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1.
Psychon Bull Rev ; 30(4): 1227-1242, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36732445

ABSTRACT

Predictions about upcoming content play an important role during language comprehension and processing. Semantic similarity as a metric has been used to predict how words are processed in context in language comprehension and processing tasks. This study proposes a novel, dynamic approach for computing contextual semantic similarity, evaluates the extent to which the semantic similarity measures computed using this approach can predict fixation durations in reading tasks recorded in a corpus of eye-tracking data, and compares the performance of these measures to that of semantic similarity measures computed using the cosine and Euclidean methods. Our results reveal that the semantic similarity measures generated by our approach are significantly predictive of fixation durations on reading and outperform those generated by the two existing approaches. The findings of this study contribute to a better understanding of how humans process words in context and make predictions in language comprehension and processing. The effective and interpretable approach to computing contextual semantic similarity proposed in this study can also facilitate further explorations of other experimental data on language comprehension and processing.


Subject(s)
Eye Movements , Semantics , Humans , Reading , Comprehension
2.
Journal of Experimental Hematology ; (6): 1797-1803, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1010040

ABSTRACT

OBJECTIVE@#To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism.@*METHODS@#A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein.@*RESULTS@#Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4+CD69+ T cells and CD8+CD69+ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4+ and CD8+ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4+ and CD8+ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05).@*CONCLUSION@#MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.


Subject(s)
Humans , Anemia, Aplastic/genetics , CD40 Ligand/metabolism , Interleukin-10 , Leukocytes, Mononuclear/metabolism , Luciferases , MicroRNAs/genetics , RNA, Messenger/metabolism , Lymphocyte Activation , T-Lymphocytes/metabolism
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008738

ABSTRACT

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.


Subject(s)
Animals , Humans , Medicine, Chinese Traditional/adverse effects , Cardiotoxicity , Induced Pluripotent Stem Cells , Arrhythmias, Cardiac/chemically induced , Myocytes, Cardiac , Organoids , Drugs, Chinese Herbal/adverse effects
4.
Chinese Journal of Biotechnology ; (12): 1548-1561, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-981153

ABSTRACT

Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious infectious disease caused by foot-and-mouth disease virus (FMDV), which seriously endangers the development of animal husbandry. The inactivated FMD vaccine is the main product for the prevention and control of FMD, which has been successfully applied to control the pandemic and outbreak of FMD. However, the inactivated FMD vaccine also has problems, such as the instability of antigen, the risk of spread of the virus due to incomplete inactivation during vaccine production, and the high cost of production. Compared with traditional microbial and animal bioreactors, production of antigens in plants through transgenic technology has some advantages including low cost, safety, convenience, and easy storage and transportation. Moreover, since antigens produced from plants can be directly used as edible vaccines, no complex processes of protein extraction and purification are required. But, there are some problems for the production of antigens in plants, which include low expression level and poor controllability. Thus, expressing the antigens of FMDV in plants may be an alternative mean for production of FMD vaccine, which has certain advantages but still need to be continuously optimized. Here we review the main strategies for expressing active proteins in plants, as well as the research progress on the expression of FMDV antigens in plants. We also discuss the current problems and challenges encountered, with the aim to facilitate related research.


Subject(s)
Animals , Foot-and-Mouth Disease Virus/genetics , Foot-and-Mouth Disease/prevention & control , Antigens, Viral/genetics , Viral Vaccines
5.
Chinese Journal of Pediatrics ; (12): 256-260, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970277

ABSTRACT

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3rd to May 31st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Young Adult , China/epidemiology , COVID-19/genetics , Nucleic Acids , Retrospective Studies
6.
Chinese Journal of Pediatrics ; (12): 136-140, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970252

ABSTRACT

Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.


Subject(s)
Child , Infant, Newborn , Humans , Infant , Pulmonary Atresia/surgery , Ductus Arteriosus , Retrospective Studies , China , Heart Defects, Congenital , Ductus Arteriosus, Patent/surgery , Heart Septal Defects, Ventricular , Stents
7.
Chinese Journal of Oncology ; (12): 519-524, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-984752

ABSTRACT

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).


Subject(s)
Humans , Antineoplastic Agents/adverse effects , Maximum Tolerated Dose , Neoplasms/drug therapy , Neutropenia/chemically induced , Prospective Studies
8.
Journal of Geriatric Cardiology ; (12): 469-478, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-982206

ABSTRACT

BACKGROUND@#The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear.@*METHODS@#PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI.@*RESULTS@#Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I2 = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I2 = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I2 = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I2 = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I2 = 0) in a subgroup of very elderly patients > 75 years of age.@*CONCLUSIONS@#Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.

9.
Chinese Journal of Oncology ; (12): 282-290, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-935212

ABSTRACT

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.


Subject(s)
Humans , Colorectal Neoplasms , Liver/pathology , Lung/pathology , Prospective Studies , Radiosurgery/methods
10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-940509

ABSTRACT

Atopic dermatitis (AD) is a chronic, recurrent and inflammatory skin disease. Modern medical research suggests that AD is related to immune function, genes, skin barrier and other factors, while the specific etiology and pathogenesis remains unclear. The disease has a long course and is prone to reoccur, which seriously affects people’s production and life. Steroids, antihistamines and immunosuppressants are commonly used western medicines for the treatment of AD, which, however, will cause adverse reactions after long-term application. Traditional Chinese medicine (TCM) has a long history, good therapeutic effect and rich clinical experience in the prevention and treatment of AD, and the research on the treatment of AD with TCM has been intensifying. Centering on the theory of TCM, we systematically summarized the research progress related to AD, discussed the etiology and pathogenesis of AD, and summarized the TCM syndrome differentiation of AD from the aspects of eight principles, etiology, Qi-blood-body fluid, zang-fu organs, six meridians, defense-Qi-nutrient-blood and triple energizer. According to the etiology and pathogenesis of AD, we proposed the therapeutic regimens corresponding to the type and stage of the disease. Considering the research progress achieved in the recent years in the prevention and treatment of AD by TCM and the modern pharmacological research on Chinese medicinal materials, we reviewed the classic famous prescriptions, self-made prescriptions and Chinese patent medicines, and expounded the mechanisms of single Chinese medicinal materials in the treatment of AD at the molecular level. The TCM external therapies such as wet compress, medicated bath, gel and ointment are safe and effective. Acupuncture and moxibustion play a role in the prevention and treatment of AD, which is worthy of promotion in clinical practice, and the syndrome differentiation methods of Qi-blood-body fluid and triple energizer are novel in the treatment of this disease. TCM, characterized by diverse therapeutic methods and good clinical efficacy, is worthy of promotion in the treatment of AD, which will contribute to the development of TCM in China.

11.
Acta Anatomica Sinica ; (6): 347-353, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015329

ABSTRACT

Objective To investigate the protective effect of micro RNA(miR)-98-5p targeting Kruppel-like factor 9(KLF9) against myocardial isehemia-reperfusion(MI/R) injury in rats. Methods Totally 50 rats were randomly divided into sham operation group, model group, miR-98-5p agomir group, agomir-NC group, and miR-98-5p agomir+pcDNA-3. 1-KLF9 group, 10 in each group. MI/R model was established by coronary artery ligation. The pathological changes of myocardial tissue were detected by HE staining. The myocardial apoptosis were detected by TUNEL. The levels of creatine kinase (CK), creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) in serum were detected by ELISA. The expression levels of miR-98-5p and KLF9 mRNA were detected by Real-time PCR. The expression of KLF9, Bax and JAK2/STAT3 pathway relative protein were detected by Western blotting. Dual luciferase assay verified the relationship between miR-98-5p and KLF9. Results Compared with the sham operation group, the arrangement of myocardial cells in the model group was disordered, and the myocardial cells appeared necrosis. The apoptosis rate of myocardial cells, serum CK, CK-MB and LDH contents increased, the expression level of miR-98-5p decreased, and the expression levels of KLF9 mRNA and protein, p-JAK2 and p-STAT3 protein increased (P < 0. 05) . After the overexpression of miR-98-5p, the myocardial cells arranged more orderly and the myocardial cell necrosis decreased. The apoptosis rate of myocardial tissue, the contents of CK, CK-MB and LDH in serum and the expression of p-JAK2 and p-STAT3 protein were decreased (P< 0. 05) . The result of dual luciferase assay showed that KLF9 was the target gene of miR-98-5p. The overexpression of KLF9 reversed the effects of miR-98-5p agomir on myocardial injury. Conclusion MiR-98-5p targeting KLF9 can improve the myocardial injury of MI/R rats. The mechanism may be related to the regulation of JAK2/STAT3 signal pathway by miR-98-5p which inhibit myocardial cell apoptosis.

12.
Preprint in English | medRxiv | ID: ppmedrxiv-21260139

ABSTRACT

COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.

13.
Biochem Biophys Res Commun ; 545: 46-53, 2021 03 19.
Article in English | MEDLINE | ID: mdl-33545631

ABSTRACT

Diabetic nephropathy (DN) is a major cause of renal failure in diabetic patients. RING-finger protein 166 (RNF166), composed of an N-terminal RING domain and C-terminal ubiquitin interaction motif, plays a critical role in mediating various cellular processes. However, its potential in DN has not been investigated. In the present study, we found that DN patients exhibited significantly increased expression of RNF166 in renal tissues compared with the normal individuals, and abundant RNF166 was detected in podocytes. We then showed that podocyte-conditional RNF166 knockout (RNF166cKO) markedly reduced blood glucose levels and ameliorated renal dysfunction in streptozotocin (STZ)-induced diabetic mice. Additionally, abnormal histological changes and podocyte injury were observed in STZ-induced diabetic mice, while being markedly ameliorated by RNF166cKO. Furthermore, podocyte-specific RNF166 deficiency considerably mitigated apoptosis and mitochondrial impairments in glomeruli podocytes of STZ-challenged mice through suppressing Caspase-3 cleavage and improving mitochondrial fission-associated molecules. In vitro studies further confirmed that high glucose (HG) induced mitochondrial dysfunction, along with enhanced releases of Cyto-c from mitochondria and elevated expression of cleaved Caspase-9, contributing to intrinsic apoptosis in podocytes. Intriguingly, these effects triggered by HG were dramatically ameliorated by RNF166 knockout. Mechanistically, we demonstrated that RNF166 directly interacted with cylindromatosis (CYLD), and negatively regulated CYLD expression. Notably, RNF166 knockout-attenuated mitochondrial damage and apoptosis were mainly through CYLD in podocytes upon HG stimulation. Together, all these findings provided new insights into the novel effects of RNF166 on maintaining mitochondrial function and apoptosis in podocytes during DN progression both in vivo and in vitro through interacting with CYLD, indicating that RNF166/CYLD may be an innovative therapeutic target for developing effective strategy against DN development.


Subject(s)
Deubiquitinating Enzyme CYLD/metabolism , Diabetic Nephropathies/therapy , Podocytes/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Apoptosis/physiology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Gene Expression , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Podocytes/pathology , RING Finger Domains/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ubiquitin-Protein Ligases/deficiency , Ubiquitin-Protein Ligases/genetics
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-907270

ABSTRACT

Congenital heart disease(CHD)is one of the most common congenital defects that caused by fetal cardiovascular dysplasia.The global incidence rate is about 9/1 000 and is still rising.Previous reports have shown that congenital heart disease(CHD)incidence can be influenced by genetic etiology and environmental risk factors.And the gene-environmental interaction can affect the development and differentiation of myocardium through epigenetic regulation by means of DNA methylation, histone and RNA modification, etc.In this paper, we review the epigenetics of congenital heart disease to discuss the current progress and point out future direction of the etiology of congenital heart disease.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-907267

ABSTRACT

Congenital bicuspid aortic valves(BAV)is one of the most common congenital heart diseases.It is generally diagnosed by echocardiography when deterioration of the abnormal leaflets becomes clinically evident.Patients with BAV are at increased risks of developing serious complications, including aortic stenosis, aortic regurgitation, aortic dilation, aortic dissection and/or aneurysm, which seriously threatens the health of patients.Although its diagnosis and surgical treatment have been clear, the specific pathogenesis has not been completely revealed.Recently, studies have found that gene mutations and related signaling pathway abnormalities are associated with BAV and its complications.And epigenetics and environmental factors are involved in the development and progress of BAV.Understanding the underlying cellular and molecular basis of normal and pathological aortic valve development may improve the preventative and therapeutic approaches to valve degeneration.

16.
Chinese Journal of School Health ; (12): 1020-1023, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-886314

ABSTRACT

Objective@#To assess the effectiveness of sexual education intervention among seventh grade students, and to provide support tools for sex education for middle school students.@*Methods@#Seventh grade students from six schools in Longnan, Gansu Province were randomly assigned to an intervention group (251 students) and a control group (222 students). After 8 weeks of school based sex education in the intervention group, the results were compared before and after the intervention using self assessment knowledge and attitude scales.@*Results@#The knowledge score in the control group decreased by (2.46±1.21) in the follow up survey compared to the baseline survey. The intervention group scored (30.54±1.34) significantly higher than baseline ( t =22.76, P <0.01). After adjusting the sex ratio to 1∶1, the mean difference between the two groups after the intervention was (27.86±1.87) ( t =14.90, P <0.01). The interaction dit between time and intervention was (33.01±2.50) ( t =13.19, P <0.01) in difference analysis. The intervention effect size Hedge s g on knowledge in the intervention group was 1.27. The proportion of positive attitudes towards sex increased in the intervention group on 12 out of 14 questions, with percentage ranging from 7.5% to 25.9%. At the follow up, the improvement in attitudes towards 12 questions was substantial for girls and 8 questions for boys in the intervention group. The attitude effect size Hedge s g was 0.99 in the intervention group.@*Conclusion@#The implementation of school based sex education is capable of significant improving students sexual knowledge and attitude in the short term.

17.
Article in English | WPRIM (Western Pacific) | ID: wpr-922771

ABSTRACT

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.


Subject(s)
Animals , Mice , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome , Mice, Inbred C57BL , Molecular Docking Simulation , Network Pharmacology , Stroke/drug therapy
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-887501

ABSTRACT

OBJECTIVE@#To observe the effect of moxibustion on postpartum urodynamics and recovery of pelvic floor function based on the pelvic floor muscle function training.@*METHODS@#A total of 150 puerperal women were randomly divided into an observation group (75 cases, 15 cases dropped off) and a control group (75 cases, 15 cases dropped off). The control group was treated with pelvic floor muscle function training, twice a day. Based on the treatment in the control group, the observation group was treated with @*RESULTS@#Compared before treatment, the levels of FUL, MUCP, BC, Pdet Qmax and SLPP in the observation group after treatment were increased (@*CONCLUSION@#The moxibustion combined with pelvic floor muscle function training could improve postpartum urodynamics and pelvic floor muscle strength.


Subject(s)
Female , Humans , Exercise Therapy , Moxibustion , Pelvic Floor , Postpartum Period , Urinary Incontinence, Stress , Urodynamics
19.
Preprint in English | medRxiv | ID: ppmedrxiv-20124305

ABSTRACT

Clinical symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections. One Sentence SummaryCfDNA analysis in COVID-19 patients reveals severity-related tissue damage.

20.
BMC Med Genet ; 21(1): 95, 2020 05 07.
Article in English | MEDLINE | ID: mdl-32380971

ABSTRACT

BACKGROUND: Conotruncal heart defects (CTDs) are a group of congenital heart malformations that cause anomalies of cardiac outflow tracts. In the past few decades, many genes related to CTDs have been reported. Serum response factor (SRF) is a ubiquitous nuclear protein that acts as transcription factor, and SRF was found to be a critical factor in heart development and to be strongly expressed in the myocardium of the developing mouse and chicken hearts. The targeted inactivation of SRF during heart development leads to embryonic lethality and myocardial defects in mice. METHODS: To illustrate the relationship between SRF and human heart defects, we screened SRF mutations in 527 CTD patients, a cross sectional study. DNA was extracted from peripheral leukocyte cells for target sequencing. The mutations of SRF were detected and validated by Sanger sequencing. The affection of the mutations on wild-type protein was analyzed by in silico softwares. Western blot and real time PCR were used to analyze the changes of the expression of the mutant mRNA and protein. In addition, we carried out dual luciferase reporter assay to explore the transcriptional activity of the mutant SRF. RESULTS: Among the target sequencing results of 527 patients, two novel mutations (Mut1: c.821A > G p.G274D, the adenine(A) was mutated to guanine(G) at position 821 of the SRF gene coding sequences (CDS), lead to the Glycine(G) mutated to Asparticacid(D) at position 274 of the SRF protein amino acid sequences; Mut2: c.880G > T p.G294C, the guanine(G) was mutated to thymine (T) at position 880 of the SRF CDS, lead to the Glycine(G) mutated to Cysteine (C) at position 294 of the SRF protein amino acid sequences.) of SRF (NM_003131.4) were identified. Western blotting and real-time PCR showed that there were no obvious differences between the protein expression and mRNA transcription of mutants and wild-type SRF. A dual luciferase reporter assay showed that both SRF mutants (G274D and G294C) impaired SRF transcriptional activity at the SRF promoter and atrial natriuretic factor (ANF) promoter (p < 0.05), additionally, the mutants displayed reduced synergism with GATA4. CONCLUSION: These results suggest that SRF-p.G274D and SRF-p.G294C may have potential pathogenic effects.


Subject(s)
Atrial Natriuretic Factor/genetics , GATA4 Transcription Factor/genetics , Heart Defects, Congenital/genetics , Serum Response Factor/genetics , Amino Acid Sequence/genetics , Animals , Cross-Sectional Studies , Female , Gene Expression Regulation/genetics , Genetic Predisposition to Disease , Heart Defects, Congenital/pathology , Homeodomain Proteins/genetics , Humans , Male , Mice , Mutation, Missense/genetics , Myocardium/metabolism , Myocardium/pathology , Promoter Regions, Genetic/genetics
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