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1.
Int J Behav Nutr Phys Act ; 21(1): 12, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38308373

RESUMEN

BACKGROUND: Previous studies on physical activity (PA) and pelvic organ prolapse (POP) were largely limited to self-reported PA in athletes, soldiers, and women in postpartum. We aimed to investigate the association of accelerometer-measured PA and sedentary behavior with the risk of POP in middle-aged and elderly women. METHODS: In this prospective cohort derived from the UK Biobank, the intensity and duration of PA and sedentary behavior were measured with wrist-worn accelerometers over a 7-day period in 2013-2015 for 47,674 participants (aged 42.8-77.9 years) without pre-existing POP. Participants were followed up until the end of 2022, during which incident POP was ascertained mainly by the electronic health records. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to assess the associations of interest. Isotemporal substitution models were applied to test the effects of substituting a type of activity with equivalent duration of others. RESULTS: During a median follow-up of 8.0 years, 779 cases of POP were recorded. The duration of light-intensity PA (LPA) was positively whereas sedentary time was negatively associated with the risk of POP. Every additional 1 h/day of LPA elevated the risk of POP by 18% (95% confidence interval [CI], 10%-26%). In contrast, the risk decreased by 5% (95% CI, 0-8%) per 1 h/day increment in sedentary behavior. No associations were found between moderate-intensity PA (MPA) or vigorous-intensity PA (VPA) and POP, except that women who had a history of hysterectomy were more likely to develop POP when performing more VPA (53% higher risk for every additional 15 min/day). Substituting 1 h/day of LPA with equivalent sedentary time was associated with a 18% (95% CI, 11%-24%) lower risk of POP. The risk can also be reduced by 17% (95% CI, 7%-25%) through substituting 30 min/day of LPA with MPA. CONCLUSIONS: More time spent in LPA or less sedentary time was linked to an elevated risk of POP in middle-aged and elderly women, while MPA or VPA was not. Substituting LPA with equivalent duration of sedentary behavior or MPA may lower the risk of POP.


Asunto(s)
Conducta Sedentaria , Biobanco del Reino Unido , Anciano , Persona de Mediana Edad , Humanos , Femenino , Estudios Prospectivos , Bancos de Muestras Biológicas , Acelerometría , Ejercicio Físico
2.
Biochem Biophys Res Commun ; 671: 246-254, 2023 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-37307708

RESUMEN

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.


Asunto(s)
Disfunción Cognitiva , Demencia Vascular , Fármacos Neuroprotectores , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/patología , Ratas Sprague-Dawley , Transducción de Señal , Autofagia , Glucósidos/farmacología , Glucósidos/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Disfunción Cognitiva/metabolismo , Hipoxia/tratamiento farmacológico
3.
Plant Cell Rep ; 43(1): 5, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38127154

RESUMEN

KEY MESSAGE: The content of flavonoids could increase in A. canescens under saline conditions. Overexpression of AcCHI in transgenic A. thaliana promotes flavonoid biosynthesis, thereby functioning in the tolerance of transgenic plants to salt and osmotic stress by maintaining ROS homeostasis. Atriplex canescens is a halophytic forage shrub with excellent adaptation to saline environment. Our previous study showed that a large number of genes related to the biosynthesis of flavonoids in A. canescens were significantly up-regulated by NaCl treatments. However, it remains unclear whether flavonoids are involved in A. canescens response to salinity. In this study, we found that the accumulation of flavonoids significantly increased in either the leaves or roots of A. canescens seedling under 100 and 300 mM NaCl treatments. Correspondingly, AcCHS, AcCHI and AcF3H, which encode three key enzymes (chalcone synthases (CHS), chalcone isomerase (CHI), and flavanone 3-hydroxylase (F3H), respectively) of flavonoids biosynthesis, were significantly induced in the roots or leaves of A. canescens by 100 or 300 mM NaCl. Then, we generated the transgenic Arabidopsis thaliana overexpressing AcCHI and found that transgenic plants accumulated more flavonoids through enhancing the pathway of flavonoids biosynthesis. Furthermore, overexpression of AcCHI conferred salt and osmotic stress tolerance in transgenic A. thaliana. Contrasted with wild-type A. thaliana, transgenic lines grew better with greater biomass, less H2O2 content as well as lower relative plasma permeability in either salt or osmotic stress conditions. In conclusion, our results indicate that flavonoids play an important role in A. canescens response to salt stress through reactive oxygen species (ROS) scavenging and the key enzyme gene AcCHI in flavonoids biosynthesis pathway of A. canescens has the potential to improve the stress tolerance of forages and crops.


Asunto(s)
Arabidopsis , Atriplex , Plantas Tolerantes a la Sal/genética , Tolerancia a la Sal/genética , Atriplex/genética , Especies Reactivas de Oxígeno , Arabidopsis/genética , Peróxido de Hidrógeno , Cloruro de Sodio/farmacología , Plantas Modificadas Genéticamente , Flavonoides
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(12): 1321-1325, 2022 Dec 15.
Artículo en Zh | MEDLINE | ID: mdl-36544413

RESUMEN

OBJECTIVES: To study the clinical efficacy of volume-targeted ventilation (VTV) versus high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory distress syndrome (NRDS). METHODS: A retrospective cohort analysis was performed on the medical data of 140 neonates with severe NRDS who were admitted from September 2016 to February 2022, with 55 neonates in the VTV group and 85 in the HFOV group. The neonates in the VTV group received conventional mechanical ventilation and target tidal volume, and those in the HFOV group received HFOV. Arterial blood gas parameters were collected at 48 hours after admission, and related indices during hospitalization were recorded, including mortality rate, duration of invasive mechanical ventilation, duration of oxygen therapy, and the incidence rates of complications. RESULTS: Compared with the VTV group, the HFOV group had significantly lower incidence rates of grade Ⅲ-Ⅳ periventricular-intraventricular hemorrhage and neonatal necrotizing enterocolitis (P<0.05), and there were no significant differences between the two groups in the duration of invasive mechanical ventilation, the duration of oxygen therapy, mortality rate, and the incidence rates of bronchopulmonary dysplasia, hypocapnia, hypercapnia, periventricular leukomalacia, and retinopathy of prematurity (P>0.05). CONCLUSIONS: HFOV has a better clinical efficacy than VTV in the treatment of NRDS.


Asunto(s)
Ventilación de Alta Frecuencia , Síndrome de Dificultad Respiratoria del Recién Nacido , Recién Nacido , Humanos , Estudios Retrospectivos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Respiración Artificial , Hemorragia Cerebral , Oxígeno
5.
BMC Anesthesiol ; 21(1): 240, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620093

RESUMEN

BACKGROUND: Better protection can be provided during neurosurgery due to the establishment of somatosensory-evoked potential (SEP) and motor-evoked potential (MEP) monitoring technologies. However, some studies have showed that inhaled halogenated anesthetics have a significant impact on neurophysiological monitoring. METHODS: A total of 40 consecutive patients undergoing neurosurgery were randomly assigned to two groups receiving inhaled anesthetics, either desflurane or sevoflurane. Multiples levels (concentrations of 0.3, 0.6 and 0.9) of anesthetics were administered at minimum alveolar concentration (MAC), and then the latencies and amplitudes of SEPs and MEPs were recorded. RESULTS: SEP and MEP signals were well preserved in patients who underwent neurosurgery under general anesthesia supplemented with desflurane or sevoflurane at concentrations of 0.3, 0.6 and 0.9 MAC. In each desflurane or sevoflurane group, the amplitudes of SEPs and MEPs decreased and the latencies of SEPs were prolonged significantly as the MAC increased (P < 0.05). The SEP latencies of both the upper and lower limbs in the desflurane group were significantly longer, and the SEP amplitudes were significantly lower than those in the sevoflurane group (P < 0.05). The MEP amplitudes in the desflurane group were significantly lower than those in the sevoflurane group (P < 0.05), only the amplitudes of the upper limbs at 0.3 MAC did not vary significantly. CONCLUSIONS: SEPs and MEPs were inhibited in a dose-dependent manner by both desflurane and sevoflurane. At the same MAC concentration, desflurane appeared to have a stronger inhibitory effect than sevoflurane. All patients studied had normal neurological examination findings, hence, these results may not be applicable to patients with preexisting deficits. TRIAL REGISTRATION: The study registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ), Clinical Trials identifier ChiCTR2100045504 (18/04/2021).


Asunto(s)
Desflurano/farmacología , Potenciales Evocados Motores/efectos de los fármacos , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos , Sevoflurano/farmacología , Adulto , Anestésicos por Inhalación/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad
6.
Vascular ; 29(3): 408-414, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32951561

RESUMEN

OBJECTIVE: Venous thromboembolism is a major cause of morbidity, mortality, and increased medical costs in tumor patients. In the current review, we summarize the progress made in the study of cancer-associated venous thromboembolism. METHODS: By searching cancer-associated venous thromboembolism-related literature on PubMed, the epidemiology, pathological mechanisms, risk factors, risk prediction models, and prevention and treatment of cancer-associated venous thromboembolism were reviewed. RESULTS: The pathophysiological mechanisms of cancer-associated venous thromboembolism are multifactorial. Various blood cell counts (such as platelets and white blood cells) and biomarkers (such as D-dimer and sP-selectin) were considered predictors of thrombosis in cancer patients and were incorporated into the venous thromboembolism risk stratification models. Thromboprophylaxis is currently recommended for all hospitalized cancer patients. In addition, outpatient thromboprophylaxis can be used for selected high-risk patients. Low-molecular-weight heparin was the preferred treatment for cancer-associated venous thromboembolism, but some issues arose in the long-term treatment. In this case, direct oral anticoagulants were a treatment option for tumor patients. The efficacy of direct oral anticoagulant in treating cancer patients is not inferior to low-molecular-weight heparin, but is associated with a higher risk of bleeding. Therefore, there were concerns regarding their safety. CONCLUSION: Since thrombocytopenia, thrombosis recurrence, and bleeding are common in tumor patients, the selection of anticoagulants in this circumstance is a considerable challenge for clinicians.


Asunto(s)
Neoplasias , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Administración Oral , Animales , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Biomarcadores/sangre , Hemorragia/inducido químicamente , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/prevención & control , Embolia Pulmonar/terapia , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/terapia , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/prevención & control , Trombosis de la Vena/terapia
7.
Heliyon ; 10(3): e24791, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38318020

RESUMEN

Backgrounds: The association between anesthesia and long-term oncological outcome after cancer surgery remains controversial. This study aimed to investigate the effect of propofol-based anesthesia and inhalation anesthesia on long-term survival in cancer surgery. Methods: A comprehensive literature search was performed in PubMed, Medline, Embase, and the Cochrane Library until November 15, 2023. The outcomes included overall survival (OS) and recurrence-free survival (RFS). The hazard ratio (HR) and 95 % confidence interval (CI) were calculated with a random-effects model. Results: We included forty-two retrospective cohort studies and two randomized controlled trials (RCTs) with 686,923 patients. Propofol-based anesthesia was associated with improved OS (HR = 0.82, 95 % CI:0.76-0.88, P < 0.00001) and RFS (HR = 0.80, 95 % CI:0.73-0.88, P < 0.00001) than inhalation anesthesia after cancer surgery. However, these positive results were only observed in single-center studies (OS: HR = 0.76, 95 % CI:0.68-0.84, P < 0.00001; RFS: HR = 0.76, 95 % CI:0.66-0.87, P < 0.0001), but not in multicenter studies (OS: HR = 0.98, 95 % CI:0.94-1.03, P = 0.51; RFS: HR = 0.95, 95 % CI:0.87-1.04, P = 0.26). The subgroup analysis revealed that propofol-based anesthesia provided OS and RFS advantages in hepatobiliary cancer (OS: HR = 0.58, 95 % CI:0.40-0.86, P = 0.005; RFS: HR = 0.62, 95 % CI:0.44-0.86, P = 0.005), gynecological cancer (OS: HR = 0.52, 95 % CI:0.33-0.81, P = 0.004; RFS: HR = 0.51, 95 % CI:0.36-0.72, P = 0.0001), and osteosarcoma (OS: HR = 0.30, 95 % CI:0.11-0.81, P = 0.02; RFS: HR = 0.32, 95 % CI:0.14-0.75, P = 0.008) surgeries. Conclusion: Propofol-based anesthesia may be associated with improved OS and RFS than inhalation anesthesia in some cancer surgeries. Considering the inherent weaknesses of retrospective designs and the strong publication bias, our findings should be interpreted with caution. Well-designed multicenter RCTs are still urgent to further confirm these findings.

8.
Heliyon ; 10(10): e31108, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38826749

RESUMEN

The fabrication of highly efficient yet stable noble-metal-free bifunctional electrocatalysts that can simultaneously catalyse both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) remains challenging. Herein, we employ the heterostructure coupling strategy, showcasing an aerosol-assisted chemical vapour deposition (AACVD) aided synthetic approach for the in-situ growth of cobalt molybdenum sulphide nanocomposites on carbon paper (CoMoS@CP) as a bifunctional electrocatalyst. The AACVD allows the rational incorporation of Co in the Mo-S binary structure, which modulates the morphology of CoMoS@CP, resulting in enhanced HER activity (ŋ10 = 171 mV in acidic and ŋ10 = 177 mV in alkaline conditions). Furthermore, the CoS2 species in the CoMoS@CP ternary structure extends the OER capability, yielding an ŋ100 of 455 mV in 1 M KOH. Lastly, we found that the synergistic effect of the Co-Mo-S interface elevates the bifunctional performance beyond binary counterparts, achieving a low cell voltage (1.70 V at 10 mA cm-2) in overall water splitting test and outstanding catalytic stability (∼90 % performance retention after 50-/30-h continuous operation at 10 and 100 mA cm-2, respectively). This work has opened up a new methodology for the controllable synthesis of self-supported transition metal-based electrocatalysts for applications in overall water splitting.

9.
Int J Mol Sci ; 14(7): 15092-104, 2013 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-23877836

RESUMEN

Uveal melanoma (UM) is the most common primary intraocular malignancy and the leading potentially fatal primary intraocular disease in adults. Melanoma antigen recognized by T-cells (MART-1) has been studied extensively as a clinically important diagnostic marker for melanoma, however, its biological function remains unclear. In the present study, the UM cell line SP6.5, which showed a high level of MART-1 expression, was subjected to small interfering RNA-mediated silencing of MART-1. Silencing of MART-1 expression increased the migration ability of SP6.5 cells and down-regulated the expression of the metastasis suppressor NM23. Our results suggest that MART-1 is a candidate target for the development of therapeutic strategies for UM and in particular for the suppression of metastasis associated with this malignancy.


Asunto(s)
Antígeno MART-1/metabolismo , Interferencia de ARN , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Antígeno MART-1/química , Antígeno MART-1/genética , Melanoma/metabolismo , Melanoma/patología , Nucleósido Difosfato Quinasas NM23/genética , Nucleósido Difosfato Quinasas NM23/metabolismo , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/patología
10.
ACS Appl Mater Interfaces ; 15(30): 37069-37076, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37486721

RESUMEN

Halide perovskites are promising photoelectrocatalytic materials. Their further development requires understanding of surface processes during electrochemistry. Thin films of tellurium-based vacancy-ordered perovskites with formula A2TeI6, A = Cs, methylammonium (MA), were deposited onto transparent conducting substrates using aerosol-assisted chemical vapor deposition. Thin film stability as electrodes and photoelectrodes was tested in dichloromethane containing tetrabutylammonium PF6 (TBAPF6). Using photoemission spectroscopy, we show that the formation of a solid electrolyte interphase on the surface of the Cs2TeI6, consisting of CsPF6, enhances the stability of the electrode and allows extended chopped-light chronoamperometry measurements at up to 1.1 V with a photocurrent density of 16 µA/cm2. In contrast, (CH3NH3)2TeI6 does not form a passivating layer and rapidly degrades upon identical electrochemical treatment. This demonstrates the importance of surface chemistry in halide perovskite electrochemistry and photoelectrocatalysis.

11.
Ear Nose Throat J ; 102(2): 90-95, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36250504

RESUMEN

Objective: A retrospective study was conducted to explore the immune-inflammatory responses in sudden sensorineural hearing Loss (SSNHL) patients with different audiogram shapes. Methods: One hundred and ten inpatients with SSNHL were assigned to 4 subgroups according to the audiogram shape and treated with systemic methylprednisolone. The numbers of white blood cells, neutrophils, lymphocytes, platelets, and monocytes were counted. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR) were calculated and statistically analyzed. Results: Neutrophil-to-lymphocyte ratio, MLR, and systemic immune index (SII) of SSNHL patients were significantly higher than the control group, while PLR was not statistically significant. There were no statistical differences in NLR, PLR, MLR, and SII among the 4 subgroups. Conclusion: Immune-inflammatory response may be a common pathogenesis in all SSNHL patients with different audiogram shapes. The predictive value of these hematologic markers needs further research in the future.


Asunto(s)
Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Pronóstico , Estudios Retrospectivos , Linfocitos , Plaquetas , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Súbita/tratamiento farmacológico
12.
Medicine (Baltimore) ; 102(14): e33399, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37026960

RESUMEN

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.


Asunto(s)
Pneumocystis carinii , Neumonía por Pneumocystis , Síndrome de Dificultad Respiratoria , Humanos , Neumonía por Pneumocystis/diagnóstico , Estudios Prospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Caspofungina , Muerte , Pneumocystis carinii/genética , Síndrome de Dificultad Respiratoria/diagnóstico
13.
Hum Reprod ; 27(11): 3347-57, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22926839

RESUMEN

STUDY QUESTION: What are the implications of multiple alterations of the forkhead box L2 (FOXL2) gene in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients? SUMMARY ANSWER: A multi-mutation of FOXL2, consisting of the expansion of the polyalanine tract from 14 to 24 residues (FOXL2-Ala24), an novel Y186C substitution from c.557A>G, and a synonymous variant (c.505G>A), had a cumulative effect on ovarian phenotypes in BPES patients. WHAT IS KNOWN ALREADY: Mutations in FOXL2, a gene encoding a forkhead transcription factor cause BPES. Overall, the expansion of the polyalanine tract of FOXL2 from 14 to 24 residues (FOXL2-Ala24) accounts for 30% of intragenic mutations. STUDY DESIGN, SIZE, DURATION: In this study, patients from seven BPES families and six sporadic cases were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted an extensive clinical, hormonal and functional study in 20 patients carrying the expansion of the polyalanine tract of FOXL2 associated with BPES. A multi-mutation of FOXL2 was detected in one BPES family that showed more severe BPES symptoms. Subcellular localization and transactivation studies were performed for the constructs of FOXL2-Ala24, Y186C and FOXL2-Ala24-Y186C. MAIN RESULTS: We described the first multi-mutation of FOXL2 (c. [672_701dup30; 557A>G]) that leads to the polyalanine expansion of +10 residues (FOXL2-Ala24) combined with an Y186C substitution and a synonymous variant in a Chinese BPES family. This multi-mutation genotype was associated with more serious BPES clinical manifestations and the development of esotropia in the right eye. In in vitro studies, the multi-mutation affected the function of FOKL2 on the StAR promoter and DK3, and induced more aggressive aggregation and mislocalization of FOXL2 protein. The synonymous variant, while not affecting amino acid coding, causes a change in the RNA stem-loop structure. LIMITATIONS, REASONS FOR CAUTION: The multi-mutation of FOXL2 was detected in one BPES family and it needs to be validated further by more BPES subjects. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study contribute new insights into the research field of BPES caused by the multi-mutation of FOXL2. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Shanghai Leading Academic Discipline Project (Grant number S30205) and Shanghai Jiao Tong University School of Medicine Doctor Innovation Fund (Grant number 201131). The authors have no competing interests to declare.


Asunto(s)
Blefarofimosis/genética , Factores de Transcripción Forkhead/genética , Mutación , Ovario/fisiopatología , Anomalías Cutáneas/genética , Adolescente , Adulto , Sustitución de Aminoácidos , Blefarofimosis/metabolismo , Blefarofimosis/fisiopatología , Niño , Preescolar , China , Femenino , Proteína Forkhead Box L2 , Factores de Transcripción Forkhead/química , Factores de Transcripción Forkhead/metabolismo , Estudios de Asociación Genética , Células HEK293 , Humanos , Masculino , Mutagénesis Insercional , Mutación Missense , Linaje , Transporte de Proteínas , Pliegue del ARN , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Índice de Severidad de la Enfermedad , Anomalías Cutáneas/metabolismo , Anomalías Cutáneas/fisiopatología , Anomalías Urogenitales
14.
Artículo en Inglés | MEDLINE | ID: mdl-36118091

RESUMEN

Introduction: Febuxostat is a novel inhibitor of xanthine oxidase that suppresses cell adhesion molecules-mediated (CAMs) inflammation by activating KLF6. In this study, we explored the therapeutic function and potential mechanisms of febuxostat against allergic rhinitis (AR). Methods: We investigated the role of febuxostat through in vitro cell and in vivo animal experiments. Human nasal epithelial cells (hNECs) were cultured with histamine as an in vitro model. To establish the AR animal model, rats were exposed to ovalbumin. Rats were randomly grouped into control, model, 7.5 mg/kg febuxostat, and 15 mg/kg febuxostat groups. Results: In the in vitro study, we found significantly increased release of lactate dehydrogenase, elevated production of inflammatory factors and chemokines, and upregulated CAMs in histamine-treated hNECs. However, these results were significantly reversed for the 10 and 20 µM febuxostat treatments. The enhanced adhesion between hNECs and monocytes induced by histamine was dramatically repressed by febuxostat. In the vivo experiments, we observed that febuxostat ameliorated the increased sneezing times, the number of nose scratching episodes, and elevated HE pathological scores as well as alleviated the inflammation in nasal mucous tissues of AR mice. We found that KLF6, which was downregulated in histamine-treated hNECs, was significantly upregulated by febuxostat. The inhibitory effects of febuxostat on the expression levels of CAMs and adhesion between histamine-treated hNECs and monocytes were significantly abolished by the knockdown of KLF6. Conclusion: Febuxostat alleviates AR by inhibiting inflammation and monocyte adhesion in human nasal epithelial cells through the regulation of KLF6.

15.
Front Public Health ; 10: 913897, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35875004

RESUMEN

Background: Postoperative pneumonia is a preventable complication associated with adverse outcomes, that greatly aggravates the medical expenses of patients. The goal of our study is to identify risk factors and outcomes of postoperative pneumonia. Methods: A matched 1:1 case-control study, including adult patients who underwent surgery between January 2020 and June 2020, was conducted in the Second Affiliated Hospital of Kunming Medical University in China. Cases included all patients developing postoperative pneumonia within 30 days after surgery, defined using consensus criteria. Controls were selected randomly from the matched eligible population. Results: Out of 17,190 surgical patients, 264 (1.54%) experienced postoperative pneumonia. Increased age, chronic obstructive pulmonary disease, emergency surgery, postoperative reduced albumin, prolonged ventilation, and longer duration of bed rest were identified as significant risk factors independently associated with postoperative pneumonia. Regarding prognostic implications, postoperative pneumonia was associated with longer length of hospital stay, higher ICU occupancy rate, higher unplanned re-operation rate, and higher in-hospital mortality rate. Postoperative pneumonia was most commonly caused by Gram-negative pathogens, and multidrug resistant bacteria accounted for approximately 16.99% of cases. Conclusions: Postoperative pneumonia is associated with severe clinical outcomes. We identified six independent risk factors that can aid in risk stratification and management of patients at risk of postoperative pneumonia, and the distribution of causative pathogens can also help in the implementation of effective interventions. Clinical Trial Registration: www.chictr.org.cn, identifier: chiCTR2100045986.


Asunto(s)
Neumonía , Adulto , Estudios de Casos y Controles , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Neumonía/epidemiología , Neumonía/etiología , Factores de Riesgo
16.
Front Oncol ; 12: 996866, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36568186

RESUMEN

Background: Over the last 2 decades, patients with low rectal cancer have had better outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trends in sphincter-preserving surgeries for low rectal cancer over 20 years in a top tertiary hospital in China. Methods: Between 1999 and 2021, a cohort of patients with primary malignant rectal tumor ≤5cm from the anal verge and who received elective surgeries at Changhai Hospital, Shanghai, China, was identified. Data were extracted from electronic medical records. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). Adjusted Cox proportional hazards regression model was used to assess overall survival. Results: Among a total of 4,172 patients during the study period, 3,111 (74.6%) underwent a sphincter-preserving surgery and 1,061 (25.4%) received APR. Sphincter-preserving surgery increased 3.6% per year (95%CI, 2.3-4.9). Low anterior resection was the most performed procedure (86.3%) and maintained a steady trend, while intersphincteric resection increased 49.4% annually (95%CI, 19.5-86.7) after initiation. Laparoscopic techniques increased 15.1% per year (95%CI, 8.4-43.4) after initiation. Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-≤3cm and 3-≤4cm from the anal verge (AAPC 7.1, 4.5-9.8; 4.7, 3.1-6.3; 2.7, 1.7-3.6, respectively). Furthermore, patients with sphincter-preserving surgery had a better overall survival than abdominoperineal resection (APR) patients (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01). Conclusions: Utilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.

17.
Sci Bull (Beijing) ; 67(3): 270-277, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36546076

RESUMEN

Recently, research on two-dimensional (2D) semiconductors has begun to translate from the fundamental investigation into rudimentary functional circuits. In this work, we unveil the first functional MoS2 artificial neural network (ANN) chip, including multiply-and-accumulate (MAC), memory and activation function circuits. Such MoS2 ANN chip is realized through fabricating 818 field-effect transistors (FETs) on a wafer-scale and high-homogeneity MoS2 film, with a gate-last process to realize top gate structured FETs. A 62-level simulation program with integrated circuit emphasis (SPICE) model is utilized to design and optimize our analog ANN circuits. To demonstrate a practical application, a tactile digit sensing recognition was demonstrated based on our ANN circuits. After training, the digit recognition rate exceeds 97%. Our work not only demonstrates the protentional of 2D semiconductors in wafer-scale integrated circuits, but also paves the way for its future application in AI computation.


Asunto(s)
Programa de Seguro de Salud Infantil , Molibdeno , Redes Neurales de la Computación , Simulación por Computador , Semiconductores
18.
Mol Cell Biochem ; 355(1-2): 9-15, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21526343

RESUMEN

There is a growing evidence that regucalcin (RGN) plays a multifunctional role in liver cancer cells. Previous reports showed that the presence of phorbol 12-myristate 13-acetate (PMA) caused a significant increase in RGN mRNA expression and promoter activity in rat hepatoma cells. In this study, we confirmed that human RGN is also up-regulated by PMA treatment independent of translation, and we identified the mechanism by which PMA up-regulates the expression of human RGN via driving SP1 away from a SP1 motif located within -188/-180 of the promoter in HepG2 cells. Overexpression of SP1 dramatically reduces PMA-induced up-regulation of both internal expression of mRNA and promoter activity, whereas knockdown of SP1 has the opposite effect. Therefore, the present study delineates the fundamental elements in the promoter which will be helpful in the future studies on the regulation of RGN expression in liver cancer.


Asunto(s)
Proteínas de Unión al Calcio/genética , Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Factor de Transcripción Sp1/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Regulación hacia Arriba/efectos de los fármacos , Secuencia de Bases , Proteínas de Unión al Calcio/metabolismo , Inmunoprecipitación de Cromatina , Regulación de la Expresión Génica , Genes Reporteros , Células Hep G2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Hepáticas , Luciferasas de Luciérnaga/biosíntesis , Luciferasas de Luciérnaga/genética , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Unión Proteica , Factor de Transcripción Sp1/genética
19.
World J Clin Cases ; 9(33): 10362-10368, 2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34904111

RESUMEN

BACKGROUND: Iodophor (povidone-iodine) is widely used clinically because of its broad-spectrum antibacterial effects. Although extremely rare, it may cause anaphylactic shock, which itself carries the life-threatening risk of cardiac arrest. CASE SUMMARY: We present a case in which a patient with postoperative infection went into anaphylactic shock and cardiac arrest caused by povidone-iodine during secondary surgery. The patient was successfully resuscitated by 2 h of cardiopulmonary resuscitation. CONCLUSION: This is the first known case of cardiac arrest caused by povidone-iodine allergy.

20.
Food Funct ; 10(10): 6517-6532, 2019 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-31538163

RESUMEN

Pyracantha fortuneana fruits are consumed as a dietary supplement in China and attenuate obesity and metabolic disorders. Obesity is known to be associated with intestinal barrier dysfunction driven by hyperglycemia and gut dysbiosis. However, whether the health benefits of P. fortuneana fruits are linked with the intestinal barrier function (IBF) remains unknown. This study aimed to evaluate the restorative effects of P. fortuneana fruit extract (PFE) on the IBF. Sprague Dawley rats were fed with a chow, a high-fat diet (HFD), or a PFE-supplemented diet for 8 weeks. Results showed that PFE intervention ameliorated HFD-induced intestinal barrier dysfunction by attenuating impaired structural integrity, reducing the elevated lactulose/mannitol ratio, and improving the mRNA and protein expression levels of tight junction proteins in HFD-fed rats. The ameliorations were associated with a beneficial effect on glycolipid homeostasis, as evidenced from the PFE decreasing intestinal absorptive capacity based on the d-xylose excretory rate, lowering the expression of GLUT2 and inhibiting digestive enzyme activities. The proanthocyanidins in the PFE showed greater in vitro inhibition on α-amylase, α-glucosidase, and lipase compared with triterpenoid saponins. Furthermore, the ameliorations on the IBF were also associated with effects on the microbial composition based on 16S rRNA gene sequence analysis. Several bacterial groups, which were linked with gut barrier integrity, were modulated after PFE administration, that is, Actinobacteria, Bacteroidaceae, Corynebacteriaceae, Lactobacillaceae, and S24-7 were elevated and the HFD-induced increase in Clostridia, Ruminococcaceae, Oscillospira, and Flexispira was restored. These data provide evidence for the ameliorative effect of the PFE on diet-induced intestinal barrier functional alternations in association with its capacity to modulate glycolipid digestion and gut microbiota in HFD-fed obese rats.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Glucolípidos/metabolismo , Mucosa Intestinal/efectos de los fármacos , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Pyracantha/química , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Dieta Alta en Grasa/efectos adversos , Frutas/química , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Masculino , Obesidad/genética , Obesidad/metabolismo , Obesidad/microbiología , Ratas , Ratas Sprague-Dawley
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