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Idiopathic pulmonary fibrosis(IPF)is a chronic progressive interstitial lung disease of unknown etiology,with a rapid disease course,poor prognosis,and the absence of effective therapeutic drugs.Mitochondrial dys-function is one of the crucial causes of inducing IPF.Silent information regulator 3(SIRT3)can restore mitochondrial ho-meostasis by inhibiting mitochondrial oxidative stress,repairing mitochondrial DNA damage,and ameliorating abnormal mitochondrial lipid metabolism.This paper summarizes the role and mechanism of SIRT3 in attenuating mitochondrial dys-function based on delineating the relationship between mitochondrial dysfunction and IPF,aiming to provide references for finding effective treatment methods for IPF.
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【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.
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Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.
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ObjectiveThrough the review of the literature about Asari Radix et Rhizoma, we extracted the key information affecting the toxicity of Asari Radix et Rhizoma, aiming to provide a basis for the rational application of Asari Radix et Rhizoma in the classical prescriptions. MethodThe bibliometric method was employed to analyze the ancient and modern literature and thus reveal the relationship of Asari Radix et Rhizoma toxicity with the medicinal plants, medicinal part, processing method, dosage form, prescription compatibility, medication method, and patients' physical factors. ResultThe dosage of Asari Radix et Rhizoma in Danggui Sinitang and Houpo Mahuangtang was 9 g and 6 g, respectively, and the decocting time should be longer than 120 min. The single dosage of Asari Radix et Rhizoma in Xinyisan, Sanbitang, Daqinjiao Tang, and Qingshang Juantongtang were 0.8, 1.2, 0.9, and 1.1 g, respectively. The rhizome of Asarum heterotropoides var. mandshuricum or A. sieboldii var. seou1ense should be selected for Danggui Sinitang, Houpo Mahuangtang, and Qingshang Juantongtang, while that of A. siebodii var. seou1ense should be selected for Xinyisan. In terms of processing, Asari Radix et Rhizoma can be processed with wine when being used in Danggui Sinitang, Houpo Mahuangtang, Sanbitang, and Daqinjiaotang, and it can be stir-fried when being used in Xinyisan and Qingshang Juantongtang. In addition, the toxicity of Asari Radix et Rhizoma is associated with the compatibility of drugs and the physical conditions of patients. ConclusionBy reviewing the literature on Asari Radix et Rhizoma toxicity, we obtained the key information affecting the toxicity of Asari Radix et Rhizoma and explored the effective ways to avoid the toxicity. This study provides a sufficient basis for the rational development and safe application of the classical prescriptions containing Asari Radix et Rhizoma.
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Ulcerative colitis(UC)is an inflammatory bowel disease induced by multiple factors,which causes abnormal activation of intestinal immune cells and excessive release of antibodies and inflammatory factors,repeatedly damaging the intestinal mucosa.Macrophages,as innate intestinal immune cells,often maintain the balance of M1/M2 macrophages polarization to normalize the regression inflammation,and the imbalance of their polarization will cause repeated damage of intestinal mucosa and persistent inflammation,which is a main cause of UC.Nuclear factor E2-related factor 2(Nrf2),as an important regulator of antioxidant and anti-inflammatory,is often used as a target for the treatment of autoimmune diseases.Nrf2 alleviates intestinal high oxidative stress and inflammatory factors by balancing macrophage polarization,which may be of great significance for the prevention and treatment of UC.Summarizing the mechanism of macrophage polarization imbalance on the course of UC and the possible regulatory mechanism of Nrf2 may provide basis for the development of UC targeted therapeutic drugs.
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Objective:To investigate the relationship between plasma N-terminal B-type natriuretic peptide precursor (NT-proBNP), hypersensitive C-reactive protein (hs-CRP), troponin Ⅰ (cTnⅠ) and carbohydrate antigen 125 (CA125) and cardiac function in patients with acute heart failure.Methods:From May 2017 to May 2019, 97 patients with acute heart failure admitted to Hangzhou Dajiangdong Hospital were selected as the observation group.According to the cardiac function classification of New York Heart Association (NYHA), 29 patients were classified as grade Ⅱ group, 51 patients as grade Ⅲ group and 17 patients as grade Ⅳ group.Fifty healthy people were selected as control group.The changes of plasma NT-proBNP, hs-CRP, cTnⅠ and CA125 levels, left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were compared between the two groups.The changes of plasma NT-proBNP, hs-CRP, cTnⅠ and CA125 levels, as well as the changes of LVED and LVEF in the different heart function grading group were compared.The correlation between plasma NT-proBNP, hs-CRP, cTnⅠ, CA125 and LVEDD, LVEF was analyzed.Results:The plasma NT-proBNP[(5 684.21±174.39)ng/L], hs-CRP[(16.54±3.27)mg/L], cTnⅠ[(0.43±0.13)g/L] and CA125[(83.24±15.46)U/mL] in the observation group were higher than those in the control group( t=216.813, 25.684, 19.432, 34.138, all P<0.05). The LVEDD in the observation group[(63.21±4.87)mm] was higher than that in the control group[(48.97±2.41)mm], and the LVEFin the observation group[(39.27±3.25)%] was lower than that in the control group[(62.87±4.36)%], the differences were statistically significant ( t=19.461, 37.008, all P<0.05). The levels of NT-proBNP[(7 368.18±201.05)ng/L], hs-CRP[(24.19±4.18)mg/L], cTnⅠ[(0.63±0.14)μg/L] and CA125[(164.52±27.48)U/mL] in the grade Ⅳ group were higher than those in the grade Ⅱ group and grade Ⅲ group(grade Ⅲ group: t=31.109, 6.557, 5.321, 13.017; grade Ⅱ group: t=75.873, 16.582, 11.755, 23.178, all P<0.05). The plasma NT-proBNP[(5 751.42±180.34)ng/L], hs-CRP[(15.98±4.56)mg/L], cTnⅠ[(0.41±0.15)g/L] and CA125[(87.97±18.45)U/mL] in the grade Ⅲ group were higher than those in the grade Ⅱ group[(3 481.34±145.26)ng/L, (8.23±2.37)mg/L, (0.25±0.08)μg/L and (28.43±12.21)U/mL]( t=57.893, 8.507, 5.320, 15.530, all P<0.05). The LVEDD[(67.95±5.15)mm] in the grade Ⅳ group was higher than that in the grade Ⅱ group and grade Ⅲ group(grade Ⅲ group: t=3.553, grade Ⅱ group: t=8.157, P<0.05), while the LVEF[(34.28±2.36)%] in the grade Ⅳ group was lower than that in the grade Ⅱ group and grade Ⅲ group(grade Ⅲ group: t=6.673, grade Ⅱ group: t=10.417, all P<0.05). The LVEDD[(62.78±5.21)mm] in the grade Ⅲ group was higher than that in the grade Ⅱ group[(57.87±3.25)mm]( t=4.586, P<0.05), while the LVEF in the grade Ⅲ group[(39.98±3.24)%] was lower than that in the grade Ⅱ group[(45.98±4.25)%]( t=7.097, P<0.05). LVEDD was positively correlated with NT-proBNP, hs-CRP, cTnⅠ and CA125, while LVEF was negatively correlated with NT-proBNP, hs-CRP, cTnⅠ and CA125. Conclusion:The levels of NT-proBNP, hs-CRP, cTnⅠ and CA125 in plasma of patients with acute heart failure are elevated, and they are significantly correlated with cardiac function grading and cardiac function indicators.
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Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
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Objective To investigate the quality of life in young patients with hemodialysis and influencing factors .Methods Totally 128 young patients aged 18-44 years old with maintenance hemodialysis were performed the questionnaire investigation by using the self‐designed demographic information questionnaire ,Medical Outcomes Study Health Status Short Form (SF‐36) , Herth Hope Index(HHI)and Social Support Rating Scale(SSRS) .Results The mean total score of physical health in the hemodial‐ysis young patients was (202 .49 ± 53 .94) points and the mean total score of mental health was (190 .85 ± 77 .81) points .In the va‐rious dimensional scores of living quality ,the scores of physical functioning and bodily pain were highest ,while the scores of physi‐cal function and emotional function were lowest ,moreover the scores of various dimensions were lower the the national norm (P<0 .01) .The multiple regression analysis showed that the quality of life was significantly correlated with hope level ,social support and economic condition ,which could explained 62 .8% of living quality variation amount .Conclusion The quality of life in hemodi‐alysis young patients needs to be improved .The medical care workers formulate the intervention measures ,meanwhile should pay attention to enchance patients′hope leve and social support .At the same time it is appealed that the government helps to solve the patients′economic problem in order to better improve their living quality and promote them return to society .
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Objective To examine the status of self-perceived burden in patients with continuous ambulatory peritoneal dialysis and explore the relationships among social support,coping styles and self-perceived burden.Methods 103 elderly patients with peritoneal dialysis of outpatient follow-up were recruited.They were investigated using Self-Perceived Burden Scale,Social Support Rating Scale,and Simplified Coping Style Questionnaire.Results The total score of self-perceived burden was at a moderate level and the average score was (36.67±3.67).The total score of social support,the average score of positive coping and negative coping were (40.27±5.83),(1.69±0.26),(1.80±0.40),then the difference was statistically significant when compared with domestic norm (34.56±3.73),(1.78±0.52),(1.59±0.66) (P<0.05).The analysis found that self-perceived burden was negatively correlated with positive coping styles,social support and each dimension (r =-0.239,-0.668,-0.725,-0.252,-0.647,P<0.05).Conclusions Medical personnel should inspire elderly patients to make full use of social resources and guide them to take positive attitude to deal with dialysis event.It would help them maintain well psychological condition for a long time and reduce the self-perceived burden of patients.
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OBJECTIVE:To study the effects of rosiglitazone(RH)on body weight,FPG,FFA and other indicators in diabe-tes model rabbit. METHODS:18 rabbits were evenly randomized into control group,model group and dextran group. The latter 2 groups were given alloxan intravenously to induce diabetes model. 3 groups were given RH(0.5 mg/kg)intragastrically,and dex-tran group was additionally given dextran 40 glucose injection(5 ml/kg)intravenously,once a day,for consecutive 3 weeks. Body weight,serum level of FPG,FFA,AngⅡ and NO were determined before and after medication. RESULTS:Compared with be-fore medication,body weight of rabbits in control group were increased after medication,while the levels of FFA and AngⅡ were decreased;the levels of FPG and FFA were decreased in model group;body weight of rabbits were decreased in dextran group af-ter medication,with statistical significance (P0.05). The level of FFA in dextran group was higher than in model group after medication,with statistical significance(P<0.01). CONCLUSIONS:Rosiglitazone can lead to weight gain by a mechanism which reduce the level of FFA.
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Objective To explore the value of ocular fundus artery hemodynamics in diabetes by the correlation study between ocular fundus artery and glycosylated hemoglobin(GHb).Methods GHb was checked in 98 patients (196 eyes) in diabetes,including 49 cases (98 eyes) before treatment and 49 cases (98 eyes) after treatment,and normal group of 100 cases (200 eyes)An all cases,color Doppler ultrasonography was used for monitorind ophthalmic artery(OA),central retinal artery(CRA) and posterior ciliary artery (PCA).Finally,the differences of the parameters vauels of the the OA,CRA,and PCA between diabetic and normal group were studied in order to find out the relationship with GHb.Results Of 98 patients in diabetes,peak systolic velocity and end diastolic velocity of fundus artery decreased,resistance index increased(RI).There was significant difference between diabetic and normal group(P <0.05),and a significant difference was exited between diabetic group before and after treatment(P <0.05).GHb were negatively correlated with the velocity of fundus artery,and positively correlated with RI.Conclusions Evaluation of ocular fundus artery hemodynamics in diabetes can provide useful information for diabetic retinal perfusion and function change.For evaluation of diabetic retinal disease,it is of great value in clinical application.
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To understand mechanisms for the difference of uptaking and transporting the pigments between the male and female in the silkworm, Bombyx mori strain of sex-related fluorescent cocoon, the fluorescent pigments in the midgut lumen, midgut, blood, silk glands and cocoon were analyzed with thin-layer chromatography, and showed that fluorescent colors of cocoons consisted with that of blood and silk glands. The different fluorescent colors of cocoons between the male and female may be mainly caused by the difference of accumulation and transportation for fluorescent pigments in the midgut and in the silk glands. Furthermore the midgut proteins were separated with Native-PAGE, and the proteins respectively recovered from three fluorescent regions presenting on a Native-PAGE gel for the female silkworms were determined using shotgun proteomics and mass spectrometry sequencing, of which 60, 40 and 18 proteins respectively from the region 1, 2 and 3 were identified. It was found that the several kinds of low molecular mass 30 kDa lipoproteins and the actins could be detected in all three regions, troponin, 30 kDa lipoprotein and 27 kDa glycoprotein precursor could be detected in the region 2 and 3, suggesting these proteins may be fluorescent pigments binding candidates proteins. Analysis of gene ontology indicated that the identified proteins in the three regions linked to the cellular component, molecular function, and biological process categories. These results provide a new clew to understand the formation mechanism of sex-related fluorescent cocoon of silkworm.
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Bombyx/fisiología , Fluorescencia , Pigmentos Biológicos/fisiología , Seda/fisiología , Animales , Transporte Biológico/fisiología , Bombyx/genética , Cromatografía Liquida , Cromatografía en Capa Delgada , Biología Computacional , Electroforesis en Gel de Poliacrilamida , Femenino , Glicoproteínas/genética , Glicoproteínas/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo , Masculino , Pigmentos Biológicos/sangre , Pigmentos Biológicos/genética , Análisis de Secuencia de ADN , Factores Sexuales , Espectrometría de Masas en Tándem , Troponina/genética , Troponina/metabolismoRESUMEN
The different growing habitats of Bupleurum chinense were investigated in Donglin mountain & Wuling mountain areas, the saikosaponin a and d in samples of B. chinense collected from different habitats were determined by HPLC. Results showed that B. chinense distributed in various habitats, such as meadow, understory and brushy. Significant differences of saikosaponin contents were observed. The higher saikosaponins contents were showed in samples from meadow habitats, while the lower saikosaponins contents in samples from understory and brushy habitats. The ventilation situation and light condition showed positive correlation with the saikosaponins accumulation in B. chinense. It could be concluded that growing habitats play an important role in accumulation of saikosaponins in B. chinense.
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Bupleurum , Química , China , Cromatografía Líquida de Alta Presión , Cartilla de ADN , Genética , Ecosistema , Ácido Oleanólico , SaponinasRESUMEN
The E (envelope) protein is the smallest structural protein in all coronaviruses and is the only viral structural protein in which no variation has been detected. We conducted genome sequencing and phylogenetic analyses of SARS-CoV. Based on genome sequencing, we predicted the E protein is a transmembrane (TM) protein characterized by a TM region with strong hydrophobicity and alpha-helix conformation. We identified a segment (NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH) in the carboxyl-terminal region of the E protein that appears to form three disulfide bonds with another segment of corresponding cysteines in the carboxyl-terminus of the S (spike) protein. These bonds point to a possible structural association between the E and S proteins. Our phylogenetic analyses of the E protein sequences in all published coronaviruses place SARS-CoV in an independent group in Coronaviridae and suggest a non-human animal origin.
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Secuencia de Aminoácidos , Secuencia de Bases , Análisis por Conglomerados , Codón , Genética , Componentes del Gen , Genoma Viral , Glicoproteínas de Membrana , Metabolismo , Proteínas de la Membrana , Genética , Metabolismo , Datos de Secuencia Molecular , Filogenia , Conformación Proteica , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia , Glicoproteína de la Espiga del Coronavirus , Proteínas del Envoltorio Viral , Genética , MetabolismoRESUMEN
We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
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Secuencia de Bases , China , Análisis por Conglomerados , Componentes del Gen , Variación Genética , Genoma Viral , Genotipo , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Genética , Análisis de Secuencia de ADN , Síndrome Respiratorio Agudo Grave , GenéticaRESUMEN
Objective To explore the diagnostic value on the monitoring of 24 hours AEEG in atypical epilepsy.Methods The monitoring of 24 hours AEEG were performed in 21 patients with atypical epileptic seizures, and observed their clinical manifestation.Results 21 patients with atypical epileptic seizure were not showed epileptiform discharges in routine EEG, but could show many paroxyomal spike waves, sharp waves, spike and slow wave complex, sharp and slow wave complex in AEEG, and the patients' conditions were controlled after they were treated by antiepileptic drugs.The epilepsy can be diagnosed.Conclusion The monitoring of 24 hours AEEG can diagnose the patients with atypical epilepsy.