2.Mesenchymal stem cell transplantation for spinal cord injury:a Meta-analysis
Wentao ZHAO ; Panpan LI ; Haifeng ZHANG ; Naping WU ; Jianfang LIANG
Chinese Journal of Tissue Engineering Research 2015;(36):5865-5871
BACKGROUND:In recent years, the effectiveness of stem cel transplantation in the treatment of spinal cord injury has been validated in animal models, and mesenchymal stem cel transplantation for treatment of spinal cord injury has been studied most widely. Currently, there are a number of relevant clinical studies that have shown a good prospect. OBJECTIVE:To evaluate the efficacy and safety of mesenchymal stem cel transplantation for spinal cord injury in human with a system review. METHODS:PubMed database, EMBASE database, Cochrane Library, ISI Web of knowledge, CBM database, VIP database, CNKI database and Wanfang database were searched from their start year up to July 2015 for relevant randomized clinical trials on the treatment of spinal cord injury with mesenchymal stem cel transplantation. The key words were“spinal cord injury, paraplegia, cel transplantation, transplantation, mesenchymal stem cel , bone marrow transplantation, stem cel , randomized control ed trial”in English and Chinese, respectively. RESULTS AND CONCLUSION:A total of 260 articles were retrieved, including 6 randomized clinical trials (252 cases). In the aspects of ASIA touch sensation score, overal Frankel score and daily life activity training score, the patients undergoing mesenchymal stem cel transplantation were significantly superior to those in the control group (P<0.05). In addition, ASIA motor function score and residual urine volume were also improved in the patients undergoing mesenchymal stem cel transplantation, but there was no statistical difference (P>0.05). Compared with the control group, low fever was more common in the patients undergoing mesechymal stem cel transplantation (P<0.05). Another side effect was lower limb numbness, but there was no difference from the control group (P>0.05). These findings suggest that mesenchymal stem cel transplantation has limited efficacy in the treatment of spinal cord injury and cannot induce severe complications, but there is a need for high-quality randomized control ed trials to prove the efficiency and safety of mesenchymal stem cel transplantation for the treatment of spinal cord injury.
3.Methylprednisolone for acute spinal cord injury:a Meta-analysis of therapeutic efficacy and adverse reactions
Wentao ZHAO ; Hongbing YUAN ; Panpan LI ; Haifeng ZHANG ; Mingqing LIU
Chinese Journal of Tissue Engineering Research 2015;(42):6868-6874
BACKGROUND:Methylprednisolone has been used for the treatment of acute spinal cord injury but there is a dispute about the efficacy and safety of methylprednisolon. OBJECTIVE:To evaluate the efficacy and safety of methylprednisolon based on system review. METHODS:PubMed database, EMBASE database, Cochrane Library, ISI Web of knowledge, CBM database, VIP database, CNKI database and Wanfang database were searched from their start year up to December 2014 for relevant randomized clinical trials on the treatment of acute spinal cord injury with methylprednisolon. RESULTS AND CONCLUSION:Twelve randomized clinical trials with 642 acute spinal cord injury patients were included. The results of the Meta analysis showed: methylprednisolone+conventional therapy was better to improve American Spinal Injury Association (ASIA) motor function score, ASIA touch sensation score, ASIA pinprick sensation score and the overal Frankel score than the conventional therapy alone (control group) with statistical significance (P < 0.05). In the aspect of safety, the methylprednisolone group had higher death ratio, digestive tract reaction ratio and urinary infection ratio than the control group but with no statistical significance. The gastrointestinal bleeding ratio and lung infection ratio was significantly higher in the methylprednisolone group than the control group (P < 0.05). We conclude that methylprednisolone has protective effect on acute spinal cord injury, but the main side effects are gastrointestinal bleeding and lung infection. There is a need for high-quality randomized controled trials to prove the efficiency and safety of methylprednisolone.
4.Effects of Valproic Acid and Molecular Hydrogen on Phenotypes of Microglia Treated with Hypoxia
Xizi WU ; Renqing ZENG ; Yangzi ZHAO ; Panpan CHANG ; Chenling FAN ; Hong WANG ; Wei CHONG
Journal of China Medical University 2017;46(1):36-40
Objective To investigate the effect of VPA and molecular hydrogen(H2)on phenotypes of microglia treated with hypoxia. Methods Mouse hypoxic BV2 microglia were treated with VPA or H2. The levels of phenotypic markers of supernatant and cells were detected by ELISA, flow cytometry and real?time PCR,respectively. Results Hypoxia significantly increased mRNA level of M1 marker(iNOS)and reduced mRNA levels of M2 markers(CD206 and TGF?β)in BV2(P<0.05). Besides,the ratio between the mRNA levels of M1 increased(P<0.05). VPA significantly reduced protein level(CD16/32)and mRNA production(iNOS)of M1 markers in hypoxia?treated BV2(P<0.05). The ratio be?tween the mRNA levels of M1 markers and M2 markers(CD16:CD206,CD32:CD206,iNOS:CD206 and iNOS:TGF?β)were also significantly decreased(P<0.05). H2 significantly reduced both protein levels(TNF?α,CD16/32 and iNOS)and mRNA production(iNOS)of M1 markers and increased secretion of M2 marker(IL?10)in hypoxia?treated BV2(P<0.05). The ratio between the mRNA levels of M1 markers and M2 markers(CD16:CD206,iNOS:CD206 and iNOS:TGF?β)were also highly declined(P<0.05). Conclusion Hypoxia can induce microglial cells toward pro?inflammatory phenotype. Both VPA and H2 can inhibit hypoxia?induced inflammatory effect on microglia.
5.Effect of different extracts from Rheum palmatum on weight and tissue structure of hypothalamusand and pituitary of rats
Panpan ZHAO ; Jiming TONG ; Shuyue MA ; Fei GAO ; Yajie DONG ; Shufeng ZHANG
Drug Evaluation Research 2017;40(2):215-219
Objective To compare the effects of different extracts of Rheum palmatum on weight and tissue structure of hypothalamusand and pituitary of adult female rats,and screen the main reproductive toxicity extract.Methods The water,chloroform,ethyl acetate,and n-butanol extracts and water-soluble substance of R.palmatum were prepared by polarity gradient extraction method.Female adult rats were randomly divided into blank control group,rhubarb water extract group,and different extracts groups.The dosage of all the groups was equivalent to 4.00 g/kg crude rhubarb.Rats were administered with extracts by gavage for 60 d.Body mass growth rate of rats were calculated before and after administration.The pathological changes of hypothalamic arcuate nucleus neurons and pituitary gonadal cell were observed with light microscope.Results Compared with the blank control group,the body mass growth rate of rhubarb water extract group was decreased (P < 0.05),while those in the different extracts groups were increased (P < 0.01);The hypothalamic arcuate nucleus neurons of rhubarb water extract group showed chromatin marginalization,nissl substance dissolving,fuzzy boundary of nuclear membrane,as well as hell cells,and the total number of adenohypophysis cells reduced and the cells arranged in irregular.However,there were no apparent pathologic changes in different extracts groups.Conclusion Rhubarb water extract administration by long-term dose can reduce weight growth rate and result in pathologic changes of hypothalamic arcuate nucleus and adenohypophysis,while the different extracts can increase weight growth rate significantly and have little effects on the organizational structure ofhypothalamic arcuate nucleus and adenohypophysis.
6.Evaluation of right atrial size and function after radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation using real-time three-dimensional echocardiography
Qian YANG ; Chenyang JIANG ; Jianghong Lü ; Genshan HE ; Panpan Lü ; Bowen ZHAO
Chinese Journal of Ultrasonography 2011;20(1):1-4
Objective To assess the changes of right atrial size and mechanical function after radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation using real-time threedimensional echocardiography(RT-3DE), and to study the correlation between the changes of left atrial(LA)and right atrial(RA) volume and function. Methods Thirty-five patients with paroxysmal atrial fibrillation were undergone radiofrequency catheter ablation (RFCA) successfully. Transthoracic echocardiography (TTE),tissue Doppler imaging(TDI) and RT-3DE were performed before, 1 month and 3 months after procedure respectively. Late systolic volume and area of RA and LA,ejection fraction(EF) of RA and LA,late diastolic peak velocity of mitral valve inflow, tricuspid valve inflow and late diastolic peak velocity of mitral annulus and tricuspid annulus were recorded. Results The 3DE images of all patients were satisfied.LA max area and 3DE LA max volume were significantly reduced at 1 months and 3 months after procedure compared with basic stage [ ( 18.8 ± 6.3) cm2 vs (21.5 ± 6.2) cm2 , (38.8 ± 17.0) ml vs (46.1 ± 20.0) ml,P < 0.05]. 3DE LA EF also declined markedly at 1 month after RFCA, and restored at 3 months later compared with baseline [(41.1 ± 13.7) % vs (51.7 ± 15.9) %, (41.1 ± 13.7) % vs (45.6 ± 18.3) %, P <0.05]. The size and mechanical function of the right atrial after procedure were no obvious changes. There were no evidently correlation between the changes of LA and RA volume and function. Conclusions RT3DE can provide a precise method to quantify the value of atrial volume and function. The LA size and volume are significantly reduced after RFCA in patients with paroxysmal atrial fibrillation, however, the RA size and function are no obvious changes.
7.A nomogram for the intraoperative prediction of non-sentinel lymph node metastasis in breast cancer patients
Yan ZHANG ; Xiao SUN ; Tong ZHAO ; Yanbing LIU ; Pengfei QIU ; Panpan LI ; Chonglin TIAN ; Yongsheng WANG
China Oncology 2017;27(5):368-375
Background and purpose: When patients have positive sentinel lymph node (SLN), axillary lymph node dissection (ALND) is usually performed, but most of them have no metastasis in the non-sentinel lymph node (nSLN). It is of great significance to predict metastasis of nSLN precisely. The aim of the study was to establish a nomogram for the intraoperative prediction of nSLN metastasis in breast cancer patients using one-step nucleic acid amplification (OSNA) techniques and to direct the subsequent therapy for breast cancer effectively. Methods: Of 552 breast cancer patients who underwent SLN biopsy in the 2010 OSNA clinical trial, 103 with SLN metastasis treated with ALND were assessed to establish a nomogram for intraoperative prediction of nSLN based on the molecular diagnosis. A validation cohort of 61 patients who met the similar criteria in the 2015 OSNA clinical trial subsequently validated it. Results: Primary tumor size, total tumor load, the number of positive SLNs and negative SLNs were associated with the presence of nSLN metastasis based on the multivariable logistic regression results, and a nomogram was established with these variables. Its area under the ROC curve was 0.814 for the predictive model and it was 0.842 in the re-validation cohort. The tumor size assessed by the postoperative histological examination was replaced by the size evaluated by the imaging examination, and the area under the ROC curve was 0.838. There was no statistically significant difference in the accuracy compared with the former validation data (P=0.7406). Conclusion: The predictive nomogram based on the molecular diagnosis can predict the nSLN metastases intra/post-operatively. It appears to be obviously superior to other predictive models and may help to guide the axillary management and to make decisions about radiation target region.
8.The effect of severe intermittent hypoxia on cognitive function and expression of phosphorylated p38MAPK in rat hippocampus CA1
Hongyang WANG ; Yaning ZHAO ; Baoyuan CHEN ; Xiaoqing HAN ; Panpan ZHANG ; Sa LIU
Chinese Journal of Behavioral Medicine and Brain Science 2012;(11):972-975
Objective To explore the mechanism of severe intermittent hypoxia on oognitive function by evaluatig the effect of chronic intermittent hypoxia on cognitive function,neurons structure,damage,p38MAPK protein expression and neuronal apoptosis in rats hippocampal CA1.Methods Ninety-six mature and male Wistar rats were randomly divided into two groups:control group (UC) and 5% chronic intermittent hypoxia group (5%CIH).Rats in IH groups were suffered 8 hours intermittent hypoxia everyday,and the duration of experiment was respectively 2,4,6 and 8 weeks.After exposed for 2,4,6,and 8 weeks,the cognitive function of rats was assessed with the Morris water maze (MWM) ; the changes in the morphology of nerve cells in hippocampus CA1 region were observed; the expression of phosphorylated p38MAPK protein in hippocampus was detected by the methods of immunohistochemistry and western blot; the apoptosis of nerve cells was detected by the method of TUNEL.Results Compared with control group,with prolonged hypoxia,the time of escape latency obviously prolonged and the time of across the target quadrant shortened significantly in rats of 5% CIH group.The time of escape latency at the 8th week was the longest ((71.71 ± 5.49)s,P< 0.05) in 5% CIH group,and the time of across the target quadrant at the 8th week was the shortest ((26.82 ± 4.30) s,P < 0.05) in 5% CIH group.There appeared neuronal degeneration and necrosis in hippocampus CA1 in 5% CIH group.Compared with the control group,the density of the nerve cells survival in the region of hippocampal CA1 reduced dramatically at the 2nd,4th,6th and 8th week and was the lowest at the 8th week(14.16 ± 2.07,P < 0.05).By Immunohistochemical method,the expression of phosphorylated p38 MAPK of 5% CIH group in hippocampal CA1 was more than UC group at the 2nd,4th,6th and 8th week.By western blot,the expression of phosphorylated p38MAPK of 5% CIH group was more than UC group at the 2nd,4th,6th and 8th week and was the most at the 6th week (2.45 ± 0.14,P< 0.05) ;the index of neuronal apoptosis in hippocampal CA1 was increased significantly at the 2nd,4th,6th and 8th week than UC group and reached to the peak at the 6th week (0.608 ± 0.069,P < 0.05) in the 5 % CIH group.Conclusion Chronic intermittent hypoxia could cause the activation of p38MAPK/pathway of neuronal apoptosis and was important mechanism of cognitive dysfunction at the early and middle stage.
9.Significance and expression of miR-7 in activated CD4+T cells
Hualin XU ; Juanjuan ZHAO ; Panpan CUI ; Mengmeng GUO ; Yijing TAO ; Chao CHEN ; Lin XU
Chinese Journal of Immunology 2016;32(10):1419-1423
Objective:To investigate the change of expression of miR-7 in activated CD4+ T cells in vitro, and preliminary explore its possible significance. Methods: CD4+CD62L+T cells was purified from splenocytes of FVB mice by magnetic cell sorting system (MACS). After stimulation with anti-CD3/CD28 antibody,the relative expression of miR-7 was examined by Real-time PCR, and the expression level of CD69 molecular was analyzed by FACS. Furthermore,the relative expression of miR-7 in CD4+T cells was detected at different time points during stimulation. With the treatment of ERK inhibitor PD98059,change of miR-7 expression was de-termined by Real-time PCR. Meanwhile, the proliferation of CD4+T cells was examined by CCK-8 assay and the expression level of CD69 and CD62L molecular were analyzed by FACS. Finally,the expression of cytokines IL-6,IL-10,and IFN-γ were determined by Real-time PCR. Results:Compared with control group,the relative expression of miR-7 was increased significantly after stimulation with anti-CD3/CD28 antibody,as well as expression level of CD69 molecular was augmented(P<0. 05). In contrasted with 0 h and 24 h,the expression of miR-7 was significantly increased after 48 h and 72 h during stimulation(P<0. 05). Furthermore,the relative expression of miR-7 was significantly declined in CD4+T cells in ERK inhibitor PD98059 treatment group. Finally, the expression level of CD69 molecular,as well as cytokines IL-6, IL-10 and IFN-γ, were also decreased significantly ( P<0. 05 ) . Conclusion: The relative expression of miR-7 was significantly increased in activated CD4+T cells,closely related to ERK pathway,which provided an important foundation for successive research work on exploring the functional role of miR-7 in the CD4+T cells.
10.Prevalence Study of GJB2,SLC26A4 and mtDNA 12S rRNA1555A>G Mutations in Hui Ethnic Group Patients with Non-Syndromic Hearing Loss from Northwest China
Jianli MA ; Baicheng XU ; Panpan BIAN ; Xiaolong YANG ; Xiaowen LIU ; Qian LI ; Yiming ZHU ; Liang ZONG ; Yali ZHAO ; Yufen GUO
Journal of Audiology and Speech Pathology 2013;(5):451-455
Objective To investigate the prevalence of GJB2 ,SLC26A4 and mitochondrial DNA 12S rRNA m .1555A>G(mtDNA 1555A>G) mutations in Hui ethic group patients with nonsyndromic hearing loss (NSHL) from Northwest China .Methods A total of 420 peripheral blood samples were collected from unrelated Hui ethic group probands with NSHL in Northwest China .Amplified the target gene by polymerase chain reaction (PCR) af-ter extracting genomic DNA from whole blood .The mtDNA 1555A>G mutation was detected by PCR -Alw26I di-gestion ,then direct sequencing was used to the positive samples of mtDNA 1555A> G ,the coding region of GJB2 gene ,exon 8 and 19 of SLC26A4 gene .Results There were 11(2 .62% ) cases caused by mtDNA 1555A>G homo-zygous mutation in 420 patients with NSHL .There were 41(9 .76% ) cases including homozygote and compound het-erozygote ,caused by GJB2 gene mutation ,which was the most frequent deafness -related gene .The allel frequency of c .235delC accounted for 6 .90% ,as well as the most frequent(51 .33% ) mutational pattern in GJB2 gene .There were 20 patients(4 .76% ) were found carring two allel mutations in SLC26A4 gene .The allel frequency of c .919 -2A>G was 5 .0% ,accounting for a total of 68 .85% in all base alterations of SLC26A4 gene ,which was the major mutant form of SLC26A4 gene .Conclusion GJB2 gene is the most common deafness -gene in Hui ethnic group pa-tients with NSHL from Northwest China ,while c .235delC is the main mutant form ,and c .919-2A>G is the hot-spot mutation of SLC26A4 gene .Through this study we can provide the molecular epidemiology basis for Hui ethnic group patients with NSHL from Northwest China in genetic diagnosis ,genetic counseling and therapy by associated testing of three frequent hearing loss genes .