1.Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells
Yuan XIA ; Qingling JIANG ; Xiaoting WANG ; Minjing LI ; Qiusheng ZHENG ; Defang LI
Journal of China Pharmaceutical University 2023;54(6):757-768
The aim of this study was to investigate the effect of norcantharidin (NCTD) on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231.Western blot was used to detect the effect of NCTD on the expression levels of apoptosis-related proteins Bax/Bcl-2, cleaved-PARP/PARP/PARP, cleved-caspase-9, cleaved-caspase-3 and MCL-1 in MDA-MB-231 cells.Also, the expression levels of autophagy-related proteins LC3-II/LC3-I, Parkin and PINK1 in MDA-MB-231 cells were measured by Western blot.Flow cytometry was used to measure the effect of NCTD on the changes of mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS).The effect of NCTD on autophagy flow in cells expressing mCherry-EGFP-LC3 was detected by a confocal microscope.Moreover, the effects of NCTD combined with chloroquine (CQ) or 3-methyladenine (3-MA) on the apoptosis of MDA-MB-231 cells were detected by flow cytometry.The results showed that NCTD significantly increased the expression levels of Bax/Bcl-2, cleaved-PARP/PARP, cleaved-caspase-9, cleasved-caspase-3 and LC3-II/LC3-I proteins, and promoted the mitochondrial translocation of Parkin, and blocked the autophagic flow in MDA-MB-231 cells. Moreover, NCTD combined with CQ accelerated apoptosis, while NCTD combined with 3-MA decreased apoptosis.These results suggest that NCTD can induce autophagy accumulation and lead to apoptosis of MDA-MB-231 cells.
2.Clinical comparative analysis of domestic 16-row and imported 8-row mobile CT head scans
Zhiqiang ZHANG ; Quanle ZHENG ; Haifeng WANG ; Lei YANG ; Fei LI ; Boyun DING ; Li ZHANG ; Shunyi ZHOU ; Yaxin JING ; Zhenfang WANG ; Fei GAO ; Qiusheng DAI ; Ruxiang XU
Chinese Journal of Neuromedicine 2020;19(4):376-380
Objective:To compare the efficacy and safety of domestic 16-row and imported 8-row mobile CT in clinics.Methods:A total of 1469 patients accepted domestic 16-row mobile CT head scans (1604 times) from March 2017 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army and Langfang Aidebao Hospital; and 15510 patients accepted imported 8-row mobile CT head scans (24994 times) from January 2016 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army. All patients underwent horizontal plain and enhanced head scans, cerebral CT angiography (CTA), and helical 3D imaging; and the imaging quality, operating power consumption, computed tomography dose index volume (CTDIvol) and stability within scanning volume ranges under different scanning modes of the two CT scans were compared. Results:(1) Imaging quality: the horizontal scanning of domestic 16-row mobile CT could clearly display low-density tissues such as the eyeball, optic nerve, brain stem, sulcus and cerebral gyrus; the imaging quality of both CT scans in patients with traumatic subdural hematoma and ischemic stroke completely met the clinical diagnosis and treatment standards. (2) Operating power consumption: the per-hour operating power consumption of domestic 16-row mobile CT ([0.286±0.018] kW·h) was obviously lower than that of imported 8-row mobile CT ([0.485±0.028] kW·h). (3) Radiological hazard: the CTDIvol of the horizontal scanning volume range in domestic 16-row mobile CT ([36.270±0.281] mGy) was significantly lower than that in the imported 8-row mobile CT ([82.520±0.441] mGy, P<0.05); the CTDIvol of enhanced axis scan volume range in the domestic 16-row mobile CT ([36.270±0.335] mGy) was significantly lower than that in the imported 8-row mobile CT ([70.728±0.424] mGy, P<0.05); the CTDIvol in the volume of CTA imaging of domestic 16-row mobile CT ([20.600±0.087] mGy) was significantly lower than that in the imported 8-row mobile CT ([29.300±0.335] mGy, P<0.05). The domestic 16-row mobile CT was designed with shock absorbers and guides; domestic 16-row mobile CT had small load, a low center of gravity, and good stability as compared with imported 8-row mobile CT. Conclusion:In terms of head scanning applications, the imaging quality of domestic 16-row mobile CT and imported 8-row mobile CT is in full compliance with clinical diagnostic standards, but the energy consumption and radiation risk of domestic 16-row mobile CT is significantly lower than imported 8-row mobile CT, enjoying good stability as compared with imported 8-row mobile CT.
4.Effects of acacetin on T47D cell proliferation
Lingling SI ; Jun MA ; Huanhuan REN ; Boxue REN ; Defang LI ; Qiusheng ZHENG
Chinese Pharmacological Bulletin 2017;33(2):260-267
Aim To investigate the effect of acacetin on cell proliferation and the influence of acacetin on estrogen receptor expression in vitro.Methods The proliferation rates and the cell cycle changes of acace-tin-treated T47D cells were measured by sulforhodam-ine B(SRB)assay and flow cytometry,respectively. Moreover,the mRNA expressions of estrogen receptor-alpha(ERα),estrogen receptor-beta(ERβ)and pro-liferating antigen(Ki67)were determined by quantita-tive real time PCR (qPCR).Western blot was em-ployed to detect the ERαand ERβprotein expression. Results Acacetin significantly promoted the prolifera-tion and increased the amount of cells arrested in S and G2 /M phase under the concentration of 0.001 ~1 0μmol·L -1 .Ki67 mRNA level and the ERαprotein level in T47D cells were remarkably upregulated after acacetin treatment.To clarify which estrogen receptors played a role in acacetin induced the proliferation of T47D cells,the combination treatment of acacetin and ERαinhibitor (MPP)/ERβ inhibitor (PHTPP) was employed.We found that MPP could reverse the cell proliferation,the cell arrested in S and G2 /M phase and the increased Ki67 mRNA level induced by acace-tin.PHTPP also alleviated the T47D cell proliferation induced by acacetin,whereas no significant changes were found in cell cycle and Ki67 mRNA level.Con-clusion Acacetin stimulates the cell proliferation of T47D cells in the concentration from 0.001 μmol · L -1 to 1 0 μmol·L -1 ,which is mainly mediated by ERα.
5.Antioxidation effect of dihydroquercetin pretreatment in isolatedrat hearts during myocardial ischemia reperfusion injury
Ning LU ; Jichun HAN ; Boxue REN ; Defang LI ; Bo WANG ; Wenjin HAO ; Qiusheng ZHENG
Chinese Pharmacological Bulletin 2017;33(4):487-492
Aim To investigate the protective effects of dihydroquercetin(DDQ) against myocardial ischemis reperfusion injury(MIRI) in rats.Methods Male Sprague-Dawley rats were randomly divided into 4 groups(n=10):normal,control,I/R model, and I/R model+DDQ(5,10 mg·L-1).This study used an isolated Langendorff rat heart model.The left ventricu-lar developed pressure(LVDP),heart rate(HR) and the maximum rise and fall rate of the left ventricular pressure(±dp/dtmax) were monitored and documented using a physiological recorder.The levels of lactate dehydrogenase(LDH) and creatine kinase(CK) were analyzed using enzyme-linked immunosorbent assay(ELISA).Infarct size was measured using 2,3,5-triphenyltetrazolium chloride staining.The levels of superoxide dismutase(SOD) and malondialdehyde(MDA), as well as the ratio of glutathione/glutathione disulfide(GSH/GSSG) were measured via ELISA.HE staining was used to observe the pathological changes of myocardial tissue.Results Compared with the I/R model group, the I/R model+DDQ groups raised hemodynamic parameters, SOD level, and GSH/GSSG ratio;and reduced the amount of CK, LDH, MDA levels.Moreover, the I/R model+DDQ groups had lower infarct size and pathological changes in myocardial tissue than I/R model group.Conclusion DDQ exertes cardioprotective effects against I/R via improving the oxygen free radical scavenging ability, the inhibition of oxygen free radical and reducing lipid peroxidation.
6.A phase IV study of homoharringtonine, cytarabine, aclacinomycin and G-CSF (HCAG) regimen compared with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia patients
Zhao LIU ; Yunxiang ZHANG ; Lining WANG ; Zheng XIA ; Yuanfei MAO ; Huijin ZHAO ; Jianhua YOU ; Yang YU ; Yubing ZHAO ; Yuhong REN ; Ya LI ; Yan WANG ; Qiusheng CHEN ; Junmin LI ; Yu CHEN
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(8):1100-1105
Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients. Methods · Forty-one patients with AML (aged 55-71 years) were randomly divided into two groups (Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival (RFS). Results · A total of 29 patients (70.7%) achieved complete remission (CR). The estimated 2-year overall survival (OS) was 66.8% in Group HCAG and 75.4% in Group IA (P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA (P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.
7.Improvement Effects of Baicalein against Myocardial Ischemia/Reperfusion Injury in Rats
Meng CHEN ; Jichun HAN ; Dong WANG ; Qiusheng ZHENG
China Pharmacy 2016;27(1):23-26
OBJECTIVE:To study the improvement effects of baicalein against myocardial ischemia/reperfusion(I/R)injury in rats. METHODS:I/R injury model was induced by Langendorff method. Isolated heart of 40 rats were randomly divided into nor-mal group(continuous perfusion),model group(perfusion withdrawal 20 min)and baicalein high,medium and low concentration groups (K-H solution of baicalein 40,10 and 2.5 μmol/ml 10 min before perfusion withdrawal). The myocardial infarction rate, the activity of creatine kinase(CK)and lactate dehydrogenase(LDH)in coronary effluent liquid,SOD activity and MDA content, GSH/GSSG and apoptosis rate of cardiac muscle cell in myocardial tissue were detected. RESULTS:Compared with normal group, the myocardial infarction rate,apoptosis rate of cardiac muscle cell,the activities of CK and LDH and the content of MDA in myo-cardial tissue were increased in model group,while SOD activity and GSH/GSSG of myocardial tissue decreased(P<0.01). Com-pared with model group,the isolated myocardial infarction rate and the activities of CK and LDH in baicalein low and medium con-centration groups decreased,while SOD activity increased(P<0.05 or P<0.01);apoptosis rate of cardiac muscle cell and the con-tent MDA of myocardial tissue decreased significantly in medium concentration group,while GSH/GSSG increased (P<0.05 or P<0.01);those indicators had no significant change in high concentration group(P>0.05). CONCLUSIONS:Baicalein has cer-tain improvement effect on myocardial I/R injury in rats,and its mechanism may be associated with antioxidant and anti-apoptosis effect of baicalein.
8.Research on Mathematical Logic in Syndrome Theory of TCM and False Proposition Features of“Element of Syndrome”
Xiling SUN ; Qiusheng ZHENG ; Donglin YU ; Zhuojun LIU ; Chong HUANG ; Mengan LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(6):1274-1279
Through the study on mathematical logic relation in the syndrome theory of traditional Chinese medicine (TCM), it revealed that the mathematical logic relation among three basic elements in the judgment of syndromes, which were the disease cause (a), disease location (b), disease nature (c) and syndrome (z), was f(z)=a+b+c. The mathematical logic relation between syndrome (z) and symptom (zi) was f(z)= z1+z2+z3+…+zi. The obvious feature reflected by the complexity of syndromes was the construction number of symptoms. During the syndrome differentiation process, the mathematical logic relation between symptom and disease cause, location, nature and syndrome was z1+z2+z3+…+zi =a+b+c= f(z). However, syndromes generally exhibited a nonlinear relationship of point-set topology. After calculation, 79 major single TCM syndromes had a total of more than 6.5×105 different forms. The number within a certain range of syndrome group was approximately 6.6×10100. The super huge data “Googol” may be the root of complex TCM syndromes. The results showed that the researches on “element of syndrome” using the bayesian networks, the neural network algorithm and the algorithm of double levels of frequency power were irrelevant to the mathematical logic relation of the intrinsic relations of syndrome theory. Therefore, “element of syndrome” was a false proposition feature in the study of TCM basic theory. The established syndrome differentiation method with“element of syndrome” as its core was not conformed to the inherent law of TCM theory and clinical practice.
9.Isoliquiritigenin induced apoptosis in human melanoma A375 cells
Xinyan YAN ; Lingling SI ; Caixia GAO ; Lina YU ; Yanming WANG ; Qiusheng ZHENG
Chinese Pharmacological Bulletin 2015;(10):1426-1432
Aim To evaluate the mechanism of apopto-sis induced by the isoliquiritigenin in A375 human ma-lignant melanoma cells. Methods Sulforhodamine B ( SRB) method was used to determine the A375 cell viability;acridine orange/ethidium bromide ( AO/EB) and Hoechst 33258 staining were used to observe the morphological changes of apoptotic cells; flow cytome-try was used to detect A375 cell apoptotic rate;DCFH-DA was applied to determine the changes of total intra-cellular ROS in A375 cells;JC-1 method was used to measure the changes of mitochondrial membrane poten-tial;the kits methods were used to determine the con-tent of ATP, lactic acid and glucose in A375 cell which was treated with different concentrations of isoliquiritigenin. Results Isoliquiritigenin could in-hibit A375 cell proliferation in a concentration-depend-ent manner; A375 cells showed obvious apoptosis charateristics after treatment by isoliquiritigenin, and the apoptosis rate increased with increasing concentra-tion of isoliquiritigenin. The level of total intracellular ROS in A375 cells increased obviously after dealing with different concentrations of isoliquiritigenin;in ad-dition, the mitochondrial membrane potential, the lev-els of intracellular ATP,lactic acid and the level of glu-cose uptake all declined. Conclusions These find-ings demonstrate that isoliquiritigenin can induce apop-tosis of A375 cells. The mechanism may be related to elevation of ROS level and reduction of aerobic glycoly-sis level.
10.Correlation between hypoglycemia and increased mortality of patients with acute decompensated liver cirrhosis
Runtian LIU ; Yun BAI ; Congjing AN ; Qiusheng LI ; Jianxing ZHENG ; Haiyan ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;22(3):299-303
Objective To explore the correlation between hypoglycemia and the increased mortality of patients with acute decompensated liver cirrhosis.Methods A retrospective study was conducted on the clinical data of 120 patients with acute decompensated liver cirrhosis admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from December 2011 to December 2014. The patients were divided into three groups: hypoglycemia group (glucose < 5.0 mmol/L, 21 cases), normoglycemia group (glucose 5.1 - 10.0 mmol/L, 84 cases), and hyperglycemia group (glucose > 10.0 mmol/L, 15 cases). The differences in hepatic carcinoma, decompensation symptoms, the incidence of known glycometabolic disorder, hospitalization situation, indicators of liver function and indexes of blood gas analysis were compared among three groups. The patients' age, hepatic carcinoma, ascites, hepatorenal syndrome, encephalopathy, bleeding, jaundice and glycometabolic disorder, etc were analyzed by the univariate analysis. The resulting risk factors with statistically significant differences were analyzed by multivariate logistic regression method in order to screen out the risk factors of increased mortality.Results The incidences of hepatorenal syndrome [42.9% (9/21) vs. 22.6% (19/84), 33.3% (5/15)] and jaundice [38.1% (7/21) vs. 20.2% (17/84), 13.3% (2/15)], rate of admission into intensive care unit (ICU) [14.3% (3/21) vs. 10.7% (9/84), 13.3% (2/15)] and in-hospital mortality [23.8% (5/21) vs. 10.7% (9/84), 20.0% (3/15)] in the hypoglycemia group were significantly higher than those in the normoglycemia group and hyperglycemia group (P < 0.05 orP < 0.01). The levels of aspartate-aminotransferase (AST), total bilirubin (TBil), serum creatinine (SCr) and international normalized ratio (INR) in hypoglycemia group were obviously higher than those in normoglycemia group and hyperglycemia group [AST (U/L): 628.412±78.625 vs. 170.167±87.035, 156.716±98.047; TBil (μmol/L): 154.122±34.201 vs. 86.712±48.905, 74.313±39.883; SCr (μmol/L): 160.243±56.341 vs. 107.211±59.692, 121.342±84.059; INR: 1.951±0.987 vs. 1.439±0.919, 1.423±0.653,P < 0.05 orP < 0.01]. The levels of HCO3- and base excess (BE) in hypoglycemia group were signicantly lower than those of normoglycemia group and hyperglycemia group [HCO3- (mmol/L): 18.154±10.937 vs. 23.135±11.119, 19.081±12.022; BE (mmol/L): -7.578±2.042 vs. -1.648±0.887, -5.402±2.005, allP < 0.01]. The pH value among three groups showed significant difference (7.352±2.878, 7.461±2.036, 7.219±2.017,P < 0.01). There were no statistically significant differences in alanine transaminase (ALT), blood ammonium, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) and lactate among the three groups (all P > 0.05). Univariate analysis showed that advanced age, hepatic carcinoma, hepatorenal syndrome, bleeding, jaundice and glycometabolic disorder hypoglycemia were the risk factors of the death in patients with acute decompensated liver cirrhosis (P < 0.05 orP < 0.01). Multivariate logistic regression analysis showed that advanced age [odds ratio (OR) = 2.101, 95% confidence interval (95%CI) = 1.297 - 3.403,P = 0.000], hepatorenal syndrome (OR = 3.032, 95%CI = 1.462 - 6.286,P = 0.000) and hypoglycemia (OR = 3.267, 95%CI = 2.135 - 4.999,P = 0.031) were the independent risk factors of the patients' death.Conclusion Hypoglycemia has certain correlation to the increase of mortality in patients with acute decompensated liver cirrhosis.

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