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Objective:To explore the mechanism of Fuyuan Xingnao Decoction in treatment of cerebral infarction based on network pharmacology and molecular docking.Methods:The active components and action targets of Fuyuan Xingnao Decoction were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicine Integrated Database (TCMID),Bioactivity data of small organic molecules (PubChem),Universal Protein (Uniprot) and Swiss Target Prediction database platform. The databases of GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Drug Bank and Pharmacogenomics Knowledgebase (PharmGKB) were used to screen targets of cerebral infarction. The drug target genes in Fuyuan Xingnao Decoction were intersected with those of cerebral infarction, the intersecting targets were introduced into Cytoscape 3.8.2 software to construct the component target network, and the PPI protein interaction network was constructed by using STRING analysis platform and Cytoscape 3.8.2 software to screen the core targets. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) function enrichment analysis were carried out on the common target genes of Fuyuan Xingnao Decoction and cerebral infarction disease to obtain the relevant signal pathways. Finally, AutoDock and Pymol software were used for molecular docking between the predicted target and its corresponding components.Results:After screening, 80 effective components of Fuyuan Xingnao Decoction for treatment of cerebral infarction and 214 common targets of Fuyuan Xingnao Decoction and cerebral infarction were obtained. The core targets such as MAPK1, RELA, TP53, JUN, AKT1 and HSP90AA1 were related to the key targets of cerebral infarction, and they participated in the biological process of regulating the response to drugs, lipopolysaccharide and oxygen level, etc. The cell composition involved membrane raft, membrane micro region and nerve cell body, etc. Molecular functions mainly focused on nuclear receptor activity, ligand activated transcription factor activity, DNA binding transcription factor binding, etc.; it also involved in signal pathway of lipid and atherosclerosis, chemical carcinogen and receptor activation, fluid shear stress and atherosclerosis, etc. Molecular docking showed that good binding activities were seen between Quercetin and HSP90AA1 (-9.4 kJ/mol), between Kaempferol and HSP90AA1 (-9.4 kJ/mol), between Isorhamnetin and HSP90AA1 (-9.1 kJ/mol), and between Quercetin and JUN (-8.6 kJ/mol).Conclusion:Fuyuan Xingnao Decoction can prevent and treat cerebral infarction by regulating vascular endothelial function, promoting blood circulation, repairing and improving neural function, protecting blood-brain barrier, reducing cell apoptosis, and regulating immune and inflammatory response.
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A new wave of research has been inspired by the CRISPR-Cas system with respect to their application in genome editing. The CRISPR-Cas system can not only be applied in gene knockout and insertion, but also be used in base editing, transcriptional regulation and recombination of gene clusters. However, the low efficiency of homology-directed repair (HDR) limits its application. Unlike the CRISPR-Cas system, mobile genetic elements (MGE) can insert DNA fragments into cell chromosomes without the aid of HDR. Recently, it is reported that CRISPR-related transposable elements can guide targeted DNA insertion. Their transposition mechanisms and reprogramming abilities have brought novel opportunities to the development of this field. This review summarized the research progress and application development of natural CRISPR-related transposable elements in recent years, as well as the applications of fused dCas9-transposase. It proposed the application prospects and potential challenges of CRISPR-related transposable elements in the future, which provided a reference for the development direction of gene editing tools.
الموضوعات
DNA Transposable Elements/genetics , Gene Editing , CRISPR-Cas Systems/geneticsالملخص
Objective:To investigate the predictive value of maternal peripheral blood fetal DNA, creatine kinase (CK), and alpha-fetoprotein (AFP) in pregnant women with placenta previa complicated with adhesion or implantation.Methods:From April 2018 to April 2019, 72 patients with placenta previa confirmed by cesarean section in Chengde Central Hospital were retrospectively collected. Among them, 23 patients complicated with placental adhesion were enrolled in the placenta adhesion group, 19 patients complicated with placenta implantation were in the placenta implantation group, and 30 patients with simple placenta previa were in the simple placenta previa group. The amount of fetal DNA, CK and AFP in maternal peripheral blood were measured at 20 to 27 weeks of gestation. The general data of the three groups, the amount of fetal DNA in maternal peripheral blood, CK and AFP were compared. The value of the amount of fetal DNA, CK, and AFP in maternal peripheral blood for predivting placenta previa were analyzed. At the same time, the incidence of adverse pregnancy outcomes was counted, and patients were divided into adverse pregnancy outcomes group and good pregnancy outcomes group according to pregnancy outcomes. The fetal DNA amount, CK and AFP levels in the maternal peripheral blood of the two were compared, and the factors affecting the adverse pregnancy outcome of placenta previa were analyzed.Results:The levels of fetal DNA, CK and AFP in the maternal peripheral blood of the placenta implantation group were significantly higher than those of the placenta adhesion group and the simple placenta previa group: (1 018.96 ± 442.15) copies/ml vs. (659.27 ± 320.26) copies/ml and (390.64 ± 102.53) copies/ml , (103.54 ± 26.39) U/L vs. (88.30 ± 20.65) U/L and (62.78 ± 15.84) U/L, (319.65 ± 62.14) μg/L vs. (284.62 ± 55.96) and (232.64 ± 48.62) μg/L, and the difference was statistically significant ( P<0.01). The amount of fetal DNA in maternal peripheral blood was positively correlated with CK and AFP ( r = 0.899 and 0.769, P<0.01), and CK was positively correlated with AFP ( r = 0.782, P<0.01). The AUC of maternal peripheral blood fetal DNA in predicting placenta previa complicated with placenta adhesion was 0.842, and the sensitivity and specificity were 78.26% and 83.33% respectively. The levels of fetal DNA, CK and AFP in maternal peripheral blood of patients with adverse pregnancy outcomes were higher than those of patients with good pregnancy outcomes: (928.64 ± 257.73) copies/ml vs. (460.02 ± 188.95) copies/ml, (105.83 ± 26.88) U/L vs. (66.33 ± 20.39) U/L and (292.52 ± 58.39) μg/L vs. (259.29 ± 42.65) μg/L, and the difference was statistically significant ( P<0.05). Placenta adhesion, placenta implantation, postpartum hemorrhage, maternal peripheral blood fetal DNA, CK and AFP levels were influential factors for the adverse pregnancy outcome of placenta previa ( OR = 3.544, 4.183, 3.413, 3.222, 3.109 and 3.313, 95% CI 1.905 to 6.593, 2.401 to 7.286, 1.832 to 6.359, 1.729 to 6.005, 1.659 to 5.827 and 1.831 to 5.994, P<0.01). Conclusions:The amount of fetal DNA, CK and AFP in maternal peripheral blood have a certain predictive value in placenta previa complicated with placental adhesion or implantation, and are closely related to the pregnancy outcome of patients with placenta previa. Early detection of the above indicators will help clinically to formulate reasonable intervention measures and promote the improvement of pregnancy outcomes.
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Objective:To explore the effect of handicraft training administered over the Internet on sensation disorders and on the mental status and life quality of stroke survivors.Methods:A total of 75 stroke survivors in the sequelae stage and with sensory disturbance were randomly divided into a general training group of 26 (group A), a handicraft training group of 26 (group B), and a handicraft training group of 23 using Internet instruction (group C). In addition to 40 minutes of routine physical and sensory training rehabilitation every morning, groups A and B were given traditional training and handicraft training, while group C was given handicraft training delivered over the Internet for 40 minutes every afternoon, five days a week for 4 weeks. The traditional training involved inserting wooden boards, plate grinding, as well as sorting beans. The handicraft training involved digital painting, making non-woven flowers, silk screening flowers and paper-rolling. Before and after the 4 weeks of treatment, all of the subjects were assessed using the Fugl-Meyer sensory assessment (FMA-S), the Hamilton Anxiety Scale (HAMA), the Modified Barthel Index (MBI), and the physical component summary scale (PCS) and mental component summary scale (MCS) of the 36-item short-form health survey.Results:After the treatment, significant improvement was observed in their average scores of all three groups in all of the assessments. Groups B and C showed significantly greater improvement in the average FMA-S, HAMA and MBI scores than group A. And the average HAMA and MCS scores of group C were significantly better than those of group B.Conclusion:Handicraft training delivered over the Internet can improve the sensory functioning, mental status and life quality of stroke survivors in the sequelae stage with sensory disturbance.
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Objective To assess the specificity of white dermographism in atopic dermatitis (AD), and to investigate the relationship between its duration and severity of AD. Methods From 1st to 30th March 2018, 78 patients with AD (AD group), 100 patients with non-AD skin diseases (non-AD group)and 100 healthy controls without skin diseases(control group)were enrolled from Department of Dermatology, Wuhan No.1 Hospital. Dermographism test was conducted in each subject, and the subjects' response and duration of white dermographism were observed. Meanwhile, the severity of skin lesions of the AD patients was evaluated. Statistical analysis was carried out by using Chi-square test, analysis of variance and linear correlation analysis. Results Of the 78 patients in the AD group, 67(85.90％)were positive for white dermographism, and the positive rate of white dermographism was significantly higher in the AD group than in the non-AD group(18.00％[18/100],χ2=80.97, P<0.017)and control group(5.00％[5/100],χ2=119.05, P<0.017). Additionally, the positive rate of white dermographism was significantly higher in the non-AD group than in the control group (χ2 = 8.30, P<0.017). The average duration of white dermographism was 1.89 minutes in 30 patients with mild AD, 2.74 minutes in 25 patients with moderate AD, and 4.41 minutes in 12 patients with severe AD. There was a significant difference in the duration of white dermographism among the 3 AD subgroups(F=64.588, P<0.05). Moreover, the severity of AD was positively correlated with the duration of white dermographism(r=0.977, P=0.136). Conclusion White dermographism is a specific clinical manifestation of AD, and its duration is positively correlated with the severity of AD.
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Objective@#To assess the specificity of white dermographism in atopic dermatitis (AD) , and to investigate the relationship between its duration and severity of AD.@*Methods@#From 1st to 30th March 2018, 78 patients with AD (AD group) , 100 patients with non-AD skin diseases (non-AD group) and 100 healthy controls without skin diseases (control group) were enrolled from Department of Dermatology, Wuhan No.1 Hospital. Dermographism test was conducted in each subject, and the subjects′ response and duration of white dermographism were observed. Meanwhile, the severity of skin lesions of the AD patients was evaluated. Statistical analysis was carried out by using Chi-square test, analysis of variance and linear correlation analysis.@*Results@#Of the 78 patients in the AD group, 67 (85.90%) were positive for white dermographism, and the positive rate of white dermographism was significantly higher in the AD group than in the non-AD group (18.00% [18/100], χ2 = 80.97, P<0.017) and control group (5.00% [5/100], χ2 = 119.05, P<0.017) . Additionally, the positive rate of white dermographism was significantly higher in the non-AD group than in the control group (χ2 = 8.30, P<0.017) . The average duration of white dermographism was 1.89 minutes in 30 patients with mild AD, 2.74 minutes in 25 patients with moderate AD, and 4.41 minutes in 12 patients with severe AD. There was a significant difference in the duration of white dermographism among the 3 AD subgroups (F = 64.588, P<0.05) . Moreover, the severity of AD was positively correlated with the duration of white dermographism (r = 0.977, P = 0.136) .@*Conclusion@#White dermographism is a specific clinical manifestation of AD, and its duration is positively correlated with the severity of AD.
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Objective To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1)The BRCA genes were detected by next-generation sequencing (NGS) method. (2)The serum tumor markers included carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson′s chi square test, Fisher′s exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics(FIGO)stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM). Results (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA199, and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA125 was much higher in BRCA mutation group than that in controls (t=-3.536,P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA125 and HE4 group (r=0.494,P0.05), while significant differences were found in CA125 and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (P<0.05). The multiple factors analysis showed that the high level of CA125 was a independent risk factor of BRCA mutations in sporadic HGSOC (P=0.007). Conclusion The combination of CA125 with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.
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Objective To investigate the relationship between single nucleotide polymorphism (SNP) of BARD 1 gene and BRCA1 gene in epithelial ovarian cancer (EOC).Methods Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected,and all EOC were diagnosed by pathological method.BARD1 gene variants were detected by next generation sequencing (NGS).The SNP of BARD1 gene was analyzed by Pearson linear correlation.Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP.Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met,Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk.Results (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients,in which Val507Met,Arg378Ser and Pro24Ser were common variants,and the rate of mutation were all 54％ (37/69).(2) There was a significant linear correlation among Val507Met,Arg378Ser and Pro24Ser (all P＜0.01).(3) Obvious differences were found in Val507Met,Arg378Ser and Pro24Ser of BARD1 gene between BRCA1+ and BRCA1 (all P＜0.05).(4) No differences were found between BARD1 gene Val507Met,Arg378Ser and Pro24Ser and the clinicopathologic features (all P＞0.05),while obvious differences were found in BRCA1 gene mutation compared to the controls group.The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history,positive menopause history,negative tubal ligation,onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P＜0.05),while Pro24Ser was only more evident in positive menopause history of EOC (P＜0.05).Conclusions BARD1 Val507Met,Arg378Ser and Pro24Ser are the common genotypes,which are associated with BRCA1 mutation in EOC.The family history,menopause history,tubal ligation,onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.
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Objective:To investigate the expression and clinical significance of PD-L1 in colorectal cancer (CRC). Methods:A total of 210 CRC patients who accepted radical surgery in our hospital from January 2015 to January 2016 were divided into three groups, namely, high-frequency microsatellite instability (MSI-H), low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS). The expression of PD-L1 was detected by immunohistochemistry, and the expression characteristics of PD-L1 in different types of CRC were analyzed. Results:CRC cases with low differentiation had a higher expression of PD-L1 than CRC patients with high differ-entiation (P<0.05). PD-L1 had a positive rate of 75.8%in the MSI-H group and a rate of 9.3%in the MSI-L and MSS groups, wherein the difference between the two groups was statistically significant (P<0.05). Conclusion:PD-L1 was positively expressed in some CRC tu-mor tissues, and its positive rate was significantly higher in MSI-H than in MSI-L and MSS. The therapeutic effect of a PD-L1 blocker for patients with MSI-H CRC might be preferable.
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Breast cancer is a heterogeneous disease.Its invasion and metastasis,recurrence and part of the chemotherapy drug tolerance are currentlv difficulties of treatment.Breast cancer stem cells have the ability of selfrenewal,proliferation and differentiation potential,which may correlate closely with breast cancer recurrence,treatment failure.This assay aims to briefly analyse markers and significance of breast cancer stem cells,and the relationship between the treatment of breast cancer and breast cancer stem cells.
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Objective To analyze the effect of implementing traditional Chinese medicine (TCM) clinical pathway on family sickbed patients.Methods Those family sickbed patients with herpes zoster or facial neuritis were involved in this study.Their medical records and data of ‘Family sickbed quality control scale’ were collected,in which there are methods of TCM clinical pathway,decoction of the Chinese Medicine,ingredients and treatment procedures of the topically used TCMs,and acupuncture treatment procedures were documented.The family sickbed days,prognosis,informed rate and satisfaction rate were analyzed before and after TCM clinical pathway treatment.Results In the treatment group,the family sickbed days (11.67± 1.91)d and referral rate 12.20％ (10/82) were significantly lower (P＜ 0.01) than those in the control group [(1 3.88 ± 2.61) d,50.00％ (41/82) respectively].The rate of cure87.80％ (72/82),the rate of informed patient 97.56％ (80/82) and the rate of satisfaction91.46％ (75/82) were significantly higher(P＜ 0.01)than those in the control group [50.00％ (41/82)、65.85％ (54/82)、50.00％ (41/82) respectively].Conclusion The clinical pathways for family sickbed patients with herpes zoster or facial neuritis were effective.