1.Clinical trial of insulin therapy in elderly patients with coronary heart disease combined with type 2 diabetes
Ya-Tao DING ; Zhong-Hua WANG ; Bo CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(1):3-6
Objective This study aimed to investigate the correlation between insulin resistance score after insulin treatment in elderly patients with coronary heart disease and type 2 diabetes mellitus and cardiovascular outcomes.Methods Elderly patients with coronary heart disease complicated with type 2 diabetes mellitus were selected as the study subjects.All enrolled patients received insulin treatment with an initial dose of 3 U,administered subcutaneously before meals.The total daily dose of insulin was controlled at 0.3-0.8 U·kg-1.The occurrence of major adverse cardiovascular events(MACE)was recorded,and the correlation between insulin resistance score(METS-IR)and cardiovascular outcomes,as well as the predictive value for the occurrence of adverse cardiovascular events was analyzed.Results Before and after insulin treatment in elderly patients with coronary heart disease and type 2 diabetes mellitus,the average body mass index(BMI)were(26.03±3.12)and(25.23±0.02)kg·m-2,triglycerides(TG)were(123.60±21.46)and(113.70±19.75)mg·dL-1,total cholesterol(TC)were(155.80±14.19)and(153.40±13.98)mg·dL-1,low-density lipoprotein cholesterol(LDL-C)were(94.58±9.85)and(91.74±9.56)mg·dL-1,high-density lipoprotein cholesterol(HDL-C)were(46.02±4.47)and(49.73±4.83)mg·dL-1,and fasting blood glucose(FBG)were(98.55±10.58)and(93.62±10.05)mg·dL-1,respectively.The METS-IR scores were 39.26±4.80 and 36.89±4.50,respectively.Except for plasma TC,the differences in the above indicators before and after treatment were statistically significant(all P<0.05).Among the enrolled patients,a total of 48 cases(22.2%)experienced MACE,including 23 cases of hypertension,14 cases of angina pectoris,8 cases of hospitalization for myocardial infarction,3 cases of hospitalization for heart failure.Spearman correlation analysis showed that METS-IR was significantly positively correlated with the incidence of adverse cardiovascular events(P<0.01).ROC curve analysis indicated that METS-IR had a high predictive value for the occurrence of MACE in elderly patients with coronary heart disease and type 2 diabetes mellitus.Conclusion After insulin treatment in elderly patients with coronary heart disease and type 2 diabetes mellitus,METS-IR was significantly positively correlated with the incidence of adverse cardiovascular events and had good predictive value for cardiovascular outcomes.
2.Clinical trial on preemptive analgesia of parecoxib sodium for modified radical resection of breast cancer
Qi ZHAO ; Li-Li FU ; Xiao-Yun LIU ; Guang-Wei ZHOU ; Xin-Ting WANG ; Ying WANG
The Chinese Journal of Clinical Pharmacology 2024;40(1):7-11
Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P<0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P<0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P<0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P<0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P<0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61%(38 cases/46 cases)and 63.04%(29 cases/46 cases),respectively,and the difference was statistically significant(P<0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04%(6 cases/46 cases)and 8.70%(4 cases/46 cases),respectively,the difference was no statistically significant(P<0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.
3.Clinical trial of the therapeutic effect of ritodrine hydrochloride on pregnant women with threatened abortion in the second trimester of pregnancy
The Chinese Journal of Clinical Pharmacology 2024;40(1):12-16
Objective To observe the effect of ritodrine hydrochloride on uterine blood flow,progesterone,serum D-dimer(D-D),left ventricular ejection fraction(EF)and stroke volume(SV)in pregnant women with threatened abortion in the second trimester of pregnancy.Methods Pregnant women with threatened abortion in the second trimester were included in the study.The control group was treated with intravenous drip of 25%magnesium sulfate 15 g,qd,for 3 d.The treatment group was treated with intravenous drip of ritodrine hydrochloride 100 mg and the intravenous drip lasted for 12-18 h after uterine contraction stopped.Then,patients in the group were treated with ritodrine tablets(10 mg/2 h in the former 24 h and then 10 mg/4-6 h)no more than 120 mg every day,for 3 d.Uterine hemodynamics[resistance index(RI),pulsatility index(PI)and systolic/diastolic ratio(S/D)],progesterone[progesterone(P),human chorionic gonadotropin(HCG)and estradiol(E2)],serum D-D,EF,SV,disappearance time of symptoms,success rate of fetal protection,adverse neonatal outcomes,and adverse drug reactions were compared between two groups.Results After treatment,RI in the treatment group and the control group were 0.74±0.13 and 0.81±0.17;PI were 2.08±0.39 and 2.63±0.42;S/D were 3.14±0.57 and 3.65±0.62;D-D levels were(0.60±0.12)and(0.58±0.13)mg·L-1;P levels were(44.83±7.62)and(41.35±7.96)μg·L-1;HCG levels were(20 958.63±2 143.72)and(20 043.82±2 125.64)mU·mL-1;E2 levels were(538.72±83.16)and(503.69±87.42)ng·L1;EF were(61.34±8.05)%and(72.52±8.37)%;SV were(75.06±7.92)and(80.29±8.34)mL;the disappearance time of bleeding were(2.65±0.43)and(2.87±0.39)d;the disappearance time of abdominal pain were(2.57±0.38)and(2.80±0.42)d;the disappearance time of soreness of waist were(2.36±0.35)and(2.74±0.38)d;the success rates of fetal protection were 98.04%and 77.55%;the premature delivery rates were 12.00%and 18.42%;the incidence rates of adverse neonatal outcomes were 6.00%and 10.53%;there were statistically significant differences between the treatment group and the control group except for D-D,preterm delivery rate,and the incidence of neonatal adverse outcomes(all P<0.05).The total incidence of adverse drug reactions in the treatment group and the control group were 7.84%and 6.12%,respectively,and the difference were not statistically significant(P>0.05).Conclusion Ritodrine hydrochloride can effectively improve uterine hemodynamics,increase progesterone levels,and achieve good fetal protection effect in pregnant women with threatened abortion in the second trimester of pregnancy.
4.3-butylphthalideimproves neuronal apoptosis induced by oxidative stress through PRDM5
Kang HE ; Yong-Tao GAO ; Chen-Yang XU ; Guo-Qing DUAN
The Chinese Journal of Clinical Pharmacology 2024;40(1):17-21
Objective To investigate the effects of 3-Butylphthalideon oxidative stress-induced apoptosis of neuronal cells PC-12 and its mechanism.Methods PC-12 cells were divided into four groups,Vector group:DMSO treated and transfected with vector plasmid;3-butylphthalide+vector group:DMSO+25 μmol·L-1 3-butylphthalidewas treated with vector plasmid was transfected;PRDM5 group:PR domain zinc finger protein 5(PRDM5)overexpression plasmid was transfected with DMSO;3-butylphthalide+PRDM5 group:Treated with DMSO+25 μmol·L-1 3-butylphthalide and transfected with PRDM5 overexpression plasmid.Apoptosis levels of neurons were detected by flow cytometry;Cleaved cysteine aspartate proteinase 3(Cleaved-caspase 3),B cell lymphoma-2(Bcl-2)and Bcl-2 associated X(Bax)expression levels were detected by Western blotting;binding sites of 3-Butylphthalideand PRDM5 were analyzed by molecular docking.Results The apoptosis levels of vector group,3-butylphthalide+vector group,PRDM5 group and 3-butylphthalide+PRDM5 group were(63.52±5.72)%,(20.48±3.56)%,(79.48±8.13)%and(22.58±3.01)%;Cleaved-caspase 3 expression levels were 0.89±0.09,0.29±0.03,1.12±0.09 and 0.31±0.05;the expression levels of Bcl-2 were 0.31±0.02,0.79±0.05,0.12±0.01 and 0.89±0.11;the expression levels of Bax were 0.83±0.08,0.25±0.03,1.03±0.11 and 0.27±0.03,respectively.The above indexes of Vector group were significantly different from those of PRDM5 group(all P<0.05).That 3-Butylphthalidewas bound to PRDM5(free energy-12.55 kcal·mol-1),and binding sites were K413R and D414A.Conclusion 3-butylphthalidebinds to K413R and D414A of PRDM5,inhibiting the function of PRDM5 and improving the apoptosis of neuronal cells induced by oxidative stress.
5.Prognostic lncRNAs for stomach adenocarcinoma and drug sensitivity analysis
Yu-Mei HUANG ; Jing HUANG ; A-Zhen WU
The Chinese Journal of Clinical Pharmacology 2024;40(1):22-26
Objective To explore the prognostic value of long non-coding RNAs(lncRNAs)as novel biomarkers for stomach adenocarcinoma(STAD).Methods RNA-seq transcriptome data and clinical details for STAD were downloaded from the The Cancer Genome Atlas(TCGA)database.Differentially expressed lncRNAs were identified by bioinformatics analysis.Survival analysis,independent prognostic analysis and receiver operating characteristic(ROC)curve were used to identify lncRNAs with independent prognostic value.Then,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to evaluate the biological profiles of the co-expressed genes.Finally,oncoPredict R package was used to predict the drug sensitivity.Results A total of 1 583 differentially expressed lncRNAs were identified from STAD tumor tissues.A lncRNAs AP000695.1 with survival and independent prognostic value was screened.The area under 5-year survival ROCs was 0.836.AP000695.1 was co-expressed with 16 genes involved in tumor cell invasion,metastasis and diffusion.Finally,anti-tumor drug sensitivity prediction revealed that patients in the low expression group were more sensitive to anti-tumor drugs.Conclusion This study discovered a risk factor lncRNAs AP000695.1 with independent prognostic value,may provide insight for individualized antitumor therapy and prognosis prediction for STAD patients.
6.Effects of scutellarin on endometrial carcinoma Ishikawa cells based on PI3K/Akt signaling pathway
Li-Li DAI ; Jing WANG ; Xu-Rui WEI ; Qing-Ya MA ; Na WANG ; Zhi-Xiang DU
The Chinese Journal of Clinical Pharmacology 2024;40(1):27-31
Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)%,(78.51±7.54)%,(52.93±4.91)%and(41.62±5.33)%;the clone formation rate were(100.00±0.00)%,(56.59±6.34)%,(35.23±4.62)%and(10.66±1.91)%;the scratch healing rate were(53.70±6.19)%,(40.59±4.75)%,(34.25±4.40)%and(15.78±2.14)%;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)%,(15.83±2.42)%,(22.72±3.85)%and(34.41±4.67)%;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P<0.05 or P<0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.
7.Capparis spionosa polysaccharide affects proliferation,migration and invasion of pancreatic cancer cells by up-regulating LINC00476
The Chinese Journal of Clinical Pharmacology 2024;40(1):32-36
Objective To investigate the effect of Capparis spionosa polysaccharides on the proliferation,migration and invasion of pancreatic cancer cells by regulating LINC00476.Methods Pancreatic cancer cells SUIT-2 were divided into blank group and experimental-L,-M,-H groups,which were treated with 0,200,400,600 μg·mL-1 Capparis spionosa polysaccharides,respectively.Clone formation experiments were used to detect cell proliferation ability,Transwell experiments were used to detect cell migration and invasion ability,real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of LINC00476 and human antigen R(HuR)mRNA,and Western blot was used to detect the expression levels of HuR proteins.Results The colony formation number in blank group and experimental-L,-M,-H groups were 137.31±9.43,109.57±4.72,77.28±5.76 and 50.74±6.76;the number of migrating cells were 229.21±27.67,188.69±9.29,150.98±20.25 and 109.37±8.04;the number of invasive cells were 125.96±9.20,100.52±7.60,81.65±8.62 and 66.01±5.79;the expression levels of LINC00476 mRNA were 0.96±0.07,1.38±0.16,1.68±0.18 and 2.18±0.30;the expression levels of HuR mRNA were 1.05±0.07,0.81±0.06,0.58±0.10 and 0.32±0.04;the relative expression levels of HuR protein were 1.00±0.09,0.74±0.05,0.55±0.03 and 0.32±0.02.Compared with blank group,the proliferation,migration and invasion abilities of experimental-L,-M,-H groups were decreased,the expression levels of HuR were decreased,and the expression levels of LINC00476 mRNA were increased,the differences were statistically significant(all P<0.05).Conclusion Capparis spionosa polysaccharides may inhibit the proliferation,migration and invasion of pancreatic cancer cells by up-regulating LINC00476.
8.Effect and mechanism of microRNA-133A-3p on breast cancer cells
Cai-Ping TIAN ; Jian-Ping MIN ; Xiao JING ; Sui-Sheng YANG
The Chinese Journal of Clinical Pharmacology 2024;40(1):37-41
Objective To explore the effect and mechanism of microRNA-133a-3p(miR-133a-3p)on invasion and apoptosis of breast cancer cells through targeted regulation of cullin-associated NEDD8-dissociated 1(CAND1).Methods MCF-7 cells were divided into overexpression group(mimics miR-133 a-3p transfection),NC group(mimics control transfection),co-transfection group(mimics miR-133a-3p transfection with pcDNA-CAND1 co-transfection)and control group(only adding the same amount of transfection reagents).Flow cytometry was used to detect cell apoptosis,Transwell assay was used to detect cell invasion,and real-time fluorescence quantitative polymerase chain reaction was used to detect miR-133a-3p and CAND1 expression.Results After transfection,the expression levels of miR-133a-3p in control group,NC group,overexpression group and co-transfection group were 0.50±0.08,0.51±0.09,1.06±0.10 and 1.05±0.15,respectively;the expression of CAND1 mRNA were 0.91±0.09,0.91±0.07,0.80±0.10 and 1.21±0.10,respectively.There were statistically significant differences in the above indexes between the co-transfection group and the control group,the NC group(all P<0.05),and there were statistically significant differences between the overexpression group and the control group,the NC group(all P<0.05).The apoptosis rates in control group,NC group,overexpression group and co-transfection group were(7.88±1.62)%,(8.87±2.01)%,(53.41±5.46)%,(29.54±3.78)%,respectively.The number of invasive cells in control group,NC group,overexpression group and co-transfection group were 161.02±10.31,155.87±12.30,85.21±9.11 and 118.37±10.84,respectively.There were statistically significant differences in the above indexes between transfection group and overexpression group,control group and NC group(all P<0.05),and there were statistically significant differences between overexpression group and control group and NC group(all P<0.05).Conclusion Overexpression of miR-133a-3p in human breast cancer cells MCF-7 can inhibit CAND1 and promote apoptosis and invasion of MCF-7 cells.
9.Influences of Lycium barbarum polysaccharide on apoptosis of corneal epithelial cells induced by hypertonicity through regulation of AMPK/ULK1 autophagy pathway
Wen-Wen TIAN ; Zhi-Xue DUAN ; Jian-Zhong PU ; Jing WANG ; Peng LÜ
The Chinese Journal of Clinical Pharmacology 2024;40(1):42-46
Objective To investigate the influences of Lycium barbarum polysaccharide on apoptosis of corneal epithelial cells induced by hypertonicity through regulating adenosine monophosphate activated protein kinase(AMPK)/uncoordinated 51-like kinase 1(ULK1)autophagy pathway.Methods The ophthalmoxerosis cell model was established by osmotic pressure of 500 mOsm·L-1 on corneal epithelial cells.They were divided into model group,positive control group(0.3%sodium hyaluronate eye drops),inhibitor group(1 mg·mL-1 Lycium barbarum polysaccharide+10 μmol·L-1compound C),experimental-L,-H groups(0.5,1.0 mg·mL 1 Lycium barbarum polysaccharide),and normal cultured CRL-11135 cells were taken as blank group(no treatment was performed).Cell apoptosis was detected by flow cytometry.Autophagy was detected by MDC staining.Western blot was used to detect the expressions of p-AMPK/AMPK and p-ULK1/ULK1.Results The apoptosis rates of experimental-L,experimental-H,positive control,inhibitor,model and blank groups were(26.47±2.13)%,(13.68±2.21)%,(12.54±2.16)%,(18.73±2.12)%,(37.56±3.25)%and(6.35±2.14)%;the relative contents of autophagosomes were(59.63±8.14)%,(89.89±9.04)%,(90.31±9.13)%,(62.75±7.26)%,(43.11±6.45)%and(100.00±0.00)%;p-AMPK/AMPK were 0.45±0.07,0.64±0.08,0.66±0.06,0.53±0.04,0.34±0.05 and 0.87±0.06;p-ULKl/ULKl were 0.54±0.06,0.75±0.05,0.77±0.03,0.65±0.04,0.46±0.04 and 0.92±0.08,respectively.The above indexes in experimental-L,-H groups and positive control group were significantly different from those in model group(all P<0.05);the above indexes in inhibitor group were significantly different from those in experimental-H group(all P<0.05).Conclusion Lycium barbarum polysaccharide can inhibit the apoptosis of corneal epithelial cells induced by hypertonicity by activating the AMPK/ULK1 autophagy pathway.
10.Effects of rhynchophylline on methamphetamine-dependent SH-SY5Y cells model and expression of miR-375-3p/Elavl4
Han-Cheng LI ; Ming ZENG ; Yi-Ling CHEN ; Ling-Hong CHEN ; Zhi-Xian MO
The Chinese Journal of Clinical Pharmacology 2024;40(1):47-51
Objective To investigate the effects of rhynchophylline on methamphetamine-dependent SH-SY5Y cells model and microRNA-375-3p(miR-375-3p)/embryonic lethal abnormal vision drosophila-like 4(Elavl4)expression.Methods A methamphetamine-dependent cell model by maximum safe dose induction was established.The cells were divided into normal group(complete culture medium),control group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 48 h),model group(complete culture medium+100 μmnol·L-1 methamphetamine incubated for 48 h)and experimental group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 15 min,then 100 μmol·L-1 methamphetamine incubated for 48 h).The cyclic adenosine monophosphate(cAMP)and 5-hydroxytryptamine(5-HT)expression were detected by enzyme-linked immunosorbent assay(ELISA),miR-375-3p expression was detected by quantitative real time polymerase chain reaction(qRT-PCR),and Elavl4 expression was detected by Western blot.Results The cAMP expression levels of normal group,control group,model group and experimental group were(6.33±0.93),(6.57±1.12),(10.89±1.03)and(7.81±1.32)pmol·mg-1;5-HT were(682.46±17.32),(690.31±15.09),(510.11±27.67)and(649.99±21.42)pg·mL-1;miR-375-3p expression were 1.00±0.13,1.13±0.24,3.48±0.18 and 1.58±0.19;Elavl4 expression were 1.00±0.05,0.89±0.10,0.50±0.09 and 0.90±0.11,respectively.The differences between above indicators in model group and normal group were statistically significant(P<0.01,P<0.05);the differences between above indicators in experimental group and model group were statistically significant(P<0.01,P<0.05).Conclusion This study preliminarily established a methamphetamine-dependent cell model,and also found that rhynchophylline may regulate miR-375-3p/Elavl4 expression to antagonize methamphetamine addiction.

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