Table of Content

Volume 25 Issue 7
26 July 2020

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lncRNA PCAT19 inhibits the proliferation and invasion of nasopharyngeal carcinoma cells by adsorbing miR-142-5p and regulating the expression of ING3 gene

HOU Bin, HUANG Weiping, YIN Zhongpu, HU Shousen

2020, 25(7):  721-727.  doi:10.12092/j.issn.1009-2501.2020.07.001

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AIM: To investigate the expression of long non-coding RNA (lncRNA) PCAT19 in nasopharyngeal carcinoma tissues and cell lines, and to explore its molecular mechanism of inhibiting proliferation and invasion of nasopharyngeal carcinoma cells. METHODS: Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the relative expression of PCAT19 in nasopharyngeal carcinoma tissues and five nasopharyngeal carcinoma cell lines. The lowest expressing nasopharyngeal carcinoma cell line was transfected with empty plasmid (control group) or high expression PCAT19 plasmid (experimental group). qRT-PCR was used to detect transfection efficiency. MTS method and Transwell invasion test were used to detect the effect of overexpressing PCAT19 on the proliferation and invasion ability of nasopharyngeal carcinoma cells. Bioinformatics predicts target genes for PCAT19. qRT-PCR and Western blot were used to detect target gene expression at mRNA and protein levels. RESULTS: Compared with adjacent tissues, the expression of PCAT19 in nasopharyngeal carcinoma tissues was decreased (P<0.01). Compared with immortalized nasopharyngeal epithelial cells, the expression of PCAT19 in five nasopharyngeal carcinoma cell lines was significantly reduced (P<0.05), and the expression was the lowest in SUNE-1 cells (P<0.01). Transfection of high-expressing PCAT19 plasmid could significantly promote the expression of PCAT19 (P<0.01). High expression of PCAT19 could inhibit the proliferation ability (P<0.01) and invasive ability (P<0.01) of nasopharyngeal carcinoma SUNE-1 cells. The target gene of PCAT19 was miR-142-5p, the target gene of miR-142-5p was inhibitor of growth gene 3 (ING3). After high expression of PCAT19, miR-142-5p expression was significantly reduced (P<0.01), and the expression of ING3 at both mRNA and protein levels was significantly increased (P<0.01). CONCLUSION: PCAT19 expression is down-regulated in nasopharyngeal carcinoma tissues and cell lines. Up-regulating PCAT19 can inhibit the proliferation and invasion of nasopharyngeal carcinoma SUNE-1 cells. The mechanism may be that PCAT19 promotes the expression of ING3 gene by adsorbing miR-142-5p.

Sesamol improves inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization

KONG Xiang, HUA Qiang, YAO Xinming, MENG Xiangjian, ZHONG Min, GUO Liqun

2020, 25(7):  728-733.  doi:10.12092/j.issn.1009-2501.2020.07.002

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AIM: To investigate whether sesamol could improve inflammation and insulin resistance in adipose tissue of obese mice by regulating macrophage polarization. METHODS: An obese animal model was established in mice by inducing obesity with high-fat diet. The obese mice were administrated with sesamol (100 mg/kg) for 8 weeks. The mice were sacrificed after the intraperitoneal glucose tolerance test and insulin tolerance test, and the plasma lipid and insulin levels were measured. The expression of p-Akt and p-JNK in adipose tissue of epididymis was detected by Western blotting. F4/80 and Cd11c immunohistochemistry and immunofluorescence staining were performed on the adipose tissue sections. The mRNA expression of cytokines and chemokines in adipose tissue was measured by Real-time fluorescence quantitative PCR. RESULTS: Sesamol treatment reduced body weight and lipid level of obese mice, improved glucose tolerance and insulin resistance. In sesamol treated group, macrophage infiltration in adipose tissue was decreased, p-Akt expression was enhanced, p-JNK expression was reduced, mRNA expression of M1 type of macrophage markers (Cd11c, iNOS, TNF-α and IL-6) was down-regulated, mRNA expression of M2 type markers (chi3l3, Arg1 and Mgl1) was up-regulated. CONCLUSIONS: sesamol could alleviate inflammation and insulin resistance in adipose tissue of obese mice. These effects maybe associated with inhibition of JNK signal pathway and improvement of polarization imbalance of macrophages in adipose tissue.

Azone combined with menthol has penetration-promoting effect on 5-fluorouracil

LIANG Qing, WANG Hui

2020, 25(7):  734-739.  doi:10.12092/j.issn.1009-2501.2020.07.003

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AIM: To compare the effect of azone and menthol by using the 5-fluorouracil (5-FU) as drug model, and explore the mix effect of the two transdermal enhancers. METHODS: The test acts on the self-made instrument. After the test, calculate the total amount of the drug which has permeate through the skin was calculated and the mixed effect of azone and menthol was estimated by multiple quantity method.RESULTS: Both azone and menthol of concentrations of 0.25%, 0.50%, 1.00% and 2.00% had significant penetration promoting effect on 5-fluorouracil, which were significantly different from the control group (P<0.01). No synergistic effect was detected when evaluating the combined effect of the two drugs by multiple dose method. CONCLUSION: Both azone and menthol have promotion effect on 5-fluorouracil, but the combined use of the two drugs of same concentration show no synergistic effect.

Bioequivalence of cefdinir capsules in Chinese healthy population under fasting/high-fat fed condition

ZHANG Zeyu, ZHANG Xingfei, YANG Shuang, YANG Xiaoyan, YE Ling, CUI Chang, YANG Guoping, HUANG Jie

2020, 25(7):  740-745.  doi:10.12092/j.issn.1009-2501.2020.07.004

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AIM: To evaluate the bioequivalence and safety of two cefdinir capsules under a fasting/high-fat fed condition in healthy people. METHODS: Twenty-six healthy volunteers were randomized to cross-test single-dose oral cefdinir capsules or reference preparations for fasting. Thirty-six healthy volunteers were randomized to crossed single-dose oral cefdinir capsule test preparations or reference preparations after high-fat meals. The blood concentration of cefdinir was determined by liquid chromatography-mass spectrometry (LC-MS/MS). Pharmacokinetic parameters and equivalence were calculated and evaluated using WinNonlin 6.4 and SAS 9.4 software. RESULTS: The 90% confidence intervals of the geometric mean ratios of the Cmax, AUC0-t, and AUC0-∞ for the test and reference preparations of cefdinir capsules taken by twenty-five healthy volunteers for fasting were 93.01%-109.22%, 96.16%-110.06%, and 96.38%-110.16%, all at 80.00%-125.00% within the range of bioequivalence. The 90% confidence intervals of the geometric mean ratios of the Cmax, AUC0-t, and AUC0-∞ for the test and reference preparations of cefdinir capsules taken by thirty-six healthy volunteers for a high-fat fed were 93.91%-103.28%, 92.93%-100.72% and 92.97%-101.26%, all at 80.00%-125.00% within the range of bioequivalence. The incidences of adverse reactions in healthy volunteers taking cefdinir capsules for the fasting test and reference preparations were 12.0% and 11.5%, respectively. The incidence of adverse reactions in healthy volunteers taking cefdinir capsules after the meal was 25.0% and 27.8%, respectively. CONCLUSION: The test preparation of cefdinir capsules and the reference preparation are bioequivalent, and the volunteers show good safety and tolerability under the test dose.

Correlation study between cytochrome P4502C19 gene polymorphism or metabolic type and ADP induced-platelet aggregation inhibition and clopidogrel resistance

PENG Jing, LIU Jun, XU Huifang, LI Yueran, JIANG Jia, WANG Sheng, ZHOU Dexi, ZHU Yanhong, YANG Kui, LUAN Jiajie

2020, 25(7):  746-751.  doi:10.12092/j.issn.1009-2501.2020.07.005

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AIM: To investigate the effect of the polymorphism and metabolic type of cytochrome P450 (CYP) 2C19 gene on the inhibitory rate of platelet aggregation induced by ADP and relationship with resistance of clopidogrel. METHODS: A total of 163 patients that are administrated with aspirin and clopidogrel were collected from the Yijishan Hospital of Wannan Medical College from June 2016 to July 2017. The CYP2C19*2, *3 and *17 genotypes of patients were detected with fluorescence staining in situ hybridization, according to the genotype, CYP2C19 enzyme activity was divided into fast metabolic (RM), intermediate metabolic (IM), slow metabolic (PM) and ultrafast metabolic type (UM). After 5 days of drug delivery, the platelet aggregation inhibition rate (IPAADP) induced by ADP was detected by thrombus elasto graph. IPAADP differences between CYP2C19*2, *3 and *17 genotype and CYP2C19 enzyme metabolic type were evaluated. CYP2C19 genotype and metabolic type as well as their distribution in clopidogrel resistance group (CR) and non clopidogrel resistance group (NCR) were observed. RESULTS: The mutation rates of CYP2C19*2, *3 and *17 were 30.98%, 6.75% and 1.23%, respectively. The average IPAADP was (67.03±26.79)% and the incidence of CR was 26.99%, and the IPAADP was (31.29±12.60)%. The IPAADP of CYP2C19*2 and *3 gene carriers were decreased significantly (P<0.001), and the IPAADP of *17 gene carriers were increased significantly (P<0.001). Twenty-four cases (14.72%) were type PM, and there was no statistical difference in IPAADP between each metabolic type (P>0.05). There was no statistical difference in the distribution of CYP2C19 genotypes and metabolic types in NCR and CR (P>0.05). CONCLUSION: CYP2C19 genotypes have significant effect on IPAADP, but there is no association with the occurrence of CR, and the related study needs to be further verified.

Curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and CIART, AFP-L3 and GP73

WANG Gaoqing, JIANG Wei, HUA Yongfei

2020, 25(7):  752-756.  doi:10.12092/j.issn.1009-2501.2020.07.006

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AIM: To study the curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and the effects of diurnal transcription suppressor (CIART), fetoprotein heterosomes (AFP-l3), golgi membrane protein-73 (GP73). METHODS: A total of 100 patients with primary liver cancer who were treated in our hospital from July 2012 to July 2019 were selected as study subjects, the patients were divided into observation group (n=52) and control group (n=48) according to the order of admission. The control group was treated with laparoscopic hepatectomy, and the observation group was treated with retetroxel on the basis of the control group. Serum CIART, AFP-L3, GP73, ALT, AST, TBIL, 1-year, 3-year, 5-year tumor recurrence rates and adverse reactions were compared between the two groups before and after treatment. RESULTS:Before treatment, CIART, AFP-L3, GP73, ALT, AST and TBIL levels were not significantly different between the two groups. After treatment, the levels of CIART, AFP-L3 and GP73 in the observation group were significantly lower than those in the control group (P<0.05). There was no significant difference in serum ALT, AST and TBIL levels between the two groups (P>0.05). The 5-year recurrence rate in the observation group was significantly lower than that in the control group (P<0.05). There was no significant difference in the 1-year and 3-year recurrence rates between the two groups (P>0.05). The total incidence of adverse reactions in the two groups was 53.84% and 52.08%, respectively, with no significant difference (P>0.05). CONCLUSION:Laparoscopic resection combined with letetrexed in the treatment of primary liver cancer can effectively reduce the level of ciart, AFP-L3 and GP73, and it is safe.

Retrospective analysis of voriconazole in the monitoring of therapeutic drugs in patients with liver dysfunction

GUO Mingxing, GUO Heng, SHEN Su, SUN Liying, CUI Xiangli

2020, 25(7):  757-763.  doi:10.12092/j.issn.1009-2501.2020.07.007

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AIM: To evaluate relationship between dosing schedules and safety of voriconazole by analyzing the monitoring results of voriconazole in patients with liver dysfunction, and to provide reference for the clinical individualized medication. METHODS: The blood concentration and safety information of voriconazole in patients with liver dysfunction was searched in PubMed, Cochrane Library, Wanfang, Weipu, and Chinese Journal Full-text Database from the establishment of the databases to December 2019, the dosing schedule and safety range of voriconazole for patients with liver dysfunction was analyzed. RESULTS: A total of 10 literatures were selected, 5 of which were multi-sample retrospective studies and 1 of which was prospective study, and the remaining 4 were case reports. In Child-Pugh grade C liver dysfunction, a maintenance dose of 100 mg q12h is more secure. The incidence of adverse reactions of voriconazole is generally within 7 days. When the target trough concentration is less than 5 mg/L or 5.3 mg/L, the incidence of adverse reactions is still high. The main adverse reactions include neurotoxicity, hallucinations, visual disturbances, gastrointestinal reactions and rash. CONCLUSION: The dose of voriconazole in patients with liver dysfunction should be reduced, and the drug concentration should be monitored in a timely manner. It is recommended that on the basis of ensuring the efficacy, trough concentration can be further reduced to reduce the occurrence of adverse reactions in patients with liver dysfunction.

Advances in farnesoid X receptor antagonists and their pharmacological activities

LIU Weiyi, SUN Jianguo, CAO Weiling, WANG Guangji, WANG Hong

2020, 25(7):  764-774.  doi:10.12092/j.issn.1009-2501.2020.07.008

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Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily. It has extensive physiological functions in maintaining homeostasis of bile acids, lipids, and glucose. It also participates in the development of various tumors. Therefore, regulation of its transcriptional activity is accepted as an important strategy for treatment of many diseases, and various FXR agonists have been developed. In recent years, it has been found that inhibition of FXR transcriptional activity also shows beneficial effects on various diseases, therefore several FXR antagonists have been developed and their pharmacological activities have been tested in preclinical animal models. This article provides an update review on FXR antagonists and their pharmacological activities.

Function and regulation of miRNAs associated with Parkinson's disease

LU Chenyu, YANG Jun, LIU Yixi, ZHENG Yun

2020, 25(7):  775-783.  doi:10.12092/j.issn.1009-2501.2020.07.009

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Parkinson's disease (PD) is a common neurological degenerative disease in the elderly people. The causes of PD are complicated, and its pathogenesis is still unknown. At present, it is generally believed that the occurrence of PD is related to multiple factors such as environment, genetics and age. microRNAs (miRNAs) are endogenous small non-coding RNAs that are involved in regulating about one-third of genes in the human genome at post-transcription level. A large number of studies have shown that miRNAs play important roles in PD. This review discusses recent researches on miRNAs relevant to PD, and summarizes the specific expression of miRNAs in the pathogenesis and diagnosis of PD.

Risk management of medication in transitional care

ZHANG Xueting, ZHOU Xin, HU Xu, XIE Xuefeng

2020, 25(7):  784-790.  doi:10.12092/j.issn.1009-2501.2020.07.010

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Transitional care is an important step in the process of treating disease. Medication risk during this period of time has become a public safety issue and attracted more attention. It not only threatens patients' health, but also increases the unnecessary cost of medical resources. Through systematically analyzing the medication risk in each link of the transition care, this paper discusses the strategies to improve the medication risk management of patients in the process of transition, and provides references for improving the level of rational medication use and optimizing the allocation of medical resources in transition care.

Progress on TMPRSS2-ERG fusion gene product transcription regulation mechanism in prostate cancer cells

CAO Ying, TU Linglan, WANG Xiaoju, ZHENG Xiaoliang

2020, 25(7):  791-795.  doi:10.12092/j.issn.1009-2501.2020.07.011

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Prostate cancer is the most common malignant tumor in men in Europe and the United States, but the mechanism of prostate cancer occurrence and development is not completely clear. In prostate cancer, the TMPRSS2-ERG fusion gene has a high incidence, which promotes ERG overexpression and causes changes in target genes and signaling pathways, such as androgen receptors, spotted zinc finger structural proteins, Notch pathways. In-depth understanding of the transcriptional regulation mechanism of TMPRSS2-ERG fusion gene products in prostate cancer cells can provide new targets for drug action in the treatment of prostate cancer.

Advances in research on long non-coding RNA in drug resistance of colorectal cancer

WANG Ziyuan, SUN Mingyu

2020, 25(7):  796-802.  doi:10.12092/j.issn.1009-2501.2020.07.012

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Colorectal cancer is the third most prevalent cancer in the world. Surgical resection is the preferred method for the treatment of colorectal cancer, assisted by chemotherapy, targeted therapy and other methods to reduce recurrence and metastasis. However, drug resistance is an important factor in postoperative recurrence and death. Long non-coding RNA (lncRNA) has been found to be involved in drug resistance of colorectal cancer. Therefore, it is of great significance to study the mechanism of lncRNA regulating drug resistance in colorectal cancer. This paper reviewed the progress of lncRNA in drug resistance of colorectal cancer.

microRNA and drug-induced liver injury

XU Lina, LI Yue, PENG Jinyong

2020, 25(7):  803-809.  doi:10.12092/j.issn.1009-2501.2020.07.013

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The liver is one of the most important organs in human body, which participates in metabolism and detoxification. The liver is easily affected by various drugs and their metabolites. Drug-induced liver injury, also known as drug-induced liver disease, refers to the liver damage or allergic reaction to liver caused by drugs and their metabolites. MicroRNA (miRNA) is a kind of small non-coding RNA, which plays an important regulatory role in many diseases. In this review, the effects and mechanisms of miRNAs in drug-induced liver injury were summarized.

Advances in antitumor drugs based on glutamine metabolism#br#

LI Danyun, NIU Peiguang, SHI Daohua

2020, 25(7):  810-816.  doi:10.12092/j.issn.1009-2501.2020.07.014

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Glutamine, as a conditionally essential amino acid of many kinds of tumors, has a great influence on the occurrence and development of tumors. In recent years, the research on glutamine metabolism has made rapid progress, and many related drugs have been in preclinical and clinical research. Glutamine is involved in energy generation, redox balance, macromolecular synthesis and signal transmission in tumor cells. Transporters and metabolic enzymes of glutamine are potential targets for tumor treatment. This paper reviews the anti-tumor drugs based on glutamine metabolism and provides guidance for the development of new drugs. 

Influence of CYP2D6 gene polymorphism on the effect of tropisetron in preventing chemotherapy induced nausea and vomiting

TANG Mufei, SHEN Yunzhu, ZHANG Baoguo

2020, 25(7):  817-822.  doi:10.12092/j.issn.1009-2501.2020.07.015

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Tumors pose a great threat to human health. As a systemic treatment, chemotherapy has held an unshakable position in tumor treatment. Chemotherapy induced nausea and vomiting (CINV) is a common adverse reaction during chemotherapy, which seriously affects patients' mood, quality of life and tumor control. The prevention and treatment of CINV is very important for cancer patients. As a more commonly used 5-HT3 receptor antagonist, tropisetron has a good clinical effect in the prevention and treatment of CINV. However, there are still some patients who do not have a good effect after using tropisetron. More and more studies indicated that these individual differences might be closely related to genetic polymorphisms. In order to provide ideas for clinical individualized medication under the guidance of gene polymorphisms, this article reviewed the influence of CYP2D6 gene polymorphisms on the effect of tropisetron in preventing CINV.

Advances in the study of new oral anticoagulants in cancer-associated venous  thromboembolism

QIN Wenjie, YANG Zhiling, CAO Ailin, GAO Hang, JIANG Xianrui, SHEN Yue, QIAN Jiao

2020, 25(7):  823-828.  doi:10.12092/j.issn.1009-2501.2020.07.016

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Venous thromboembolism (VTE) is one of the common complications of cancer and the second cause of death in cancer patients. Low molecular weight heparin(LMWH) is the standard of care but the high cost and the inconvenience of daily injections have led to low persistence with therapy. New oral anticoagulants (NOACs) have recently emerged as a new therapeutic option due to the ease of administration, especially compared to warfarin. The patients do not have to do laboratory monitoring for NOACs and there is less food or drug interactions. Several large randomized clinical trials have been performed and indicated that specific NOACs are more effective in the treatment of cancer-associated VTE compared with LMWH, but might increase the risk of bleeding. In some kinds of tumors, NOACs will be the reasonable alternative agents in the management of cancer-associated VTE. This review summarizes the current evidences for NOACs in the prevention and treatment of CAT, and there are ongoing studies providing more evidences for NOACs in CAT as well.

Research progress on roles of gut microbiota in cardiovascular disease and treatment

YAN Yu, LIU Kang, LIAN Wenwen, ZHANG Zhen, HE Jun

2020, 25(7):  829-834.  doi:10.12092/j.issn.1009-2501.2020.07.017

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Cardiovascular disease (CVD), a chronic disease endangering human health, remains the highest morbidity and mortality globally. The human gut is inhabited by communities of bacteria and viruses, along with their genome, are collectively known as the gut microbiota. Recent reserch suggests that gut microbiota affects various metabolic pathways in the host by producing and releasing important metabolites such as trimethylamine oxide, bile acids and short chain fatty acids, and play an important role in pathologies of CVD, such as atherosclerosis, hypertension, myocardial infarction, heart failure and dyslipidemia. Individual treatment based on gut microbiota, including diet intervention, fecal microbiota transplantation and small molecule antimicrobial enzyme therapeutics, may provide a potential novel strategy for therapeutics.

Four dimensions of receiving overseas clinical trial data about drug and medical devices

JIANG Haihong, LI Xiao, LIU Yang

2020, 25(7):  835-840.  doi:10.12092/j.issn.1009-2501.2020.07.018

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China has started to accept the overseas clinical trial data about drug and medical devices, and the data in accordance with the requirements can be used to register in China. To do this work well, we should consider four key dimensions: data acceptance principle, data quality and reliability, data evaluation usability and data international difference. Among them, the authenticity, integrity, accuracy and traceability of data are the main factors to determine the quality reliability of data. Receiving data from overseas clinical trials about drug and medical devices will be conducive to the establishment of international mutual recognition system for clinical trial data, and to enhance the importance of data management in domestic clinical trials, and to promote the formation of quality management system on clinical trial data.