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Table of Content

    Volume 24 Issue 9
    26 September 2019
    Paeoniflorin inhibits mast cell activation and degranulation through PI3K/AKT/m-TOR signaling pathway
    YU Jiaojiao, YANG Yang, LIU Ying, GUO Xiaoxi, XU Tianrui, AN Shu
    2019, 24(9):  961-968.  doi:10.12092/j.issn.1009-2501.2019.09.001
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    AIM: To study the effects of paeoniflorin on the activation and degranulation of mast cells (P815), and further to explore the mechanism. METHODS: The toxicity of paeoniflorin on P815 cells was evaluated by CCK-8 method. The effects of paeoniflorin on the release of histamine and β-HEX and the secretion of inflammatory factors IL-1β, IL-4, IL-8 and IL-12 were determined by ELISA method and chromogenic method. The effects of paeoniflorin on the expression of inflammatory factors and PARs were detected by qRT-PCR. Western blot was used to study the phosphorylation levels of PI3K, AKT and m-TOR. RESULTS: Paeoniflorin had no cytotoxicity to P815 cells when the concentration was 1, 10, 100 μg/mL, but effectively inhibited the release of histamine, β-HEX and IL-1β, IL-4, IL-8 and IL-12 after mast cells activation, and reduced the expression of PARs at the mRNA level. Additionally, paeoniflorin greatly reduced the phosphorylation levels of PI3K, AKT, m-TOR in mast cells treated with agonists. CONCLUSION: Paeoniflorin is an efficient inhibitor for mast cell activation and degranulation by blocking the PI3K/AKT/m-TOR signalling pathway.

    Differential effects of nicotine addiction withdrawal on psychological and physical dependence
    LI Zhiyu, WANG Qin, LI Bo, WU Tong, GAO Daokuan, ZHANG Huanhuan, WANG Mengya, ZHENG Chao
    2019, 24(9):  969-976.  doi:10.12092/j.issn.1009-2501.2019.09.002
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    Roles of Prunella vulgaris L. in the proliferation and migration of vascular smooth muscle cells and its molecular mechanisms
    NIE Juan,CAO Yumei,YANG Dongmei,SUN Siyu,WANG Qiaoqiong, XIE Xuejiao, TUO Qinhui
    2019, 24(9):  977-982.  doi:10.12092/j.issn.1009-2501.2019.09.003
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    AIM: To investigate the effects of Prunella vulgaris L. (PV) on Ang II-induced proliferation of VSMCs and the effect of Daxx/PTEN/NF-κB signaling pathway. METHODS: The VSMCs line was cultured, and the cell proliferation model was induced by Ang-II (1 μmol/L) in vitro. The MTT and BrdU methods were used to detect the effects of VSMCs activity and proliferation by different concentrations of PV (10, 20, 40, 80,160 μg/mL) for 24 h. Cell migration was observed by scratch method, and Daxx, PTEN and NF-κB protein expression was detected by Western blot. RESULTS:Compared with the control group, the viability and cell migration ability of VSMCs in the model group were significantly enhanced. At the same time, the expression of Daxx and PTEN protein was significantly decreased, and the NF-κB protein was significantly up-regulated.Compared with the model group, PV (20, 40, 80 μg/mL) significantly inhibited VSMCs viability and cell migration ability in a concentration-dependent manner, with the most significant concentration at 80 μg/mL.Meanwhile, the expression of Daxx and PTEN protein were significantly up-regulated and NF-κB protein was down-regulated in VSMCs treated by PV. CONCLUSION: PV can inhibit the proliferation and migration of VSMCs induced by Ang-II , and the mechanism may be associated with increasing expression of Daxx and PTEN, inhibiting expression of NF-κB.

    Effects of intrauterine perfusion of growth hormone on thin endometrium
    CAO Zhiwen, HU Weihua
    2019, 24(9):  983-988.  doi:10.12092/j.issn.1009-2501.2019.09.004
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    AIM: To study the therapeutic effect of intrauterine perfusion of growth hormone on thin endometrium. METHODS: Thirty female SD rats were randomly divided into three groups: control group, model group and GH group. The control group was not treated and routinely reared. The model group and GH group were perfused with 95% ethanol during estrus to establish a thin endometrial model. Six to eight hours after modeling, the model group was perfused with 0.2 mL normal saline, and the GH group was perfused with 0.2 mL growth hormone. HE staining was used to observe the thickness of endometrium, the number of blood vessels and glands. The expression of keratin and vimentin in rat endometrium was detected by immunoblotting and immunohistochemistry. RESULTS:The intima thickness, endometrial gland and intimal vessels in the GH group were increased compared with the model group (P<0.01). The intimal thickness, endometrial gland and intimal vessels were increased in the control group compared with the model group (P<0.01). There was no significant difference in intimal thickness, intimal glandular and intimal vessels between the control group and the GH group. The expression of vimentin and keratin in the GH group was increased (P<0.01). The expression of vimentin and keratin in the control group was increased (P<0.01). There was no significant difference in the expression of vimentin and keratin between the control group and the GH group. CONCLUSION:Intrauterine perfusion of growth hormone can promote the regeneration and repair of thin endometrium in rats.

    Regulation of N-acetylcysteine on peripheral circulatory and hepatic myeloid-derived suppressor cells in non-alcoholic fatty liver disease mice
    WU Jiayuan, ZHENG Li, MO Juanfen, GUO Li, CAO Chenxi, BAO Yi
    2019, 24(9):  989-996.  doi:10.12092/j.issn.1009-2501.2019.09.005
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    AIM: To observe the local and systemic dysregulation of immune cells myeloid-derived suppressor cells (MDSCs) in high fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) mice, and to study the regulation function of N-acetylcysteine (NAC) on MDSCs and associated pro-inflammatory cytokines. METHODS: Thirty male C57B/L6 mice were equally divided into three groups: normal chow diet group (Lean), high fat diet group (HFD) and NAC group (NAC). After 16 weeks, liver pathological change was evaluated by HE and oil red O staining. The levels of MDSCs in peripheral blood and liver tissue were measured through flow cytometry and immunohistochemistry, respectively. The changes of MDSCs secreted pro-inflammatory cytokines S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding proteinA9 (S100A9) in mice liver were tested by real-time quantitative reverse transcription-polymerize chain reaction and western blot. RESULTS:Compared with lean group, HFD group mice exhibited hepatic steatosis and inflammatory cell infiltration. The frequencies of CD11b+Gr-1+ MDSCs in peripheral blood and Gr-1+ cells in liver tissue were elevated in HFD group as well (P<0.01). The mRNA and protein levels of S100A8 and S100A9 also were increased in the livers of HFD group mice (P<0.05). Hepatic steatosis was alleviated and liver-infiltrated inflammatory cells were reduced after NAC treatment. The frequencies of MDSCs in peripheral blood and liver tissue, as well as the levels of S100A8 and S100A9 were decreased by NAC (P<0.05). In addition, NAC effectively suppressed α-SMA level and ameliorated liver fibrosis. CONCLUSION:NAC may slow the progression of NAFLD by regulating MDSCs accumulation, inhibiting inflammation and fibrosis.

    Effects of trans-cinnamaldehyde on proliferation and apoptosis of LOVO cells of colon cancer
    ZENG Qiongyao, ZHANG Wenjing, ZHANG Yu, GUO Qiang
    2019, 24(9):  997-1001.  doi:10.12092/j.issn.1009-2501.2019.09.006
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    AIM: To explore the effects of trans-cinnamaldehyde on proliferation and apoptosis of LOVO cells of colon cancer. METHODS: The cell proliferation was detected by CCK-8 assay, and clone forming ability of colon cancer cells was detected by colony formation assay. The cell apoptosis was assessed by flow cytometry, and the expression of Bcl-2, Bax, and Caspase-3 was detected via Western blot. RESULTS:Trans-cinnamaldehyde significantly inhibited the proliferation and clone forming ability of the colon cancer cells LOVO in vitro. Compared with the control group, apoptosis rate of LOVO cells was significantly increased in the trans-cinnamaldehyde group (P<0.05). Expressions of Bcl-2 and Caspase-3 were increased in the trans-cinnamaldehyde group, with fragmented Bcl-2. CONCLUSION: The trans-cinnamaldehyde can inhibit cell growth and induce apoptosis of LOVO cells, which involves the up-regulation of Bax and Caspase-3 and the down-regulation of Bcl-2. (E)-cinnamaldehyde is a potnetial anti-tumor target of colon cancer.

    Effects of thymidine phosphorylase genetic variation on the prognosis of Her2 negative metastatic breast cancer patients treated with capecitabine based first line chemotherapy
    YIN Ziyi, WANG Feng, ZHAO Meng, ZHANG Tie, WANG Pilin
    2019, 24(9):  1002-1008.  doi:10.12092/j.issn.1009-2501.2019.09.007
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    AIM: To investigate the effect of thymidine phosphorylase genetic variation the (TYMP) prognosis of Her2 negative metastatic breast cancer patients treated with capecitabine based first line chemotherapy. METHODS: For retrospective analysis, 215 patients with metastatic breast cancer who were diagnosed as Her2 negative and received capecitabine-based first-line treatment in the Department of Mammary and Oncology, Beijing Tiantan Hospital Affiliated to Capital Medical University between January 2010 and December 2017 were enrolled in the study. The patients' peripheral blood was collected for TYMP gene mutation site typing, and the patients' biological specimens were retained for gene expression determination. The prognostic data were obtained by telephone follow-up. Kaplan-Meier survival analysis was used to analyze the association between different genotypes and prognosis, and Cox model was used to correct other variables.RESULTS:The genetic variation included in this study wAS collected in the NCBI database with the minor allele frequency >10% in Chinese population. Of the variations analyzed, only 1412C>T was of clinical significance. The prevalence of 1412C>T in analysis population were as follows: CC 137 cases (63.72%), CT 70 cases (32.56%), TT 8 cases (3.72%), minor allele frequency of 1412C>T is 0.20, the distribution of genetic variation were in accordance with Hardy-Weinberg Equilibrium (P=0.798). The efficacy analysis of patients with CT/TT and CC genotypes found that Objective remission rates (ORR) were 56.41% and 40.15% (P=0.021). And median progression-free survival (mPFS) was 11.5 and 7.6 months, respectively (P=0.001). Furthermore, the median overall survival (mOS) of the two genotypes was 26.6 and 24.7 months, respectively (P=0.022). After the analysis in Cox proportional hazards model for PFS, CT/TT was an independent factor for PFS (OR=0.56, P=0.011). Additionally, of the 87 postoperative tissue specimens, the results showed that the mRNA expression of TYMP in cancer tissues of the patients with CT/TT and CC genotype were significant difference (P<0.001). CONCLUSION: The clinical outcomes of Her 2 negative metastatic breast cancer patients receiving capecitabine based first line chemotherapy may be influenced by TYMP 1412C>T genetic variation through mediating the mRNA expression of TYMP.

    Pharmacokinetics and bioequivalence study of indapamide tablets
    PEI Tong, GAO Dan, WANG Chunhua, CHEN Xiaoping, GONG Shili, HU Xiao, HU Chaoying, ZHANG Lan
    2019, 24(9):  1009-1014.  doi:10.12092/j.issn.1009-2501.2019.09.008
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    AIM: To evaluate the pharmacokinetics and bioequivalence of 2 indapamide tablets in Chinese healthy subjects. METHODS: A single dose, randomized, open label, two- formulation, two-period crossover design was used. A total of 28 healthy subjects were randomly divided into 2 groups and given 1 tablet of test formulation (indapamide tablet, 2.5 mg/ tablet) or reference formulation (Natrilix, 2.5 mg/tablet) on fasted state. A total of 17 blood samples were collected before and within 72 h after administration, and the whole blood was fully mixed and packaged and stored in the refrigerator at -80 ℃ for storage. The indapamide concentration in human whole blood was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated and the bioequivalence was evaluated. During the study period, vital sign, physical examination and laboratory test were measured after administration for safety assessment. RESULTS:All 28 subjects completed the test. The 90% confidence intervals of the geometric mean ratios of the tested and reference preparations Cmax, AUC0-t and AUC0-∞ were 104.94%-119.90%, 98.90%-106.34% and 98.59%-104.40%, respectively, all of which were within the bioequivalence range of 80.00%-125.00%. During the study, a total of 4 subjects reported 4 mild adverse events and no serious adverse events. CONCLUSION: Two indapamide tablets were safe and bioequivalent in the empty stomach of healthy subjects.

    Research progress in population pharmacokinetics of voriconazole in adults
    LIU Simin, CAI Jun, LI Huixin, YANG Li, ZHAO Yan, ZHANG Jinping
    2019, 24(9):  1015-1023.  doi:10.12092/j.issn.1009-2501.2019.09.009
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    AIM: Voriconazole has strong antifungal activity and broad antifungal spectrum, but its pharmacokinetics is highly variable due to various factors. In this paper, the pharmacokinetic characteristics of voriconazole were described based on the population pharmacokinetic model, which provided a theoretical basis for the individualized use of voriconazole. METHODS: The pharmacokinetics of voriconazole was characterized by searching the literatures of voriconazole population pharmacokinetics in CNKI, Pubmed and Web of Science. RESULTS:Nine studies reported the PPK model of voriconazole was one-compartment models and 4 studies were two-compartment models. The main influencing factors of voriconazole pharmacokinetics were age, body weight, CY2C19 phenotype, liver function and concomitant medication. CONCLUSION: There is considerable variation between voriconazole individuals. For specific populations, it is especially important to develop a personalized dosing regimen.

    Influential factors of serum concentration/dosage ratio for schizophrenia patients after oral administration of olanzapine
    WAN Ping, LIU Liang, ZHANG Ping, ZHANG Zhongdong
    2019, 24(9):  1024-1029.  doi:10.12092/j.issn.1009-2501.2019.09.010
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    AIM: To investigate the factors affecting the serum concentration/dose ratio of olanzapine in schizophrenic patients. METHODS: The data of 304 schizophrenic inpatients in our hospital in 2018 were retrospectively collected, and the patients' medical records and medical orders were consulted. The C/D values of olanzapine were calculated. The effects of gender, age, BMI, source of olanzapine (domestic or imported), smoking, combined use of drugs and CYP1A2 metabolic enzyme genotype polymorphism on the C/D values were studied. RESULTS:The C/D mean value of male patients was (2.59±1.08) ng·mL-1·mg-1·d, and that of female patients was (3.14±1.80) ng·mL-1·mg-1·d. The C/D mean of female patients was significantly higher than that of male patients (P=0.032). The combination of hepatic enzyme inducers or inhibitors could significantly affect the C/D value of patients. Smoking could significantly reduce the C/D value of patients (P=0.024). The C/D value of patients with different ages and CYP1A2 genotype showed no significantly difference. BMI and the source of olanzapine (domestic or imported) had no significant effect on the C/D value of patients. CONCLUSION:The C/D value of olanzapine is mainly related to the gender of patients and the combination of drugs and smoking, and the genotype of patients should be fully considered.

    Methods and progress of clinical research on drug-drug interactions
    SHA Bijun, ZHOU Sufeng, WANG Lu, ZHAO Yuqing, CHEN Xijing, SHAO Feng
    2019, 24(9):  1037-1045.  doi:10.12092/j.issn.1009-2501.2019.09.012
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    Advanced of HER-2/neu epitope anti-tumor vaccine
    LIN Zhong, XIE Qunli, LI Shengying, JIN Hui, XU Fenfen, XIE Liyun, JIANG Zhengli
    2019, 24(9):  1046-1052.  doi:10.12092/j.issn.1009-2501.2019.09.013
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    Overexpression of HER-2/neu oncogene is a frequent molecular event in multiple human cancer, including breast cancer (20%-40%), colorectal cancer (54%-100%), ovarian cancer (25%). Therefore, HER-2/neu protein is one of the candidate target antigens for cancer, and has been proved to have the potential to develop anti-breast cancer vaccines. At present, a series of studies have been carried out on different types of HER-2 vaccines, including whole-cell vaccines, full-sequence protein vaccines, peptide vaccines and DC-induced vaccines, and some progress has been made. A baidu Scholar, PubMed, Springer and ScienceDirect database search was performed to review the advanced of the preparation technology and the mechanism of antineoplastic activity of tumor vaccine based on HER-2/neu antigen. As the conclusions shown in the present paper, CD4+T and CD8+T were activated successfully and the anti-tumor specific immune response was induced by the antigen presenting cells (APCs) presented with the HER-2/neu tumor vaccine antigenic epitope. The immunological and anti-tumor activity would be improved by the change of vaccine design process, such as the reform of composition structure, fusion expression with immune-boosting short peptides and dendritic cell induced. The defect of drug resistance and repeated administration accompanied by HER-2 monoclonal antibody treatment and the serious toxicity of traditional chemotherapy drugs treatment could be reduced by HER-2 anti-tumor vaccine treatment with the stable anti-tumor activity in the clinic trail, which would provide a new perspective of tumor treatment.

    Relevance of CYP2R1 genetic polymorphism and individual therapy
    LI Ling, ZHAO Huijia, CHEN Binyao, LIU Xiaohong, SUN Gongpeng, HAO Zhuowen, FAN Zhipeng, YUE Jiang, WU Jianguo, YE Qifa
    2019, 24(9):  1053-1059.  doi:10.12092/j.issn.1009-2501.2019.09.014
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    CYP2R1 is a member of the cytochrome P450 family 2 subfamily. As a 25-hydroxylase of vitamin D, it is responsible for the hydroxylation of vitamin D to 25-hydroxyvitamin D (25-OH-D), affecting the production of active hormone 1,25(OH)2D. The CYP2R1 mutation triggers a vitamin D-dependent rickets type 1B. The polymorphism of CYP2R1 is significantly correlated with the level of 25-OH-D, especially rs10741657. The CYP2R1 gene polymorphism affects its protein expression level and enzyme activity, and has a significant impact on the metabolic processes that it catalyzes. CYP2R1 regulates the immune response by regulating gene function and affects the risk of type 1 diabetes. Its polymorphism is associated with a variety of cancer risks, including breast cancer, prostate cancer, and colorectal cancer. Studying the CYP2R1 gene polymorphism is helpful for understanding the role of metabolic pathway changes in the development of related diseases, deepening the understanding of diseases such as cancer, rickets and type 1 diabetes, and promoting the detection and assessment of the risk of related diseases from the genetic level. This article reviews the research progress of metabolic pathways and gene polymorphisms involved in CYP2R1 in recent five years.

    Advances in the sensitization mechanism of chemotherapeutic drugs for bladder cancer
    XU Weiping, ZHOU Weiying
    2019, 24(9):  1060-1064.  doi:10.12092/j.issn.1009-2501.2019.09.015
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    In recent years, chemoresistance has seriously restricted the therapeutic effect of bladder cancer, and the recurrence rate and metastasis rate remain high. Therefore, it is very important to reverse the resistance of bladder cancer to chemotherapy, and find more effective target of chemosensitizion and explore its mechanism. Transurethral resection of bladder tumors is commonly used in treatment of bladder cancer currently, and adjuvant chemotherapy drugs are utilized after operation. The most chemotherapy drugs used in bladder cancer include cisplatin, gemcitabine, adriamycin and epirubicin. At present, the target genes and molecules for enhancing chemosensitivity of these drugs display various expression states in bladder cancer cells, and the mechanisms for enhancing chemosensitivity through these targets are also different. In this paper, we will review the research progress of target and mechanism of chemosensitizing drugs for bladder cancer, and explore new ideas for chemosensitizion of bladder cancer.

    Progress in basic research and clinical application of CDK4/6 inhibitor in tumor therapy
    WU Limei, CHENG Liyan, ZHENG Xiaoliang, WANG Xiaoju
    2019, 24(9):  1065-1069.  doi:10.12092/j.issn.1009-2501.2019.09.016
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    Cyclin-dependent kinase 4/6 (CDK4/6) is a serine/threonine kinase that regulates the phosphorylation state of retinoblastoma protein (Rb) by binding to cyclin D.Phosphorylated Rb releases E2F that freely activates a series of gene expression to participate in DNA replication and cell division, which mediates cell G1/S phase transition, affects the progression of the cell cycle. Recent studies have found that CDK4/6 plays a central role in tumorigenesis and development, and has become an important molecular target for clinical treatment of various tumors. This article will review the latest research progress in the relationship between CDK4/6 and tumors and the clinical application of CDK4/6 inhibitors.

    Research progress on the safety and effectiveness of escitalopram in the treatment of pregnant women with depression
    WANG Sijie,ZHANG Jun,LI Qian,HUANG Hua,WANG Jingjing,ZHOU Qiong,YAO Qin
    2019, 24(9):  1070-1074.  doi:10.12092/j.issn.1009-2501.2019.09.017
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    5-hydroxytryptamine reuptake inhibitor (SSRIs) has become a first-line anti-depressant in clinic,among which escitalopram is widely used in the treatment of major depression,and has achieved good therapeutic effect.However,for patients with gestational depression,the safety of using escitalopram during pregnancy is still uncertain.The safety and effectiveness of escitalopram in patients with gestational depression was reviewed in this paper.

    Application of traditional Chinese medicine extract in repairing spinal cord injury
    LU Yubao, CHEN Yutong, HE Gege, CAI Zongyan, CHENG Yue, CHENG Zihua, GUO Jiamin, GUO Yanzhi
    2019, 24(9):  1075-1080.  doi:10.12092/j.issn.1009-2501.2019.09.018
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    Spinal cord injury (SCI) is a highly debilitating central nervous system disease that usually results in loss of movement, sensation, and excretory function below the injured segment of the patient. However, there is currently no effective treatment in clinical practice to reconstruct damaged neurological function in patients. Through experimental research, Chinese herbal extracts can be used as an important complementary treatment to improve the neurological function and reconstruction after spinal cord injury. However, the systematic analysis involving this field is still rare. Therefore, this paper gives a comprehensive review of the research progress of traditional Chinese medicine extracts in the treatment of spinal cord injury in recent years.