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In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation.
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Proliferación Celular , ADN Helicasas , Miocitos Cardíacos , Proteínas Nucleares , ARN Circular , Factores de Transcripción , Ubiquitinación , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Animales , Factores de Transcripción/metabolismo , ADN Helicasas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Ratones , ARN Circular/metabolismo , ARN Circular/genética , HumanosRESUMEN
Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.
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In the online teaching of Biochemistry course, a variety of network resource platforms (such as Zhihuishu learning network, teleconference, WeChat, QQ, etc) were used to establish a learning community. The teaching content and teaching plan were carefully designed and implemented, enriching the knowledge system of the learning community. And then blending teaching was performed through the combination of live broadcasting and online interaction. In addition to teaching students the basic knowledge of biochemistry, it is also combined with clinical cases and life examples to interact and discuss with students in various forms, giving full play to the advantages of learning community and improving the quality and effect of online learning.
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Autoimmune retinopathy (AIR) is a rare immune retinopathy characterized by decreased visual acuity, scotoma, visual field defect, and photoreceptor dysfunction.AIR is divided into paraneoplastic AIR (pAIR) and non-neoplastic AIR (npAIR). pAIR is further divided into cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse uveal melanocytic proliferation (BDUMP). Circulating anti-retinal antibodies often exist in peripheral blood of patients with various types of AIR, accompanied by electroretinogram abnormalities, but no significant abnormality in fundus examination (except BDUMP). A variety of anti-retinal antibodies such as anti-recoverin protein antibody and anti-α-enolase antibody have been identified in the serum of AIR patients.However, anti-retinal antibodies can also be negative in some AIR patients' serum.At present, the diagnostic criteria and laboratory examination criteria for AIR are not uniform, and there are large differences in clinical examination performance among patients, which may lead to misdiagnosis and missed diagnosis.Therefore, a thorough examination is required to rule out other possible causes before making a speculative diagnosis.So far, the treatments for different types of AIR are not unified.Most clinicians choose a combination of various immunomodulatory therapies, including systemic or topical application of corticosteroids, intravenous immunoglobulin, plasmapheresis, and the use of antimetabolites or anti-CD20 monoclonal antibody.The clinical characteristics of different AIR types, serum anti-retinal autoantibodies detection, differential diagnosis and treatment prognosis of AIR were reviewed in this article to improve the understanding of clinicians and researchers toward the disease, and to achieve early diagnosis and early treatment of AIR.
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Objective:To calculate the conversion coefficient from dose area product (DAP) to organ absorbed dose by Monte Carlo method in order to conveniently estimate doses to patient organ during coronary intervention procedure.Methods:The Geant4 Monte Carlo simulation kit was used to calculate the organ absorbed dose conversion coefficients by simulating exposure scene.Results:The conversion coefficients used in coronary angiography (CAG) for lung, bone marrow, liver and heart were (0.283±0.068), (0.169±0.049), (0.110±0.077) and (0.080±0.032) mGy/(Gy·cm 2) for male, and (0.376±0.121), (0.192±0.056), (0.153±0.105), and (0.102±0.033) mGy/(Gy·cm 2) for female, respectively. These were similar to those in the case of percutaneous coronary intervention (PCI). The DAPs for different interventional procedures were statistically significant ( t=-6.012, P<0.05). The DAPs for difference gender groups had no statistically significant ( P>0.05). Conclusions:Conversion coefficient for organ absorbed dose has little correlation with CAG and PCI in the same sex group. Dose conversion coefficients for female group are greater than those for male group in the same procedure. Conversion coefficients from DAP to organ absorbed dose calculated with Monte Carlo method can provide convenience for rapidly estimating the organ absorbed dose to clinical patients.
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OBJECTIVE:To estab lish the evaluation criteria for repeated usage of TCM decoction pieces and Chinese patent medicine,and to provide reference for prescription comment. METHODS :By modified Delphi method ,15 experts of TCM were selected,who had plenty of clinical experience. The questionnaire data and expert opinion were collected and summarized to establish related evaluation index system with two rounds of questionnaire survey. RESULTS :In this two-rounded survey ,experts’ positive coefficients were 100%;authority coefficient were 0.711 and 0.752;reliability of questionaire were 0.830 and 0.926; coordination degree of experts were 0.579(P<0.01)and 0.721(P<0.01),respectively. The evaluation criteria for cross-using and repeated usage of TCM decoction pieces and Chinese patent medicine ,which contained 4 first-level items (component repetition,function and indication repetition ,tumor repetition and others )and 10 second-level items ,were established finally. CONCLUSIONS:Established criteria are with well expert ’s positive coefficient and high authority ,and good reliability of questionnaire. The evaluation criteria for repeated usage of TCM decoction pieces and Chinese patent medicine is formulated preliminarily.
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Objective:To explore the outcome of extended internal limiting membrane (ILM) peeling combined with releasing the edge technique for primary failed idiopathic macular hole (IMH) surgery.Methods:A retrospective analysis was performed. The data of 18 eyes of 18 IMH patients who were failed in primary surgery from August 2013 to June 2019 in Peking University People’s Hospital were enrolled in the study. Among them, 5 patients were males and 13 patients were females. The average age was 66.2±6.4 years. The BCVA were measured by ETDRS charts. The minimum macular hole size was measured on OCT B-scan image. The average preoperative BCVA and minimum macular hole size of primary surgery was 32.6±13.1 letters and 621.1±161.8 μm. The average preoperative BCVA and minimum macular hole size of second surgery was 34.4±12.3 letters and 499.0±148.6 μm. Average interval period of first and second surgery was 3.4±1.3 weeks. The surgical technique used in the reoperation included the extended ILM peeling combined with releasing the MH edges. The extended ILM peeling area ranged from 4 DD diameter to vascular arcades. The technique of releasing the macular hole edges was performed by using a silicone soft-tip extrusion cannula, with which tapping the edges softly or aspirated vacuum the edges concentricly. The average follow-up was 9.3±5.2 months. The clear OCT image can be obtained for confirming MH closure which was considered as the closure time in the first time. The comparison of preoperative and postoperative was performed by paired t-test. Results:The closure rate of second surgery was 94.4% (17/18), and average closure time was 2.1±1.0 weeks. Only 1 eye experienced the second surgical failure and received the third surgery to achieved macular hole closure. Average final follow-up BCVA was 51.5±13.0 ETDRS letters, with average improvement of 18.9 ETDRS letters (>3 lines) compared with preoperative BCVA of primary surgery. There was significantly statistical difference between the final BCVA and preoperative BCVA ( t=5.412, P <0.001). Eleven patients (61.1%) had 3 lines BCVA improvement, 15 patients (83.3%) had more than 1 line improvement, and 3 patients (16.7%) had on improvement. The final BCVA of patients significantly improved compared with preoperative BCVA of the second surgery ( t=7.595, P<0.001), with average improvement of 17.1±9.5 letters. Conclusion:The extended ILM peeling combined with releasing macular hole edges technique is effective to improve the closure rate and BCVA of primary failed IMH eyes.
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Objective To observe the changes of retinal microstructure in lamellar macular hole (LMH)after vitrectomy.Methods A retrospective clinical observational study.Forty patients (41 eyes) with LMH and received vitrectomy in Ophthalmology Department of Peking University People's Hospital from January 2014 to September 2018 were included in this study.Among them,14 patients (15 eyes) were males and 26 patients (26 eyes) were females,with an average age of 67.8±8.6 years.There were 37 eyes with a lens and 4 eyes with an IOL.There were 29 eyes with LMH of tractional type,7 eyes of degenerative type,and 5 eyes of mixed type.All patients underwent BCVA and OCT examinations.The BCVA examination was performed using the international standard visual acuity chart,which was converted into logMAR visual acuity.The average logMAR BCVA was 0.57±0.27;the mean macular retinal thickness (CRT) was 192.3 ± 108.9 μtm,the mean macular thickness (MRT) was 427.5± 110.2 μm.Among the 29 eyes of tractional type,there were 17 eyes with retinal cavity,8 eyes with macular retinoschisis,and 3 eyes with incomplete ellipsoid zone.Among the 7 eyes of degenerative type,there were 5 eyes with lamellar hole-associated epiretinal proliferation (LHEP),5 eyes with retinal cavity,and 5 eyes with incomplete ellipsoid zone.Among the 5 eyes of mixed type,2 eyes with LHEP,1 eye with macular epiretinal membrane,and 4 eyes with incomplete ellipsoid zone.The average follow-up time after surgery was 12.8±5.2 months.Among them,10 eyes were followed up for equal or greater than 24 months.After the surgery,the same equipment and method before the surgery were used for relevant examination.The changes of BCVA,CRT,and MRT before and after surgery were observed.Continuous variables were compared by t test.Results At the last follow-up,the mean logMAR BCVA was 0.37± 0.26.Compared with before surgery,the difference was statistically significant (t=5.98,P<0.01).The mean CRT and MRT were (245.2 ± 90.8) and (347.0 ±46.7) μtm,respectively.Compared with before surgery,the differences were statistically significant (t=-2.49,-5.24;P< 0.05,< 0.01).CRT and MRT changed greatly within 6 months after surgery,and then tended to be gentle.Among the 3 eyes with incomplete ellipsoid zone of tractional type before surgery,ellipsoid zone recovered in 2 eyes and partially recovered in 1 eye.Among the 17 eyes with retinal cavity and 8 eyes with macular retinoschisis before surgery,there were still 4 eyes with retinal cavity,but all the retinoschisis were disappeared.Among the 5 eyes with retinal cavity of degenerative type before surgery,there were still 2 eyes with retinal cavity and all the eyes with incomplete ellipsoid zone.Among 10 eyes with a follow-up time of equal or greater than 24 months,the macular ganglion cell complex partially atrophied in 6 eyes,and the nerve fiber layer separated in 2 eyes.There was no full-thickness macular hole after surgery.Conclusion For most LMH patients,vitrectomy can effectively improve the visual acuity and promote the recovery of retinal microstructure.
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Objective To observe the clinical and multimodel imaging characteristics ofparacentral acute middle maculopathy (PAMM).Methods Retrospective case series study.From January 2014 to August 2018,12 eyes of 12 patients with PAMM diagnosed in Department of Ophthalmology,Peking University People's Hospital,were included in this study.There were 9 males and 3 females,with the mean age of 57 years.All patients were referred for sudden impaired vision,with or without paracentral scotoma.The patients underwent BCVA,slit lamp examination,fundus photography,FFA and OCT.Simultaneously,OCT angiography (OCTA) was performed in 10 eyes,visual field was performed in 5 eyes,near infrared fundus photography was performed in 1 eye.Clinical and multimodal imaging findings were reviewed and analyzed.Results Among 12 eyes,there were 5 eyes with BCVA 0.05-≤0.1,4 eyes with BCVA 0.3-0.5,3 eyes with BCVA 0.6-1.0.There were 1 eye with central rentinal artery obstruction (CRAO),7 eyes with branch retinal artery obstruction (BRAO).Among them,BRAO with central retinal vein occlusion (CRVO) in 1 eye,with non-arteritic anterior ischemic optic neuropathy in 1 eye,with diabetic retinopathy in 1 eye;old BRAO in 3 eyes;pure BRAO in 1 eye.There were 4 eyes with pure CRVO,including 3 eyes with ischemic CRVO.All eyes demonstrated hyperreflective lesions at the level of the inner nuclear layer and/or outer plexus layer on OCT.En face OCT highlighted the areas with hyperreflectivity corresponding to these lesions.OCTA demonstrated significant deep capillary dropout,abnormal morphology and enlargement of foveal avascular zone.Conclusion Hyperreflective band-like lesions at the level of the inner nuclear layer on OCT and middle retinal perivascular hyperreflectivity on en face scan are characteristic in PAMM.
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Objective@#To observe the changes of retinal microstructure in lamellar macular hole (LMH) after vitrectomy.@*Methods@#A retrospective clinical observational study. Forty patients (41 eyes) with LMH and received vitrectomy in Ophthalmology Department of Peking University People’s Hospital from January 2014 to September 2018 were included in this study. Among them, 14 patients (15 eyes) were males and 26 patients (26 eyes) were females, with an average age of 67.8±8.6 years. There were 37 eyes with a lens and 4 eyes with an IOL. There were 29 eyes with LMH of tractional type, 7 eyes of degenerative type, and 5 eyes of mixed type. All patients underwent BCVA and OCT examinations. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. The average logMAR BCVA was 0.57±0.27; the mean macular retinal thickness (CRT) was 192.3±108.9 μm, the mean macular thickness (MRT) was 427.5±110.2 μm. Among the 29 eyes of tractional type, there were 17 eyes with retinal cavity, 8 eyes with macular retinoschisis, and 3 eyes with incomplete ellipsoid zone. Among the 7 eyes of degenerative type, there were 5 eyes with lamellar hole-associated epiretinal proliferation (LHEP), 5 eyes with retinal cavity, and 5 eyes with incomplete ellipsoid zone. Among the 5 eyes of mixed type, 2 eyes with LHEP, 1 eye with macular epiretinal membrane, and 4 eyes with incomplete ellipsoid zone. The average follow-up time after surgery was 12.8±5.2 months. Among them, 10 eyes were followed up for equal or greater than 24 months. After the surgery, the same equipment and method before the surgery were used for relevant examination. The changes of BCVA, CRT, and MRT before and after surgery were observed. Continuous variables were compared by t test.@*Results@#At the last follow-up, the mean logMAR BCVA was 0.37±0.26. Compared with before surgery, the difference was statistically significant (t=5.98, P<0.01). The mean CRT and MRT were (245.2±90.8) and (347.0±46.7) μm, respectively. Compared with before surgery, the differences were statistically significant (t=-2.49, -5.24; P<0.05, <0.01). CRT and MRT changed greatly within 6 months after surgery, and then tended to be gentle. Among the 3 eyes with incomplete ellipsoid zone of tractional type before surgery, ellipsoid zone recovered in 2 eyes and partially recovered in 1 eye. Among the 17 eyes with retinal cavity and 8 eyes with macular retinoschisis before surgery, there were still 4 eyes with retinal cavity, but all the retinoschisis were disappeared. Among the 5 eyes with retinal cavity of degenerative type before surgery, there were still 2 eyes with retinal cavity and all the eyes with incomplete ellipsoid zone. Among 10 eyes with a follow-up time of equal or greater than 24 months, the macular ganglion cell complex partially atrophied in 6 eyes, and the nerve fiber layer separated in 2 eyes. There was no full-thickness macular hole after surgery.@*Conclusion@#For most LMH patients, vitrectomy can effectively improve the visual acuity and promote the recovery of retinal microstructure.
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Gallbladder carcinoma is the most common malignancy in biliary tract.Early dissemination,rapid and silent progression and delayed diagnose could portend a dismal prognosis.The 5-year survival rate is less than 10%.Clarifying the etiological feature can improve the early diagnosis.Comprehending surgical indications of benign lesions can provide the methods for rational prophylactic resections.Standardized treatment of accident gallbladder carcinoma could improve the patients' prognosis.Efficient serologic markers could be used for early diagnosis and screening.
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Objective To investigate the mechanisms of hypoxia inducible factor-2 alpha (HIF-2a) regulating human umbilical vein endothelial cells (HUVECs) under hypoxic conditions.Methods The experimental study was adopted.(1) HUVECs in logarithmic growth phase were taken:HUVECs without any disposals as control group,HUVECs with shRNA transfection control as shRNA control group,HUVECs with HIF-2α shRNA transfection as HIF-2α shRNA group and HUVECs with HIF-2α shRNA transfection then added rhAng-2 as HIF-2α ± rh-Ang-2 group.(2) Western blot testing:the expressions of Ang-2 and HIF-2α proteins in HUVECs were cultured under hypoxia conditions at 0,2,4,8,12,16,20 hours,and the levels of which were detected in the control group,shRNA control group and HIF-2α shRNA group.(3) Enzyme-linked immunosorbent assay(ELISA):the level of Ang-2 protein in supernatant of HUVECs was detected in the control group,shRNA control group and HIF-2α shRNA group.(4)The amounts of endothelial cell tubes in HUVECs among the 4 groups were detected by tube formation experimental testing.(5) Transwell method was performed to detect the amounts of cells migration in HUVECs and hepatoma cells SMMC-7721 migration intervened by supernatant of HUVECs among the 4 groups.Measurement data with normal distribution were presented as x ± s,repeated measurement data were analyzed by the repeated measures ANOVA,comparison among groups and pairwise comparison were conducted respectively by the one-way ANOVA and Dunnett's test.Results (1) Western blot test:the expression levels of Ang-2 and HIF-2α proteins in HUVECs under hypoxia conditions at 0,2,4,8,12,16,20 hours were 0.110 ±0.011,0.120 ±0.020,0.210 ±0.070,0.410 ±0.100,0.520 ± 0.090,0.790±0.130 1.010 ±0.220 and 0.180 ±0.090,0.410 ±0.070,0.470 ±0.110,0.470 ±0.070,0.580 ± 0.120,0.690 ± 0.140,0.920 ± 0.130,respectively,and which were increased after culturing under hypoxia conditions and had an ascending tendency as the hypoxia time extended,with statistically significant differences (F =403.550,3 265.587,P < 0.05).The expression levels of Ang-2 and HIF-2α proteins in the control group,shRNA control group and HIF-2α shRNA group were 1.030 ±0.180,1.070 ±0.120,0.210 ± 0.070,and 0.940 ± 0.110,0.930 ± 0.190,0.170 ± 0.021,respectively,showing statistically significant differences (F =290.242,26.688,P < 0.05).(2) The results of ELISA:the expression levels of Ang-2 in the control group,shRNA control group and HIF-2α shRNA group were (433.2 ±9.7)ng/L,(438.3 ± 2.6)ng/L,(114.6 ± 4.2) ng/L,with a statistically significant difference (F =2 642.180,P < 0.05).(3) The results of tube formation experiments:the number of endothelial cell tubes in the control group,shRNA control group,HIF-2α shRNA group and HIF-2α ± rh-Ang-2 group were 48.3 ± 2.5,47.4 ± 3.1,19.7 ± 1.5 and 38.3 ± 2.1,respectively,with a statistically significant difference (F =148.196,P < 0.05).(4) The results of Transwell method:① the number of HUVECs migration in the control group,shRNA control group,HIF-2α shRNA group and HIF-2α + rh-Ang-2 group were 140.3-± 3.5,142.7 ± 2.1,42.7 ± 3.1 and 78.1 ± 4.2,respectively,showing a statistically significant differences (F =212.205,P < 0.05).②The results of Transwell method:the number of SMMC-7721 cells migration after intervening using four different supernatant in the control group,shRNA control group,HIF-2α shRNA group and HIF-2α ± rh-Ang-2 group were 106.7 ± 5.5,102.7 ± 6.6,63.0 ± 3.3 and 96.7 ± 2.1,respectively,showing a statistically significant difference (F =55.122,P < 0.05).Conclusion HIF-2a could not only affect HUVECs formation but also promote SMMC-7721 cells migration via regulating Ang-2 expression.