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BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.
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Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.
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OBJECTIVE To study the cost-utility threshold （WTP/Q） based on the preference of the population in Liaoning province with willingness-to-pay（WTP） survey method， and to provide reference for decision-making. METHODS Using the method of questionnaire survey， quota sampling combined with snowball sampling were used to conduct telephone interviews with the general population in Liaoning province， collect data and analyze it. Probit regression combined with generalized linear model was used to analyze the relevant factors affecting WTP/Q. RESULTS A total of 755 general people were recruited. The WTP/Q of Liaoning population was 119 175 yuan，the average WTP/Q for improving the quality of life was 84 902 yuan， and the average WTP/Q for extending the survival period was 188 005 yuan. The analysis of influential factors showed that the older the age， the lower the probability of people purchasing medical interventions； the higher the education level and income， the greater the WTP/ Q； at the same time， the physical feelings of the interviewee， such as pain and depression， could also affect the WTP/Q results； compared with the scenario of improving quality of life， the WTP/Q for the extended survival period was higher. CONCLUSIONS The WTP/Q of Liaoning province based on the WTP survey method is about 2.07 times of the per capita gross domestic product of Liaoning province in the same period. The WTP/Q for extending survival period is about 2.21 times that of improving the quality of life. Therefore， interventions to improve quality of life and to extend the survival period need to be treated differently， in measurement or decision-making.
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Hashimoto thyroiditis (HT) is one of the most common autoimmune thyroid disease, and its pathogenesis has not been fully clarified at present. Most people believe that it is induced by mental stress, overwork, infection, stress, environmental pollution, unreasonable diet structure (such as high iodine diet) and other factors on the basis of genetic defects and genetic susceptibility. Vitamin D is a steroid hormone that maintains the balance of calcium and phosphorus metabolism in the body, regulating bone and mineral salt metabolism. Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine CC family. It binds to chemokine receptor (CCR) and participates in immune inflammatory response. In recent years, more and more studies have found that vitamin D and MCP-1 are involved in the occurrence and development of many immune diseases, including Hashimoto thyroiditis. This article reviews the new research progress of the role of vitamin D and MCP-1 in Hashimoto thyroiditis.
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Objective To investigate the relationship between serum levels of bone morphogenetic protein(BMP)9,Drosophila mother anti-cerebral palsy protein(SMAD)3 and growth and bone age in children with idiopathic short stature(ISS).Methods A total of 110 children with ISS admitted to the Qingdao Eighth Peo-ple's Hospital from September 2020 to September 2022 were selected as the ISS group,and 110 healthy chil-dren who underwent physical examination in the hospital during the same period were selected as the control group.The serum BMP9 and SMAD3 levels were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between BMP9,SMAD3 and sexual development status,height,weight,body mass index(BMI),osteocalcin(Ost),Leptin,bone age index(BAI),bone age difference(BAD)in children with ISS.Re-ceiver operating characteristic(ROC)curve was used to analyze the diagnostic value of BMP9 and SMAD3 in ISS.Multivariate Logistic regression was used to analyze the risk factors of ISS.Results Compared with the control group,the level of BMP9 was significantly increased and the level of SMAD3 was significantly de-creased in the ISS group(P<0.05).There were significant differences in sexual development status,BMI,BAI,BAD,Ost and Leptin levels between the control group and ISS group(P<0.05).Correlation analysis showed that the serum level of BMP9 was negatively correlated with SMAD3,sexual development status,height,weight,BMI,Ost,Leptin,BAI,and BAD in children with ISS(r=-0.497,-0.523,-0.447,-0.486,-0.501,-0.465,-0.502,-0.434,-0.520,P<0.05).Serum SMAD3 level was positively corre-lated with sexual development status,height,weight,BMI,Ost,Leptin,BAI,and BAD(r=0.432,0.458,0.431,0.465,0.503,0.467,0.515,0.527,P<0.05).ROC curve analysis showed that BMP9,SMAD3 joint in-spection ISS area under curve was higher than the two separate detection(Z=2.774,2.958,P<0.05).Multi-variate Logistic regression analysis showed that serum BMP9 level was an independent risk factor for ISS,and SMAD3 level was an independent protective factor(P<0.05).Conclusion The serum level of BMP93 is in-creased and SMAD3 is decreased in children with ISS,and they are closely related to the growth and bone age of children with ISS,which can be used as molecular markers to evaluate the condition of children with ISS.
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Objective:To investigate the effects of Xiaoyu-Jiangzhi capsules on blood lipid, carotid artery atherosclerosis (CAA) and plaque in apolipoprotein E knockout (ApoE -/-) mice. Methods:The ApoE -/- mice were fed with high-fat food to establish carotid atherosclerosis model. The ApoE -/- mice were randomly by weight divided into model group, Atorvastatin group, low- and high-dose Xiaoyu-Jiangzhi capsules group. The C57BL/6cnc mice were used as control group and fed with normal diet. The Atorvastatin group was given atorvastatin suspension 1.3 mg/kg, low and high dose groups were given Xiaoyu-Jiangzhi capsule suspension 325 and 975 mg/kg, and the control group and model group were given equal volume of distilled water. The mice were gavaged with 0.1 ml/10 g body weight, once a day, and the weight of mice was recorded weekly. After 12 weeks of continuous intragastric administration, the blood lipid and liver /body weight index of the mice were measured. Carotid arteries were sliced to conduct oil red O staining and VG staining for the pathological analysis. Results:After 12 weeks of drug administration, the weight of mice in the high-dose group was significantly lower than the model group. The level of TC (25.92 ± 4.21 mmol/L vs. 30.39 ± 4.67 mmol/L) and LDL-C (7.97 ± 2.14 mmol/L vs. 10.26 ± 1.97 mmol/L) in the high-dose group significantly decreased ( P<0.05), the level of HDL-C in the low and high-dose group significantly increased ( P<0.05). The pathological results showed that after 12 weeks of administration, the carotid artery lipid deposition blockage rate in the Atorvastatin group and the high dose group were significantly smaller than the model group( P<0.05), and no vascular plaque has been formed. Conclusion:The Xiaoyu-Jiangzhi capsules could reduce LDL-C, increase HDL-C levels, reduce the constriction of arterial stenosis and slow down the formation process of carotid plaque.
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Objective@#To explore the application effect of self-made nursing strategy of device in the severe diarrhea or fecal incontinence.@*Methods@#A total of 60 patients with severe diarrhea or fecal incontinence were randomly divided into study group and control group according to the order of admission, each with 30 patients. The control group received traditional nursing strategy, while the study group was applied self-made perianal skin nursing strategy of device. The change of perianal skin injury, nursing workload and patients′ pain index of two groups were compared.@*Results@#The study group perianal skin injury, nursing workload and patients pain index were (0.40±0.11) points, (2.14±0.22) times/day, (1.36±0.40) points, which were better than (0.84±0.14) points, (3.58±0.29) times/day, (3.28±0.60) points in the control group (t=2.475, 3.934, 2.652, P<0.05).@*Conclusion@#self-made perianal skin nursing strategy of device could reduce the incidence of perianal skin injury, liberation of nursing work, reduce the pain of patients. Which is worthy of clinical application for its convenience.
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Objective:To explore the application effect of self-made nursing strategy of device in the severe diarrhea or fecal incontinence.Methods:A total of 60 patients with severe diarrhea or fecal incontinence were randomly divided into study group and control group according to the order of admission, each with 30 patients. The control group received traditional nursing strategy, while the study group was applied self-made perianal skin nursing strategy of device. The change of perianal skin injury, nursing workload and patients ′ pain index of two groups were compared. Results:The study group perianal skin injury, nursing workload and patients pain index were (0.40±0.11) points, (2.14±0.22) times/day, (1.36±0.40) points, which were better than (0.84±0.14) points, (3.58±0.29) times/day, (3.28±0.60) points in the control group ( t=2.475, 3.934, 2.652, P<0.05). Conclusion:self-made perianal skin nursing strategy of device could reduce the incidence of perianal skin injury, liberation of nursing work, reduce the pain of patients. Which is worthy of clinical application for its convenience.
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Objective:To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS).Method:The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS.Results:Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%( P=0.014)and 90.5%( P=0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions:FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.
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PURPOSE: The hand knob area is the cortical representation of motor hand function. The current study aimed to investigate the effects of eloquent area gliomas on the morphometry of the hand motor cortex and preoperative hand motor function. METHODS: A retrospective study of 320 glioma patients was conducted. Seventy-eight patients with gliomas involving motor functional area were finally enrolled. Using axial T2-weight magnetic resonance images, the width and height of the hand knob were measured in both hemispheres, and differences were compared between the affected and unaffected hemispheres. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to estimate the degree of correlation between distance measurements and motor impairment. RESULTS: The width and height of the hand knob in the affected and unaffected hemispheres were significantly different (pâ¯< 0.0001). The width, height and distance from the tumor to hand knob were reduced in the functionally impaired group compared to the unimpaired group (pâ¯= 0.0003, pâ¯< 0.0001, pâ¯= 0.0005, respectively). The three parameters were significantly correlated and remained significant in ROC and logistic regression analysis. The optimal cut-off value of width, height and distance for identifying preoperative hand muscle strength were 5.73â¯mm, 5.80â¯mm and 5.92â¯mm, respectively. CONCLUSION: The morphometry of the hand knob is often changed by the infiltration or extrusion of the tumors that were located in or near the hand knob. The width, height of hand knob and the distance from tumor to hand knob could serve as anatomic biomarkers related to preoperative neurological motor deficits.