1.A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells
Zhenhai ZHANG ; Jing ZHU ; Jian'an WANG ; Jie CHEN ; Yingying PANG ; Chengzhu WU
Journal of Zhejiang University. Medical sciences 2024;53(4):509-518
Objective:To synthesize new bakuchiol aminoguanidine derivatives and test their effect on viability and apoptosis of human triple-negative breast cancer(TNBC)cells.Methods:Two bakuchiol derivatives 1 and 2 were obtained by formylation and Shiff base reaction of bakuchol.The structures of derivatives 1 and 2 were identified by 1H-NMR,13C-NMR,and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)analysis.Human TNBC MDA-MB-231 cells were treated with bakuchiol and its derivatives and cell viability was measured by MTT assay.Apoptosis was detected by fluorescence microscopy and flow cytometry with Annexin V-FITC/PI staining.The expressions of apoptosis-related proteins were analyzed with Western blotting.The JC-1 and reactive oxygen species(ROS)assay kits were used to determine the effect of new bakuchiol derivatives on mitochondrial function.Results:Based on spectroscopic analysis,a new bakuchiol schiff base derivative was elucidated as 2-{(E)-5-[(S,E)-3,7-dimethyl-3-vinylocta-1,6-dien-1-yl]-2-hydroxylbenzylidene}hydrazine-1-carboximidamide(derivative 2).Bakuchiol and its derivatives 1 and 2 all showed cytotoxic activity against the MDA-MB-231 cells.Derivative 2 exhibited the most potent cytotoxic activity to MDA-MB-231 cell with IC50 of(13.11±1.09),(6.91±1.78),and(2.23±1.32)μmol/L after 24,48,and 72 h.It had low toxicity to normal mouse liver(AML-12)cells with IC50 of(31.23±1.58)μmol/L at 72 h.Fluorescence microscopy and flow cytometry demonstrated apoptosis in breast cancer cells after treating with derivative 2 in a concentration dependent manner.Western blotting showed that after derivative 2 treatment,the expression of apoptosis-related proteins cytochrome C,cleaving caspase-3 and Bax/Bcl-2 radio in MDA-MB-231 cells increased;in addition,apoptosis was associated with the decreased mitochondrial membrane potential and increased reactive oxygen species accumulation.Conclusion:The novel bakuchiol aminoguanidine derivative(derivative 2)is capable of inducing apoptosis in MDA-MB-231 cells,but has low toxicity to normal liver cells,suggesting that it may be used as a lead compound for an anti-TNBC agent.
2.The study of puncture wound infections from the high pressure resistant injectable PICC catheter in patients undergoing hematopoietic stem cell transplantation
Xueqing YANG ; Chenghong ZHU ; Zheng ZHANG ; Yanfang ZHENG ; Zhaohua DANG ; Yufei GUO ; Yanjun LIU ; Chengzhu WANG
Chinese Journal of Geriatrics 2020;39(8):910-913
Objective:To analyze the causes of puncture wound infections induced by the high pressure resistant injectable PICC catheter in patients undergoing hematopoietic stem cell transplantation and management measures.Methods:linical data of 75 patients undergoing hematopoietic stem cell transplantation who were treated with the high pressure resistant injectable PICC catheter in our hospital from Nov.2017 to Nov.2019 were retrospectively analyzed.According to whether there were puncture wound infections, patients were divided into the infection group(n=26)and the non-infection group(n=49). Bacterial culture results of the infection group were recorded, and the related factors for puncture wound infections caused by the injectable PICC catheter were analyzed.Effective strategies to prevent high-risk factors, treatment frequency, treatment effect and healing time for patients with different degrees of puncture wound infections were discussed.Results:There were 26 patients in the infection group.The proportions of bacteria types associated with PICC catheter-related infections, in descending order, were as follows: Staphylococcus aureus(46.51%), Klebsiella pneumoniae(30.77%), Corynebacterium(15.38%)and others(7.69%). Significant differences were found in materials used, season of tube placement, timing of dressing changes, duration of catheterization, success rate of first tube placement and condition of dressing films between the non-infection and infection groups( t=5.5, 4.9, 5.0, 13.6, 9.4 and 6.2, all P<0.05). Logistic multi-factor analysis showed that non-U-shaped fixation, delay in dressing changes, long duration of tube placement, low success rate of first tube placement, and loose dressing films were the high-risk factors for PICC catheter-related infections( OR=2.78, 2.42, 3.16, 2.66 and 2.32, all P<0.05). Compared with patients with moderate and mild infections, patients with severe infections had a higher frequency of treatment, a lower total effectiveness rate and a longer healing time( F=10.353, 8.775 and 12.341, all P<0.05). Conclusions:Materials, timing of dressing changes, catheterization time, success rate of first tube placement and condition of dressing films are the high-risk factors for puncture wound infections caused by high pressure resistant injectable PICC catheters in patients undergoing hematopoietic stem cell transplantation.Developing effective intervention strategies can help control the incidence of wound infections.
3.Effects of comprehensive geriatric assessment on health management outcomes in elderly patients with coronary heart disease
Wei ZHANG ; Jie BAI ; Xueqing YANG ; Jie CHEN ; Chunpei MIAO ; Yan HE ; Yuyu SONG ; Chengzhu WANG
Chinese Journal of Geriatrics 2019;38(4):371-374
Objective To investigate the effect of comprehensive geriatric assessment on health management outcomes and quality of life in elderly patients with coronary heart disease.Methods A total of 100 elderly patients with coronary heart disease admitted into our hospital from April 2017 to April 2018 were enrolled in this study and randomly divided into a control group(n=50)receiving routine nursing intervention and an observation group (n =50)undergoing individualized health management after comprehensive geriatric assessment.Length of hospital stay,incidence of adverse events and quality of life were compared between the groups.Results The length of hospital stay was shorter in the observation group than in the control group[(10.6 ± 1.4) d vs.(15.5 ± 1.5) d,t =16.7,P<0.05].Patients in the observation group had higher satisfaction than those in the control group[(55.6±1.4)vs.(45.5±1.5),t =34.2,P<0.05],The incidence of cardiac adverse events was lower in the observation group than in the control group(20.0% vs.52.0%%,x2 =5.0,P<0.05).The scores for quality of life were higher in the observation group than in the control group(P<0.05).Conclusions Comprehensive geriatric assessment can effectively shorten the length of hospital stay,reducethe incidence of cardiac adverse events,and improve the satisfaction and quality of life in elderly coronary heart disease patients,and should be recommended in clinical practice.
4.Nutrition management in obese patients with type 2 diabetes mellitus after laparoscopic sleeve gastrectomy.
Weihong TANG ; Yuhua CHEN ; Meizhen PAN ; Lihua CHEN ; Lele ZHANG ; Tingfeng WANG ; Xiong ZHANG ; Peng ZHANG ; Chengzhu ZHENG ; Bo YU
Chinese Journal of Gastrointestinal Surgery 2017;20(4):411-416
OBJECTIVETo explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).
METHODSClinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation.
RESULTSThe average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/mto (27.9±3.5) kg/m(t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) μg/L to (0.7±0.3) μg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) μg/L to (1.5±0.7) μg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively.
CONCLUSIONAs for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.
Adolescent ; Adult ; Aged ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Weights and Measures ; C-Peptide ; blood ; physiology ; Caloric Restriction ; Combined Modality Therapy ; Comorbidity ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Diet Therapy ; methods ; Diet, Diabetic ; Endoscopy ; Fatty Liver ; complications ; surgery ; Female ; Food, Formulated ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Gout ; complications ; surgery ; Hashimoto Disease ; complications ; Humans ; Hypertension ; complications ; surgery ; Insulin ; blood ; physiology ; Lipids ; blood ; physiology ; Male ; Menstruation Disturbances ; complications ; surgery ; Middle Aged ; Obesity ; complications ; therapy ; Perioperative Care ; methods ; Thyroiditis ; complications ; Treatment Outcome ; Triglycerides ; blood ; physiology
5.Tetramethylpyrazine protects learning memory of hypoxichypoxia rats through interfering expression of GABA receptor and FOXP2
Xiaona LI ; Xiaojun WANG ; Yanmei ZHU ; Chengzhu CAO ; Chunyan YANG ; Yunfei YAN ; Yanli ZHAO ; Shenghua LI
Chinese Pharmacological Bulletin 2017;33(9):1285-1290
Aim To examine the influence of tetramethylpyrazine on learning and memory function of hypoxic hypoxia rats, and the expression of gamma aminobutyric acid(GABA) receptor and forkhead box P2(FOXP2) in hippocampus of rats.Methods A total of 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups, then according to different time points every group was divided into 1 d, 3 d, 7 d 15 d, 30 d group, with 12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline, respectively.The hypoxic hypoxia environment was achieved by putting the rats in a hypobaric chamber at a simulated altitude of 5 500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by Western blot.Results ① Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group was longer than that in the tetramethylpyrazine group(P<0.01) and the number of crossing the bestride platform increased compared with that in the hypobaric hypoxia control group(P<0.01) from the third day;② Western blot results showed that the expression of GABAAα1 receptor have no statistical significance(P>0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05).The expression of GABAAα1 receptor and FOXP2 protein expression were correlated to total distance of Morris water maze in the control group(r=-0.738, P<0.05;r=-0.693, P<0.05), and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834, P<0.05).Conclusion The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats, which may be ameliorated by tetramethylpyrazine intervention, and this effect might be related to the increase of GABAB1R receptor and FOXP2 expression in hippocampus of rats.
6.The correlation study between FGFR2 gene polymorphisms and breast cancer in Qinghai Tibetan areas
Guoshuang SHEN ; Fangchao ZHENG ; Chengzhu CAO ; Faxiang JI ; Jinzhang LI ; Shuyan WANG ; Jiuda ZHAO
Chongqing Medicine 2016;45(16):2209-2211
Objective To explore the relationship between the fibroblast growth factor 2 (FGFR2) gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) and the breast cancer risk in Tibetan population ,Qinghai province .Methods This is a case con‐trol study .Peripheral blood samples from 210 breast cancer patients and 230 healthy women in Qinghai area were collected .DNA samples were extracted from peripheral blood cells .FGFR2 gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) were typed by Taqman‐MGB probe based on PCR and DNA sequencing ,then analyzed its correlation with breast cancer in Tibetan population , Qinghai province .Results The genotype frequencies of rs 2981582 CC ,CT and TT were 40 .48% ,39 .05% and 20 .47% among the breast cancer patients while 36 .09% ,48 .69% and 15 .22% among the controls .The genotype frequencies of rs 1219648 GG ,AG and AA were 24 .76% ,26 .19 % and 49 .05% among the patients while 23 .91% ,47 .39% and 28 .70% among the controls .The genotype frequencies of rs 2420946 CC ,CT and TT were 29 .05% ,45 .24% and 25 .71% among the patients while 30 .87% , 51 .74% and 17 .39% among the controls .The genotype frequencies of all genetic loci had no significant difference between rs 2981582 and rs 2420946 (P>0 .05) .But the genotype frequencies of rs 1219648 AA have statistical sense (P< 0 .05) ,compared with GG ,the incidence of breast cancer was remarkably increased with AA [OR=1 .65 ,95% CI= (1 .01 ,2 .69)] .Conclusion This study shows that FGFR2 rs1219648 AA is related to breast cancer risk among Tibetan population .
7.Relationship Between the Ratio of Neutrophil/Lymphocyte and In-hospital Major Adverse Cardiac Events in Patients With Acute ST-elevation Myocardial Infarction at the Early Admission
Wei HE ; Jihong FAN ; Zhitao JIN ; Liping DING ; Xin LU ; Chengzhu WANG ; Taohong HU
Chinese Circulation Journal 2016;31(1):36-39
Objective: To explore the relationship between the ratio of neutrophil/lymphocyte (NLR) and in-hospital major adverse cardiac events (MACE) in patients with acute ST-elevation myocardial infarction (STEMI) at early admission.
Methods: A total of 420 acute STEMI patients admitted and received primary PCI in our hospital from 2010-01 to 2014-12 were retrospectively studied. The patients were divided into 2 groups:In-hospital MACE group, n=47 and Normal discharged group, n=373. Uni-and multivariate analyses were conducted to assess whether high NLR is the independent predictor for in-hospital MACE occurrence.
Results: Univariate regression analysis indicated that the occurrence rate of in-hospital MACE in high NLR patients were higher than those in low NLR patients (OR=3.19, 95%CI 1.55-2.65, P=0.012). Multivariate regression analysis showed that high NLR was the independent risk factor for in-hospital MACE occurrence in STEMI patients (OR=3.05, 95%CI 1.59-10.54, P=0.015).
Conclusion: High NLR is the independent risk factor for in-hospital MACE occurrence in STEMI patients at the early admission.
8.Risk Factor Analysis for Contrast-induced Nephropathy in Patients of Acute Coronary Syndrome With Normal or Slightly Impaired Renal Function After Percutaneous Coronary Intervention
Jihong FAN ; Taohong HU ; Wei HE ; Zhitao JIN ; Zheng ZHANG ; Liping DING ; Guojie GAO ; Junke YANG ; Chengzhu WANG
Chinese Circulation Journal 2016;31(1):31-35
Objective: To evaluate the risk factors for contrast-induced nephropathy (CIN) in patients of acute coronary syndrome (ACS) with normal or slightly impaired renal function after percutaneous coronary intervention (PCI).
Methods: A total of 254 consecutive ACS patients with normal or slightly impaired renal function received PCI in the Second Artillery General Hospital from 2013-06 to 2015-06 were retrospectively studied. All patients had eGRF≥60 ml (min?1.73 m2) and they were divided into 2 groups:CIN group, the patients with serum creatinine increased by 0.5mg/dl (44.2μmol/L) or elevated to 25%higher than the baseline, n=23;Non-CIN group, n=231. The basic condition with laboratory tests, operative indexes were recorded and eGRF value were calculated in all patients.
Results: There were 9%(23/254) patients suffered from CIN after PCI. Multivariate regression analysis indicated that emergent PCI (OR=0.370, 95%CI 0.060-2.297), increased plasma level of NT-proBNP (OR=4.209, 95%CI 1.202-14.742) and without pre-operative aspirin administration (OR=7.950, 95%CI 1.108-57.034) were the clinical risk factors for post-operative CIN occurrence.
Conclusion: Emergent PCI, higher plasma level of NT-proBNP and no pre-operative aspirin administration were the risk factors for CIN occurrence in ACS patients with normal or slightly impaired renal function after PCI.
9.Determination of L-Cysteine Based on Energy Transfer between Cu2-x Se Nanoparticles and Rhodamine B
Xue WANG ; Kuncheng YANG ; Zhuyuan MAO ; Chengzhu HUANG ; Juan WANG
Chinese Journal of Analytical Chemistry 2016;44(10):1482-1486
The fluorescence of Rhodamune B could be quenched by the manner of photo-unduced electron transfer wuth Cu2-x Se nanopartucles as the energy receptor and Rhodamune B as the energy donor. However, L-cysteune was capable of recoverung the fluorescence of Rhodamune B, and the fluorescence untensuty was proportuonal to the concentratuons of L-cysteune. Based on that, a novel method for detectung L-cysteune was establushed. After muxung L-cysteune and Rhodamune B pretreated by Cu2-x Se nanopartucles at pH 4. 6 and 30℃ for 2 mun, a lunear relatuonshup was obtauned between the fluorescence untensuty of Rhodamune B at 575 nm and the concentratuons of L-cysteune un the range of 2. 5 ×10-7-1. 1 ×10-6 mol/L. Thus method was used un the determunatuon of L-cysteune wuth a detectuon lumut (3σ/k) of 5. 5×10-8 mol/L. The common amuno acuds presented luttle unterference for the L-cysteune detectuon.
10.The risk factors of paroxysmal atrial fibrillation in very olderly hypertensive patients
Zhangjun SHEN ; Zheng ZHANG ; Liping DING ; Zhitao JIN ; Fengchi KANG ; Chengzhu WANG ; Taohong HU
Tianjin Medical Journal 2016;44(8):935-937,938
Objective To analyze the risk factors of paroxysmal atrial fibrillation (PAF) in very olderly hypertensive patients. Methods According to the electrocardiograph (ECG) and history data, two hundred and six older old-hypertensive patients were divided into PAF group (n=66) and sinus rhythm (SR) group (n=140). Data of age, gender, body mass index (BMI), the use of angiotension-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and statin drug history, 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, pulse wave velocity (PWV), blood lipid profile and renal function were recorded in two groups. Logistic regression analyses of the relevant factors were compared between groups. Results Data of age, the diameter of the left atrium (LAD), the 1eft ventricular mass index (LVMI) and the PWV were significantly higher in PAF group than those of SR group [(88.92±3.42) years old vs. (86.36±4.67) years old, (39.00±6.66) mm vs. (33.54±7.77) mm, (132.49±14.83) g vs. (119.00±11.35) g, (13.45±4.85) m/s vs. (9.89±2.74) m/s, respectively]. Values of three acyl glycerin (TG), blood pressure smoothing index (SI) were lower in PAF group than those of SR group [(1.33±0.91) mmol/L vs. (1.95±1.29) mmol/L, 0.75±0.06 vs. 0.79±0.04, respectively]. Results of two classification Logistic regression analyses showed that the reduced SI, the enlarged LAD and LVMI and the increased PWV were the risk factors of PAF in very olderly hypertensive patients. Conclusion Unstable blood pressure, left atrial enlargement, left ventricular hypertrophy and arterial stiffness are the risk factors of PAF in very olderly hypertensive patients.

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