1.Adipose-derived mesenchymal stem cell therapy for radiation-induced vascular injury in small intestine of rat
Pengyu CHANG ; Shuang CUI ; Xin JIANG ; Chao QU ; Xinping JIANG ; Jinghua LUO ; Yaqin QU ; Lihua DONG
Chinese Journal of Radiological Medicine and Protection 2014;(9):652-657
Objective To assess the therapeutic effect of human adipose-derived mesenchymal stem cells on radiation-induced vascular injury in the small intestine of rat. Methods A total of 34 male Sprague-Dawley rats were enrolled in this study. To establish a model of radiation-induced intestinal injury, each rat was irradiated with 15 Gy in whole abdomen. 17 rats were randomly selected and infused intraperitoneally with passage 6 ( P6 ) Ad-MSCs, and the other 17 rats that received PBS were set as control. 10 days post-irradiation, the number of CD31+ endothelial cells in the small intestine villus was measured by flow-cytometry, the expressions of CD31, CD105 and isolectin-B4 in the na?ve endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of na?ve endothelial cells within injured intestine was also analyzed. In addition, total mRNA were extracted from irradiated small intestine to assay the expressions of VEGF, bFGF, Flk-1 and SDF-1 using quantitative Real-time PCR. Results Compared to the control, the amount of CD31-postive endothelial cells within irradiated intestine was significantly increased after Ad-MSCs infusion ( t=12?15, P<0?05). The microvascular density in the injured sites was also significantly increased by the infusion of Ad-MSCs (20 d:t=10?33, P<0. 05;30 d:t=32?85, P<0?05). Moreover, the expressions of VEGF, bFGF, Flk-1 and SDF-1 were significantly up-regulated after delivery of Ad-MSCs ( VEGF:t =10?34, bFGF:t=11?25,Flk-1:t=6?73, SDF-1:t=6?73, all P<0?05), which was beneficial in maintaining the integrity of intra-villus blood-vessels as well as promoting neovascularization in the injured sites. Conclusion Ad-MSCs had potentials in healing radiation-induced vascular injury in rat small intestine.
2.Therapeutic effects of gensenoside-Rg3 combined with radiotherapy on advanced non-small cell lung cancer
Xin JIANG ; Ying XIN ; Jinghua LUO ; Pengyu CHANG ; Qi FENG ; Yaqin QU
Chinese Journal of Radiological Medicine and Protection 2012;32(2):196-198
Objective To study the efficacy and toxicity of gensenoside-Rg3 (Rg3) combined with radiotherapy on non-small cell lung cancer ( NSCLC ) at advanced stages (Ⅲ and Ⅴ ).Methods Sixty-three patients with stage Ⅲ or Ⅳ NSCLC were divided randomly into two groups:treatment group ( n =35 ) treated with Rg3 combined with radiotherapy and control group ( n =28 ) treated with radiotherapy alone.The efficacy and side effects were compared after the treatment.Results The response rate ( CR + PR) of the treatment group was 57.14%,significantly higher than that of the control group (32.14%,x2 =3.91,P < 0.05).The median survival time of the treatment group was 14.2 months,significantly longer than that of the control group ( 11.2 months,x2 =2.07,P < 0.05 ).The one-year survival rate of the treatment group was 62.86%,significantly higher than that of the control group (39.29%,x2 =4.40,P <0.05).The incidence rates of side effects of the treatment group were all lower than those of the control group,but there were not significant difference. Conclusions Gensenoside-Rg3 combined with radiotherapy is effective for advanced stage NSCLC,with attenuation and synergistic effects.
3.Therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis
Pengyu CHANG ; Shuang CUI ; Jinghua LUO ; Chao QU ; Xin JIANG ; Yaqin QU ; Lihua DONG
Chinese Journal of Radiological Medicine and Protection 2014;34(10):729-734
Objective To evaluate the therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis.Methods A total of 52 male Sprague-Dawley rats were used in the present study.Herein,46 rats were randomly selected and irradiated with a dose of 15 Gy at their abdomens.Two hours post-irradiation,23 rats were randomly selected and infused intraperitoneally with adipose-derived mesenchymal stem cells in passage 6 from young-female donor.The other 23 rats were intraperitoneally infused with PBS.The rest 6 rats were set as normal control.During the first 10 days post-irradiation,peripheral blood-samples from irradiated rats were harvested for testing the levels of IL-10 in serum using ELISA assay.Additionally,after isolating the thymic cells and peripheral blood mononuclear cells,the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in thymus and peripheral blood were tested by flow-cytometry.Finally,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were analyzed by H&E staining and Masson Trichrome staining,respectively.Based on the MPO-immunohistochemistry staining,the type of infiltrated cells was identified.The Kaplan-Meier method was used for analyzing the survival rate of irradiated rats.Results During a period of 30 days post-irradiation,the irradiated rats receiving adipose-derived mesenchymal stem cells survived longer than those receiving PBS (t =4.53,P < 0.05).Compared to the irradiated rats with PBS-treatment,adipose-derived mesenchymal stem cells could elevate the level of IL-10 in serum (7 d:t =13.93,P < 0.05) and increase the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in both peripheral blood (3.5 d:t =7.72,7 d:t=11.11,10 d:t =6.99,P <0.05) and thymus (7 d:t =16.17,10 d:t =12.12,P< 0.05).Moreover,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were mitigated by adipose-derived mesenchymal stem cells.Conclusions Adipose-derived mesenchymal stem cells were capable of curing radiation enteritis.
4.Efficacy of different doses of urapidil in preventing pituitrin-induced cardiovascular responses in patients undergoing laparoscopic myomectomy
Tieying SONG ; Pengyu MA ; Guohua GAO ; Yanchao YANG ; Chunping WANG ; Jian YA ; Bo JIANG ; Kun MA ; Yunshui PENG
Chinese Journal of Anesthesiology 2011;31(7):792-794
ObjectiveTo evaluate the efficacy of different dones of urapidil in preventing pituitrin-induced cardiovascular responses in patients undergoing laparoscopic myomectomy.MethodsSixty ASA Ⅰ or Ⅱ patients,aged 27-41 yr,weighing 55-65 kg,scheduled for elective laparoscopic myomectomy under general anesthesia,were randonly divided into 4 groups (n =15 each):control group (group C) and urapidil 0.3,0.5 and 0.8 mg/kg groups (groups U1-3).Urapidil 0.3,0.5 and 0.8 mg/kg were injected intravenously in U1-3 groups respectively,while normal saline 5 ml was given in group C.The mixture of pituitrin 6 U and normal saline 20 ml was injected into the site of hysteromyoma 5 min later.The operation was then started.BIS value was maintained at 45-55.The occurrence of cardiovascular responses was recorded.ResultsThe incidences of cardiovascular responses were 100%,67%,40% and 20% in groups C and U1-3 respectively.The incidence of cardiovascular responses was significantly lower in groups U1-3 than in group C,and in groups U2.3 than in group U1 ( P < 0.01 ).There was no significant difference in the incidence of cordiovascular responses between U2 and U3 groups (P > 0.05).ConclusionUrapidil can prevent pituitrin-induced cardiovascular responses in patients undergoing laparoscopic myomectomy and the optimal dose is 0.5 mg/kg.
5.Research of detecting the development of mechanical variation in necrotic femoral head in daily activities by finite ele-ment method
Song WANG ; Xinlong MA ; Pengyu ZHANG ; Jianxiong MA ; Ying WANG ; Guangshui LYU ; Xuan JIANG ; Chen WANG ; Zhe HAN ; Feng ZHAO ; Tao ZHANG
Chinese Journal of Orthopaedics 2015;(9):962-969
Objective To propose an optimal therapeutic scheme, finite element analysis was used to evaluate the biome?chanical status of femoral head under daily activities. Methods Non?necrotic femoral head volunteers (11 people) and necrotic femoral head patients (7 cases) were included in this study. All these participants were divided into two groups:control group and abnormal group. The DICOM imaging files of each participant were imported into ScanIP software to form a mask showing the prox?imal femurs. Then the finite element models of proximal femurs were progressively reconstructed. The generated models were im?ported into Abaqus, and the forces were added on these models to simulate daily activities, including standing, sitting, upstairs, and squatting etc. The loads and boundary conditions of digital daily activities simulation were collected from Orthoload database. All of the femoral finite element models were progressed in Abaqus under above activity conditions. After the models were pro?cessed, stress concentrating region was defined in each models respectively, which expressed the main bearing structure in each model based on the result of finite element analysis. At last, the elastic modulus (E?modulus) and strain of the stress concentrating region in each femoral model were extracted and calculated. Results There was no significant difference in age, weight, and height between these two groups. In control group, no significant differences of E?modulus (7 125±745 MPa on left, and 7 112±751 MPa on right) and strain (micro?strain:952 on left, and 954 on right)were found between their bilateral proximal femurs;however in abnormal group, the patients' E?modulus (5 798±1036 MPa on normal side, and 6 667±888 MPa on necrotic side) and strain (mi?cro?strain:1 261 on normal side, and 987 on necrotic side) of necrotic side were significantly lower than normal side. As to all the daily activities which were considered in this study, in abnormal group, the E?modulus among each postures of abnormal side were significantly lower than the E?modules of healthy side;the micro?strain in downstairs was also significantly lower than other pos?tures. Conclusion Daily activities with different intensity could generate different mechanical effects on femoral head, espe?cially on necrotic femoral head. The higher intensity of posture, the greater damage would be found in necrotic femoral head.
6.The protective effect of nicotinamide riboside on mitochondrial function of retinal ganglion cell
Xizhi DENG ; Nan ZHANG ; Wen ZENG ; Min ZHU ; Pengyu ZHANG ; Fang LI ; Bin JIANG ; Min KE
China Pharmacist 2024;27(1):1-7
Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P<0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P<0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.
7.Professionalism Education Function of Ceremony in Medical Colleges from the Perspective of Interaction Ritual Chains Theory: Take the Graduation Ceremony of Peking University Health Science Center in 2020 as an Example
Yuxin ZHONG ; Pengyu JIANG ; Lijuan ZHANG
Chinese Medical Ethics 2022;35(2):129-134
Taking the graduation ceremony of Peking University Health Science Center in 2020 as the observation object, this paper used Collins’ Interactive Ritual Chains Theory to analyze the form, theme and featured part of this ceremony from the dimensions of physical co-presence, barrier to outsiders, joint focus of attention and shared mood. It was found that the ceremony in medical colleges had an impact on the cognition, behavior and spirit of junior medical students in terms of group identity, emotional energy, group symbols and moral sense, which played a good role in professionalism education. Some enlightenment and thinking were obtained on this basis to provide some references for medical colleges to give full play to the educational function of the professionalism in the post-epidemic era.
8.Gandou Bushen Decoction improves spermatogenesis and promotes spermatogenic cell proliferation in Wilson disease TX mice by activating testicular ERK signaling pathway
Miaozhu YIN ; Kuiyu CHEN ; Limin WU ; Pengyu JIANG ; Zhihui JI ; Nian ZHANG ; Huan ZHOU ; Hui HAN
Journal of Southern Medical University 2024;44(11):2063-2073
Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.
9.Gandou Bushen Decoction improves spermatogenesis and promotes spermatogenic cell proliferation in Wilson disease TX mice by activating testicular ERK signaling pathway
Miaozhu YIN ; Kuiyu CHEN ; Limin WU ; Pengyu JIANG ; Zhihui JI ; Nian ZHANG ; Huan ZHOU ; Hui HAN
Journal of Southern Medical University 2024;44(11):2063-2073
Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.
10.Expression analysis of hypoxic-related differentially expressed genes in ischemic stroke based on gene expression omnibus database
Yunqi SU ; Xingwei JIANG ; Jun MA ; Jiayuan GONG ; Fenghua GAO ; Huaying AN ; Changwen NING ; Hanqi WEI ; Pengyu LIU ; Zhe WANG ; Qun YU
Chinese Journal of Cerebrovascular Diseases 2023;20(12):825-836
Objective Based on the gene expression omnibus(GEO)database,bioinformatics methods were employed to analyze the expression characteristics of hypoxia-related differentially expressed genes(HRDEGs)in ischemic stroke,and key genes were screened,to provide important support for a deeper understanding of ischemic stroke.Methods The GSE16561 and GSE58294 datasets were downloaded from the GEO database,and Python software was used for data integration.The Combat method was employed to eliminate batch effects while retaining disease grouping characteristics.Principal component analysis was conducted to reduce dimensionality of the data before and after batch effect removal,and intraclass correlation coefficient(ICC)testing was performed on the ischemic stroke and normal control groups.Gene set enrichment analysis(GSEA)and single-sample GSEA were conducted on the merged and batch effects eliminated dataset,with a nominal P-value(NOM P-val)<0.05 and false discovery rate P-value(FDR P-val)<0.25 used as criteria to select significantly different gene sets.Differential expression genes between the ischemic stroke samples and normal control samples after merging and eliminating batch effects of the GSE16561 and GSE58294 datasets were identified using R software,with an absolute value of log2 gene expression fold change(FC)≥0.58 and adjusted P-value(Padj)<0.05 as selection criteria.Intersection with hypoxia-related genes obtained from the National Center for Biotechnology Information(NCBI)in the United States yielded the HRDEGs.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed on the HRDEGs,and the STRING database was used to construct a protein-protein interaction network of differentially expressed genes.The top 10 key genes were filtered using Cytoscape 3.8 software.Results The ICC analysis results showed excellent consistency in the ischemic stroke and normal control samples after batch effect removal,with ICC values of 0.94 and 0.98 for the GSE16561 and GSE58294datasets,respectively.GSEA results demonstrated significant enrichment of 34 gene sets in the stroke samples in the newly merged and batch effects removed dataset from GSE16561 and GSE58294,leading to the identification of 404 differentially expressed genes(all with Padj<0.05),including 354 upregulated genes and 50 downregulated genes.Intersection with hypoxia-related genes yielded 64 HRDEGs.GO enrichment analysis indicated significant enrichment of HRDEGs in vesicle lumen,cytoplasmic vesicle lumen,secretory granule lumen,with molecular functions such as amide binding,peptide binding,phospholipid binding,and enzyme inhibitor activity.These genes are primarily involved in the positive regulation of cytokine production,regulation of immune response,response to bacterium-derived molecules,and response to lipopolysaccharide,among other biological processes.KEGG enrichment analysis revealed enrichment of HRDEGs in pathways related to lipid and atherosclerosis,Salmonella infection,neutrophil extracellular trap formation,nucleotide-binding oligomerization domain-like receptor signaling pathway,protein glycosylation in cancer,tuberculosis,and necroptosis.Based on the protein-protein interaction network,10 key genes were identified,including arginase1(ARG1),caspase1(CASP1),interleukin1 receptor type 1(IL-1R1),integrin subunit alpha M(ITGAM),matrix metalloproteinase9(MMP9),prostaglandin-endoperoxide synthase 2(PTGS2),signal transducer and activator of transcription 3(STAT3),Toll-like receptor2(TLR2),TLR4,and TLR8.Conclusion This study has identified 10 key genes associated with ischemic stroke and hypoxia through bioinformatics mining,which maybe provid potential targets for subsequent research and diagnostic and therapeutic interventions.