1.Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.
Dongyuan SU ; Biao HONG ; Shixue YANG ; Jixing ZHAO ; Xiaoteng CUI ; Qi ZHAN ; Kaikai YI ; Yanping HUANG ; Jiasheng JU ; Eryan YANG ; Qixue WANG ; Junhu ZHOU ; Yunfei WANG ; Xing LIU ; Chunsheng KANG
Acta Pharmaceutica Sinica B 2025;15(7):3632-3645
The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
2.Application of deep learning technology in the diagnosis of gastrointestinal stromal tumors
Tingting CHEN ; Fan YANG ; Zeyang LI ; Shixue XU ; Fei YANG ; Xiang LIU
Journal of China Medical University 2024;53(2):178-181
Gastrointestinal stromal tumor(GIST),with a certain malignant potential,are currently the most common subepithelial tumors of the gastrointestinal tract.Early diagnosis and prediction of malignant potential are very important for the formulation of a treatment plan and determining the prognosis of GIST.Deep learning technology has made significant progress in the diagnosis of digestive tract diseases,and it can also effectively assist physicians in diagnosing GIST and predicting their malignant potential,preoperatively.The application of deep learning technology in the diagnosis of GIST includes CT,gastrointestinal endoscopy and endoscopic ultrasound.This paper aims to review the application of deep learning technology in the diagnosis and prediction of malignant potential of GIST.
3.Effect of paracrine of hypoxia preconditioned umbilical cord mesenchymal stem cells on function of osteoblasts
Xiaoli XU ; Shixue GAO ; Ying LIU ; Lidong ZHOU ; Desheng YANG
Military Medical Sciences 2016;40(4):289-293
Objective To study the paracrine effect of hypoxic preconditioned umbilical cord mesenchymal stem cells (UCMSCs) on the proliferation,migration and osteogenic differentiation of osteoblasts.Methods UCMSCs were cultured under hypoxia and normal oxygen condition before two UCMSCs conditioned media were obtained.After that,MG-63 cells were cultured in three groups:hypoxia conditioned medium group,normoxia conditioned medium group and DMEM control group.The proliferation of MG-63 cells was detected by mosmann tetrazoline colorimetry( MTT) method after 1,3 and 5 days.The migratory ability of MG-63 cells was detected by scratch assay .After 21 days′culture , the formation of osteogenic calcium nodules was detected by Alizarin red staining.ELISA method was used to detect the content of vascular endothelial growth factor ( VEGF) in hypoxia and normoxia conditioned medium.Results The MTT test showed that the proliferation ability of MG-63 cells in hypoxia conditioned medium group and normoxia conditioned medium group was greater than in the DMEM control group.The difference was statistically significant ( P <0.05).Furthermore, the proliferation ability of cells in hypoxia conditioned medium group were much greater than cells in normoxia culture medium group.The difference was statistically significant (P<0.05).Scrath assay showed that the migratory ability of MG-63 cells in hypoxia conditioned medium group and normoxia conditioned medium group was greater than cells in DMEM control group,and cells in hypoxia conditioned medium group was much greater than cells in normoxia conditioned medium group. After 21 days′culture,we found that the number of calcium nodules was the largest in hypoxia conditioned medium group, followed by normoxia conditioned medium group and DMEM control group.ELISA showed that the content of VEGF in hypoxia conditioned medium was higher than that in normoxia conditioned medium and the difference was statistically significant (P<0.01).Conclusion The paracrine function of UCMSCs can be enhanced by hypoxia,thus improving the proliferation,migration and osteogenic differentiation of osteoblasts.
4.Analysis on the level of financing, structure and variation trend of total health expenditure from 1995 to 2011 in Xinjiang
Yang LU ; Elim MARDAN ; Yanan GONG ; Chen LU ; Shixue LI
Chinese Journal of Hospital Administration 2015;31(1):33-36
Objective To analyze the principal components and trends of total health expenditure from 1995 to 2011 in Xinjiang,in order to put forward policy recommendations to improve health financing.Methods Calculating the total health expenditure in Xinjiang using the financing source method,and analyzing the calculation results.Results Total health expenditure increase in Xinjiang averaged 14.75% from 1995 to 2011.The total health expenditure in Xinjiang and per capita health expenses maintained a growing trend,and the level of financing was higher than regional economic development,but the health consumption elasticity coefficient was unstable; Residents' individual health burden was gradually decreasing,the health expenses of financing structure were relatively reasonable; Urban and rural residents health care spending grew faster than the per capita income,and the proportion in people's living consumption was found rising.Conclusion It is recommended to continue with the health reform,make full use the policy of strategic health support to Xinjiang,promote primary health service equity,develop economy and improve the urban and rural income,strengthen social health care security systems,tighten macro-control and curb the fast rising trend of health expenses.
5.Implement the major hospital indexes examination using clinical pathway as an opportunity
Yang LU ; Feng XI ; Ajuan GUO ; Chen LU ; Shixue LI
Chinese Journal of Primary Medicine and Pharmacy 2014;21(2):168-170
Objective To explore the method of the major hospital indexes examination using clinical pathway as an opportunity.Methods Based on the material of our hospital from 2008 to 2010,reference the data of the same level hospital in Xinjiang Uygur Autonomous Region,we set the benchmark and formulated the examination standard of three examination indexes:average length of stay (ALOS),average hospitalization expense and drug proportion.Meanwhile,we took the subentry incentives to give the corresponding reward to clinical departments according to the decreases rate compared with the benchmark monthly.Results ALOS,average hospitalization expense and drug proportion of department and the whole hospital were obviously decreased compared with the same period last year,and the differences were statistically significant (Medical system:t =27.479,14.462,11.362,all P < 0.01 ; Surgical system:t =18.944,16.029,12.071,all P < 0.01).Conclusion After using the examination methods and combining clinical pathway,the effects are obvious,which can effectively shorten ALOS,reduce average hospitalization expense and drug proportion,so as to relieve the patients' economic burden.
6.THE GLYCEMIC INDEX OF COMMON CEREALS AND TUBERS PRODUCTS
Yuexin YANG ; Hongmei CUI ; Yan WANG ; Shixue XIANG ; Lianda YU ; Shuiying ZHOU ;
Acta Nutrimenta Sinica 1956;0(02):-
Objective: To determine the glycemic index of common cereals and tubers products in China, and to examine the relationship among the response of blood glucose and the type of carbohydrate, food processing, and food digestion and absorption. Methods: 8-12 subjects in each group were assigned randomly. Fasting blood sugar was measured first and then 50 g glucose or the test meal was taken, and blood glucose was measured again 2 hours later.The food used in the test meal contained the carbohydrate content, equivalent to 50 g glucose according to the Table of Food Composition (1991). 50 g glucose was used as the control food. GI of test meal was calculated by Wolver method. Results:The study showed the glycemic index of common foods, including 9 sugars, 62 cereals and tubers products. Conclusion: The different foods with same amount of carbohydrate have different GI. The characteristics of starch and food processing are more important in predicting GI value, and GI varies also with the rate of starch digestion and hydrolysis in man.

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