Table of Content

Volume 24 Issue 2
26 February 2019

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Mechanism of PI3K/AKT/mTOR signaling pathway on apoptosis of hepatocyte induced by GCDC

WENG Dandan, WANG Junbo, LI Guangxiao

2019, 24(2):  121-127.  doi:10.12092/j.issn.1009-2501.2019.02.001

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AIM: To investigate the effects of PI3K/AKT/mTOR signaling pathway on proliferation and apoptosis of human hepatocyte HL-7702 induced by GCDC. METHODS: HL-7702 cells were divided into control group, GCDC group (1 mmol/L GCDC pretreated cells for 4 hours), GCDC+LY294002 group (GCDC treated cells for 4 hours, LY294002 treated cells for 24 hours) and GCDC+IGF-1 group (GCDC treated cells for 4 hours, 20 nmol/L of IGF-1 treated cells for 24 hours). After treatment, the expressions of PI3K, AKT, p-AKT, mTOR, p-mTOR, Bcl-2, Bax and Nrf2 were detected by Western blot; the proliferation and apoptotic rates were detected by MTT and Annexin V-FITC/PI double staining,respectively.The content of ROS was detected by fluorescent DCFH-DA probe. RESULTS: GCDC could significantly down-regulate the expression of PI3K, p-AKT, p-mTOR, Bcl-2 and Nrf2 in HL-7702 cells, up-regulate the expression of Bax, inhibit cell proliferation, induce apoptosis and induce ROS production (P<0.05). LY294002 could enhance the effect of GCDC on proliferation, apoptosis, ROS level and PI3K, p-AKT, p-mTOR, Bcl-2, Bax and Nrf2 expression of HL-7702 cells; IGF-1 vice versa. CONCLUSION: Activation of PI3K/AKT/mTOR signaling pathway can improve bile liver fibrosis, and the mechanism may be related to anti-apoptosis and anti-oxidation.

Mechanism of 17β-estradiol on p38MAPK signal transduction pathway in propofol-induced hippocampal neuronal apoptosis in developing rats

DU Tianping, MENG Zudong

2019, 24(2):  128-133.  doi:10.12092/j.issn.1009-2501.2019.02.002

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AIM: To investigate the mechanism of 17β-estradiol on the apoptosis of rat hippocampal neurons induced by propofol. METHODS: Sixty SD rats were randomly divided into 5 groups: control group (NS group), propofol group (P group) and 17β estradiol group (D1, D2 and D3 groups), with 12 rats in each group. The rats in the NS group were intraperitoneally injected with equal volume of fat emulsion. The rats in the P group were only intraperitoneally injected with propofol. The rats in the D1, D2 and D3 groups were intraperitoneally injected with 300, 600 and 900 μg/kg 17β estradiol, respectively. After 30 min, propofol was intraperitoneally injected. The respiratory rate (R0, R30, R60, R90), escape latency (TD1, TD2, TD3, TD4, TD5), hippocampal neuronal apoptosis index (AI) and cleaved caspase-3, p-p38 and p-NF-κB protein expression level were observed. RESULTS: Compared with the NS group, the respiratory rate of the rats in the P group was increased after the injection of propofol (P＜0.05). Compared with the P group, the respiratory rate of the D1, D2 and D3 groups was slower (P＜0.05). The escape latency of rats in group P was significantly longer than that in NS group (P＜0.05). The escape latency of group D1, D2 and D3 was significantly lower than that of group P (P＜0.05). The AI of the rats in the P group was significantly higher than that in the NS group, and the D1 group, the D2 group and the D3 group were significantly lower than the P group (P＜0.01). Compared with NS group, the expression of cleaved caspase-3, p-p38 and its downstream p-NF-κB increased in group P (P＜0.01). Compared with group P, group D1 and D2, D3, the expression of p-p38, cleaved caspase-3 and its downstream p-NF-κB was down-regulated (P＜0.01). CONCLUSION: 17β-estradiol can alleviate the apoptosis of rat hippocampal neurons induced by propofol, and its mechanism may be related to the inhibition of p38MAPK signaling pathway.

Effects of dexamethasone on the Notch signaling pathway and apoptosis-associated genes in acute pancreatitis

KONG Lingyu, XI Zan, YANG Yaqin, MA Wenting, WU Wei, HAO Tongqin

2019, 24(2):  134-139.  doi:10.12092/j.issn.1009-2501.2019.02.003

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AIM: To explore the effect of dexamethasone on the expression of Notch1，Hes1, Bax and Bcl-2 in pancreas in acute pancreatitis(AP). METHODS: Caerulein was used to set up AP animal model. The experimental groups were the saline group (control group), the model group (AP group) and dexamethasone group (DEX group). The content of TNF-α and IL-6 in serum in each group was detected using ELISA method. RT-qPCR was used to detect expression of Notch1, Hes1, Bax and Bcl-2 mRNA in pancreas in each group. Western blot was used to detect expression of Notch1, Hes1, Bax and Bcl-2 protein in pancreas in each group. RESULTS:The results of ELISA test showed that dexamethasone could significantly reduce the content of TNF-α and IL-6 in serum, comparing with the model group. The RT-qPCR and Western blot results showed that dexamethasone could significantly reduce the expression of Notch1, Hes1, Bcl-2 mRNA and protein in pancreas, but increase the expression of Bax mRNA and protein, as compared with the AP group. CONCLUSION: Dexamethasone could inhibit activation of the Notch signaling pathway, reduce expression of Notch1 and Hes1, further inhibit expression and antiapoptotic effect of Bcl-2 and promote expression and pro-apoptotic effect of Bax, promote apoptosis and reduce necrosis of pancreatic acinar cells, reduce the synthesis and release of TNF-α and IL-6.

Effects of coumarins from Angelica dahurica on chemotherapeutic sensitivity of human breast cancer cells

DONG Wei, TANG Xilan, ZHAO Guowei, JIANG Qieying, LIAO Zhenggen, LIANG Xinli

2019, 24(2):  140-146.  doi:10.12092/j.issn.1009-2501.2019.02.004

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AIM: To investigate the effects of coumarins from Angelica dahurica (imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, isopsoralen) on chemotherapeutic sensitivity of two different breast cancer cell lines, MCF-7 and MDA-MB-231. METHODS: MCF-7 and MDA-MB-231 cells were treated with different concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay.MCF-7 and MDA-MB-231 cells were treated with different doses of adriamycin in combination with the maximum nontoxic concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay. RESULTS:Five furanocoumarins, especially imperatorin, byakangelicolin caused an antiproliferative effect in MCF-7 cells. The IC50 values of imperatorin, byakangelicolin in MCF-7 cells at 72 h post-treatment were 68.24 μg/mL and 54.20 μg/mL, respectively. Imperatorin, isoimperatorin, oxypeucedanin and isopsoralen caused an antiproliferative effect in MDA-MB-231 cells. The IC50 values of isoimperatorin, imperatorin in MDA-MB-231 cells at 72 h post-treatment were 44.64 μg/mL and 71.11 μg/mL respectively. Byakangelicolin had weak or no effects on the proliferation. Compared with the adriamycin group, the inhibitory effect of adriamycin combined with imperatorin, isoimperatorin and byakangelicolin on the proliferation of MCF-7 and MDA-MB-231 cells was more obvious. The value of IC50 was decreased and the potentiation folds of adriamycin was increased.CONCLUSION: Imperatorin, oxypeucedanin and byakangelicol can inhibit proliferation of MCF-7 cells and MDA-MB-231 cells, and enhance the chemotherapeutic sensitivity.

Protective effect of Liquiritigenin on H9C2 cardiomyocytes apoptosis induced by high glucose

ZHUO Fengqiao, HUANG Zhanhong, LIU Yujie

2019, 24(2):  147-151.  doi:10.12092/j.issn.1009-2501.2019.02.005

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AIM: To evaluate the potential effect and mechanism of Liquiritigenin on apoptosis of H9C2 cardiomyocytes induced by high glucose. METHODS: H9C2 cardiomyocytes were cultured and were divided into the following groups: control group, high glucose group (HG group), high glucose with Liquiritigenin treated group (final concertration: 10, 30, 100 nmol/L). CCK-8 assay was used to detected cell viability. Malonaldehyde (MDA) levels and superoxide dismutase (SOD) activity were measured by certain kits. Reactive oxygen species (ROS) production and the percentage of apoptosis of the H9C2 cardiomyocytes were determined by flow cytometry. Western blot was used to evaluate the expression levels of Bcl-2 and Bax. RESULTS:CCK-8 assay demonstrated that Liquiritigenin (final concertration: 30, 100 nmol/L) significantly enhanced cell viability after high glucose treated (P<0.05, P<0.05). Meanwhile, Liquiritigenin (final concertration: 30, 100 nmol/L) decreased the generation of MDA (P<0.05，P<0.05) and ROS (P<0.05，P<0.05), but increased the activity of SOD (P<0.05，P<0.05). Moreover, Liquiritigenin (final concertration 100 nmol/L) reduced apoptosis rate by high glucose though increasing the ratio of Bcl-2/Bax ratio (P<0.01). CONCLUSION: Liquiritigenin protected H9C2 cardiacmyocytes from high glucose injury through reducing oxidative stress and apoptosis.

Mechanism of butylphthalide activating cAMP/CREB/BDNF signaling to improve cognitive impairment after ischemia-reperfusion in mice

GUAN Qiaobing, HAN Chenyang, CHU Zhiyuan, YANG Yi, ZHANG Xiaoling

2019, 24(2):  152-157.  doi:10.12092/j.issn.1009-2501.2019.02.006

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AIM: To study the mechanism of butylphthalide to improve the cognitive impairment after ischemia-reperfusion in mice by stimulating cAMP/CREB/BDNF signal and to provide support for the study of butylphthalide.  METHODS: The cognitive impairment model （VCI）was induced by repeated ligation of bilateral common carotid arteries in mice with ischemia-reperfusion injury. The mice were divided into sham operation group, model group and drug group. The drug group was treated with 5, 10, 20 mg/kg butylphthalide (NBP). The Morris water maze test was used to detect the cognitive ability of mice. Nissl staining was used to observe the morphology of neurons in the hippocampus of mice. The activity of SOD, the level of malondialdehyde (MDA) and nitric oxide (NO) were detected by colorimetric method. The expression of cyclic adenosine phosphate (cAMP), phosphorylated cyclic phosphoric acid (p-CREB) and brain derived neurotrophic factor (BDNF) in the hippocampus were detected by Western blot. RESULTS:Compared with the sham operation group, the cognitive function of the model group was decreased (P<0.05), the SOD expression level in the hippocampus tissue of the model group was decreased, and the levels of MDA and NO were increased (P<0.05), and Nissl staining showed that the neuron cell degeneration and necrosis were found in the model group and the expression of cAMP/CREB/BDNF signal was inhibited (P<0.05). Compared with the model group, after NBP intervened, the cognitive ability of mice was significantly improved (P<0.05), the level of SOD in hippocampus was up-regulated, and the levels of MDA and NO were decreased in a dose-dependent manner (P<0.05). The cAMP/CREB/BDNF signal activated the expression of key proteins cAMP, p-CREB and BDNF increased. Nissl staining showed that the apoptosis of neurons in hippocampus was reduced after NBP intervention. CONCLUSION: NBP can activate cAMP/CREB/BDNF signal to improve cognitive function after ischemia and reperfusion, which is one of the mechanisms of butylphthalide improvement of cognitive impairment after stroke.

Population pharmacokinetics of vancomycin in elderly infectious patients

ZHU Min, ZHANG Cuifeng, GUO Yiyun, ZHU Ziming

2019, 24(2):  158-163.  doi:10.12092/j.issn.1009-2501.2019.02.007

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AIM: To develop a population pharmacokinetic model of vancomycin in elderly infectious patients and evaluate the effect of individual factors on the pharmacokinetics of vancomycin. METHODS: A total of 130 steady state blood vancomycin concentration monitoring data were collected from 71 cases of elderly infectious patients. Phoenix NLME (Version 8.0) software was used to assess the influence of demographic characteristics on pharmacokinetic characters of vancomycin and establish the vancomycin population pharmacokinetics model in elderly patients. Then, verify the final model. RESULTS:One-compartment model was fitted to the vancomycin concentration data. The population value of V and CL were 33.44 L and 2.16 L/h, respectively. CL was found to be significantly related to the covariate of Ccr (P<0.01). CONCLUSION: The population pharmacokinetic model of vancomycin was established successfully in elderly infectious patients. The final model could be used to provide accurate individual pharmacokinetic parameters. CL was significantly influenced by the covariate of Ccr, which showed that it is better to administer drug according individual Ccr in clinical practice.

Sample size estimation for average bioequivalence for highly variable drugs using two replicated crossover designs

WANG Ao, CAI Jingjing, BAI Jianling, LIU Yue, YU Xuanxuan, CHEN Feng, ZHAO Yang, YU Hao

2019, 24(2):  164-170.  doi:10.12092/j.issn.1009-2501.2019.02.008

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AIM: To study the sample size estimation for average bioequivalence for highly variable drug using two replicate crossover designs recommended by FDA and EMA. METHODS: The variance of two replicated crossover designs is derived under the framework of statistical model, and the method of Reference-Scaled Average Bioequivalence recommended by FDA and EMA is combined to estimate the sample size by the relationship between power and sample size. SAS program is compiled to facilitate the application in research for researchers. RESULTS:The variance of two replicated crossover designs is equal, at the same time, combining the Reference Scaled Average Bioequivalence recommended by FDA and EMA, it is found that the sample size required under EMA is larger than the sample size of FDA under the same parameter configuration. When CV equals 30%, sample size estimation of EMA is continuous, while the sample size of FDA is discontinuous. When CV is greater than 50%, because EMA uses a fixed equivalent boundary, the sample size begins to increase, and FDA is still scaled equivalent boundary, so the sample size is decreasing or remains unchanged. CONCLUSION: The sample size estimation based on the variances of two replicated crossover designs using best linear unbiased estimator and Reference-Scaled Average Bioequivalence has the rigorous mathematical statistics. It is hoped to provide a help for sample size estimation for highly variable drugs bioequivalence studies.

Association of insulin-like growth factor(IGF)-1 polymorphisms and efficacy of antihypertensive drugs

CHEN Yan, ZHU Lijun, FANG Zhengmei, ZHU Hui, JIN Yuelong, SHEN Chong, YAO Yingshui

2019, 24(2):  171-179.  doi:10.12092/j.issn.1009-2501.2019.02.009

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AIM: To evaluate the association between IGF-1 genetic polymorphisms and blood pressure response to antihypertensive drugs. METHODS:A case-sectional study of 780 hypertension patients taking compound reserpine, Jiang Ya Tablet and Zhenju Jiang Ya Tablet were recruited.Five tagging single nucleotide polymorphisms of IGF-1 gene (rs5742612, rs35767, rs6214, rs6218, rs6219) were selected, and the genotyping was performed by TaqMan technique. A quantitative trait analysis and stratification analysis were performed for evaluating the relation between IGF-1genetic variation and blood pressure by taking different antihypertensive drugs. RESULTS:Quantitative trait analysis showed that there were significant differences in diastolic blood pressure (DBP) among the genotypes(GG,GA and AA) of rs6219 in hypertensive taking Jiang Ya Tablet after adjusting the covariant (P=0.01). In hypertensive taking compound reserpine, rs5742612 T/C and rs6218 T/C were significantly associated with systolic blood pressure（SBP）after adjustment for covariates, P values of 0.04 and 0.017, respectively. In hypertensive taking Zhenju Jiang Ya Table, after adjusting the covariant, the variation of rs6218 significantly related to DBP, and the variation of rs6219 was associated with SBP(The P values were 0.017 and 0.033, respectively).Further stratification analysis indicated that in female hypertensive taking Jiang Ya Tablet, SBP significantly decreased with the variation (T>C) of rs37567 (P=0.028). Interestingly, in male hypertensive taking Jiang Ya Tablet, DBP significantly increased with the variation of rs37567 (P=0.038). CONCLUSION: IGF-1 gene polymorphism is significantly related to efficacy of antihypertensive drugs including compound reserpine, Jiang Ya Tablet and Zhenju Jiang Ya Tablet, and may serve as a useful biomarker for the treatment of hypertension and gene therapy.

Influence of programmed death-ligand 1 genetic variation on the clinical outcomes of postoperative CRC patients received 5-FU based adjuvant chemotherapy

BAI Yan, ZHENG Xiaoyong, YANG Yage, FANG Lifeng

2019, 24(2):  180-187.  doi:10.12092/j.issn.1009-2501.2019.02.010

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AIM: To investigate the association between PD-L1 genetic variation and clinical outcomes of postoperative CRC patients received 5-FU based adjuvant chemotherapy. METHODS: Designed as a retrospective analysis, a total of 213 CRC patients who underwent surgical treatment and received 5-FU based adjuvant chemotherapy were included in this study. Baseline characteristics and the clinical outcomes data of the patients included in this study were managed. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of the genetic variation and PD-L1 mRNA expression, respectively. The correlation between genetic variation and other baseline characteristics was analyzed by chi square test and non-parametric test. The mRNA expression of PD-L1 in different genotypes was analyzed by non-parametric test. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate was adjusted by Cox regression analysis. RESULTS:The single nucleotide polymorphism included in this this study were collected in the NCBI database with the minor allele frequency >10% in Chinese population (901T>A, -1813G>C and -1349T>A). Of the polymorphisms analyzed, only 901T>A was of clinical significance. Located in the Intron region, the prevalence of 901T>A among the CRC patients were as follows: TT genotype 148 cases (69.48%), TC genotype 59 cases (27.70%), CC genotype 6 cases (2.82%), the minor allele frequency was 0.17.The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.967). TC genotype and CC genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Disease-free survival (mDFS) of patients with TT and TC/CC genotypes was 4.7 and 3.3 years, which was statistically significant (P=0.001). In terms of overall survival (OS), the median OS (mOS) of the two genotypes were 6.5 and 4.7 years respectively, which was statistically significant as well (P<0.001). Adjusted in multivariate Cox regression analysis for OS, TC/CC genotype was an independent factor for OS (OR=1.89, P=0.006). Additionally, of the 79 postoperative tissue specimens, the results showed that the mRNA expression of PD-L1 in cancer tissues of the patients with TC/CC genotypes were significantly higher than those of the TT genotype patients (P<0.001). CONCLUSION: The clinical outcomes of CRC patients receiving 5-FU based adjuvant chemotherapy may be influenced by PD-L1 901T>A through mediating the mRNA expression of PD-L1.

Effects of ABCB13435C/T and 2677T/G gene polymorphisms on serum concentration of digoxin in Han population

JIANG Hui，MIAO Miao，XU Wenke

2019, 24(2):  188-191.  doi:10.12092/j.issn.1009-2501.2019.02.011

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AIM: To investigate the effect of ABCB1 gene polymorphism on serum concentration of digoxin. METHODS: Patients with chronic congestive heart failure who received digoxin treatment from January to December 2016 were selected. ABCB13435C/T and 2677T/G genotyping were performed on patients by fluorescence staining in situ hybridization analysis. All patients were treated with digoxin 0.125 mg/daily，5 days after continuous use，fluorescence polarization immunoassay was used to detect digoxin serum valley concentration.To compare the differences of digoxin serum concentrations in patients with different genotypes of ABCB13435C/T and 2677T/G. RESULTS:In 93 patients，the mutation rates of ABCB13435C/T and 2677T/G genes were 38.17% and 28.49% respectively，and there was no significant difference in gene distribution frequency between male and female.Compared with 3435CC/CT and 2677TT/TG genotype patients, the serum concentrations of 3435TT and 2677GG digoxin increased significantly (P<0.001). CONCLUSION: ABCB1 gene polymorphism can affect digoxin serum concentration，but it needs further clinical validation.

Pharmacokinetic study and safety assessment of lacosamide tablets in Chinese healthy subjects under fasting condition

KANG Hui, YONG Xiaolan, HU Tingting, CHU Bixin, WANG Lantian

2019, 24(2):  192-197.  doi:10.12092/j.issn.1009-2501.2019.02.012

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AIM: To investigate the pharmacokinetic properties and safety of a single dose of 100 mg of lacosamide tablets in Chinese healthy subjects under fasting condition. METHODS: One single-dose, open-label, randomized and crossover study of oral lasosamide tablets was conducted in 24 healthy subjects,who were administrated test or reference preparation 100 mg under fasting condition. After a washout period of 7 days, the subjects were orally administrated with another preparation. Plasma samples were collected before and after each 24 subjects given a tablet.Concentrations of lacosamide were determined by LC-MS/MS. Pharmacokinetic parameters, including AUC0-t，AUC0-∞，Cmax，etc., were calculated with WinNonlin 6.3. Safety assessment was performed throughout the experiment. Vital signs, laboratory tests and adverse events were recorded, which was used to assess the safety of preparations.RESULTS:All 24 subjects completed the trial and were taken into pharmacokinetic analysis and safety judgment. The main pharmacokinetic parameters of the two preparations, including AUC0-t,AUC0-∞,Cmax, were basically consistent and no significant differences were found. The overall incidence of adverse events during the trial was 50%. The incidence of adverse events of the test preparation was 12.5%, and that of reference preparation was 4.2%. The severity of all adverse events was grade 1 and there was no serious adverse events observed.CONCLUSION: Domestic lacomide tablet has good safety and tolerance in Chinese healthy volunteers, and its pharmacokinetic parameters are basically same as that of imported drugs.

Effects of Qingchang zhili soup and moxibustion on ulcerative colitis and inflammatory factors

ZHENG Weiwei, WANG Jiajia

2019, 24(2):  198-204.  doi:10.12092/j.issn.1009-2501.2019.02.013

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AIM:To expolre the effect of Qingchang zhili soup and moxibustion on ulcerative colitis and inflammatory factors. METHODS:From July 2016 to May 2017,a total of 110 patients with ulcerative colitis in our hospital were randomly divided into combined treatment group(55 cases) and control group(55 cases),the control group was treated with methalazine,0.8 g,3 times/d, and the combined treatment group received extra Qingchang zhili soup,100 mL,1 time/d and moxibustion,30 min/d,the course of treatment were 2 weeks.The curative effect,TCM syndrome scoring,the Improve Mayo activity index,Baron endoscopy grading,inflammatory cytokines including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8) before and after treatment were compared,the adverse reactions during the treatment were also recorded and compared. RESULTS:The total effective rate of the combined treatment group was significantly higher than that of the control group（χ2=6.111，P=0.013）.There was no significant difference in TCM syndrome score between the two groups before treatment（P＞0.05）,both groups decreased significantly after treatment（P＜0.05）,the syndrome score of the combined treatment group was significantly lower than control group（P＜0.05）.There was no significant difference in Improve Mayo activity index and Baron endoscopy grading between the two groups before treatment（P＞0.05）,they were significantly reduced in both groups after treatment（P＜0.05）,the scores in combined treatment group were significantly lower than those of the control group（t=-17.407，-13.671；P=0.000，P=0.000）.There was no significant difference in levels of TNF-α, IL-6, IL-8 between the two groups before treatment（P＞0.05）, they were significantly reduced in both groups after treatment（P＜0.05）,the levels in combined treatment group were significantly lower than the control group（t=-19.611，-7.391，-5.404；P=0.000，P=0.000，P=0.000）.There was no significant difference in incidence of adverse reactions between the two groups（7.27% vs.14.55%；χ2=0.842，P=0.359）.CONCLUSION:The efficacy of Qingchang zhili soup and moxibustion in the treatment of ulcerative colitis is positive;it can better control the intestinal mucosal inflammation and inflammatory factor levels.

Clinical effect observation of Ping gan zi yin tong yu Fang combined with amlodipine besylate in the treatment of hypertension

WANG Jiaxin, YANG Guanlin, PENG Bo

2019, 24(2):  205-211.  doi:10.12092/j.issn.1009-2501.2019.02.014

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AIM: To explore the clinical effect of Ping gan zi yin tong yu Fang combined with amlodipine besylate in the treatment of hypertension. METHODS: From June 2017 to June 2018, 90 patients who met the inclusion criteria were randomly divided into treatment group and control group, each group of 45 cases, the control group was given amlodipine besylate, the treatment group was given amlodipine besylate combined with Ping gan zi yin tong yu Fang. After 15 days of treatment, the clinical effects of the two groups were observed. RESULTS: After treatment, the total effective rate, blood pressure drop level, TCM syndromes and quality of life of patients in the treatment group were better than those in the control group (P<0.05). CONCLUSION: Ping gan zi yin tong yu Fang combined with amlodipine besylate is effective in the treatment of hypertension with low incidence of adverse reactions, which can be further applied in clinical practice.

Effects of vertebroplasty combined with Bushen Buxue Recipe on postoperative inflammatory factors and re-fracture in patients with vertebral fracture

SHI Tieying, ZHOU Qihao, FENG Li, ZHOU Dongming, HOU Zhenhai

2019, 24(2):  212-217.  doi:10.12092/j.issn.1009-2501.2019.02.015

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AIM: To study the effect of vertebralplasty combined with Bushen Buxue Recipe on postoperative inflammatory factors and re-fracture in patients with vertebral fracture.  METHODS: From April 2013 to May 2016, 96 patients with vertebral fracture treated with vertebroplasty were selected and randomly divided into study group (combined with the Chinese herbal compound of tonifying kidney and blood) and control group, 48 cases in each group. The clinical efficacy was evaluated by comparing the levels of TNF-α, IL-1, IL-6, lumbar vertebrae and thoracic vertebrae bone mineral density, re-fracture rate, pain and swelling and so on after treatment in two groups. RESULTS:After treatment, the levels of TNF-α, IL-1 and IL-6 in the study group were significantly lower than the control group, the difference was significant (P<0.01); the pain, swelling and Barthel index (BI) were significantly better than the control group, the difference was statistically significant (P<0.01); lumbar vertebrae bone density and thoracic vertebrae bone density were significantly higher than the control group, the difference was statistically significant (P<0.05); the incidence of re-fracture was significantly higher in the study group during the 12-month follow-up period. The lower than the control group, the total effective rate of treatment was significantly higher than the control group, the difference was statistically significant (P<0.05). CONCLUSION:Vertebral fracture patients treated with vertebroplasty combined with Chinese herbal compound of tonifying kidney and blood can effectively inhibit postoperative inflammatory response, relieve pain and swelling, improve bone mineral density, reduce the risk of fracture and improve the quality of life and efficacy.

Effects of conbercept combined with vitrectomy on the aqueous humor VEGF and SDF-1 in patients with diabetic macular edema

ZHANG Huang, QUAN Chanjuan, YANG Xinhuai, HUANG Shulan, GAO Songzhe, WANG Xiao, CHEN Rong, CHEN Lan

2019, 24(2):  218-222.  doi:10.12092/j.issn.1009-2501.2019.02.016

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AIM: To discuss the effect of conbercept combined with vitrectomy (VT) on the aqueous humor vascular endothelial growth factor (VEGF) and human stromal cell derived factor 1 (SDF-1) in patients with diabetic macular edema (DME). METHODS: A total of 100 patients with DME were selected from March 2015 to March 2018 in our Hospital according to the random digital table method, they were divided into VT group and conbercept group, 50 cases in each group.VT group was given VT treatment while conbercept group was given extra intravitre injection therapy of conbercept. The aqueous humor VEGF, SDF-1 and complications, macular central retinal thickness (CMT), best corrected visual acuity (BCVA) were compared between the two groups. RESULTS: The postoperative aqueous humor VEGF and SDF-1 in the VT group and the conbercept group were significantly lower than those in the preoperative, the postoperative aqueous humor VEGF and SDF-1 in the VT group were significantly lower than those in the conbercept group, the difference was statistically significant (P<0.05). The complication rate in the VT group were significantly lower than those in the conbercept group, the difference was statistically significant (P<0.05). The 1 d, 1 month, 3 months postoperative BCVA and CMT in the VT group and the conbercept group were significantly lower than those in the preoperative, the 1 d, 1 month, 3 months postoperative BCVA and CMT in the VT group were significantly lower than those in the conbercept group, the difference was statistically significant (P<0.05). CONCLUSION: Conbercept combined with VT can effectively improve the aqueous humor VEGF and SDF-1 in patients with DME, which is beneficial to reduce the complications, and it can effectively improve BCVA and CMT in patients, it's worth for further clinical promotion.

Study and rationality evaluation on off-label drug use of traditional Chinese medicine injection

SHEN Bin，JIANG Liya，WANG Xiaoling，XU Longsheng，LU Xiaolei，HE Jiayang，SUN Peiyu，ZHOU Yuehong，ZHANG Xiaoping

2019, 24(2):  223-227.  doi:10.12092/j.issn.1009-2501.2019.02.017

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AIM: To understand off-label drug use of traditional Chinese medicine injection, and to provide reference for establishing off-label drug use evaluation standard and standardized management of off-label drug use. METHODS: Based on the drug instructions, 24 cases of each of the top 10 Chinese medicine injections discharged from hospital in 2017 were statistically analyzed from the indication, dosage, route of administration, frequency of administration, drug concentration, course of treatment, selection of solvent, taboo and compatibility. Reference was made to the Chinese Medicine Diagnosis and Treatment Prescription issued by the State Administration of Traditional Chinese Medicine. The reasonableness of the case, the principle of syndrome differentiation, treatment of traditional Chinese medicine, and the literature were evaluated. RESULTS:Among the 240 discharge cases, 123 cases were treated with off-label drugs, among which the first three were super-functional attending treatment, over-dose course and super-solvent selection, some of which were recommended by TCM Diagnosis and Treatment Program or related guidelines, and 24 were suspected adverse drug reactions. CONCLUSION: Off-label drug use of traditional Chinese medicine injection is common, safety management should be strengthened and rational clinical use should be standardized.

Advances in the treatment of tacrolimus in idiopathic membranous nephropathy

FANG Xi, QU Qiang, XIAO Xiangcheng

2019, 24(2):  228-234.  doi:10.12092/j.issn.1009-2501.2019.02.018

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Tacrolimus is a calcineurin inhibitor that acts as an immunosuppressive agent. Idiopathic membranous nephropathy is the most common type of primary nephrotic syndrome. Compared with other immunosuppressive agents, tacrolimus has a smaller adverse effect and is more widely used in idiopathic membranous nephropathy. The application of tacrolimus in idiopathic membranous nephropathy has been studied in recent years. This paper summarizes the research progress of tacrolimus in idiopathic membranous nephropathy and its individualized usage.

Effects of genetic polymorphisms on metabolic kinetics, pharmacodynamics and adverse reactions of amitriptyline

WANG Ente, ZHANG Xiaodan, ZHOU Shuang, ZHAO Xia, ZHOU Ying, CUI Yimin

2019, 24(2):  235-240.  doi:10.12092/j.issn.1009-2501.2019.02.019

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Amitriptyline is a tricyclic antidepressant for the treatment of severe depression, post-traumatic stress disorder and other psychiatric diseases, which is widely used in clinical application. However, there are significant individual differences in the response of amitriptyline. Research has shown that genetics polymorphisms of CYP2D6, CYP2C19 and ABCB1 have certain effects on the pharmacokinetics (PK), pharmacodynamics (PD) and adverse reactions (ADR) of amitriptyline. In this paper, we have drawn a preliminary conclusion by comparing the effects of CYP2D6 and CYP2C19 gene polymorphisms on amitriptyline PK, PD and ADR. For CYP2C19 ultrarapid metabolizers or extensive metabolizers, the genetic polymorphism of CYP2D6 has a greater effect on the overall metabolism of amitriptyline. However, for CYP2C19 poor metabolizers, the genetic polymorphisms of CYP2C19 have greater influence. Hopefully, this article can provide genetic-based advice and assistance for the individualized administration of amitriptyline.