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Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.
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Conjuntivitis Alérgica , Rinitis Alérgica Estacional , Rinitis Alérgica , Humanos , Rinitis Alérgica Estacional/epidemiología , Estudios Transversales , Polen/efectos adversos , Alérgenos , Rinitis Alérgica/epidemiologíaRESUMEN
PurposeThe role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism.MethodsThe metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis.ResultsWe identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference.ConclusionsOur research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.
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Humanos , Autofagia , Línea Celular Tumoral , Neoplasias Pulmonares , Neoplasias de la Próstata/patología , Proteínas Nucleares , RatonesRESUMEN
OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.
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Glioblastoma , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , TemozolomidaRESUMEN
PURPOSE: The role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism. METHODS: The metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis. RESULTS: We identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference. CONCLUSIONS: Our research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.
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Neoplasias Pulmonares , Neoplasias de la Próstata , Animales , Autofagia , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas Nucleares , Neoplasias de la Próstata/patología , Proteína 1 Relacionada con TwistRESUMEN
OBJECTIVE: This study was probed to uncover the mechanism of miR-142-5p in septic liver injury. MATERIALS AND METHODS: In this study, in-vitro and in-vivo models of sepsis were used. For in-vitro sepsis model, hepatocyte cell line (L02 cells) was treated with LPS (lipopolysaccharide). Whereas for in-vivo sepsis model, cecal ligation and puncture were performed in mice. Mice were assigned into three groups: control, CLP (Cecal Ligation Puncture), CLP + miR-142-5p inhibitor group. Liver injury was assessed via H&E staining. IL-6, TNF-α, and IL-1ß expressions were assayed through ELISA kits. C-caspase-9, C-caspase-3, ERK, p65, and IκBα expressions were determined via western blot and RT-qPCR. Apoptosis in LPS-induced L02 cells was detected by TUNEL staining. RESULTS: Our results show that miR-142-5p exhibited perspicuous upregulation in CLP mice tissues and LPS-induced L02 cells. On the other hand, inhibition of miR-142-5p could promote LPS-induced L02 cell activity and reduce apoptosis and inflammation. In terms of molecular mechanism, downregulation of miR-142-5p could abate sepsis-mediated acute hepatic injury by targeting SOCS1, through ERK and NF-κB pathway. CONCLUSIONS: Overall our results demonstrate that miR-142-5p inhibitors can mitigate septic liver injury by downregulating the inflammation and apoptosis via targeting SOCS1. Thus, miR-142-5p can serve a potential therapeutic target for sepsis mediated acute hepatic injury.
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Hepatocitos/patología , Fallo Hepático/fisiopatología , MicroARNs/genética , Sepsis/complicaciones , Animales , Apoptosis/fisiología , Línea Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo , Humanos , Inflamación/etiología , Inflamación/patología , Lipopolisacáridos , Fallo Hepático/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Regulación hacia ArribaRESUMEN
OBJECTIVE: Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose of this study was to conduct meta-analysis to verify the clinical efficacy and safety of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: All available literature of clinical trials about docetaxel, bevacizumab, trastuzumab and metastatic breast cancer was pooled from PubMed, Embase and Cochrane library database. The meta-analysis combined the progression free survival (PFS), overall response rate (ORR) and incidence of all grades adverse events in MBC patients. RESULTS: Seven clinical trials were included by two reviewers. Docetaxel and bevacizumab with trastuzumab show the pooled PFS was 16.53 months (95% CI: 13.95-19.11 months), the pooled ORR was 0.75 (95% CI: 0.69-0.80) in HER2-positive MBC patients. Docetaxel and bevacizumab show that the pooled PFS was 8.49 months (95% CI: 7.80-9.18 months), the pooled ORR was 0.51(95% CI: 0.47-0.55) in HER2-negative MBC patients. CONCLUSIONS: Both for patients with HER2-positive and negative metastatic breast cancer, docetaxel and bevacizumab with or without trastuzumab as first-line treatment resulted in long survival, especially in terms of progression-free survival. Although the overall response rates are also significantly improved, it is still controversial based on the current evidence.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Bevacizumab/administración & dosificación , Neoplasias de la Mama/patología , Docetaxel/administración & dosificación , Femenino , Humanos , Supervivencia sin Progresión , Receptor ErbB-2/metabolismo , Tasa de Supervivencia , Trastuzumab/administración & dosificaciónRESUMEN
Objective: To explore the characteristics of cortical morphology in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID) and its relationship with clinical symptoms. Methods: A total of 88 patients with CSVD in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to July 2020. The subjects were divided into CSVD-non depression group (CSVD-ND, n=58) and SID group (n=30) according to the geriatric depression scale (GDS). The 3D-T1 MRI images were obtained from all subjects. The computed anatomy toolbox 12 (CAT 12) was used for image processing and cortical segmentation to obtain the cortical thickness (CTh) and surface metrics, including gyrification index (GI), sulcus depth (SD) and fractal dimension (FD). A comparison at the vertex- and region-of-interest (ROI)-wise levels were performed by the general linear model, and correlation analysis were conducted between cortical morphometric measurements and GDS scores. Finally, mean CTh (mCTh) was extracted for binary logistic regression analysis. Results: At the vertex-wise level, compared with the CSVD-ND group, the SID patients showed increased CTh in clusters mainly located in the posterior default mode network (pDMN), such as the precuneus(Pcu), the superior parietal gyrus (SPG) and the right postcentral gyrus (PoCG). As for the surface measurements, the GI value and the FD value were increased in clusters of Pcu and inferior temporal gyrus (ITG), respectively, in the SID group. ROIs analyses showed that apart from the Pcu, the SPG and the right PoCG, CTh alterations in the SID group were involved in a wider range of regions, extending to the right precentral gyrus ((2.27±0.20) cm3 vs (2.12±0.26) cm3, P=0.007), the left paracentral gyrus ((2.18±0.20) cm3 vs (2.05±0.23) cm3, P=0.008) and so on, than that in the CSVD-ND group.Compared with the CSVD-ND patients, the SID patients showed increased GI in the right PoCG ((25.31±1.11) vs (24.23±1.27), P<0.05). Correlation analysis showed that CTh in the right Pcu was positively correlated with the GDS scores (r=0.4, P<0.05). Further binary logistic regression analysis showed that in comparison with the subjects in the reference group (<2.367 cm3), the odds ratio(95%CI) for SID patients in the highest tertile of mCTh (>2.473 cm3) were 6.373 (1.254-32.389) after multivariable adjustment (sex, age, years of education, total intracranial volume, traditional imaging findings of CSVD, cognitive function (CAMCOG-C) and mCTh). Conclusion: Both CTh and cortical complexity were increased in CSVD patients with SID, especially in the clusters of pDMN, and CTh may be an important risk factor for SID.
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Enfermedades de los Pequeños Vasos Cerebrales , Depresión , Anciano , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Lóbulo Frontal , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia MagnéticaRESUMEN
Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2â¶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.
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Fármacos Cardiovasculares , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Implantes Absorbibles , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sirolimus , Resultado del TratamientoRESUMEN
Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase â ¢ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage â ¢A-â £A ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Terapia Combinada , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Femenino , Fluorouracilo , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: To assess the impact of enteral nutrition support on response and toxicity of the first-line chemotherapy in those patients with advanced or metastatic esophageal cancer. METHODS: We collected the clinical data of 118 patients with unresectable advanced or metastatic esophageal cancer who received the first-line chemotherapy in our center from July 2014 to December 2016. All these 118 esophageal cancer patients were then divided into two groups: the nutrition group (received enteral nutrition support in addition to chemotherapy) and the control group (received chemotherapy only). Differences were analyzed before and after chemotherapy in each of the nutritional indicators including Karnofsky performance status (KPS), weight, body mass index (BMI), hemoglobin (Hb), number of lymphocytes (Lymph), total protein (TP), albumin (Alb), triglycerides (TG), total cholesterol (TC) in both groups. And differences of the efficacy and toxicities of the first-line chemotherapy between the two groups were also analyzed. RESULTS: (1) Weight, BMI and Hb were all significantly decreased after chemotherapy in the control group (P<0.001), while there was no significant change of weight and BMI in the nutrition group, just with Hb decrease only. However, there was no significant change of all the other nutrition indicators after chemotherapy in both groups. (2) Compared with the control group, the nutrition group had significantly lower incidence of grade 3 to 4 hematologic toxicities after chemotherapy (15.4% vs. 42.1%, P=0.004). In addition, the incidence of grade 3 to 4 nonhematologic toxicities after chemotherapy was also lower in the nutrition group but without statistical significance (0 vs. 9.2%, P=0.123). Logistic regression model was then used for multivariate analysis to identify the factors that affected the toxicity of chemotherapy in these patients, and the results showed that nutrition therapy was an independent influencing factor of grade 3 or higher hematological toxicity after chemotherapy in the patients with esophageal cancer (P=0.008, RR=6.048, 95%CI: 1.589-23.027). (3) The response rate of chemotherapy between the control group and the nutrition group had not significant difference. CONCLUSION: Enteral nutrition support in addition to chemotherapy could improve nutrition status and reduce toxicity of chemotherapy in advanced or metastatic esophageal cancer patients.
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Nutrición Enteral , Neoplasias Esofágicas , Índice de Masa Corporal , Peso Corporal , Humanos , Metástasis de la Neoplasia , Estado NutricionalRESUMEN
Objective: To explore the relationships between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and KIM-based white matter lesion (WML) and carotid atherosclerotic plaque. Methods: From November 2018 to July 2019, 155 patients admitted to the Department of Neurology of the First Affiliated Hospital of Anhui Medical University were enrolled, with 125 cases of brain MRI manifestations of white matter lesions allocated to WML group and 30 cases of normal MRI in control group (NC group). According to KIM classification, WML patients were further divided into juxtaventricular white matter lesion (JVWML) group (n=30), periventricular white matter lesion (PVWML) group (n=33), juxtacortical white matter lesion (JCWML) group (n=30) and deep white matter lesion (DWML) group (n=32). Clinical Data of vascular risk factors in all subjects was collected and reviewed. Serum Lp-PLA2 content was determined by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Carotid atherosclerosis plaques were detected by carotid artery ultrasonography and divided into stable and vulnerable plaques, and thus total score of each plaque was subsequently calculated according to the Crouse method. Results: The Lp-PLA2 ((117±37) ng/ml vs (95±30) ng/ml), stable Crouse plaque integral (CPI) (0 (0,2.5) vs 0) and unstable CPI (0 (0,3.4) vs 0) in the WML group were significantly higher than those in the NC group (all P<0.05). Lp-PLA2 ((138±41) ng/ml) and unstable CPI (1.5(0,3.8)) in the PVWML group were significantly higher than those in the NC group (all P<0.05). Lp-PLA2 levels in the PVWML group were significantly higher than those in the JVWML group ((100±28) ng/ml) and JCWML group ((101±27) ng/ml) (all P<0.05). Correlation analysis revealed that blood glucose (r=0.600, P=0.000), triglyceride (TG) (r=0.371, P=0.034), low-density lipoprotein cholesterol (LDL-C) (r=0.367, P=0.036) and Lp-PLA2 (r=0.567, P=0.001) were positively correlated with unstable CPI in PVWML group, while it is negatively correlated with HDL-C (r=-0.368, P=0.035). Multivariate linear regression of all relevant factors and unstable CPI in the PVWML group showed that blood glucose (b=0.463, P<0.01) and Lp-PLA2 (b=0.347, P<0.05) were still positively correlated with unstable CPI. Conclusions: Serum Lp-PLA2 is an indicator of atherosclerosis, which is associated with carotid instability plaques in periventricular WML, suggesting that inflammatory mechanism plays an important role in the development of ischemic white matter lesions.
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Placa Aterosclerótica , Sustancia Blanca , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Aterosclerosis , Biomarcadores , Humanos , Lipoproteínas , Fosfolipasas A2RESUMEN
OBJECTIVE: Retinal pigment epithelium (RPE) degenerative death is an evident hallmark of advanced age-related macular degeneration (AMD). The present study aims to evaluate the protective effects of S-allyl L-cysteine (SAC), a bioactive component from aged garlic extracts, on the oxidative stress-related apoptosis of RPE cells and to investigate the potential underlying mechanisms. MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were performed to evaluate the effects of SAC on the hydroquinone-treated human ARPE19 cells. The Reactive Oxygen Species (ROS) production was measured by virtue of flow cytometry or determined under an inverted fluorescence microscope. Furthermore, the expression of antioxidant factor Nrf2, as well as downstream antioxidant genes, including NQO1, SOD1, SOD2, and HO1 was assessed in hydroquinone stimulated ARPE19 cells, in the presence or absence of SAC pretreatment. RESULTS: Hydroquinone incitement contributed to a marked decrease in cell viability, but enhanced cell apoptosis, whereas SAC addition did not cause significant alterations. When cells were pre-treated with SAC, cell proliferation was dramatically enhanced whereas apoptosis was mitigated, and the ROS generation induced by hydroquinone was also significantly suppressed, indicating a prominent function of SAC in preventing ARPE19 cells from oxidant-related apoptosis. The elevated expression levels of Nrf2 and other antioxidant genes driven by hydroquinone were downregulated by SAC addition. CONCLUSIONS: These data suggest that SAC can effectively attenuate hydroquinone-induced oxidative damage in human RPE cells. Our work is the first to demonstrate that SAC modulates oxidative stress-induced RPE apoptosis, thereby potentially proving new insights into the treatment of AMD.
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Antineoplásicos/farmacología , Cisteína/análogos & derivados , Epitelio Pigmentado de la Retina/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células Cultivadas , Cisteína/farmacología , Humanos , Hidroquinonas/antagonistas & inhibidores , Hidroquinonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Epitelio Pigmentado de la Retina/metabolismoRESUMEN
OBJECTIVE: We hope it will provide a reference for early detection, early diagnosis, and early treatment of atypical Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-typical autonomic dysfunctions as the first symptom. PATIENTS AND METHODS: We present a 15-year-old girl with the repetition of conscious disturbance at different levels, but no abnormal movements. Initially, there were no positive findings on routine electroencephalography (EEG) and dynamic video-electroencephalography (V-EEG), but the head-up tilt test (HTT) suggested neurocardiogenic syncope (vascular rejection type), which seemed to be the final diagnosis. However, the patient later experienced several episodes of disturbance of consciousness with unexplained abdominal pain. Abnormalities were discovered on EEG, which indicated the possibility of "epileptic seizures with autonomic-gastrointestinal features". Based on these findings, we finally tested the autoimmune encephalitis-related antibodies for the patient after the literature search and review. RESULTS: The patient was finally diagnosed with anti-NMDAR encephalitis. Her symptoms were fully controlled after glucocorticoid and gamma globulin treatment, and she left the hospital with complete recovery. CONCLUSIONS: Although autonomic nervous dysfunction occurred in our patient, her prognosis was good because she did not have respiratory or (and) circulatory failure. Exclusive diagnosis and early treatment are important in patients with anti-NMDAR encephalitis. Abdominal pain with positive HTT may be a manifestation of autonomic dysfunction in this disease.
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Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Glucocorticoides/uso terapéutico , gammaglobulinas/uso terapéutico , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética , gammaglobulinas/administración & dosificaciónRESUMEN
Objective: To investigate the key issues in the diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations. Methods: A retrospective study was performed for 11 pediatric patients who were treated in Department of Otorhinolaryngology and Head and Neck Surgery, Henan Province People's Hospital after a diagnosis of foreign body aspiration with tracheobronchial variations between January 2015 and December 2017. There were 7 males and 4 females among the 11 cases of foreign body aspiration with tracheobronchial variations, ranging between 9 months and 11 years of age. Results: Among 11 cases, the types of variationswere tracheal bronchus in 9 cases, bridging bronchus in 1 case and simple tracheal stenosis in 1 case. All of the pediatric patients were under general anesthesia, and the foreign bodies were removed by bronchoscopy successfully with no significant complications. Conclusions: The possibility of tracheobronchial variations should be considered in children with recurrent wheezing and poor efficacy of regular treatment before foreign body aspiration. Removal of foreign body via rigid bronchoscope under general anesthesia is a safe and effective treatment. These children are needed to combine the situation oftracheobronchial variations and the location of foreign bodies to guide the operation, and strengthened the perioperative treatment.
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Cuerpos Extraños/diagnóstico , Cuerpos Extraños/terapia , Aspiración Respiratoria/diagnóstico , Aspiración Respiratoria/terapia , Enfermedades Respiratorias/complicaciones , Bronquios/anomalías , Broncoscopía , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Anomalías del Sistema Respiratorio/complicaciones , Estudios Retrospectivos , Tráquea/anomalías , Estenosis Traqueal/complicacionesRESUMEN
OBJECTIVE: Acute lung injury (ALI) is the most common complication of severe acute pancreatitis (SAP) in the early stage, which causes systemic inflammatory response and organ damage. Human runt-associated transcription factor 3 gene (RUNX3) has been reported to participate in various inflammatory diseases. However, the exact role of RUNX3 in SAP and its-related ALI remains unclear. MATERIALS AND METHODS: To establish the model of SAP, rats were retrogradely injected with 5% sodium taurocholate (1 mg/kg body weight) into the biliary-pancreatic duct. Cytokine level in serum was measured by ELISA, and the polymorphonuclear neutrophil (PMN) was isolated from rat's blood 12 h-post SAP induction. RESULTS: We found RUNX3 expression was significantly decreased with the progression of SAP. Both pancreas damages and cytokine production abilities were reduced in RUXN3-overexpressed SAP rats compared with control rats. Moreover, SAP-associated ALI was also improved upon RUNX3 overexpression in SAP rats. RUNX3 upregulation enhanced PMN apoptosis and inhibited Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation. CONCLUSIONS: Our study indicates that RUNX3 protects against SAP and SAP-associated ALI through controlling PMN apoptosis and regulating JAK2/STAT3 signaling pathway. RUNX3 could be regarded as a potent therapeutic target in SAP for future studies.
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Lesión Pulmonar Aguda/inmunología , Neutrófilos/inmunología , Pancreatitis/complicaciones , Transducción de Señal/inmunología , Lesión Pulmonar Aguda/diagnóstico , Lesión Pulmonar Aguda/patología , Amilasas/sangre , Animales , Apoptosis/inmunología , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Janus Quinasa 2/metabolismo , Masculino , Neutrófilos/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/diagnóstico , Pancreatitis/inmunología , Fosforilación/inmunología , Ratas , Factor de Transcripción STAT3/metabolismo , Índice de Severidad de la Enfermedad , Ácido Taurocólico/administración & dosificación , Ácido Taurocólico/toxicidadRESUMEN
Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and hydrogen proton magnetic resonance spectroscopy ((1)H-MRS) in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment(aMCI). Methods: The cognitive function of 35 AD patients (AD group), 35 aMCI patients (aMCI group) and 36 normal controls (NC group) were evaluated by neuropsychological scales, including Mini-mental State Examination (MMSE) and Cambridge Cognitive Examination-Chinese version (CAMCOG-C). The genotypes of ApoE were analyzed by high-resolution melting assay. Brain regional metabolites were measured via (1)H-MRS technique with the regions of interest (ROIs) located in the left frontal lobe and left hippocampus. Results: The CAMCOG-C (NC group 94.00 (8.50);aMCI group 86.00(8.00);AD group 61.00(18.0)) and MMSE (NC group 29.00 (2.00);aMCI group 26.00(2.00);AD group 13.00(9.5)) scores in AD and aMCI group were significantly lower in comparison with that in NC group (P<0.05). There was multi-domain cognitive impairment both in AD and aMCI. The CAMCOG-C (ε4 carriers 76.00(28.00);no-ε4 carriers 89.00 (17.00)) and MMSE (ε4 carriers 23.00(16.00);no-ε4 carriers (27.00 (6.00))scores in ε4 carriers were significantly lower than those in no-ε4 carriers (P<0.05). The AD and aMCI groups showed decreased NAA/Cr ratio in the left hippocampus as well as elevated Cho/Cr ratio and MI/Cr in the left frontal lobe compared to the NC group (P<0.05). This change was even more pronounced in AD group when compared to aMCI group. The NAA/Cr ratio and Cho/Cr ratio in the left hippocampus in ε4 carriers were lower, the MI/Cr ratio in left frontal lobe in ε4 carriers was higher (P<0.05). Conclusions: ApoE gene polymorphism affects the alteration of (1)H-MRS in AD and aMCI patients. The combination of ApoE gene polymorphism and (1)H-MRS may be more useful to differentiate and diagnose AD and aMCI early.
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Enfermedad de Alzheimer , Apolipoproteínas E/genética , Disfunción Cognitiva , Enfermedad de Alzheimer/genética , Disfunción Cognitiva/genética , Genotipo , Humanos , Espectroscopía de Resonancia Magnética , Pruebas NeuropsicológicasRESUMEN
Objective: To explore the correlation of left heart function changes with cognitive impairment in patients with cerebral small vessel diseases (CSVD). Methods: From February 2012 to June 2018, 199 CSVD patients admitted to the Department of Neurology of the First Affiliated Hospital of Anhui Medical University were enrolled as CSVD group. A total of 103 healthy elderly persons without cognition disorders were included as normal control group (NC group). According to the diagnostic criteria, CSVD patients were divided into 112 CSVD patients with vascular cognitive impairment (CSVD-VCI group) and 87 CSVD patients without cognitive impairment (CSVD-NCI group). Neuroimaging markers of CSVD (including lacunar infarction and white matter hyperintensity) were assessed through brain MRI. Cognitive function was evaluated by The Mini-Mental State Examination (MMSE), the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C), etc. Routine echocardiography was performed to evaluate left ventricular ejection fraction (LVEF), left atrial diameter (LAD) and other parameters. Results: Compared with NC group, the LVEF level was significantly decreased in CSVD group [(65±5)% and (63±6)%, respectively] (P=0.007), while LAD level was significantly increased in CSVD group (P=0.024). The LVEF level of CSVD-VCI group [(62±6)%] was significantly lower than that of CSVD-NCI group [(64±5)%] (P=0.02). Correlation analysis revealed MMSE and CAMCOG-C scores in CSVD group were positively correlated with LVEF level (r=0.210, P=0.003; r=0.238, P=0.001). Logistic regression analysis revealed that declined LVEF was an independent risk factor associated with CSVD (OR=0.937, 95%CI 0.890-0.986) and CSVD-VCI (OR=0.900, 95%CI 0.829-0.977). Conclusions: Left heart function changes play important roles in the occurrence of CSVD and severity of its cognitive impairment. The declined LVEF may represent an independent risk factor for CSVD and its cognitive impairment.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Disfunción Cognitiva/etiología , Humanos , Leucoaraiosis , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVE: To explore the correlation between change in sclerostin level and heart valve calcification in patients with chronic kidney disease (CKD) in stages 3-5, as well as the possible underlying mechanism, which could provide a clinical reference for the diagnosis and treatment of cardiovascular disease (CVD). PATIENTS AND METHODS: 110 patients were divided into a healthy control group and three groups of patients with CKD stages 3, 4, and 5 according to CKD staging guidelines. Scr, BUN, AKP, TC, TG, HDL, LDL, Ca, Pi, and CRP were measured, and calcium-phosphate product (Ca×Pi) calculated. ELISA was used to measure the sclerostin level, and the estimated glomerular filtration rate (eGFR) was calculated by MDRD. Heart valve calcification was measured by a physician in the Cardiac Department of our hospital. The correlations between sclerostin-level change and heart valve calcification, as well as each index in CKD patients in stages 3-5, were analyzed. RESULTS: Compared with the healthy control group, the serum Ca in CKD stage-3, stage-4, and stage-5 groups (p < 0.05) was reduced, and PTH was increased (p < 0.05). Blood Pi and Ca×Pi in the stage-4 and stage-5 groups were increased (p < 0.05). The serum sclerostin level increased with renal hypofunction in stage-3 CKD patients, and was significantly increased compared with that of the control group, reaching the highest level in the terminal stage (p < 0.01). Pearson correlation analysis indicated that serum sclerostin was negatively correlated with eGFR (r = -0.91, p < 0.001) and blood Ca (r= -0.271, p < 0.001), and positively correlated with SCr (r = 0.608, p < 0.001), blood Pi level (r = 0.295, p < 0.001), PTH (r = 0.334, p < 0.001), and Ca×Pi (r = 0.275, p < 0.001). The rate of heart valve calcification in the CKD patients in stage 5 was relatively high (11/30, 36.67%), and significantly higher than that in healthy controls (1/20, 5%; p < 0.01). Logistic regression analysis of heart valve calcification indicated that sclerostin was a risk factor for heart valve calcification in CKD patients in stages 3-5. CONCLUSIONS: The sclerostin level gradually increased with renal hypofunction in CKD patients in stages 3-5, and the increase in serum sclerostin level in the CKD patients occurred earlier than the change in Pi and Ca×Pi. The risk of heart valve calcification in stage-5 CKD patients was significantly increased. Sclerostin is an independent risk factor for heart valve calcification in CKD patients.
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Proteínas Morfogenéticas Óseas/sangre , Calcinosis/diagnóstico , Enfermedades de las Válvulas Cardíacas/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores/sangre , Calcinosis/sangre , Creatinina/sangre , Femenino , Marcadores Genéticos , Tasa de Filtración Glomerular , Enfermedades de las Válvulas Cardíacas/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The endoplasmic reticulum (ER) -resident caspase-12 was identified as a mediator of Aß neurotoxicity. Recent evidence indicates that mitochondrial ATP-sensitive potassium (KATP) channel openers mediate their neuroprotective role by adjusting ER stress pathways, but the molecular details remain largely unknown and have been investigated. MATERIALS AND METHODS: In this study, the protein expression levels of calreticulin (CRT) and caspase-12 activation and phosphorylated p38 MAPK were observed by immunoblotting in cultured PC12 cells from different groups: treatment with Aß25-35 (group Aß25-35), treatment with diazoxide (group diazoxide), pretreatment with diazoxide and then exposure to Aß25-35 (group diazoxide + Aß25-35), pretreatment with p38 MAPK inhibitor SB 203580 and then exposure to diazoxide and Aß25-35 (group SB 203580 + diazoxide + Aß25-35), and the control (group control). RESULTS: In response to the treatment with Aß25-35 (10 µM) for 24 h, the protein expression levels of CRT and caspase-12 activation were increased and phosphorylated p38 MAPK was decreased significantly. Diazoxide reduced CRT overexpression and caspase-12 activation and increased the up-regulation of phosphorylated p38 MAPK. When SB 203580 was presented before exposure to diazoxide and Aß25-35, CRT expression was markedly suppressed, and the inhibition effect of diazoxide on caspase-12 activation was almost eliminated. CONCLUSIONS: We showed that diazoxide induced ERS-related neuroprotection mediated by p38 MAPK against Aß25-35 insults. From the clinical point of view, these results are of considerable importance for the understanding of AD pathogenesis. However, further studies are required to explore more detailed mechanisms of the observed effects.
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Péptidos beta-Amiloides/toxicidad , Diazóxido/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Neuroprotección , Fragmentos de Péptidos/toxicidad , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Apoptosis/efectos de los fármacos , Caspasa 12/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Células PC12 , Ratas , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To investigate the role of miR-5692a in hepatocellular carcinoma (HCC), and to further study the relationship between miR-5692a expression and clinical pathology as well as the prognosis of HCC. PATIENTS AND METHODS: The expression level of miR-5692a in 96 pairs of HCC tissues and para-cancerous tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The relationship between miR-5692a and pathological indicators as well as the prognosis of HCC was analyzed by Kaplan-Meier curves. For in vitro experiments, qRT-PCR was used to detect the expression of miR-5692a in HCC cell lines. Furthermore, small interference sequence of miR-5692a was constructed. Cellular functions of HCC cells after miR-5692a knockdown were detected by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. The underlying mechanism of miR-5692a in regulating the development of HCC was detected by Western blot. RESULTS: MiR-5692a was overexpressed in HCC tissues than that of para-cancerous tissues. HCC patients with higher miR-5692a expression exhibited a higher prevalence of lymph node metastasis and distant metastasis, as well as lower overall survival than those patients with lower level of miR-5692a expression. In vitro experiments demonstrated that miR-5692a knockdown resulted in decreased proliferation and invasion, and increased apoptosis of HCC cells. Western blot results revealed that EMT-related (epithelial-mesenchymal transition) genes, including N-cadherin, Vimentin, ß-catenin and MMP9, were downregulated after miR-5692a knockdown. Rescue experiments indicated that miR-5692a promoted malignant progression of HCC via regulating MMP9. CONCLUSIONS: MiR-5692a was overexpressed in HCC patients, which was remarkably correlated with HCC stage, distant metastasis and poor prognosis. In addition, miR-5692a promoted the malignant progression of HCC via regulating MMP9.