1.Mechanistic Study of ATO and MET Synergistically Promoting Apoptosis in Leukemia Cells
Meng LIU ; Li-Wen-Hui HUANG ; Xiao-Hui SI ; Xin-Qing NIU
Journal of Experimental Hematology 2025;33(6):1609-1616
Objective:To study the mechanism of arsenic trioxide(ATO)combined with metformin(MET)in promoting apoptosis of leukemia cells.Methods:CCK-8 method was used to detect the viability of leukemia cell line KG1a,K562,and THP1 cells treated by ATO monotherapy,MET monotherapy,and ATO combined with MET.Flow cytometry was used to detect cell cycle and apoptosis.RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes.Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.Results:Compared with the ATO monotherapy group,ATO combined with MET significantly inhibited the growth of KG1a,K562 and THP1 cells,and the difference in KG1a cells was more statistically significant.The combination of the two drugs induced KG1a cell cycle arrest,promoted apoptosis,increased the expression of autophagy-related protein LC3B and P62,up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes,as well as the expression of LKB1/AMPK pathway-related proteins,and down-regulated the expression of PI3K/Akt pathway-related proteins.Conclusion:ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.
2.Mechanistic Study of ATO and MET Synergistically Promoting Apoptosis in Leukemia Cells
Meng LIU ; Li-Wen-Hui HUANG ; Xiao-Hui SI ; Xin-Qing NIU
Journal of Experimental Hematology 2025;33(6):1609-1616
Objective:To study the mechanism of arsenic trioxide(ATO)combined with metformin(MET)in promoting apoptosis of leukemia cells.Methods:CCK-8 method was used to detect the viability of leukemia cell line KG1a,K562,and THP1 cells treated by ATO monotherapy,MET monotherapy,and ATO combined with MET.Flow cytometry was used to detect cell cycle and apoptosis.RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes.Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.Results:Compared with the ATO monotherapy group,ATO combined with MET significantly inhibited the growth of KG1a,K562 and THP1 cells,and the difference in KG1a cells was more statistically significant.The combination of the two drugs induced KG1a cell cycle arrest,promoted apoptosis,increased the expression of autophagy-related protein LC3B and P62,up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes,as well as the expression of LKB1/AMPK pathway-related proteins,and down-regulated the expression of PI3K/Akt pathway-related proteins.Conclusion:ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.
3.Inhibitory Effect of Metformin and Arsenic Trioxide on KG1a Cell Proliferation
Meng LIU ; Shu-Min GUI ; Ming-Ming FENG ; Hui LIU ; Xiao-Hui SI ; Xin-Qing NIU
Journal of Experimental Hematology 2024;32(1):66-70
Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P<0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P<0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.
4.Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma (version 2024)
Zhu GUO ; Chao WANG ; Hongfei XIANG ; Zhongqiang CHEN ; Liang CHEN ; Tongwei CHU ; Shucai DENG ; Jian DONG ; Xinru DU ; Shiqing FENG ; Baorong HE ; Xijing HE ; Jianzhong HU ; Yong HAI ; Qingquan KONG ; Guiqing LIANG ; Qi LIAO ; Zhongjun LIU ; Shaoyu LIU ; Baoge LIU ; Xiaoguang LIU ; Weishi LI ; Li LI ; Fang LI ; Bin LIN ; Shibao LU ; Tao NIU ; Zhenli QIAO ; Dike RUAN ; Yueming SONG ; Haipeng SI ; Jun SHU ; Zhongyi SUN ; Qing WANG ; Zili WANG ; Huan WANG ; Hongli WANG ; Yan WANG ; Xiaolin WU ; Zhanyong WU ; Jinglong YAN ; Tengbo YU ; Qiang ZHANG ; Guoqing ZHANG ; Xuesong ZHANG ; Fengdong ZHAO ; Jie ZHAO ; Zhaomin ZHENG ; Qingsan ZHU ; Dingjun HAO ; Bohua CHEN
Chinese Journal of Trauma 2024;40(12):1057-1070
Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.
5.Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma (version 2024)
Zhu GUO ; Chao WANG ; Hongfei XIANG ; Zhongqiang CHEN ; Liang CHEN ; Tongwei CHU ; Shucai DENG ; Jian DONG ; Xinru DU ; Shiqing FENG ; Baorong HE ; Xijing HE ; Jianzhong HU ; Yong HAI ; Qingquan KONG ; Guiqing LIANG ; Qi LIAO ; Zhongjun LIU ; Shaoyu LIU ; Baoge LIU ; Xiaoguang LIU ; Weishi LI ; Li LI ; Fang LI ; Bin LIN ; Shibao LU ; Tao NIU ; Zhenli QIAO ; Dike RUAN ; Yueming SONG ; Haipeng SI ; Jun SHU ; Zhongyi SUN ; Qing WANG ; Zili WANG ; Huan WANG ; Hongli WANG ; Yan WANG ; Xiaolin WU ; Zhanyong WU ; Jinglong YAN ; Tengbo YU ; Qiang ZHANG ; Guoqing ZHANG ; Xuesong ZHANG ; Fengdong ZHAO ; Jie ZHAO ; Zhaomin ZHENG ; Qingsan ZHU ; Dingjun HAO ; Bohua CHEN
Chinese Journal of Trauma 2024;40(12):1057-1070
Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.
6.Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats.
Li-Ling SI ; Lu NIU ; Xiao-Yan WANG ; Hui ZHANG ; Ming-Liang ZHANG ; Shuang XU ; Xian-Qing REN ; Jin-Fa TANG ; Wei-Xia LI
China Journal of Chinese Materia Medica 2023;48(21):5915-5931
This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats
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Animals
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IgA Vasculitis/drug therapy*
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Monoterpenes
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Administration, Oral
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Liquid Chromatography-Mass Spectrometry
7.Feasibility of single-stage stent implantation following rotational atherectomy combined with TAVR.
Mo Yang WANG ; Guang Yuan SONG ; Guan Nan NIU ; Yun Qing YE ; Yu Bin WANG ; Tong LUO ; Si Yong TENG ; Yong Jian WU
Chinese Journal of Cardiology 2021;49(1):66-70
Objective: To explore the feasibility of the single-stage stent implantation following rotational atherectomy combined with transcatheter aortic valve replacement (TAVR) in treating patients with severe aortic stenosis(AS) and severe calcified coronary artery stenosis. Methods: Three patients who received single-stage stent implantation following rotational atherectomy combined with TAVR in Fuwai hospital from April to October 2019 were included in this retrospective analysis. Clinical and anatomical features (including echocardiography and aortic CT) of the patients were collected, efficacy and safety of this operation strategy were observed and 6 months follow up results were summarized. Results: Three patients (2 females, 66-80 years old) were included. The mean Society of Thoracic Surgeons (STS) risk score was 7.8%. The mean maximum velocity of aortic valve was 4.4 m/s, the mean transvalvular pressure gradient was 53.2 mmHg (1 mmHg=0.133 kPa), mean left ventricular ejection fraction (LVEF) was 48.6%. All three patients had severe calcified coronary artery stenosis: left anterior descending artery (LAD, n=2) and left main coronary artery (LM, n=1), requiring rotary grinding. The mean SYNTAX score was 20. All the procedures were performed through transfemoral access. After aortic valve crossing, all coronary lesions were successfully treated with stent implantation following rotational atherectomy, transfemoral TAVR was then immediately performed with a self-expandable Venus-A valve. One patient underwent"valve-in-valve"implantation due to the high-implantation position of the first valve. The procedures were completed without complications in all the three patients. The immediate effect was satisfactory. Echocardiography results showed that the mean maximum velocity of aortic valve was 2.1 m/s, mean gradient was 9.3 mmHg, and mean LVEF was 59% after the procedure. There was no death and revascularization during the 6 months follow-up. Conclusion: In patients with severe calcified coronary artery and severe AS with high risk of cardiac surgery, the single-stage stent implantation following rotational atherectomy combined with TAVR is feasible and results are satisfactory in this patient cohort.
8.Synthesis and anti-inflammatory activity of novel isobutyl benzophenone derivatives
Lu YANG ; Hang SHI ; Yun-lan LI ; Xi CHEN ; Si-qing NIU ; Xiao-zhi QIAO ; Jia-qi MAI ; Qing-shan LI
Acta Pharmaceutica Sinica 2018;53(2):256-262
Twenty target compounds were synthesized by the reduction reaction of HUANG Minglong and Friedel-Crafts acylation reaction in this study. The inhibitory effects of the new compounds were tested on NO production in LPS-induced mouse macrophage RAW264.7 cells, a cellular inflammation model. The structure-activity relationships were discussed. The structures of target compounds were confirmed by ESI-MS, 1H NMR and 13C NMR. In vitro activity experiments showed that 18 compounds had certain anti-inflammatory effects at the concentration of 40 μmol·L-1, of which 9a, 8b, 7c and 9c showed strong anti-inflammatory activities, and IC50 of 7c and 9c were comparable to the positive control drug ibuprofen.
9.Correlation between Ultrasound-guided Diffuse Optical Tomography and Hypoxia-inducible Factor-1Α of Breast Cancer.
Si-hua NIU ; Qing-li ZHU ; Yu-xin JIANG ; Jia-an ZHU ; Meng-su XIAO ; Shan-shan YOU ; Wei-xun ZHOU ; Yu XIAO
Acta Academiae Medicinae Sinicae 2016;38(3):341-345
Objective To investigate the correlation between ultrasound-guided diffuse optical tomography (US-DOT) and hypoxia-inducible factor-1Α (HIF-1Α) of breast cancer. Methods Totally 69 patients with pathologically confirmed breast cancer underwent preoperative conventional breast ultrasonography examinations and US-DOT at Peking Union Medical College Hospital From October 2007 to February 2010 were enrolled in this study.After surgery,immunohistochemical staining of HIF-1Α and CD34 were performed,and the differences of total hemoglobin concentration (THC) and microvessel density (MVD) between HIF-1Α positive and negative groups were analyzed. Results HIF-1Α was positive in 12 cases (17.4%) and negative in 57 cases (82.6%). The average THC and MVD of HIF-1Α-positive cases were (274.763±77.661) Μmol/L and (33.8±10.8)/0.2 mm(2) respectively. The average THC and MVD of HIF-1Α-negative cases were (228.059±65.760)Μmol/L and (28.4±7.4)/0.2 mm(2). MVD(t=2.049,P=0.04) and THC(t=2.167,P=0.034) of HIF-1Α-positive group were significantly higher than those of HIF-1Α-negative group. Conclusions HIF-1Α can promote tumor angiogenesis and thus increase the blood supply and THC. As an indicator of tumor blood supply,THC can indirectly reflect the angiogenic activity of breast cancer.
Breast Neoplasms
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diagnostic imaging
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metabolism
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Female
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit
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metabolism
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Neovascularization, Pathologic
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Tomography, Optical
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Ultrasonography, Mammary
10.Causes of Missed Diagnosis and Misdiagnosis of Abdominal Organ Lesions in Preoperative Transabdominal Ultrasound
Zhen-Zhen LIU ; Meng YANG ; Yi-Xiu ZHANG ; Qing DAI ; Jian-Chu LI ; Jie HAN ; Kang-Ning LI ; Xiao-Yan ZHANG ; Wen XU ; Si-Hua NIU ; Hong-Yan WANG
Medical Journal of Peking Union Medical College Hospital 2015;(3):173-178
Objective To analyze the causes of missed diagnosis and misdiagnosis of abdominal organ le -sions through reviewing preoperative transabdominal ultrasound reports .Methods Data of the patients who re-ceived abdominal operation for abdominal organ lesions ( including liver , gallbladder , biliary tract , pancreas , spleen, kidney, adrenal gland, and appendix) in Peking Union Medical College Hospital within the period from March 1 to August 31 in 2013 were exported from pathological workstation .The preoperative ultrasound reports of these patients were reviewed .The missed diagnosis and misdiagnosis cases were recorded , and causes of the mis-takes were analyzed .Results Altogether 58 cases of missed diagnosis or misdiagnosis were identified from 1081 ultrasound reports (5.37%, 58/1081), including 6 liver lesions (5.77%, 6/104, all misdiagnosed), 6 gall-bladder and biliary tract lesions ( 1.30%, 6/462 , 5 missed and 1 misdiagnosed ) , 14 pancreatic lesions (19.72%, 14/71, all missed), 20 kidney and adrenal lesions (6.47%, 20/309, 11 missed and 9 misdiag-nosed), and 12 appendical lesions (16.00%, 12/75, 11 missed and 1 misdiagnosed).The average maximum diameter of the missed nodular lesions was significantly smaller than that of the misdiagnosed lesions ( P =0.001 ) .Conclusions Missed diagnosis and misdiagnosis of ultrasound are attributable to various causes , inclu-ding the nature , location , and size of abdominal organ lesions and the limitation of transabdominal ultrasound technology .The clinical ultrasound examination should be carried out very carefully and thoroughly .Ultrasound radiologists should have a thorough understanding of characteristics of different organ lesions and the limitation of ultrasound technique , in order to avoid missed diagnosis and misdiagnosis in clinical practice .

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