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The patient is a 2-year-old male. The family consulted the Department of Ophthalmology, Shanghai Ninth People's Hospital, after noticing a white reflection in the pupil area of the child's right eye for 6 days. Following a thorough ocular and systemic examination, the patient was diagnosed with retinoblastoma (Group E, cT2bN0M0) of the right eye. The right eye was enucleated and classified as pathological stage pT3cN0M0. Postoperatively, systemic intravenous chemotherapy with the VEC regimen was administered. Genetic testing revealed a germline mutation in the RB1 gene: c.874 (exon9) delT (p.Tyr292fsTer9), necessitating close monitoring of the socket during follow-up visits. Three months after the operation, fundus examination revealed yellow-white lesions in the left eye, and bilateral retinoblastoma was diagnosed (Group E in the right eye, Group C in the left eye). Based on the ICRB and pTNM stages, the patient underwent six rounds of systemic intravenous chemotherapy and three rounds of cryotherapy in the left eye. No recurrence was detected with a 4-year follow-up. The patient was initially diagnosed with unilateral retinoblastoma, but later developed the disease in the contralateral eye during treatment, which was a case of metachronous bilateral retinoblastoma.
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Neoplasias de la Retina , Retinoblastoma , Humanos , Masculino , Preescolar , Neoplasias de la Retina/terapia , Enucleación del Ojo , Mutación de Línea Germinal , Proteínas de Unión a Retinoblastoma/genética , Crioterapia , Ubiquitina-Proteína LigasasRESUMEN
In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.
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Hepatocitos , Factores de Transcripción , Animales , Ratas , Diferenciación Celular/genética , Proliferación Celular/genética , Hepatocitos/metabolismo , Hígado/metabolismo , Penicilinas/metabolismo , Factores de Transcripción/genéticaRESUMEN
The Dzyaloshinsky-Moriya interaction (DMI) at the Co/h-BN interface can emerge and be enhanced by applying a downward electric field. The height of the Co atom relative to the h-BN layer with the electric field determines the variation of DMI. One half reduction of J1 is beneficial to generate skyrmions. Tuning the DMI by an electric field sheds new light for research on skyrmions.
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Objective: To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44. Methods: CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44. Results: The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation (P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively(P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 (P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F (P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells (P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells (P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells(r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) (P<0.01). Conclusions: Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.
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Carcinoma , Neoplasias Nasofaríngeas , Línea Celular Tumoral , Proliferación Celular , Humanos , Receptores de Hialuranos , Carcinoma Nasofaríngeo , Transducción de Señal , Células MadreRESUMEN
Objective: To observe the biocompatibility of porcine omental derived extracellular matrix (ECM) hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the feasibility of ECM hydrogel as a delivery vector of cell transplantation. Methods: A series of chemical, physical and enzymatic methods were applied to acellularize the porcine omentum. Subsequently, the extracted ECM was prepared into thermosensitive hydrogel. The biochemical composition of the hydrogel was identified by histological staining. The microstructure was observed by scanning electron microscopy. The hydrogel was then injected into the myocardium of mice to observe its in situ gelation ability. Differentiation of human induced pluripotent stem cells into cardiomyocytes was achieved by small molecule induction, and then the obtained hiPSC-CMs were cultured. hiPSC-CMs cultured onto the prepared hydrogel were defined as the hydrogel group, while conventionally cultured hiPSC-CMs were defined as the control group. Cardiomyocyte viability and growth patterns were detected using live/dead staining, CCK-8 and phalloidin staining. Immunofluorescence staining and Western blot of cardiomyocytes were used to determine the survival and phenotypic maintenance markers of cardiomyocytes in materials. Results: The results of HE staining, oil red O staining and DAPI fluorescence staining showed that there was no significant cell debris, nucleus and lipid residue in the prepared ECM hydrogel. The Sirius red staining and Alcian blue staining showed that the hydrogel retained collagen and glycolaminoglycan, which were the main components of ECM. The prepared hydrogel behaves as a viscous liquid at 4 â and as a gel state at 37 â. Scanning electron microscope results showed that the microstructure of the hydrogel was composed of irregular fibers and pores of different sizes. Under the guidance of ultrasound, the prepared ECM hydrogel could be successfully injected into the myocardium of mice. Immediately after the injection, the hyperechoic signal could be observed under ultrasound, suggesting that the hydrogel remained in the myocardium. HE staining of myocardial tissue evidenced that there was lump of gel in the injection area. The differentiated hiPSC-CMs were co-cultured with the prepared ECM hydrogel, and the results of live/dead staining showed that most of the hiPSC-CMs in the hydrogel group and the control group were alive, dead cells were scanty. The results of CCK-8 test showed that the absorbance values of the two groups were similar (P>0.05). The results of phalloidin staining showed that hiPSC-CMs could extend normally when co-cultured with ECM hydrogel. The cell morphology of the hydrogel group was similar with that of the control group, and there was no statistically significant difference in the F-actin coverage area per cell between the two groups (P>0.05). Immunofluorescence staining of cardiomyocyte markers showed that there was no significant difference in the coverage area of α-actinin and connexin-43 (Cx-43) per field between the hydrogel group and the control group (both P>0.05), the quantitative results of DAPI staining showed that there was no statistically significant difference in the number of cells between the two groups (P>0.05). Meanwhile, the results of Western blot showed that the expression levels of α-actinin and Cx-43 in cardiomyocytes in the hydrogel group were similar as those in the control group (both P>0.05). Conclusions: These results show that preparation of the ECM hydrogel from porcine omentum is successful. The hydrogel has good biocompatibility and no obvious cytotoxicity. Besides, the hydrogel can support the survival of hiPSC-CMs in vitro and maintain its phenotype. These properties make it a promising injectable cardiac tissue engineering material.
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Células Madre Pluripotentes Inducidas , Animales , Diferenciación Celular , Células Cultivadas , Matriz Extracelular , Humanos , Hidrogeles , Ratones , Miocitos Cardíacos , PorcinosRESUMEN
Objective: To investigate the impact of obstructive sleep apnea (OSA) on long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Methods: This is a single-center, prospective cohort study. Between June 2015 to January 2020, consecutive ACS patients hospitalized at Beijing Anzhen Hospital, Capital Medical University were enrolled. All patients underwent portable sleep breathing monitoring, and they were then divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 events/hour) and no/mild OSA group (AHI<15 events/hour). The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, ischemia-driven revascularization and hospital admission for unstable angina or heart failure. MACCE were compared yearly by the log-rank test. Multivariable Cox regression analyses were performed to determine the independent predictors of MACCE. Results: A total of 1 927 patients with ACS were enrolled, including 1 629 males (84.5%), aged (56.4±10.5) years. Moderate/severe OSA was present in 1 014 (52.6%) patients. Compared with no/mild OSA group, moderate/severe OSA group exhibited a higher body mass index (P<0.05). Hypertension, prior PCI were more prevalent in moderate/severe OSA group (both P<0.05). The difference of ACS category between the two groups was statistically significant (P=0.021). The rate of patients who underwent PCI and the number of stents were higher in the moderate/severe OSA group. During a 5-year follow-up (median 2.9 years (IQR 1.5-3.6 years)), the cumulative incidence of MACCE was significantly higher in the moderate/severe OSA group than in the no/mild OSA group (34.0% vs. 24.0%, HR=1.346, 95%CI 1.100-1.646, log-rank P=0.004). The cumulative incidence of MACCE remained statistically higher at 4 and 5 year in the moderate/severe OSA group as compared to the no/mild OSA group (33.3% vs. 22.9%, HR=1.397, 95%CI 1.141-1.710, log-rank P=0.001; 34.0% vs. 24.0%, HR=1.341, 95%CI 1.096-1.640, log-rank P=0.004, respectively). Multivariate analysis showed that moderate/severe OSA (HR=1.312, 95%CI 1.054-1.631, P=0.015) was an independent predictor of long-term MACCE in ACS patients. Conclusions: Moderate/severe OSA is observed in more than 52% ACS patients. Moderate/severe OSA is an independent predictor of long-term MACCE.
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Objective: To identify predictors of massive blood loss after posterior hemivertebra resection for patients with congenital scoliosis. Methods: The data of 106 children with congenital scoliosis were collected from June 2017 to June 2019 in Beijing Children's Hospital. All the cases received posterior hemivertebra resection and internal fixation. The blood volume was estimated by weight and height. The visible blood loss was recorded according to medical record, and the hidden blood loss was calculated by OSTHEO formula. Perioperative information including age, gender, height, weight, Cobb and kyphosis angle, level fused, number of screws, operative time, and laboratory examinations was collected. Then multivariable linear regression was performed to determine the independent risk factors of blood loss. Results: All the surgeries were completed successfully. The mean age of the children was (7.3±2.3) years and the operative time was (162±56) min. The mean fused levels were 3 and the correction rate for deformity was 78.4%. The amount of blood loss was (568±208) ml which accounted for 42.3% of total blood volume. The visible and hidden blood loss was (334±193) ml and (234±199) ml, respectively, and which accounted for 58.8% and 41.2% of total blood loss. Multivariable linear regression analysis indicated that age, preoperative Cobb angle, the time of surgery and the number of fused levels were independent risk factors of total blood loss. Preoperative Cobb angle ≥40°, spinal fusion ≥4 levels and operative duration ≥140 min indicated more blood loss (all P<0.05). Conclusions: The perioperative blood loss of congenital scoliosis is massive with a high percentage of hidden blood loss. The patients with severe deformity, more fused levels and increased operative time brings higher risk of massive blood loss.
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Escoliosis , Fusión Vertebral , Pérdida de Sangre Quirúrgica , Niño , Preescolar , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To investigate the relationship between different waist-hip ratios and sleep-disordered breathing (SDB) in patients with acute coronary syndrome (ACS) and its effect on patients' long-term prognosis. Methods: A total of 725 patients who were diagnosed with ACS in the emergency ward of Beijing An Zhen Hospital from June 2015 to May 2017 were included, and all the patients were monitored for sleep and breathing. Patients were divided into four groups according to their waist-hip ratios. The differences of SDB-related indicators among the four groups were compared, and the correlation between different waist-hip ratios and SDB was analyzed using multiple logistic regression. COX regression analysis and Kaplan-Meier curve were used to compare the prognostic differences among the four groups. Results: As the waist-hip ratio increased, the apnea hypopnea index (AHI) (P=0.004) and the proportion of sleep apnea hypopnea syndrome (OSAHS) increased (39.3% vs 46.0% vs 53.2% vs 60.0%, P=0.004). Meanwhile, the number of hypoventilation increased, and the mean and minimum arterial oxygen saturation (SaO(2)) decreased (all P<0.001). Logistic regression analysis showed that high waist-hip ratio was significantly related with OSAHS (OR=2.579, 95%CI 1.521-4.373, P<0.001). The survival curves showed the highest incidence of major cardio-cerebral vascular events (MACCE) occurred in the high waist-hip ratio group (Log Rank P=0.036). COX regression analysis showed that high waist-hip ratio was an independent risk factor for MACCE in ACS patients (HR=2.855, 95%CI 1.375-5.929, P=0.005). Conclusions: In ACS patients, central obesity is related with SDB. Patients with high waist-hip ratio have a poor prognosis. Elevated waist-hip ratio and SDB jointly impact the prognosis of ACS patients.
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Síndrome Coronario Agudo , Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Humanos , Pronóstico , Factores de Riesgo , Relación Cintura-CaderaRESUMEN
Objective: To investigate the effect of obstructive sleep apnea (OSA) on cardiac structure and function in patients with acute coronary syndrome (ACS). Methods: A total of 767 patients with ACS consecutively hospitalized at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017 were enrolled in this study. There were 637 males and 130 females. Patients who met the inclusion criteria according to the sleep apnea hypopnea index (AHI) were examined with portable sleep respiration monitoring. Patients were divided into moderate or severe OSA group (AHI≥15,n=389) and non or mild OSA group (AHI<15, n=78). The general information and echocar diographic results were analyzed. The data fitted normal distribution were compared between the groups with independent sample t test. Results: The body mass index [(27.8±3.6) vs (25.8±3.4) kg/m(2), t=-7.854, P<0.01], neck circumference [(41.1±4.2) vs (39.3±3.2) cm, t=-6.717, P<0.01] and waist-to-hip ratio (0.99±0.54 vs 0.97±0.53, t=-4.735, P<0.01) at admission were significantly higher in moderate or severe OSA group than those in non or mild OSA group. The left ventricular end-diastolic diameter, inter-ventricular septum thickness, left atrial diameter,right atrial diameter were all significantly higher, and the E/A peak ratio was remarkably lower in the moderate or severe OSA group (t=-2.130, 0.278, -3.045, -2.241, 2.260, all P<0.05). Conclusion: Moderate or severe OSA may aggravate cardiac remodeling and diastolic function in ACS patients.
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Síndrome Coronario Agudo , Apnea Obstructiva del Sueño , Síndrome Coronario Agudo/complicaciones , Diástole , Femenino , Ventrículos Cardíacos , Humanos , Masculino , Polisomnografía , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m(2) vs. (26.6±3.5) kg/m(2), all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO(2)) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO(2) was significant (ß=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO(2), and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration: clinicalTrials.gov, NCT03362385.
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Enfermedad Coronaria/complicaciones , Hipotiroidismo/complicaciones , Síndromes de la Apnea del Sueño/fisiopatología , Índice de Masa Corporal , Peso Corporal , Enfermedad Coronaria/fisiopatología , Femenino , Humanos , Hipotiroidismo/fisiopatología , Hipoxia , Análisis Multivariante , Polisomnografía/métodos , Análisis de Regresión , Pruebas de Función Respiratoria/métodos , Sueño , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Ronquido/diagnóstico , Ronquido/fisiopatologíaRESUMEN
Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m(2) vs. (25.55±3.44) kg/m(2), t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ(2)=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ(2)=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ(2)=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration: Clinical Trial.gov, NCT03362385.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Apnea Obstructiva del Sueño , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/terapia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Apnea Obstructiva del Sueño/complicacionesAsunto(s)
Procedimientos Quirúrgicos Ambulatorios , Histeroscopía , Embarazo , Femenino , Humanos , Consenso , Pueblos del Este de AsiaRESUMEN
This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17,304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048-1·785], current smoking (aOR 1·607, 95% CI 1·177-2·195), elevated BUN (aOR 1·782, 95% CI 1·188-2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.
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Sífilis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Asunción de Riesgos , Adulto JovenRESUMEN
BACKGROUND: The latency-associated transcript (LAT) gene of herpes simplex virus (HSV)-2 is the only detectable viral gene expressed during latent infection in neurons. LAT inhibits apoptosis and maintains latency by promoting the survival of infected neurons. However, whether LAT functions during HSV-2 infection via its encoded RNAs or via its encoded proteins remain unknown. Increasing evidence has indicated that LAT is likely to functionally promote the establishment of latent infection via LAT-encoded microRNAs (miRNAs). AIM: To explore whether the RL1 fragment of the five adjacent miRNAs has an effect on cell apoptosis, then provide supporting evidence to elucidate the potential role of these miRNAs and to aid screening of their cellular targets. METHODS: A number of techniques, including MTT assay, flow cytometry and DNA ladder analysis, were used to verify the role of the RL1 fragment and the contribution of the individual miRNAs to the anti-apoptotic effect. RESULTS: Five miRNAs (miR-H3, miR-H4-3p, miR-H4-5p, miR-H24 and miR-H19) were detected by quantitative PCR in PC12 cells stably expressing RL1 after pEGFP-RL1 plasmid transfection in vitro. The data indicated that expression of HSV-2 LAT RL1 seems to provide protection against apoptosis of PC12 cells induced by ActD. Antisense miRNAs specifically inhibiting these five miRNAs could efficiently reduce their expression. Transfection of antisense-miR-H3, antisense-miR-H4-5p and antisense-miR-H19 into PC12 cells stably expressing RL1 were able to partly reverse the anti-apoptotic effect of these miRNAs. CONCLUSIONS: These findings indicate that the apoptotic role of the RL1 fragment is likely to be related to overexpression of miR-H3, miR-H4-5p and miR-H19 in PC12 cells.
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Apoptosis/genética , Regulación Viral de la Expresión Génica/fisiología , Herpesvirus Humano 2/genética , Proteínas Virales/fisiología , Latencia del Virus/genética , Animales , Técnicas de Cultivo de Célula , Dactinomicina , MicroARNs , Células PC12 , RatasRESUMEN
Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.
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Síndrome Coronario Agudo/tratamiento farmacológico , Isquemia/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Humanos , Intervención Coronaria Percutánea , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.
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Carcinoma de Células Renales , Neoplasias Renales , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Anciano , Carcinoma de Células Renales/epidemiología , Incidencia , Bases de Datos Factuales , China , Neoplasias Renales/epidemiología , Salud GlobalRESUMEN
Objective: To clarify the epidemiological characteristics and spatiotemporal clustering dynamics of COVID-19 in Shanghai in 2022. Methods: The COVID-19 data presented on the official websites of Municipal Health Commissions of Shanghai during March 1, 2022 and May 31, 2022 were collected for a spatial autocorrelation analysis by GeoDa software. A logistic growth model was used to fit the epidemic situation and make a comparison with the actual infection situation. Results: Pudong district had the highest number of symptomatic and asymptomatic infectants, accounting for 29.30% and 35.58% of the total infectants. Differences in cumulative attack rates and infection rates among 16 districts (P<0.001) were significant. The rates were significantly higher in Huangpu district than in other districts. The attack rate of COVID-19 from March 1, 2022 to May 31, 2022 had a global spatial positive correlation (P<0.05). Spatial distribution of COVID-19 attack rate was different at different periods. The global autocorrelation coefficient from March 16 to March 29, April 6 to April 12 and May 18 to May 24 had no statistical significance (P>0.05). Our local autocorrelation analysis showed that 22 high-high clustering areas were detected in eight periods.The high-risk hot-spot areas have experienced a "less-more-less" change process. The growth model fitting results were consistent with the actual infection situation. Conclusion: There was a clear spatiotemporal correlation in the distribution of COVID-19 in Shanghai. The comprehensive prevention and control measures of COVID-19 epidemic in Shanghai have effectively prohibited the growth of the epidemic, not only curbing the spatially spread of high-risk epidemic areas, but also reducing the risk of transmission to other cities.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiología , China/epidemiología , Brotes de Enfermedades , Análisis EspacialRESUMEN
BACKGROUND: The human immunodeficiency virus (HIV) epidemic and increasing use of immunosuppressive agents have increased the prevalence of both cryptococcosis and tuberculosis (TB). However, the status of co-infection with both pathogens remains unknown. METHODS: This study retrospectively reviewed patient records of cryptococcosis and TB co-infection from 1993 to 2006. The temporal sequence of co-infection was defined as either concurrent or sequential. Data collected included patient demographics, HIV status, co-morbidities, clinical manifestations, treatment strategies, and outcome at 1-year follow-up. RESULTS: There were 23 patients with cryptococcosis and TB co-infection, representing 5.4% of cryptococcosis or 0.6% of TB cases. Eleven (48%) patients were HIV-infected, and no underlying disease or immunocompromised state could be identified in six (26%) patients. Twelve (52%) patients presented with concurrent infection, but diagnosis of co-infection could be achieved simultaneously in only three (13%). Constitutional symptoms, particularly fever and weight loss, were the most common presenting symptoms, developing in more than two-thirds of the patients. The majority (83%) of the patients made a good recovery following dual antifungal and anti-TB therapy. There were three mortalities at the 1-year follow-up, which might be attributable to a delay in diagnosis and treatment of co-infection. The outcomes of HIV-infected and non-HIV-infected patients were not significantly different. CONCLUSIONS: Cryptococcosis and TB co-infection, although rare, develops in both immunocompromised and healthy individuals. Early diagnosis and treatment may improve patient prognosis. There should be a high index of suspicion in order to achieve a timely diagnosis in a TB endemic area.
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Criptococosis/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Tuberculosis/epidemiología , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Criptococosis/tratamiento farmacológico , Criptococosis/etiología , Criptococosis/microbiología , Cryptococcus neoformans/aislamiento & purificación , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán , Tuberculosis/tratamiento farmacológico , Tuberculosis/etiología , Tuberculosis/microbiologíaRESUMEN
OBJECTIVES: To help obstetric hospitals and clinics to implement newborn hearing screening and to test the feasibility of a pre-paid model for screening. PATIENTS AND METHODS: From July 2005 to August 2008, we organised a coordinated newborn hearing screening team with portable automated auditory brainstem response (AABR) to provide in-patient screening after delivery and out-patient re-screening at one month of age in birthing facilities throughout Changhua County, Taiwan. This was a community-based study organised by otolaryngologists at a tertiary referral centre. RESULTS: Ten medical facilities participated in our screening programme. 7,139 out of 12,901 neonates delivered in these facilities during the period were screened for hearing loss. 105 (1.47%) babies who did not pass the in-patient screening were re-screened at one month old. Forty (0.56%) babies referred from the re-screening were sent for diagnostic work-up and six of them failed to show up. The overall follow-up rate was 94.3% (99/105). Eleven babies with bilateral hearing loss and eight babies with unilateral hearing loss were diagnosed. The incidence of bilateral hearing loss in our programme was 1.5/1000. The screening rate descended from medical centre to clinic (p < 0.0001). There was no significant difference between the referral rates for different levels of birthing facilities (p = 0.5611). CONCLUSIONS: Our study demonstrates that a pre-paid model using AABR is feasible at all three levels of medical facilities. Pre-paid community-based screening might be an option for developing countries in the implementation of universal newborn hearing screening.
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Tamizaje Neonatal/organización & administración , Servicios de Salud Comunitaria , Potenciales Evocados Auditivos del Tronco Encefálico , Estudios de Factibilidad , Humanos , Recién Nacido , Tamizaje Neonatal/economía , Emisiones Otoacústicas Espontáneas , TaiwánRESUMEN
Sphenoid fungal balls are rare and typically indolent lesions, unless superinfected by bacteria or invasive to adjacent neurovascular structures. If the identification or treatment of underlying complications is delayed in an immunocompromised patient, a catastrophic outcome may result. We report the case of an elderly female patient with poorly controlled diabetes mellitus suffering from sphenoid fungal sinusitis that is complicated by cavernous sinus thrombophlebitis and carotid artery stenosis. In spite of reasonable diagnosis and therapy, the patient's general condition deteriorated and she eventually died. The clinical presentation, diagnosis, and treatment strategy are discussed.