1.The applicatlon of principal components:analysis in priority analysis of community health care project for elderlies
Min XIAN ; Shaoxian CHEN ; Likang WU ; Zhenwen ZHANG ; Xindong ZHANG
Chinese Journal of General Practitioners 2008;7(7):475-476
A survey was conducted among 121 health care managers and health workers in community health care institutions with questionnaire and interview.Data on health care conditions in the community and health needs of elderly people were collected and analyzed using principle component analysis method.The priority order of 17 community health care projects for elderly people was ranked with this analysis method and the development strategy of community health service was suggested.
2.Application of physiologically based pharmacokinetic models to drug evaluation:research progress
Xiying NIU ; Jingjing WU ; Guangbo GE ; Shaoxian XU ; Shunqin WANG ; Ling YANG
Chinese Journal of Pharmacology and Toxicology 2015;(6):993-1000
Currently,a physiologically based pharmacokinetic(PBPK)model plays a key role in pharmaceutical research,which has been widely used at each stage of drug discovery and develop?ment. In the process of drug discovery,the selection of drug candidates is finished using the PBPK model to predict the pharmacokinetic properties of the drugs. In the process of preclinical development , through a combination of in vitro and physiological data amplification coefficient,the PBPK model can be used to predict not only the overall pharmacokinetic behavior of drug candidates in humans and animals and in vitro metabolism experiments,but also drug-drug interactions(DDI). In the course of clinical development,the PBPK model can help predict the difference between reference populations (age,different disease state,and polymorphism),especially the dosage and sampling time of the children. At present,the input parameters of PBPK model are mostly the mean values of the population,making it difficult to serve individuals. It is hoped that the input parameters of the model can reflect more of the individual characters according to the individual requirement,and that the time parameters of the input accord more with the actual physiological condition. In this article ,we briefly introduced the characteristics of common PBPK software,and reviewd the principle and feature of the PBPK model,as well as its application to drug discovery,preclinical development and clinical development,DDI,and individualized medication.
3.Cx43 is involved in electrical remodeling of atrial myocytes through regu-lating L-type calcium current
Fang RAO ; Yumei XUE ; Chunyu DENG ; Xiyong YU ; Dingzhang XIAO ; Shaoxian CHEN ; Qiuxiong LIN ; Hui YANG ; Sujuan KUANG ; Xiaoying LIU ; Jiening ZHU ; Shulin WU
Chinese Journal of Pathophysiology 2015;(11):1986-1991
AIM:To investigate whether the association of connexin 43 ( Cx43 ) and L-type calcium channel involved in the pathogenesis of atrial fibrillation ( AF) .METHODS:The biochemical assays and whole-cell patch-clamp technique were used to study the expression of Cx43 in human atrial tissue.The co-localization of Cx43 and L-type calcium channel, and the regulation of L-type calcium current in atrial myocytes were investigated.RESULTS:The expression of Cx43 at mRNA and protein levels was decreased in human atrial tissues of AF patients.In cultured atrium-derived myocytes ( HL-1 cells) , knockdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channelα1c subunit, as well as L-type calcium current.Co-localization of Cx43 with L-type calcium channel α1c subunit in mouse atrial myocytes was observed.CONCLUSION:The decrease in Cx43 is involved in the pathogenesis of AF, probably through reducing the L-type calcium current in atrial myoctyes by co-localization with L-type calcium channel, thus representing the potential pathogenesis in atrial fibrillation.
4.Evaluation of the clinical and radiological.efficacy of recombinant human TNFR Ⅱ -Fc combined with methotrexate in the treatment of moderate and severe rheumatoid arthritis
Xiaoxiang CHEN ; Qing DAI ; Huaxiang WU ; Dongbao ZHAO ; Xingfu LI ; Shaoxian HU ; Nanping YANG ; Yi TAO ; Jianhua XU ; Anbin HUANG ; Lindi JIANG ; Chunde BAO
Chinese Journal of Rheumatology 2011;15(10):671-676
ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)%-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)%-year,P<0.05] and that of the MTX only group[(5.08±11.10)%-year,P<0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P<0.05).The ACR20 response rate of the combined group(80.4%) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1%,P<0.05) and the MTX group(56.7%,P<0.01 ).The ACRS0 response rate of the combined group(53.6%) was significantly higher than that of the MTX group(30.8%,P<0.01 ).The ACR70 response rate of the combined group was 27.7%,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8%) and MTX group (7.7%,P<0.05or P<0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9%) was significantly high than that of the MTX group(28.8%,P<0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.
5.Role of tumor necrosis factor-αin the regulation of T-type calcium channel current in HL-1 cells
Fang RAO ; Yumei XUE ; Xiyong YU ; Wei WEI ; Fangzhou LIU ; Hui YANG ; Sujuan KUANG ; Shaoxian CHEN ; Dingzhang XIAO ; Zhixin SHAN ; Jiening ZHU ; Zhi XIE ; Shulin WU ; Chunyu DENG
Chinese Journal of Pathophysiology 2016;32(8):1534-1534
AIM:Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation ( AF) .Al-though tumor necrosis factor ( TNF)-αlevels are increased in patients with AF , the role of TNF-αin the pathogenesis of AF remains unclear.Recent research has revealed that T-type Ca2+currents ( ICa,T ) play an important role in the pathogenesis of AF .METH-ODS:In this study , we used the whole-cell voltage-clamp technique and biochemical assays to explore the role of TNF-αin the regula-tion of ICa,T in atrial myocytes.RESULTS:We found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased , while TNF-αexpression levels were increased , in human atrial tissue from patients with AF .In murine atrial myocyte HL-1 cells, after cultured for 24 h, 12.5, 25 and 50 μg/L TNF-αsignificantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner .The peak current was reduced by the application of 12.5 or 25μg/L TNF-αin a concentration-dependent manner [from ( -15.08 ±1.11) pA/pF in controls to ( -11.89 ±0.83) pA/pF and (-8.54 ±1.55) pA/pF in 12.5 and 25 μg/L TNF-αgroups, respectively].TNF-αapplication also inhibited voltage-dependent inactivation of ICa,T shifted the inactivation curve to the left .CONCLUSION:These results suggest that TNF-αis involved in the path-ogenesis of AF, probably via decreasing ICa,T function in atrium-derived myocytes through impaired channel function and down -regula-tion of channel protein expression .This pathway thus represents a potential pathogenic mechanism in AF .
6.New strategies for CAR-T cell in the treatment of solid tumors
WU Shaoxian ; XIA Jianchuan ; JIANG Jingting
Chinese Journal of Cancer Biotherapy 2018;25(9):854-858
Chimeric antigen receptor modified T (CAR-T) cell, a novel adoptive immunotherapy strategy, has been used successfully against hematological tumors. However, in solid tumors, due to multiple immunosuppressive cells, immunosuppressive molecules, and extracellular matrix play a suppressive role in the cytotoxic effects of migrating CAR-T cells and severely inhibit the antitumor efficacy of CAR-T cells in the tumor microenvironment of solid tumors. Simultaneously, tumor heterogeneity, lacking proper tumor antigens, poor homing ability at solid tumor sites, along with off-target effect, resulting in poor therapeutic effect of CAR-T cells in solid tumors. Compared with hematological tumors, solid tumors have complex biological characteristics, and thus targeted strategies are demanded to ensure long-term efficacy of CAR-T cells against tumors. This review makes a summary of the development of CAR-T cells, the confusion in solid tumors and the progress of treatment strategies.
7.The research of brain glioma therapy for nude mouse using transgenic human umbilical cord mesenchymal stem cells overexpressing TRAIL
Wencui SUN ; Danying YI ; Kejing WU ; Yonggang ZHANG ; Mowen LAI ; Qiongxiu ZHOU ; Feng MA ; Yongjun CHEN ; Shaoxian LIU ; Bo CHEN
Chinese Journal of Blood Transfusion 2021;34(6):567-573
【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×106 cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×106 cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34+, CD45+, and HLA-DR+ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.
8.Study on the sensitivity of a volumetric modulated arc therapy plan verification equipment on multi-leaf collimator opening and closing errors and its gamma pass rate limit.
Jinyou HU ; Lian ZOU ; Shaoxian GU ; Ningyu WANG ; Fengjie CUI ; Shengyuan ZHANG ; Chu'ou YIN ; Yunzhu CAI ; Chengjun GOU ; Zhangwen WU
Journal of Biomedical Engineering 2023;40(1):133-140
To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans
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Radiotherapy, Intensity-Modulated
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Immune Tolerance
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Nasopharyngeal Carcinoma
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ROC Curve
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Nasopharyngeal Neoplasms/radiotherapy*