1.In vitro study and molecular modeling on 17-AAG-Ioaded polymethyl methacrylate bone cement for multiple myeloma
Xiangjun SHI ; Boran DU ; Xinru DU ; Wenming CHEN
Chinese Journal of Orthopaedics 2016;36(15):988-994
Objective To explore the possibility of polymethyl methacrylate (PMMA) bone cement as the carrier for lipophilic drugs through in vitro cytotoxicity study and molecular modeling with PMMA and 17-allylamino-17-demethoxy-geldanamycin (17-AAG) loaded PMMA bone cement.Methods The 17-AAG loaded bone cement was made by mixing method.In vitro antitumor activity with MTT assay for PMMA,17-AAG,the 24 h and 48 h released solution of 17-AAG loaded PMMA bone cement were evaluated.Through Material Studio 5.0,the interaction between 17-AAG and PMMA through the model of Amorphous Cell and energy optimization of Forcite was explored.Results The inhibition ratio of MMA for tumor cells is 9.21%±0.06% with 50 μmol/L.The 24 h released solution of 17-AAG loaded PMMA bone cement (17-AAG∶ PMMA=1∶ 4 000) inhibits the tumor cells 66.15%±0.43% which has a quick released influence on 17-AAG.The inhibition of 24 h released solution of 17-AAG-loaded PMMA bone cement (17-AAG∶PMMA=1 ∶ 1 000,1∶2 000) shows no significance compared with PMMA released solution (P<0.05).The 48 h released solution of 17-AAG-PMMA (17-AAG∶ PMMA=1∶ 1 000,1∶2 000,1∶4 000) inhibits U26630.25%±4.47%,30.24%±3.42%,50.52%±5.20%,with a significant difference with PMMA.The molecular model showed that the interaction between 17-AAG and PMMA was van der Waalz bonds,which drove 17-AAG inside or on the surface of PMMA bone cement.Conclusion PMMA bone cement can be used as a carrier for lipophilic drugs.It has antitumor activity and influences the release of 17-AAG with different ratio,for example it has a sustained-released influence on 17-AAG in 17-AAG-PMMA (17-AAG∶PMMA=1 ∶ 1 000,1∶2 000).Molecular model implies that 17-AAG exists inside or on the surface the PMMA bone cement through van der Waalz bonds.
2.An epidemiologyical study on Miao drum and hypertension in Miao women
Jiashun LUO ; Jianlin DU ; Yufeng CHEN ; Xuemei LUO ; Xiangjun WU
Chongqing Medicine 2014;(19):2467-2469,2473
Objective To study the relationship between Miao drum and hypertension in the Miao women of the countryside . Methods A survey of blood pressure measurement and questionnaire investigation were conducted among 1 069 Miao females ,by using cluster multistage sampling in countryside of Hunan ,Hubei ,Chongqing ,and Guizhou .A case-control analysis for 226 cases with new diagnosed hypertension and 226 controls with normal blood pressure .Results Among 1 069 sample ,the standardized prevalence rate of hypertemion was 24 .5% .There were significant differences in the prevalence rates of hypertension between the different age groups(χ2 =174 .46 ,P<0 .01) .The single factor logistic regression analysis(OR=0 .383 ,95% CI:0 .262-0 .558)and multi-conditional logistic regression analysis(OR=0 .379 ,95% CI:0 .255-0 .565)showed that Miao drum was probably protective factor for hypertension in the Miao women of the countryside .Conclusion Miao drum was probably protective factor for hyperten-sion in the Miao women of the countryside in Hunan ,Hubei ,Chongqing ,and Guizhou .Long-term adherence to participate in miao drum exercise may prevent high blood pressure .
3.Association of ApoB/A-1 ratio with type 2 diabetes mellitus in Chinese Han ethnic population:A cross-sectional study
Chang LIU ; Yongming HE ; Xiaojiao DU ; Dongping CAI ; Xiangjun YANG
Chinese Journal of Endocrinology and Metabolism 2017;33(4):321-325
In this cross-sectional study, consecutive Chinese Han ethnic inpatients in the Division of Cardiology, the First Affiliated Hospital of Soochow University from January 1, 2010 to December 31, 2013 were included. According to the exclusion criteria, 9 587 patients [1 604 with type 2 diabetes mellitus (T2DM) and 7 983 without T2DM]were obtained for final analysis. Logistic regression model was used to analyze the association of ApoB/A-1 ratio with T2DM and the possible interactions between ApoB/A-1 ratio and other risk factors. The results showed that the distribution of ApoB/A-1 ratio was positively skewed in Chinese Han ethic population. The median of ApoB/A-1 ratio of female was lower than that of male (0.68 vs 0.73,P<0.01). In all groups, the proportion of T2DM was increased with the raised ApoB/A-1 ratio. By the stratification analyses of sex, age, coronary artery disease, and the use of statins, ApoB/A-1 ratio was still correlated with T2DM. There existed significant interactions between ApoB/A-1 ratio and the smoking status or creatinine in T2DM.
4.Effect of ERK1/2 on ischemic preconditioning in diabetic rat hearts
Caiyun MA ; Like ZHANG ; Fenghe DU ; Lingqiao LU ; Hongxia WANG ; Xiangjun ZENG ; Ping FU ; Qingqing MAN
Chinese Journal of Pathophysiology 1986;0(01):-
AIM: To test the effect of ERK1/2 on ischemic preconditioning (IPC) in diabetic rat hearts. METHODS: The diabetic rat model was made with alloxan. After eight weeks, 24 rats were divided into 4 groups: non-diabetic IPC rats (group A); non-diabetic non-IPC rats (group B); diabetic IPC rats (group C); diabetic non-IPC rats (group D). ECGⅡ lead, left ventricular development pressure (LVDP), and first derivative of LVDP ~(?dp/dt_~max ) were recorded. Myocardial phosphorylation of extracellular signal regulated kinases1/2 (ERK1/2) was detected by Western-blotting. RESULTS: (1) The ventricular arrythmia score was significantly lower in group A than that in group C (P
5.Expression and functional role of HERG1, K+ channels in leukemic cells and leukemic stem cells.
Huiyu, LI ; Liqiong, LIU ; Tiannan, GUO ; Jiahua, ZHANG ; Xiaoqing, LI ; Wen, DU ; Wei, LIU ; Xiangjun, CHEN ; Shi'ang, HUANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(3):257-60
In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
6.Application of Essential Anatomy software in the clinical practice teaching of spinal surgery
Zhijun XIN ; Xiangjun XIN ; Sheng YE ; Weijun KONG ; Qian DU ; Jun AO ; Wenbo LIAO
Chinese Journal of Medical Education Research 2020;19(10):1186-1189
In this paper, the current situation and existing problems of spinal surgery practice are analyzed and summarized. Combined with the review of the structure and function of spinal region, we have expounded the application and advantages of Essential Anatomy software in the clinical practice teaching of spinal surgery. This software has a friendly interface, simple operation, real content, intuitive and visual model, and it can provide videos and slice function, which makes the original complex and abstract spinal anatomy practice content become novel and vivid, and greatly deepens doctors' understanding of the structure, function, movement and the disease pathogenesis of spinal region. At the same time, it also greatly mobilizes the learning interest and initiative of the clinical practice doctors, and improves the effect of clinical practice.
7.Analysis of risk factors for multiple myeloma combined with radiation-based sarcopenia
Jie REN ; Lei QI ; Xingchen YAO ; Jinzhou WANG ; Xiangjun SHI ; Wenming CHEN ; Xinru DU
Chinese Journal of Orthopaedics 2023;43(9):567-573
Objective:To analyze the risk factors of radiation-based sarcopenia in patients with multiple myeloma (MM).Methods:A total of 185 clinical and imaging data of patients with MM admitted to Beijing Chaoyang Hospital from September 2009 to October 2019 were retrospectively analyzed. The area of the erector spinae muscle and the area of fatty infiltration (FI) in the fascial compartment were measured by Image-pro Ρlus software, and the area of the fat-free erector spinae muscle and the fat infiltration rate (FI%) were calculated. Sarcopenia was defined as an erector spinae area of less than 3 197 mm 2 in males and 2 895 mm 2 in females. The differences in gender, age, body mass index, disease duration, hemoglobin, leukocytes, platelets, albumin, serum calcium, lactate dehydrogenase, serum creatinine, alkaline phosphatase, M-protein, serum β 2-microglobulin, bortezomib chemotherapy, receipt of stem cell transplantation, osteopathy, stage, recurrence and progression of MM between the sarcopenia group and the normal muscle group were compared. Binary logistic regression was used to analyze the independent risk factors of sarcopenia in MM patients. Kaplan-Meier curves were drawn to compare the survival rates between the two groups. Results:53.0% (98/185) of MM patients were complicated with sarcopenia: there were 30 males, whose fat-free erector spinae area was 25.0±6.0 cm 2, the FI of erector spinae was 12.0±4.8 cm 2, and the FI% was 31.5%±12.0%, while there were 68 females, whose fat-free erector spinae area was 22.7±4.2 cm 2, the FI of erector spinae was 10.7±4.1 cm 2, and the FI% was 30.2%±9.8%. 47.0% (87/185) of MM patients had normal muscle mass: there were 62 males, whose fat-free erector spinae area was 40.6±6.5 cm 2, the FI of erector spinae was 9.3±4.8 cm 2, and the FI% was 17.9%±7.4%, while there were 25 females, whose fat-free erector spinae area was 33.6±5.1 cm 2, the FI of erector spinae was 9.9±3.0 cm 2, and the FI% was 21.9%±5.7%. There were statistically significant differences in the gender composition ratio (χ 2=30.47, P<0.001), hemoglobin ( t=-2.73, P=0.007), serum creatinine ( Z=-2.26, P=0.024), receipt of stem cell transplantation (χ 2=4.32, P=0.038), and MM recurrence and progression (χ 2=3.85, P=0.050) between the two groups. However, there were no significant differences in age, body mass index, course of disease, leukocytes, platelets, albumin, alkaline phosphatase, lactate dehydrogenase, serum calcium, M-protein, serum β 2-microglobulin, bortezomib chemotherapy, osteopathy or MM stage ( P>0.05). Binary logistic regression analysis showed that female was an independent risk factor for sarcopenia in MM patients. The survival rates at 2, 3, 4, and 5 years were 87.9%, 71.8%, 64.4%, and 53.7% in the sarcopenia group, and 92.1%, 75.8%, 66.8%, and 66.8% in the normal muscle group, respectively, with no statistically significant differences ( HR=0.71, P=0.364). Conclusion:The incidence of radiation-based sarcopenia in MM patients is 53.0%. Low hemoglobin and blood creatinine levels, not receiving stem cell transplantation, and recurrence or progression of MM are associated with sarcopenia in MM patients, and female is an independent risk factor for sarcopenia in MM patients.
8.Expression and Fuactional Role of HERG1, K+ Channels in Leukemic Cells and Leukemic Stem Cells
Huiyu LI ; Liqiong LIU ; Tiannan GUO ; Jiahua ZHANG ; Xiaoqing LI ; Wen DU ; Wei LIU ; Xiangjun CHEN ; Shi'ang HUANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(3):257-260
In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
9.Discussion on Effects of Electroacupuncture on Intestinal Flora and Serum Inflammation Factors in Rheumatoid Arthritis Rabbits Based on"Gut-joint"Axis
Cui LIU ; Xiaozheng DU ; Weiyao JING ; Chenghong SU ; Limei LIU ; Bo YUAN ; Xinghua ZHANG ; Fengfan ZHANG ; Ping CHEN ; Xiangjun LI ; Haidong WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):124-131
Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.
10.Design of the key links and implementation path of management in the clinical comprehensive evaluation of drug
Wenwen DU ; Wei XU ; Xiangjun ZHU
China Pharmacy 2024;35(12):1413-1418
OBJECTIVE To design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China, and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug. METHODS Based on the relevant experience of drug evaluation management in typical countries regions at home and abroad, the discussion was performed and the management mechanism was designed from seven aspects, such as funding source, selection of topics, staff management, information management, data management, evaluation process and quality assessment. RESULTS & CONCLUSIONS In terms of funding sources, the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics, a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation, and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management, the specialty of team members should be specified, and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management, the national/provincial basic informational platform should be established, and the registration system should be established. In terms of data management, a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process, the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment, quality assessment and reward and punishment mechanism for project completion,that consider the quality of management first while focusing on the technical quality, can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent, and help improve the quality of clinical comprehensive evaluation projects for drugs.