were selected using a multistage stratified random sampling method. A self-administered structured questionnaire was used to collect data from 3236 GPs in China between October 2017 and February 2018. A multiple linear stepwise regression analysis was used to identify factors associated with turnover intention. Over 70.0% GPs had a moderate or high turnover intention. GPs who were male, were younger, had a higher education level, had a lower professional title, had a lower income level, and had a temporal work contract had higher turnover intention. In addition, GPs who worked night shifts, had low job satisfaction, and had few opportunities for professional development reported higher turnover intention. Substantial gender and regional differences in predictors of turnover intention among GPs were observed. The study showed that turnover intention in Chinese GPs is high, and the factors influencing turnover intention were low professional title and income level, high education level, having a temporary work contract, working night shifts, and limited opportunities for professional development.
Asunto(s)
Médicos Generales/psicología , Intención , Reorganización del Personal , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
We aim to quantitatively synthesise available epidemiological evidence on the prevalence rates of workplace violence (WPV) by patients and visitors against healthcare workers. We systematically searched PubMed, Embase and Web of Science from their inception to October 2018, as well as the reference lists of all included studies. Two authors independently assessed studies for inclusion. Data were double-extracted and discrepancies were resolved by discussion. The overall percentage of healthcare worker encounters resulting in the experience of WPV was estimated using random-effects meta-analysis. The heterogeneity was assessed using the I2 statistic. Differences by study-level characteristics were estimated using subgroup analysis and meta-regression. We included 253 eligible studies (with a total of 331 544 participants). Of these participants, 61.9% (95% CI 56.1% to 67.6%) reported exposure to any form of WPV, 42.5% (95% CI 38.9% to 46.0%) reported exposure to non-physical violence, and 24.4% (95% CI 22.4% to 26.4%) reported experiencing physical violence in the past year. Verbal abuse (57.6%; 95% CI 51.8% to 63.4%) was the most common form of non-physical violence, followed by threats (33.2%; 95% CI 27.5% to 38.9%) and sexual harassment (12.4%; 95% CI 10.6% to 14.2%). The proportion of WPV exposure differed greatly across countries, study location, practice settings, work schedules and occupation. In this systematic review, the prevalence of WPV against healthcare workers is high, especially in Asian and North American countries, psychiatric and emergency department settings, and among nurses and physicians. There is a need for governments, policymakers and health institutions to take actions to address WPV towards healthcare professionals globally.