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1.
Article in English | WPRIM | ID: wpr-937697

ABSTRACT

Background and Objectives@#Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). @*Conclusions@#Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.

2.
Article in Chinese | WPRIM | ID: wpr-940419

ABSTRACT

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules (DZSM) on chronic cerebral hypoperfusion (CCH), network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group, model group, ginaton group (48 mg·kg-1), DZSM low- and high-dose groups (0.040 5, 0.162 g·kg-1). The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem, GeneCards, Metascape and other databases were used for targets collection and enrichment analysis. Besides, the association of ingredients targets of DZSM with disease targets of CCH, core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment, the crossing times, time spent in the target quadrant, movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, cytokine-cytokine receptor interaction, tumor necrosis factor (TNF) signaling pathway, blood circulation, angiogenesis, extracellular matrix and other related biological processes and pathways, and acting as targets such as interleukin-6 (IL-6), TNF, insulin-like growth factor 1 (IGF1), vascular endothelial growth factor A (VEGFA), epidermal growth factor (EGF). The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH, and its multi-component, multi-pathway, multi-target mechanism is also revealed, which provides a basis for further study of the mechanism.

3.
Article in Chinese | WPRIM | ID: wpr-940294

ABSTRACT

ObjectiveOn the basis of determining the protective effect of berberine (BBR) on cerebral ischemia, crucial transcription factors (TFs) of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion (MCAO) was established by thread embolization. The sham operation group, model group, low-dose group of BBR (dose of 37.5 mg·kg-1·d-1) and high-dose group of BBR (75 mg·kg-1·d-1) were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate, and the expressions of inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). Then, RNA-Seq technique was used to detect the differentially expressed genes (DEGs) before and after BBR intervention, and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention, and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally, by integrating the activity of TFs and the changes of downstream target genes, crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group, the neurological impairment was significant in the model group (P<0.01), and compared with the model group, the low and high dose BBR groups could significantly reduce the neurological function damage (P<0.01) and decrease the rate of cerebral infarction (P<0.01). Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion, brain development, neuron migration, calcium signaling pathway, cyclic adenosine monophosphate (cAMP) signaling pathway, inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation, immune system process, cell proliferation and other biological processes. In addition, integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 (TFCP2L1), nuclear factor erythroid-2 like 1 (NFE2L1), neurogenic differentiation protein 6 (NeuroD6) and POU domain, class 2, transcription factor 1 (POU2F1) were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1, NFE2L1, NeuroD6 and POU2F1.

4.
Frontiers of Medicine ; (4): 429-441, 2022.
Article in English | WPRIM | ID: wpr-939872

ABSTRACT

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.


Subject(s)
Animals , Cell Differentiation , Disease Models, Animal , Ischemic Stroke , Proteomics , Rats , Stem Cell Transplantation/methods , Stroke/therapy
5.
Article in Chinese | WPRIM | ID: wpr-934409

ABSTRACT

Objective:To establish and evaluate a new real-time quality control method that can identify the random errors by using the backpropagation neural network (BPNN) algorithm and taking blood glucose test as an example.Methods:A total of 219 000 blood glucose results measured by Siemens advia 2 400 analytical system from January 2019 to July 2020 and derived from Laboratory Information System of Beijing Chaoyang Hospital Laboratory Department was regarded as the unbiased data of our study. Six deviations with different sizes were introduced to generate the corresponding biased data. With each biased data, BPNN and MovSD algorithms were used and tested, and then evaluated by traceability method and clinical method.Results:For BPNN algorithm, the block size was pre-set to 10 and the false-positive rate in all biases was within 0.1%. For MovSD, however, the optimal block size and exclusive limit were 150 and 10% separately and its false-positive rate in all biases was 0.38%, which was 0.28% higher than BPNN. Especially, for the least two error factors of 0.5 and 1, all the random errors were not detected by MovSD; for the error factor larger than 1, random errors could be detected by MovSD but the MNPed was higher than that of BPNN under all deviations. The difference was up to 91.67 times. 460 000 reference data were produced by traceability procedure. The uncertainty of BPNN algorithm evaluated by these reference data was only 0.078%.Conclusion:A real-time quality control method based on BPNN algorithm was successfully established to identify random errors in analytical phase, which was more efficient than MovSD method and provided a new idea and method for the identification of random errors in clinical practice.

6.
Article in Chinese | WPRIM | ID: wpr-934351

ABSTRACT

Objective:To prepare the control materials of point-of-care(POC) glucose testing and evaluate their homogeneity, stability and matrix effects.Methods:The high, medium and low concentration control materials were prepared from patient leftover whole blood, which was centrifuged, fixed, washed, filtered, and aliquoted. The homogeneity and stability of the control materials were evaluated according to CNAS (China National Accreditation Service for Conformity Assessment, CNAS) GL29:2010"Reference materials-General and statistical principles for certification". The control materials were used to evaluate the matrix effects in POC glucose detection systems by Deming regression, according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3. Meanwhile, these control materials were used as the internal quality control, and their coefficients of variation ( CV) were calculated. One-way ANOVA and t-Test were used to analyze the results. Results:The homemade materials at three concentrations showed good homogeneity[ F< F0.05(9, 20)]. When the control materials were stored at 2-8 ℃, the stable phases for the opened and closed bottles were 10 days and 15 days, respectively, and there was no statistically significant difference between the results of the first day( P>0.05). The control materials at three concentrations also showed good applicability and there were no matrix effects in 10 POC glucose systems. When the control materials were detected in the internal quality control, the CVs of the high, medium and low concentrations were 0.63%, 0.66% and 1.65%, respectively, which were all below 7.5%. Conclusions:The homemade human control materials of POC glucose testing showed good homogeneity, stability and applicability. They met the requirements of quality control in hospital settings, which provided a good application prospect of the quality management of POC glucose testing.

7.
Article in Chinese | WPRIM | ID: wpr-931828

ABSTRACT

Objective:To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS).Methods:A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. Results:A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO 2/FiO 2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO 2/FiO 2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO 2/FiO 2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO 2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found ( P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Conclusion:Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO 2/FiO 2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.

8.
Article in Chinese | WPRIM | ID: wpr-927852

ABSTRACT

Objective To explore the expression profiles of circulating microRNA(miRNA)and potential markers for the diagnosis of adult fulminant myocarditis(FM). Methods The expression profiles of circulating miRNA were determined by microarray analysis and verified by real-time quantitative PCR.The key role of circulating miRNA in FM was determined via KEGG pathway enrichment.The correlations between miRNA and cardiac function parameters in patients with FM were analyzed.The receiver operating characteristic(ROC)curve was established to evaluate the sensitivity and specificity of circulating miRNA in the diagnosis of FM. Results Compared with healthy controls,the FM patients had up-regulated expression levels of miR-29b(t=18.925,P<0.001)and miR-125b(t=5.981,P=0.029)in the plasma.After treatment,the expression levels of miR-29b(t=12.943,P<0.001)and miR-125b(t=14.016,P<0.001)were significantly down-regulated.KEGG pathway enrichment showed that the targets of miR-29b were involved in inflammatory response and apoptosis pathways.The results of cell proliferation and apoptosis assay demonstrated the transfection of miR-29b mimic had a more significant inducing effect on cardiomyocyte apoptosis than that of miR-125b mimic(χ 2=6.168,P=0.047),whereas there was no significant difference in the inhibition of cell proliferation between the two groups(χ2=1.452,P=0.417).The expression levels of miR-29b and miR-125b were negatively correlated with left ventricular ejection fraction(r=-0.67,P=0.071;r=-0.49,P=0.003).They were positively correlated with cardiac troponin I level(r=0.61,P=0.019;r=0.52,P=0.016),interferon β level(r=0.42,P=0.014;r=0.36,P=0.021),and myocardial edema area(r=0.86,P=0.005;r=0.73,P=0.013).The ROC curve analysis demonstrated that miR-29b had higher sensitivity for the diagnosis of FM(93.6% vs.89.2%;t=0.896,P=0.795)and specificity(72.4% vs.59.6%;t=9.478,P=0.002)than miR-125b. Conclusion The circulating miR-29b may be a potential biomarker for the diagnosis of FM.


Subject(s)
Adult , Biomarkers/metabolism , Circulating MicroRNA/metabolism , Humans , MicroRNAs/metabolism , Myocarditis/diagnosis , Stroke Volume , Ventricular Function, Left
9.
Article in Chinese | WPRIM | ID: wpr-885263

ABSTRACT

Objective:To observe the effect of local excision under ultrasonography with immediate mammoplasty in granulomatous lobular mastitis.Methods:Fifty-three patients with granulomatous lobular mastitis admitted from Jan 2017 to Jul 2020 were retrospectively analyzed. Combined with sonographic findings and clinical manifestations, patients were divided into four types: type Ⅰ, single mass; Type Ⅱ, single mass located in one quadrant with one or no skin lesion; Type Ⅲ, multi-quadrant involved with one or no skin lesion; Type Ⅳ, multiple abscesses with multiple lesions in the skin. Twenty-five patients underwent wide local excision (control group); Twenty-eight patients underwent local excision under ultrasonography with immediate mammoplasty (experiment group). Patients with erythema nodosum or in type Ⅳ were given antibiotics and corticosteroid therapy preoperatively for 1 week and postoperatively for 5 days. The others went straight to surgery.Results:All patients were followed up for 1 year. In the experiment group, 28 patients had primary wound healing, and 3 patients had poor wound healing after operation (all were of type Ⅳ). The control group had 6 cases of recurrence(were of type Ⅲ and type Ⅳ). There was significant difference of the recurrence rate between the two groups (0 vs. 24%, χ 2=6.033, P=0.014), and the aesthetic effect of local excision under ultrasonography with immediate mammoplasty was better than that of wide local excision(93% vs. 68%, χ 2=5.330, P=0.020). Conclusion:The recurrence rate of local excision under ultrasonography with immediate mammoplasty is low, and with a satisfactory cosmetic effect.

10.
Article in Chinese | WPRIM | ID: wpr-879143

ABSTRACT

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.


Subject(s)
Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Humans , Research Design , Signal Transduction
11.
Article in Chinese | WPRIM | ID: wpr-905951

ABSTRACT

Objective:Based on fingerprint, index component content and dry extract yield, a quality evaluation method for substance benchmark of Xiebaisan was established to study the key quality attributes, to explore the quantitative transfer relationship between decoction pieces and substance benchmark, and to preliminarily formulate the quality standard of substance benchmark of Xiebaisan. Method:The substance benchmark of Xiebaisan was prepared according to the records of ancient formulas, fingerprints of 15 batches of decoction pieces and substance benchmarks were collected by high performance liquid chromatography (HPLC) and the index components were determined with the mobile phase of acetonitrile-0.05% phosphoric acid solution for gradient elution. The dry extract yield, fingerprint similarity and transfer rate of index components were combined to study the quantity value transmitting. Result:Ten characteristic peaks were identified in fingerprint of the substance benchmark and two characteristic peaks from stir-fried Mori Cortex, four characteristic peaks from baked Lycii Cortex, four characteristic peaks from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. Mulberroside A, liquiritin and glycyrrhizic acid were used as index components for the determination, the contents of mulberroside A, liquiritin and glycyrrhizic acid in substance benchmark of Xiebaisan were 2.69%-4.26%, 0.09%-0.17% and 0.09%-0.16%, and their transfer rates were (31.37±4.14)%, (36.12±4.03)% and (12.25±0.88)%, respectively. The similarity of fingerprint of substance benchmarks was good, the fingerprint similarities of 14 batches of substance benchmarks and control fingerprint were >0.9. The dry extract yield of substance benchmark of Xiebaisan ranged from 8.09% to 11.29%. Conclusion:The established quality evaluation method of substance benchmark of Xiebaisan is scientific and reasonable, and the transfer process of decoction pieces to substance benchmarks is stable and controllable. The preliminary quality standard of the substance benchmark can provide basis and reference for the development of modern preparations of Xiebaisan in the future.

12.
Article in Chinese | WPRIM | ID: wpr-904624

ABSTRACT

Objective To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. Methods The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. Results The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. Conclusions E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

13.
Chinese Journal of School Health ; (12): 1544-1547, 2021.
Article in Chinese | WPRIM | ID: wpr-904603

ABSTRACT

Objective@#To explore the performances of HbA1c when identifying elevated blood glucose among pre pubertal children, and to provide scientific basis for early screening biomarkers of abnormal blood glucose in children.@*Methods@#A total of 1 208 prepubertal children aged 7 to 10 years old in Xiamen were sampled with the cluster sampling method. Fasting venous blood was drawn to measure the level of HbA1c and FPG. According to American Diabetes Association (ADA) criteria, participants were divided into normal group, HbA1c abnormal group, FPG abnormal group and combined abnormal group. Partial correlation analysis was used to analyze the correlation between HbA1c and FPG. The cutoffs of HbA1c were calculated when FPG was 5.6 mmol/L. Receiver operating curve (ROC) was used to judge the performances of HbA1c while screening abnormal blood glucose.@*Results@#With HbA1c, FPG and the combined indicators as the screening criteria, the prevalence of high blood glucose were 2.2%, 4.0%, and 5.8%, respectively. The partial correlation coefficient of FPG and HbA1c was 0.15( P <0.01), and the correlation coefficient in girls( r =0.22) and non overweight group( r =0.16) were higher. The cutoff of HbA1c was 5.15% if FPG was 5.6 mmol/L. Taking the combined indicator as the reference standard, the AUC of FPG was 0.84 (95% CI =0.79-0.90) and the AUC of HbA1c was 0.69 (95% CI =0.63-0.74).@*Conclusion@#There is a low correlation between HbA1c and FPG in pre pubertal children. The performance of HbA1c is different from FPG when used as the indicator to screen children with abnormal blood glucose. It is recommended to use the combined indicator of HbA1c and FPG to screen abnormal blood glucose in prepubertal children.

14.
Chinese Journal of Anesthesiology ; (12): 1441-1445, 2021.
Article in Chinese | WPRIM | ID: wpr-933268

ABSTRACT

Objective:To investigate the relationship between the mechanism of ulinastatin reducing perioperative myocardial injury and ferroptosis in peripheral blood mononuclear cells (PBMCs) in pediatric patients undergoing heart surgery under cardiopulmonary bypass (CPB).Methods:A total of 60 pediatric patients of either sex, aged 4-8 yr, of American Association of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective repair of ventricular septal defect under CPB, were divided into 2 groups by a random number table method: control group (C group) and ulinastatin group (UTI group), with 30 cases in each group.Combined intravenous-inhalational anesthesia was used.In UTI group, ulinastatin 20 000 U/kg was diluted to 100 ml in normal saline, 50 ml was infused through the central vein over 15 min starting from 20 min before skin incision, and the remaining 50 ml was instilled through the CPB pipeline over 15 min starting from 10 min of CPB.The equal volume of normal saline was given instead in C group.Blood samples from the internal jugular vein were collected after anesthesia induction and before skin incision (T 1), at 30 min after start of CPB (T 2), immediately after termination of CPB (T 3) and at 24 h after termination of CPB (T 4) for determination of the levels of amino-terminal B-type pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) in plasma by enzyme-linked immunosorbent assay.PBMCs were extracted by modified Ficoll density gradient centrifugation method for determination of the concentrations of Fe 2+ and malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in PBMCs (by colorimetric method) and expression of long-chain acyl-CoA synthase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in PBMCs (by Western blot). Results:Compared with the baseline at T 1, the levels of NT-proBNP, cTnI and CK-MB in plasma were significantly increased, the concentrations of Fe 2+ and MDA in PBMCs were increased, the expression of ACSL4 in PBMCs was up-regulated, and the activity of SOD was decreased, and the expression of GPX4 was down-regulated at T 2-4 in two groups ( P<0.05). Compared with C group, the plasma levels of NT-proBNP, cTnI and CK-MB were significantly decreased, the concentrations of Fe 2+ and MDA in PBMCs were decreased, the expression of ACSL4 in PBMCs was down-regulated, the activity of SOD was increased, and the expression of GPX4 was up-regulated at T 2-4 in UTI group ( P<0.05). Conclusion:The mechanism by which ulinastatin reduces perioperative myocardial injury may be related to inhibition of ferroptosis in PBMCs in the pediatric patients undergoing open heart surgery under CPB.

15.
Article in English | WPRIM | ID: wpr-914654

ABSTRACT

Background and Objectives@#Manipulating different signaling pathways via small molecules could efficiently inducecardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC).We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation. @*Conclusions@#These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.

16.
Frontiers of Medicine ; (4): 472-485, 2021.
Article in English | WPRIM | ID: wpr-888731

ABSTRACT

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.


Subject(s)
Animals , Brain Ischemia/drug therapy , Cell Differentiation , Hypoxia , Neurons , Rats , Resveratrol/pharmacology
17.
Chinese Journal of Biotechnology ; (12): 2256-2271, 2021.
Article in Chinese | WPRIM | ID: wpr-887794

ABSTRACT

The development of biotechnology and the in-depth research on disease mechanisms have led to increased application of enzymes in the treatment of diseases. In addition, enzymes have shown great potential in drug manufacturing, particularly in production of non-natural organic compounds, due to the advantages of mild reaction conditions, high catalytic efficiency, high specificity, high selectivity and few side reactions. Moreover, the application of genetic engineering, chemical modification of enzymes and immobilization technologies have further improved the function of enzymes. This review summarized the advances of using enzymes as drugs for disease treatment or as catalysts for drug manufacturing, followed by discussing challenges, potential solutions and future perspectives on the application of enzymes in the medical and pharmaceutical field.


Subject(s)
Biocatalysis , Biotechnology , Catalysis , Drug Compounding , Enzymes/metabolism
18.
Article in English | WPRIM | ID: wpr-881052

ABSTRACT

Inflammation plays important roles in the progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Microglia is responsible for the homeostasis of the central nervous system (CNS), and involved in the neuroinflammation. Therefore, it could be potential in treatment of neurodegenerative diseases to suppress the microglia-mediated neuroinflammation. Mangiferin, a major glucoside of xanthone in Anemarrhena Rhizome, has anti-inflammatory, anti-diabetes, and anti-oxidative properties. However, the effect of mangiferin on the inflammatary responses of microglia cells are still poorly understand. In this study, we investigated the mechanism by which mangiferin inhibited inflammation in LPS-induced BV

19.
Article in Chinese | WPRIM | ID: wpr-880072

ABSTRACT

The normal hematopoiesis of the body are depends on the proliferation and differentiation of hematopoietic stem/progenitor cell (HSPC), as well as the mesenchymal stem/stromal cell (MSC) that support the growth and development of hematopoietic microenvironment of bone marrow (BM). At present, the commonly used MSC for promoting hematopoiesis are mainly derived from BM, however, the acquisition of MSC from BM is limited by the number, sampling, isolation and purification. Compared with BM, adipose tissue has many advantages, including widely distributed, abundant in source, simple and easy to obtain, and contains more pluripotent stem cell, such as adipose tissue-derived stem cell (ADSC), in which Perivascular cell/pericyte (PC) are considered as the precursor cell of MSC, also is the main components of vascular microenvironment, and plays an important role in the proliferation and differentiation of HSPC. PC is especially abundant in adipose tissue, and with the advantages of easy acquisition, small damage, fast cell proliferation and low immunogenicity. Therefore, the sustaining hematopoiess of human adipose derived-perivascular stem cell (AD-PC) to HSPC requires further research and exploration. In this review, the possible supporting effects and PC subgroup of ADSC as stromal cell on HSPC are summarized briefly.


Subject(s)
Adipose Tissue , Bone Marrow Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Mesenchymal Stem Cells
20.
Article in Chinese | WPRIM | ID: wpr-799258

ABSTRACT

Hand, foot, and mouth disease(HFMD)is a global contagious disease mainly caused by enterovirus(EV)infections, among which coxsackievirus A16(CA16)and enterovirus 71(EV71)infection are the most common.In recent years, The incidence of HFMD caused by coxsackievirus A6(CA6)has increased year by year, and its rash is more specific than typical HFMD and atypical changes are more common.Some scholars define this kind of HFMD as atypical HFMD.At the same time, there are differences between typical HFMD and atypical HFMD in severity, age of preoccurrence, prognosis and other aspects.This article reviews the differences in clinical characteristics of pediatric atypical HFMD compared with that of typical HFMD, and it also discusses the research progress on clinical characteristics of atypical HFMD disease.

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