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ObjectiveTo reveal the differences of the related pathogenicity gene mutations between sebaceous adenocarcinoma (SC) of scalp and sebaceous adenoma (SA) of scalp on whole exome level. MethodsWhole exome sequencing was performed on a SC sample and a SA sample by Illumina Hiseq 2500 platform. Suspicious single nucleotide variation sites were selected for mutation conservation and functional analysis. SciClone was used to track subclone evolution and clonal map information was obtained for each tumor sample. The high-frequency significant gene mutations in the tumor sample were screened by MutSigCV software, and compared with the known driver genes. ResultsTwo driver genes TFDP1 and ACVR1B harboring mutations in scalp SC compared to SA were found. ConclusionsThe finding of mutation in driver genes TFDP1 and ACVR1B should be confirmed in a large cohort, which might reveal the mechanism of scalp SC development and find a therapeutic target for SC.
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AIM: To analyze the correlation of changes in non-contact intraocular pressure(IOPNCT)and the surgical parameters after femtosecond laser small incision lenticule extraction(SMILE)for high myopia.MOTHODS:A retrospective analysis, the clinical data of 98 patients(196 eyes)with high myopia were operated SMILE in the optometric center of Gansu Provincial Hospital from January 2018 to July 2019 were analyzed. The change of IOPNCT before and after operation was observed, and recorded the optical zone(OZ), lenticule thickness(LT), cap thickness(CT)and residual stromal thickness(RST)and the correlation with the change value of IOPNCT(△IOPNCT, △IOPNCT=IOPpreoperative-IOP postoperative at 6mo).RESULTS:After operation at 1d, 1wk, 1,3 and 6mo, the group of patients with IOPNCT(10.84±2.14,11.00±2.19,10.65±2.43,10.45±2.04,10.61±1.39mmHg)and the preoperative(16.79±1.65mmHg)comparison have a difference(P<0.001).The optical zone and lenticule thickness were positively correlated with △IOPNCT respectively(r=0.1537, 0.8161, all P<0.05). The cap thickness and residual stromal thickness were negatively correlated with △IOPNCT respectively(r=-0.8362, -0.3351, all P<0.0001). Introduce the above related factors into a multiple linear regression analysis model. The regression coefficients of variables are statistical significane. The regression equation was Y=16.189+0.227X1+0.032X2-0.083X3-0.007X4(Y=△IOPNCT, X1=OZ, X2=LT, X3=CT, X4=RST). The equation was statistically significant(F=195.704, P<0.001), and the regression model coefficient of determination R2=0.901.CONCLUSION:The intraocular pressure changes after SMILE with high myopic were correlated with optical zone, lenticule thickness, cap thickness and residual stromal thickness. The regression equation would provide reference to evaluation the real intraocular pressure after SMILE in clinic.
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Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI
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The pandemic COVID-19 has spread to all over the world and greatly threatens safety and health of people. COVID-19 is highly infectious and with high mortality rate. As no effective antiviral treatment is currently available, new drugs are urgently needed. We employed transcriptional analysis to uncover potential antiviral drugs from natural products or FDA approved drugs. We found liquiritin significantly inhibit replication of SARS-CoV-2 in Vero E6 cells with EC50 = 2.39 M. Mechanistically, we found liquiritin exerts anti-viral function by mimicking type I interferon. Upregulated genes induced by liquiritin are enriched in GO categories including type I interferon signaling pathway, negative regulation of viral genome replication and etc. In toxicity experiment, no death was observed when treated at dose of 300 mg/kg for a week in ICR mice. All the organ indexes but liver and serum biochemical indexes were normal after treatment. Liquiritin is abundant in licorice tablet (~0.2% by mass), a traditional Chinese medicine. Together, we recommend liquiritin as a competitive candidate for treating COVID-19. We also expect liquiritin to have a broad and potent antiviral function to other viral pathogens, like HBV, HIV and etc.
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Artemisinin is a kind of sesquiterpene lactone containing endoperoxide bridge,which is the most effective anti-malarial drug at present. However,low content of artemisinin in Artemisia annua,ranging from 0. 1%-1. 0% of dry weight,as well as the complicated extraction process have resulted in low yield and high cost of artemisinin,making it difficult to meet market demand.Based on the development of high-throughput sequencing and molecular biology,the related enzyme genes and transcription factors involved in the artemisinin metabolic pathway were cloned and identified. Metabolic engineering and synthetic biology methods to modify the original metabolic pathway of A. annua and genetic engineering in heterologous host cells have become one of the hotspots in this field. Therefore,the molecular mechanism of artemisin biosynthesis,different strategies of genetic modifications of A. annua,and the research status and application prospect of artemisinin synthesis in heterologous host cells( Nicotiana benthamiana,Physcomitrella patens) were summarized in our review,hoping to provide molecular basis and theoretical basis for breeding new varieties of A. annua with high artemisinin output.
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Antimaláricos , Artemisia annua , Artemisininas , Ingeniería Metabólica , Factores de TranscripciónRESUMEN
A typical clinical case of taking Dictamni Cortex(Baixianpi) powder was analyzed to study liver damage caused by Dictamni Cortex. Liver damage was diagnosed according to the integrated evidence chain method recommended by the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury. By analyzing clinical history and biochemistry and imaging examinations, underlying diseases, such as viral hepatitis, autoimmune liver disease and alcoholic liver disease, were excluded. Through the investigation of medication history, we made it clear that the patient only took Dictamni Cortex powder during the period, and thus suspected that the liver injury was induced by Dictamni Cortex. Furthermore, the quality of the drug was tested, and the results showed it was consistent with the quality standard of Chinese Pharmacopoeia. DNA barcoding showed that the drug was 100% similar with Dictamnus dasycarpus. Moreover, exogenous harmful substances and chemical drug additions were tested, and the results showed that the content of heavy metal, pesticide residues and microbial toxin were consistent with the required standards, and no chemical drug additions were found in Agilent Fake TCM-Drugs database. In summary, we confirmed that the clinical case of drug-induced liver injury was induced by D. dasycarpus with the dose of 15 g•d⁻¹, which exceeded the prescribed amount of Chinese Pharmacopoeia. According to the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury, the case of drug-induced liver injury induced by D. dasycarpus was confirmed, which provided a direct and reliable evidence for the study of risk of liver injury induced by D. dasycarpus and its relevant preparations.
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AIM:To explore the changes of intraocular pressure measured by noncontact tonometer (IOPNCT) with high myopia and analyze the relative fators after small incision lenticule extraction(SMILE).METHODS:A retrospective study.Totally 108 cases (216 eyes) with high myopia received SMILE during March 2015 to October 2016 were involved.The IOPNCT, corneal central thickness (CCT) and corneal curvature for 3mo were recorded and analyzed by ANOVA, LSD t test.The Pearson correlation analysis and multiple linear regression model analysis were used to evaluate the relationship between IOPNCT and its influence factors.RESULTS:(1) There was significant statistical difference in IOPNCT after SMILE at 1d, 1wk, 1 and 3mo compare with preoperative (t=17.785, P=0.019;t=17.981, P=0.016;t=18.841, P=0.012;t=19.364, P=0.001);the IOPNCT after SMILE decreased.The IOPNCT values at every time after SMILE was no statistical difference (t=1.871, P=0.818;t=3.062, P=0.328;t=1.143, P=0.373).(2) The IOPNCT in high myopia were positive correlated with CCT and corneal curvature after SMILE (r=0.4356, 0.295;P<0.05), respectively.(3) The multiple linear regression model analysis revealed that Y=-14.601+0.348X1+0.03X2 (Y was IOPNCT, X1 was corneal curvature, X2 was CCT,P<0.001);Y=3.679+0.28X1+0.012X2 (Y was△IOPNCT,X1 was variation of corneal curvature,X2 was△CCT, P<0.001).CONCLUSION:The IOPNCT decreased after SMILE in high myipia, and it showed that there was no significant influence to use glucocorticoid eye drops in short terms.There was positive correlation among IOPNCT, CCT and corneal curvature after SMILE.
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?The small incision lenticule extraction ( SMILE ) with femtosecond laser is a new mode of corneal refractive surgeryrecently. The safety, efficacy, stability and predictability of SMILE lead the corneal refractive surgery to a new world that only use femtosecond laser to correct myopia.With the development and popularity of SMILE, the clinical effect has aroused much concern.But there remain exited disputes in refractive stability, visual quality and corneal biomechanical property, contrast sensitivity and glare symptoms, corneal sensitivity and dye eye, corneal endothelial cells and intraocular pressure.These will be summarized in this review.
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<p><b>OBJECTIVE</b>To assess the association between single nucleotide polymorphisms (SNPs) of mannose-binding lectin 2 gene (MBL2) (rs1800450, rs1800451 and rs11003125) and protein kinase C-beta 1 gene (PRKC beta 1) (rs3700106, rs2575390) with diabetic macroangiopathy in northern Chinese Han population.</p><p><b>METHODS</b>The samples have included 318 type 2 diabetes mellitus (T2DM) patients and 448 normoglycemic controls. The five SNPs were determined by a Multiplex SnaPshot method. Biochemical indices such as fasting plasma-glucose, triglyceride and total cholesterol were also measured. Linkage disequilibrium and haplotype analysis were carried out for all samples using Haploview 4.2. Additive model was applied to assess the effect of interaction between SNPs and environment factors on macrovascular complications.</p><p><b>RESULTS</b>Genotypic frequencies of rs11003125 have differed significantly between the controls and patients with coronary heart disease and peripheral vascular disease (P=0.024 and 0.004, respectively). The allele frequency of rs11003125 was also statistically significant between the two groups (P=0.014 and 0.001, respectively). Compared with patients without macrovascular complications, the allele frequency of rs11003125 was significantly different in patients with peripheral vascular disease (P=0.031). No significant differences were found between the distribution of the genotype frequency and allele frequencies of other variants. Haplotype analysis indicated that, compared with controls and patients without macrovascular complications, individuals with G allele of rs1800450 and C allele of rs11003125 had a higher risk for macrovascular complications.</p><p><b>CONCLUSION</b>The rs11003125 polymorphism located in the promoter region of MBL2 gene is associated with macrovascular complications of T2DM in northern Chinese Han population. G allele of rs1800450 and C allele of rs11003125 may be risk factors for macrovascular complications. There were additive interactive effects for rs11003125 polymorphism (GC+CC) and hypertension, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy on macrovascular complications.</p>
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Humanos , Alelos , China , Etnología , Diabetes Mellitus Tipo 2 , Etnología , Genética , Angiopatías Diabéticas , Etnología , Genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Lectina de Unión a Manosa , Genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Proteína Quinasa C , Genética , Proteína Quinasa C betaRESUMEN
<p><b>OBJECTIVE</b>To investigate the distribution of common allergens in patients with allergic rhinitis (AR) from 2006 to 2010 in Wuhan area, and provide the objective evidence for the prevention and treatment of AR.</p><p><b>METHODS</b>The medical records of skin prick test (SPT) performed on 2707 AR patients from 2006 to 2010 were retrospectively analysed, and the positive rate of different allergens and changing trends in this time were compared. SPSS 17.0 software was used to analyse the data.</p><p><b>RESULTS</b>There were significant differences among the Dermatophagoides pteronyssinus positive rate (χ(2) = 12.11, P < 0.05) and Dermatophagoides farinae positive rate (χ(2) = 11.11, P < 0.05) in the past 5 years. Meanwhile, there was an upward trend in the positive rate of dust mite, which the positive rate of Dermatophagoides pteronyssinus increased from 84.5% in 2006 to 90.5% in 2010 (χ(2) = 6.88, P < 0.05), positive rate of Dermatophagoides farinae increased from 81.5% in 2006 to 89.0% in 2010 (χ(2) = 9.68, P < 0.05); There were significant differences among the Mugwort and Ragweed positive rate of 5 years (χ(2) = 194.10, P < 0.05; χ(2) = 67.06, P < 0.05). There were significant differences among the mold I and mold II positive rate of 5 years between (χ(2) = 18.95, P < 0.05; χ(2) = 36.62, P < 0.05). Meanwhile, there was an upward trend in the positive rate of mold and fluctuant trend in the positive rate of spring-pollen.</p><p><b>CONCLUSIONS</b>Nearly five years, dust mites is still the most common allergens in AR patients, presenting upward trend; the positive rate of mold presenting upward trend; the positive rate of wormwood and guinea wood presenting downward trend; the positive rate of pollen presenting fluctuant trend.</p>
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Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Alérgenos , Alergia e Inmunología , China , Epidemiología , Estudios Retrospectivos , Rinitis Alérgica , Rinitis Alérgica Perenne , Diagnóstico , Epidemiología , Pruebas CutáneasRESUMEN
Objective To investigate whether the mannose-binding-lectin 2 (MBL2) gene was associated with type 2 diabetes in the populations living the northern part of China. Methods The study involved 318 type 2 diabetic patients and 448 normoglycemic controls. The variances of rs1800450, rs1800451 and rs11003125 were determined by the Multiplex SNaPshot method. Fasting blood-glucose, triglyceride and total cholesterol were also measured. All of these results were analyzed by logistic regression method. Linkage disequilibrium and Haplotype measures were computed in all samples using Haploview. Results There seemed no mutation on rs 1800451 while the rs 1800450 and rs11003125 polymorphism was consistent with Hardy-Weinberg expectations in both the case and the control groups. Genotypes and allele frequencies of rs1800450 as well as rs11003125 were observed (P=0.006, P=0.003) and (P=0.010, P=0.004), respectively. Data from logistic regression analysis revealed that factors as overweight, abdominal obesity, hypercholesterolemia, GG genotype frequencies of Exonl rs1800450 polymorphism as well as (GC + CC) genotype frequencies of rs11003125 polymorphism in MBL2 conferred increased risks for type 2 diabetes. Haplotype analyses of the two SNPs (rs1800450, rs11003125) revealed similar effects as compared with the single SNP associations. Only haplotype constructed from GC alleles conferred increased trends for type 2 diabetes (OR=2.21, 95% CI: 1.47-3.33, P=0.000). Conclusion Our result suggested that the Exonl rs1800450 polymorphism and promoter region rs11003125 polymorphism in MBL2 gene were both associated with type 2 diabetes in the Chinese population living in the northern areas of China. The G allele of rs 1800450 and C allele of rs 11003125 might be the risk factors of type 2 diabetes.
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Aim:To construct the short hairpin small interfering RNA(shRNA) eukaryotic expression vector specific to mouse lectin like oxidized low density lipoprotein receptor 1(LOX-1) gene and to observe its silencing effect on LOX-1 in RAW264.7 cells.Methods:(1)The pLOX-1-shRNA expression vector was constructed by gene recombination,Then transfected into the cultured RAW264.7 cells.At 48 h after Transfection,the expression of LOX-1 mRNA in RAW264.7 cells were determined by semi-quantitative RT-PCR,the expression of LOX-1 proteins examined by Western blot.(2) Oil Red O Dyeing experiment was used to show the cellular lipid droplets in lipid-loaded cells.The method of cholesterol oxidase analysis was performed to determine the content of cellular cholesterol.The ability of uptake Dil-ox-LDL in RAW264.7 cells was assayed by fluorescence microscopy.Results: pLOX-1-shRNA expression vector was successfully constructed.Transfection of pLOX-1-shRNA expression vector into RAW264.7 cells down regulaled the expression level of LOX-1 gene,as compared with the control group,transfection of the RAW264.7 cells with LOX 1-shRNA led to a remarkable reduction of the number macrophages transformed into foam cell,and could suppress the uptake of ox-LDL.Conclusion:The pLOX-1-shRNA expression vector can inhibit the expression of LOX 1 in RAW264.7 cells and the transformation of the macrophages into foam,which may he beneficial in searching new gene therapy of atherosclerosis.