RESUMEN

OBJECTIVE: To explore the status and influencing factors of job burnout among psychiatric nurses and provide a reference for hospital managers to carry out occupational and psychological interventions. METHODS: Between September 2021 and September 2022, the psychiatric nurses in Wuhan Wudong Hospital (Wuhan Second Psychiatric Hospital) were selected as research participants using convenience sampling. The Chinese version of the nursing burnout scale was used to investigate the psychiatric nurses in the hospital, and a multiple linear regression analysis was performed on the factors affecting job burnout. RESULTS: Among the 121 psychiatric nurses, 57.85 % had no or only mild job burnout, 36.36 % had mild to moderate job burnout and 5.79 % had severe job burnout. The one-way analysis of variance indicated that there were statistical differences in the scores in terms of marital status, educational background, working years, income, work departments and shifts (p < 0.05). The multiple linear regression analysis indicated that the main influencing factors of job burnout were working years and work department (p < 0.05). CONCLUSION: The detection rate of nurses' job burnout in the featured psychiatric hospital was 42.10 %. The main influencing factors of job burnout were working years and work department, and targeted intervention can be carried out according to these two factors.

Asunto(s)

Agotamiento Profesional , Personal de Enfermería en Hospital , Humanos , Encuestas y Cuestionarios , Satisfacción en el Trabajo , Estudios Transversales , Agotamiento Profesional/psicología , Hospitales Psiquiátricos , Personal de Enfermería en Hospital/psicología

RESUMEN

OBJECTIVE: To investigate the clinical efficacy of modified electroconvulsive therapy (MECT) in patients with schizophrenia and provide a reference for the selection of safe and effective treatment options in clinical practice. METHODS: A total of 200 patients with schizophrenia, who were admitted to Wuhan Wudong Hospital Psychiatric Hospital from January 2019 to December 2020, were selected as the study subjects. They were divided into an observation group and a control group (100 cases in each group) according to a random number table. The control group was treated with conventional antipsychotics (risperidone and aripiprazole), and the observation group was given conventional antipsychotics (risperidone and aripiprazole) with MECT. After 8 weeks, the clinical efficacy, cognitive and memory functions and the occurrence of adverse reactions between the two groups were compared. RESULTS: The total clinical effective rate of the observation group was 90%, which was higher than that of the control group (74%), and the difference was statistically significant (p<0.05). The Wisconsin Card Sorting Test results of the observation group were better than those of the control group, and the cognitive function of the observation group was better than that of the control group (p<0.05). The Wechsler Adult Intelligence Scale-Fourth Edition index of the observation group was higher than that of the control group, and the memory function of the observation group was better than that of the control group (p<0.05). The overall incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (p=0.001). CONCLUSION: The application of MECT in patients with schizophrenia can produce a good clinical curative effect, which is beneficial to the improvement and promotion of memory and cognitive functions in patients. Since the occurrence of adverse reactions is controllable, and safety is ideal, MECT has value in clinical application.

Asunto(s)

Antipsicóticos , Terapia Electroconvulsiva , Esquizofrenia , Adulto , Humanos , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/efectos adversos , Risperidona/efectos adversos , Aripiprazol/uso terapéutico , Terapia Electroconvulsiva/efectos adversos , Terapia Electroconvulsiva/métodos

RESUMEN

Objective: To investigate the effectiveness and clinical value of cholangiography in the diagnosis of bile duct stones in laparoscopic cholecystectomy. Methods: 200 patients who underwent laparoscopic cholecystectomy in our hospital from January 2017 to January 2019 were randomly divided into research group and control group, with 100 cases in each group. The research group underwent choledochotomy and exploration with the help of choledochoscope, while the control group underwent cholangiography to diagnose bile duct stones. The cure rate, residual stone rate, complication rate, intraoperative bleeding, hospital stay and patient satisfaction were compared between the two groups. Results: in the control group, 9 cases were converted to laparotomy, 20 cases of common bile duct stones, 10 cases of bile duct injury and 6 cases of common bile duct variation. In the research group, there were 2 cases of conversion to laparotomy, 12 cases of common bile duct stones, 2 cases of bile duct injury and 4 cases of common bile duct variation. The cure rate of the researchgroup was higher than that of the control group, There was significant difference between the two groups (P < 0.05). The residual amount of stones in the research group was lower than that in the control group, and there was significant difference between the two groups (P < 0.05). The incidence of postoperative complications in the research group was lower than that in the control group, and there was significant difference between the two groups (P < 0.05). The patient satisfaction in the research group was higher than that in the control group, and there was significant difference between the two groups (P < 0.05). The intraoperative blood output of the research group was lower than that of the observation group, and there was significant difference between the two groups (P < 0.05). Conclusion: cholangiography is an effective method for the diagnosis of bile duct stones in laparoscopic cholecystectomy. Clarifying the variation and anatomical structure of bile duct is helpful to improve the surgical cure rate, reduce the residual rate of postoperative stones and the incidence of complications, reduce the amount of intraoperative bleeding, shorten the hospital stay, and promote the postoperative rehabilitation of patients.

RESUMEN

The study assessed long-term immunopersistence and safety of the Escherichia coli (E. coli)-produced HPV-16/18 bivalent vaccine. In total, 979 participants in the initial immunogenicity noninferiority study, including girls aged 9-14 years who were randomized in a 1:1 ratio to receive 2 doses at months 0 and 6 (n = 301) or 3 doses at months 0, 1 and 6 (n = 304); girls aged 15-17 years (n = 149) and women aged 18-26 years (n = 225) who received 3 doses of the vaccine, were invited to participate in follow-up to 30 months post vaccination (NCT03206255). Serum samples were collected at months 18 and 30, and anti-HPV-16/18 IgG antibodies were measured by enzyme-linked immunosorbent assay. Serious adverse events (SAEs) occurred from month 7 through month 30 were recorded. At month 30, in the per-protocol set, all participants remained seropositive, except for one girl in the 9-14 years (2 doses) group who seroconverted to negative for HPV-18. HPV-16 and HPV-18 antibody levels were higher in girls aged 9-17 years who received 3 doses (125.3 and 60.2 IU/ml) than in women aged 18-26 years who received 3 doses (72.6 and 28.3 IU/ml), and those in girls aged 9-14 years who received 2 doses (73.2 and 24.9 IU/ml) were comparable to those in women aged 18-26 years who received 3 doses. No SAEs were reported to be causally related to vaccination. The E. coli-produced bivalent HPV-16/18 vaccine is safe and induces persistent protective antibodies for up to 30 months after vaccination in girls aged 9-17 years receiving 2 or 3 doses.

Asunto(s)

Vacunas contra Escherichia coli , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Anticuerpos Antivirales , China , Escherichia coli , Femenino , Papillomavirus Humano 18 , Humanos , Infecciones por Papillomavirus/prevención & control , Vacunas Combinadas

RESUMEN

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , SARS-CoV-2/inmunología , Adolescente , Adulto , COVID-19/sangre , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND: We initiated the first multi-center cluster randomized trial of endoscopic screening for esophageal cancer and gastric cancer in China. The objective of the study was to report the baseline screening findings in this trial. METHODS: We recruited a total of 345 eligible clusters from seven screening centers. In the intervention group, participants from high-risk areas were screened by endoscopy; in non-high-risk areas, high-risk individuals were identified using a questionnaire and advised for endoscopy. Lugol's iodine staining in esophagus and indigo carmine dye in stomach were performed to aid in the diagnosis of suspicious lesions. The primary outcomes of this study were the detection rate (proportion of positive cases among individuals who underwent endoscopic screening) and early detection rate (the proportion of positive cases with stage 0/I among all positive cases). RESULTS: A total of 149,956 eligible subjects were included. The detection rate was 0.7% in esophagus and 0.8% in stomach, respectively. Compared with non-high-risk areas, the detection rates in high-risk areas were higher, both in esophagus (0.9% vs. 0.1%) and in stomach (0.9% vs. 0.3%). The same difference was found for early-detection rate (esophagus: 92.9% vs. 53.3%; stomach: 81.5% vs. 33.3%). CONCLUSIONS: The diagnostic yield of both esophagus and stomach were higher in high-risk areas than in non-high-risk areas, even though in non-high-risk areas, only high-risk individuals were screened. Our study may provide important clues for evaluating and improving the effectiveness of upper-endoscopic screening in China. TRIAL REGISTRATION: Protocol Registration System in Chinese Clinical Trial Registry, ChiCTR-EOR-16008577. Registered 01 June 2016-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=14372.

Asunto(s)

Detección Precoz del Cáncer , Neoplasias Esofágicas , Lesiones Precancerosas , Neoplasias Gástricas , Adulto , Anciano , China , Neoplasias Esofágicas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/diagnóstico

RESUMEN

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) and health state utility scores of gastric cancer patients in daily life at different clinical stages after treatment, and to explore influencing factors associated with HRQoL. METHODS: Gastric cancer patients discharged from hospitals and healthy controls identified by screening were recruited. The three-level EQ-5D was employed to assess HRQoL and was scored using two Chinese-specific tariffs published in 2014 and 2018. RESULTS: A total of 1,399 patients and 2,179 healthy controls were recruited. The likelihood of reporting problems in the five dimensions for patients was 4.0-23.8 times higher than controls. Based on the 2014/2018 tariff, the mean EQ-5D utility score was 0.321/0.163 lower than controls, and the mean utility scores of each patient subgroup were 0.077/0.039 (high-grade intraepithelial neoplasia/carcinoma in situ), 0.254/0.121 (Stage I), 0.249/0.123 (Stage II), 0.353/0.182 (Stage III) and 0.591/0.309 (Stage IV) lower than controls (all statistically significant). Age, occupation, duration of illness, other chronic disease status and therapeutic regimen had a significant impact upon different aspects of HRQoL in patients. CONCLUSIONS: Gastric cancer significantly impaired patients' HRQoL in daily life after treatment. More advanced cancer stages were associated with larger decrements on health state utility.

Asunto(s)

Calidad de Vida , Neoplasias Gástricas , China , Enfermedad Crónica , Estudios Transversales , Estado de Salud , Humanos , Neoplasias Gástricas/terapia , Encuestas y Cuestionarios

RESUMEN

Salicylic acid (SA) is a key natural component that mediates local and systemic resistance to pathogens in many dicotyledonous species. However, its function is controversial in disease resistance in rice plants. Here, we show that the SA signaling is involved in both pathogen-associated-molecular-patterns triggered immunity (PTI) and effector triggered immunity (ETI) to Xanthomonas oryzae pv. Oryzae (Xoo) mediated by the recessive gene xa5, in which OsNPR3.3 plays an important role through interacting with TGAL11. Rice plants containing homozygous xa5 gene respond positively to exogenous SA, and their endogenous SA levels are also especially induced upon infection by the Xoo strain, PXO86. Depletion of endogenous SA can significantly attenuate plant resistance to PXO86, even to 86∆HrpXG (mutant PXO86 with a damaged type III secretion system). These results indicated that SA plays an important role in disease resistance in rice plants, which can be clouded by high levels of endogenous SA and the use of particular rice varieties.

Asunto(s)

Genes Recesivos/inmunología , Oryza/inmunología , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Xanthomonas/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas/inmunología , Genes de Plantas/inmunología , Interacciones Huésped-Patógeno/genética , Mutación , Oryza/química , Oryza/metabolismo , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Isoformas de Proteínas/metabolismo , Ácido Salicílico/análisis , Plantones/química , Plantones/metabolismo , Transducción de Señal/genética , Transducción de Señal/inmunología , Factores de Transcripción/genética , Factores de Transcripción/inmunología , Xanthomonas/genética , Xanthomonas/patogenicidad

RESUMEN

KEY MESSAGE: The bHLH transcription factor, PPLS1, interacts with SiMYB85 to control the color of pulvinus and leaf sheath by regulating anthocyanin biosynthesis in foxtail millet (Setaria italica). Foxtail millet (Setaria italica), a self-pollinated crop with numerous small florets, is difficult for cross-pollination. The color of pulvinus and leaf sheath with purple being dominant to green is an indicative character and often used for screening authentic hybrids in foxtail millet crossing. Deciphering molecular mechanism controlling this trait would greatly facilitate genetic improvement of cultivars in foxtail millet. Here, using the F2 bulk specific-locus amplified fragment sequencing approach, we mapped the putative causal gene for the purple color of pulvinus and leaf sheath (PPLS) trait to a 100 Kb region on chromosome 7. Expression analyses of the 15 genes in this region revealed that Seita.7G195400 (renamed here as PPLS1) was differentially expressed between purple and green cultivars. PPLS1 encodes a bHLH transcription factor and is localized in the nucleus with a transactivation activity. Furthermore, we observed that expression of a MYB transcription factor gene, SiMYB85 (Seita.4G086300) involved in anthocyanin biosynthesis, shows a totally positive association with that of PPLS1. Heterologous co-expression of both PPLS1 and SiMYB85 in tobacco leaves led to elevated anthocyanin accumulation and expression of some anthocyanin-related genes. Furthermore, PPLS1 physically interacts with SiMYB85. Taken together, our results suggest that PPLS1 interacts with SiMYB85 to control the color of pulvinus and leaf sheath by regulating anthocyanin biosynthesis in foxtail millet.

Asunto(s)

Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteínas de Plantas/genética , Pulvino/genética , Setaria (Planta)/genética , Factores de Transcripción/genética , Antocianinas/química , Clorofila/química , Color , Biología Computacional , Regulación de la Expresión Génica de las Plantas , Fenotipo , Filogenia , Polimorfismo de Nucleótido Simple

RESUMEN

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Asunto(s)

Vacunas contra Escherichia coli/administración & dosificación , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Adolescente , Adulto , Anticuerpos Neutralizantes/metabolismo , Niño , China , Relación Dosis-Respuesta en la Radiación , Escherichia coli/metabolismo , Vacunas contra Escherichia coli/efectos adversos , Femenino , Humanos , Inmunogenicidad Vacunal , Vacunas contra Papillomavirus/efectos adversos , Resultado del Tratamiento

RESUMEN

BACKGROUND: Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. CASE PRESENTATION: A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred. CONCLUSIONS: Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma.

Asunto(s)

Encefalitis/complicaciones , Enfermedad de Hashimoto/complicaciones , Miastenia Gravis/complicaciones , Receptores AMPA/inmunología , Timoma/complicaciones , Neoplasias del Timo/complicaciones , Encefalitis/inmunología , Femenino , Enfermedad de Hashimoto/inmunología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Miastenia Gravis/cirugía , Timectomía , Timoma/cirugía , Neoplasias del Timo/cirugía

RESUMEN

BACKGROUND: The improvement of diagnostic and therapeutic techniques has prolonged the survival time of patients with esophageal cancer. Little is known, however, about their health-related quality of life (HRQoL) in daily life after treatment. METHODS: Esophageal cancer patients who had been discharged from hospitals more than one year and healthy controls identified by screening were recruited from seven study centers covering eastern, central, and western regions of China. Patients were categorized into severe dysplasia/carcinoma in situ and stages I, II, III, and IV cancer, respectively. The EQ-5D was employed to assess HRQoL. Multivariate regression analyses were conducted. RESULTS: A total of 1456 patients and 2179 controls were recruited. After adjusting for potential confounding factors, the likelihood of reporting problems in the five dimensions of patients was 3.8 to 23.1 times higher than controls, whilst the mean EQ-5D utility score was 0.311 (95% CI, 0.276-0.346) lower than controls. The mean utility scores of each patient subgroup were 0.158, 0.289, 0.303, 0.296, and 0.505 (95% CIs: 0.108-0.208, 0.243-0.336, 0.261-0.346, 0.244-0.347, and 0.437-0.573) lower than controls, respectively. Patients had the greatest impairment in the self-care dimension compared with controls, followed by the usual activities dimension. Therapeutic regimen, duration of illness, other chronic disease status, age, and marital status also had significant impact on different aspects of HRQoL in patients. CONCLUSIONS: Esophageal cancer significantly impaired patients' HRQoL in daily life after treatment. Advanced cancer stages were associated with larger decrements on health state utility. Utility scores reported here can facilitate further cost-utility analyses.

Asunto(s)

Neoplasias Esofágicas/patología , Calidad de Vida/psicología , Anciano , China/epidemiología , Estudios Transversales , Neoplasias Esofágicas/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo

RESUMEN

OBJECTIVE: Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereas there were few studies on the financial burden of the two cancers. METHODS: Costs per hospitalization of all patients with stomach or esophageal cancer discharged between September 2015 and August 2016 in seven cities/counties in China were collected, together with their demographic information and clinical details. Former patients in the same hospitals were sampled to collect information on annual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost was obtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness (ACI) was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost, stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalization were itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars (1 USD=6.6423 RMB). RESULTS: Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urban patients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancer patients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACI was associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries. Western medicine fee took the largest proportion of cost per hospitalization. CONCLUSIONS: The ACI of stomach and esophageal cancer was tremendous and varied substantially among the population in China. Preferential policies of medical insurance should be designed to tackle with this burden and further reduce the health care inequalities.

RESUMEN

Growth-regulating factor (GRF) interacting factors (GIFs) are involved in several developmental processes in Arabidopsis. We previously showed that upregulation of OsGIF1 expression improves rice grain size. However, whether OsGIF1 is involved in other developmental processes remains unclear. Here, we report pleiotropic effects of OsGIF1 on rice organ size regulation. Overexpression and functional knock-out via a CRISPR/Cas9 strategy revealed that OsGIF1 not only positively regulates the sizes of rice leaf, stem, and grain but also influences rice reproduction. Expression profiles based on both qRT-PCR and GUS (ß-glucuronidase) histochemical staining suggested that OsGIF1 is differentially expressed across various rice tissues, consistent with its roles in regulating the development of multiple rice organs. Additionally, we found that OsGIF1-GFP localized preferentially in the nucleus, which supports its proposed role as a transcriptional cofactor. Further histological analysis suggested that OsGIF1 affected rice organ size possibly by regulating cell size. Our results suggest that OsGIF1 plays important roles in vegetative and reproductive developmental processes, with important implications for rice breeding.

RESUMEN

HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aß) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 µg/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 µmol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Aß transfer receptors.

Asunto(s)

Antígenos de Neoplasias/metabolismo , Encéfalo/citología , Células Endoteliales/metabolismo , VIH-1/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Ocludina/metabolismo , Transducción de Señal , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/farmacología , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho/metabolismo

RESUMEN

Disrupted blood-brain barrier (BBB) integrity contributes to cerebral edema during central nervous system infection. The current study explored the mechanism of lipopolysaccharide- (LPS-) induced dysregulation of tight junction (TJ) proteins. Human cerebral microvascular endothelial cells (hCMEC/D3) were exposed to LPS, SB203580 (p38MAPK inhibitor), or SP600125 (JNK inhibitor), and cell vitality was determined by MTT assay. The proteins expressions of p38MAPK, JNK, and TJs (occludin and zonula occludens- (ZO-) 1) were determined by western blot. The mRNA levels of TJ components and MMP-2 were measured with quantitative real-time polymerase chain reaction (qRT-PCR), and MMP-2 protein levels were determined by enzyme-linked immunosorbent assay (ELISA). LPS, SB203580, and SP600125 under respective concentrations of 10, 7.69, or 0.22 µg/mL had no effects on cell vitality. Treatment with LPS decreased mRNA and protein levels of occludin and ZO-1 and enhanced p38MAPK and JNK phosphorylation and MMP-2 expression. These effects were attenuated by pretreatment with SB203580 or SP600125, but not in ZO-1 expression. Both doxycycline hyclate (a total MMP inhibitor) and SB-3CT (a specific MMP-2 inhibitor) partially attenuated the LPS-induced downregulation of occludin. These data suggest that MMP-2 overexpression and p38MAPK/JNK pathways are involved in the LPS-mediated alterations of occludin in hCMEC/D3; however, ZO-1 levels are not influenced by p38MAPK/JNK.

Asunto(s)

Sistema de Señalización de MAP Quinasas/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ocludina/metabolismo , Regulación hacia Abajo , Células Endoteliales/metabolismo , Humanos , Lipopolisacáridos/farmacología , Fosforilación

RESUMEN

Peroxisome proliferator-activated receptor gamma (PPARƔ) contributes to human immunodeficiency virus (HIV)-1-induced dysfunction of brain endothelial cells. The aim of the present study was to evaluate the protection mechanism of PPARƔ against Tat-induced responses of adhesion molecules. We measured the protein expressions of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in human brain microvascular endothelial cells (hCMEC/D3) and C57BL/6J mouse brain microvessels with Western blotting and immunofluorescent labeling. The mRNA levels of ICAM-1 and VCAM-1 were determined by real-time reverse-transcriptase polymerase chain reaction. HIV-1 Tat induced overexpression of ICAM-1 but not VCAM-1 in both hCMEC/D3 and brain microvessels, this response was attenuated by treatment with the PPARƔ agonist rosiglitazone. Tat-mediated upregulation of ICAM-1 and VCAM-1 levels were abolished by the addition of PPARƔ antagonist GW9662 and the Akt inhibitor KP3721, indicating that Akt signaling is involved in the PPARƔ-mediated protection of Tat-induced adhesion molecule upregulation. These results show that Akt signaling plays a key role in PPARƔ's vascular inflammatory effects that contribute to blood-brain barrier damage.

Asunto(s)

Antiinflamatorios/farmacología , Endotelio Vascular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Tiazolidinedionas/farmacología , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/inmunología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/citología , Endotelio Vascular/inmunología , Endotelio Vascular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt , Rosiglitazona , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo

RESUMEN

Connexin 43 (Cx43) is a major structural protein found in the gap junctions of the ventricular myocardium and a major determinant of its electrical properties. The effects of matrix metalloproteinases (MMPs), the mitogen-activated protein kinase (MAPK) signaling pathway, transcription factor NF-kB, and activator protein-1 (AP-1)/c-Jun on the regulation of Cx43 gene expression in H9c2 cardiomyocytes were assessed. The MAPK signaling pathway (MEK/ERK1/2 and PI3K) and transcription factors NF-kB and AP-1/c-Jun were inhibited, then Cx43 expression was assessed using Western blot analysis, and MMP-9 activity was assessed using gelatin zymography. Hypoxia decreased the Cx43 protein level by approximately 30-50 %. Doxycycline (10 µg/mL), an inhibitor of MMP, markedly attenuated the hypoxia-induced downregulation of Cx43 protein expression at 6 h. The hypoxia-induced decrease in Cx43 protein expression was significantly reversed by U0126 (10 µM), a MEK/ERK1/2 inhibitor, at 6 and 12 h; LY294002 (30 µM), a PI3K inhibitor, downregulated Cx43 expression. Hypoxia-induced MMP-9 activation was inhibited by treatment with LY294002, U0126, and, most especially, U0126. JSH-23 (30 µM), an NF-kB inhibitor, and SP600125 (10 µM), an AP-1/c-Jun inhibitor, attenuated the loss of Cx43. These results suggest that MAPK signaling and the activities NF-kB and MMPs play an important roles in the regulation of Cx43 expression.

Asunto(s)

Conexina 43/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Metaloproteinasa 9 de la Matriz/metabolismo , Animales , Antracenos/farmacología , Butadienos/farmacología , Hipoxia de la Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromonas/farmacología , Conexina 43/biosíntesis , Regulación hacia Abajo , Doxiciclina/farmacología , Inhibidores Enzimáticos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Regulación de la Expresión Génica , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Morfolinas/farmacología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Nitrilos/farmacología , Fenilendiaminas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Regiones Promotoras Genéticas/genética , Ratas , Factor de Transcripción AP-1/metabolismo

RESUMEN

A combinatorial library of 6 × 106 cyclic peptides was synthesized in the one bead-two compound format, with each bead displaying a unique cyclic peptide on its surface and a linear peptide encoding tag in its interior. Screening of the library against K-Ras identified compounds that bound K-Ras with submicromolar affinity and disrupted its interaction with effector proteins.

RESUMEN

BACKGROUND: More and more percutaneous coronary intervention were done from radial artery approach. But the great limitation of radial artery approach and main failure cause of transradial coronary intervention is smaller size and more variations of a radial artery approach. The aim of the study is to explore the features and variations of a radial artery approach in southern Chinese populations and their clinical significance in percutaneous coronary intervention. METHODS: A total of 1400 patients who underwent scheduled first time transradial coronary angiography between July 2007 and September 2010 were enrolled. Radial arteriography was performed in all patients to detect the anatomical variations of this vessel. All patients' radial and ulnar artery inner diameters were measured using a computer assisted quantification method. A detailed patient history was recorded. Multivariate Logistic regression analysis was performed to evaluate the predictive value of variables (including age, gender, ethnicity, height, weight, body mass index, smoking, diabetes, hypertension and dyslipidemia) in arterial tortuosities and variations of this vessel. RESULTS: In southern Chinese populations, there were no significant differences in the diameters of the forearm arteries: the mean radial artery inner diameter was (3.04 ± 0.43) mm in ethnic Han Chinese and (3.05 ± 0.42) mm in ethnic Zhuang Chinese, P > 0.05), the mean ulnar artery inner diameter was (3.03 ± 0.38) mm in Han Chinese and (3.05 ± 0.36) mm in Zhuang Chinese, P > 0.05). It was estimated that the inner diameter of the radial artery was not smaller than a 6F Cordis sheath in 86.1% of male patients and in 57.0% of female patients, and not smaller than a 7F Cordis sheath in 59.3% of male patients and 24.9% of female patients. The factors found to positively affect the size of the radial artery were sex (bj = 0.309, P < 0.01), weight (bj = 0.103, P < 0.01), and diabetes mellitus (bj = -0.088, P < 0.01) was found to negatively affect radial artery size. Arterial tortuosities occurred in 12.1% of patients and arterial variations in 4.1%. The incidence of tortuosities and variations included radial artery tortuosity (3.6%), high origin of radial artery (1.7%), radial artery loop (0.6%), double radial artery (0.1%), brachial artery tortuosity (0.4%), double brachial artery (0.1%), subclavian artery tortuosity (5.4%), small subclavian artery (0.4%), right retro-esophageal subclavian artery (0.6%), brachiocephalic trunk tortuosity (2.8%), small brachiocephalic artery (0.1%), and brachiocephalic artery anomaly (0.4%). For people in Guangxi province, tortuosities of the subclavian artery and radial artery are the most common among the vascular tortuosities of the radial artery approach. The overall rate of transradial procedural success was 96.1%. Procedural failure was more common in patients with anomalous radial artery approach than in patients with normal radial artery approach (22.8% vs. 1.8%, P = 0.000). According to multivariate Logistic regression analysis, age (OR = 2.695, 95%CI 2.232 - 3.253, P = 0.000), female gender (OR = 5.127, 95%CI 3.000 - 8.762, P = 0.000), height (OR = 0.612, 95%CI 0.465 - 0.807, P = 0.000), body mass index (OR = 2.377, 95%CI 1.834 - 3.082, P = 0.000), hypertension (OR = 1.668, 95%CI 1.132 - 2.458, P = 0.010), hyperlipidemia (OR = 1.273, 95%CI 1.425 - 2.049, P = 0.034) and smoking (OR = 5.750, 95%CI 3.636 - 9.093, P = 0.000), were independently associated with arterial tortuosities of the radial artery approach. Female gender was independently associated with arterial variations of the radial artery approach (OR = 3.613, 95%CI 3.208 - 7.826, P = 0.000). CONCLUSIONS: The diameters of the radial and ulnar arteries between the Han people and the Zhuang people in southern Chinese populations are similar. In a transradial operation, the most southern Chinese populations, the use of a 6F sheath and guiding catheter is safe, and using a 7F sheath and guiding catheter is feasible in some selected patients. Radial arterial tortuosities and variations in southern Chinese populations are relatively common and are a significant cause of the failure of transradial coronary procedure. Old age, female gender, short stature, high body mass index, hypertension, hyperlipidemia and smoking, were independently associated with an increased risk of arterial tortuosity. In addition, female gender was an independent predictor of arterial variations.

Asunto(s)

Angioplastia Coronaria con Balón/métodos , Enfermedad Coronaria/terapia , Arteria Radial/cirugía , Anciano , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad