Table of Content

Volume 24 Issue 10
26 October 2019

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Inspection about authenticity and integrity for clinical trial data of medical device

ZHANG Zhengfu, WANG Jianan

2019, 24(10):  1081-1084.  doi:10.12092/j.issn.1009-2501.2019.10.001

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In order to strengthen the supervision about clinical trials of medical devices, National Medical Products Administration (NMPA) inspects the clinical trials of medical devices to projects in the process of evaluation annually, and ensures the truth and validity about the data of clinical trials of medical devices. This paper summarizes the situation of supervision about clinical trials of medical devices in the past three years and the main problems existed in clinical trials of medical devices in China. The purpose is to strengthen the attention of applicants and clinical trial units to the quality of clinical trials, and to improve the level about clinical trials of medical devices in China.

Strategies of clinical drug-drug interaction studies and application progress of physiologically-based pharmacokinetic model

LI Li, YANG Jinbo

2019, 24(10):  1085-1091.  doi:10.12092/j.issn.1009-2501.2019.10.002

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Drug-drug interaction (DDI) might cause reduced efficacy, even induce severe safety issues of drugs, which might be one of the most common concerns in clinical therapy. Therefore, clinical DDI should be investigated during new drug development before marketing. This paper reviewed the overall research strategy and types of DDI studies. Regarding various mathematical models, physiologically-based pharmacokinetics model (PBPK) had become an important tool to assist or even partially replace DDI studies by integrating human physiological parameters, drug chemical/physical data, and drug mechanistic pharmacokinetic data to predict pharmacokinetic characteristics. Recently, PBPK analyses had been extensively applied in DDI studies in America and Europe, where relevant guidance documents had been released to direct such studies，whereas Chinese guidance on PBPK was absent. By seeing the power of model informed drug development to improve new drug research efficiency, in this review, we introduced the application of PBPK model in study design, waiver of DDI studies, and so on. How to evaluate the prediction accuracy and report PBPK study results was briefly summarized as well. Hopefully this paper could update knowledge and support new drug development in China.

Comparison of therapeutic effects of fresh and frozen human umbilical cord-derived mesenchymal stem cells on osteoarthritis in rats

ZHANG Binbin, ZHAO Yingjie, YANG Xuezhi, HAN Ping, CHANG Yan, WEI Wei

2019, 24(10):  1092-1100.  doi:10.12092/j.issn.1009-2501.2019.10.003

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Effects of Coxsackievirus B3 infection on the expression of diabetes-related LncRNA in islet cells

SHEN Yajing, LI Lanjuan

2019, 24(10):  1101-1106.  doi:10.12092/j.issn.1009-2501.2019.10.004

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AIM: To explore the specific mechanism of diabetes mellitus induced by Coxsackievirus B3.  METHODS: Human islet cells HUM-CELL-0058 were infected with Coxsackievirus B3. Total RNA was extracted 48 hours after infection and LncRNA related to diabetes mellitus was detected by fluorescence quantitative PCR. Real-time quantitative PCR and Western blot were used to monitor the transcription factors and proteins regulating the transcription of three LncRNA. The over-expression plasmids of PAX6 and NF-kappa B were constructed and transfected into B cells infected with the virus to detect the abnormal expression of LncRNA after coxsackievirus infection. RESULTS:Diabetes-related LncRNA, Lnc-P12792 and MALT1 were up-regulated, while HI-Lnc45 was down-regulated. Real-time quantitative PCR and Western blot results showed that the expression of PAX6, a transcription factor regulating HI-Lnc45 expression, decreased while the expression of NF-kappa B, a transcription factor regulating Lnc-P12792 and MALT1, increased, which was consistent with the trend of transcription factors regulated by PAX6, indicating that the expression difference of LncRNA was due to the abnormal expression of transcription factors of the gene. Real-time quantitative results showed that the three abnormal expression levels of LncRNA returned to the normal level before coxsackievirus B3 infection, which proved that this trend could be saved by regulating the expression of these two transcription factors. CONCLUSION: Coxsackievirus B3 infection of human pancreatic islet β cells can induce up-regulation of transcription factor NF-kappa B and down-regulation of PAX6, and induce abnormal expression of LncRNA related to diabetes mellitus downstream, which may be one of the pathological mechanisms of Coxsackievirus B3 induced diabetes mellitus.

Study on the anti-hyperlipidemia mechanisms and signaling pathways of traditional Chinese medicine Polygonum cuspidatum based on network pharmacology

ZHENG Li, MO Juanfen, WU Jiayuan, GUO Li, BAO Yi

2019, 24(10):  1107-1119.  doi:10.12092/j.issn.1009-2501.2019.10.005

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AIM: To analyze the anti-hyperlipidemia effects and signaling pathways of traditional Chinese medicine Polygonum cuspidatum based on network pharmacology and bioinformatics methods. METHODS: The main active ingredients were screened from Polygonum cuspidatum using TCMSP database, and the targets were predicted by Drug-CPI server with reverse pharmacophore matching method. Meanwhile, target databases such as OMIM, TTD and Genecards disease were used to obtain the disease targets of hyperlipidemia, and the intersections of active ingredient targets and disease targets were obtained for further analysis. Cytoscape 3.7.1 software was used to construct the visualization network of "drug-active ingredient-target-disease" of Polygonum cuspidatum.The protein interaction network of the intersecting targets was analyzed by STRING online platform, and the GO function and KEGG pathway enrichment analysis were performed. Furthermore, according to the results of KEGG pathway analysis, the binding energy and and binding mechanism between the active compounds and the key target protein of insulin-resistant pathway and PPAR signaling pathway, namely TNFRSF1A and PPARG were analyzed by using molecular docking software Autodock 4.2.6. RESULTS:Twelve main active ingredients were obtained from Polygonum cuspidatum by TCMSP database, and 288 targets were predicted by Drug-CPI server, meanwhile 571 hyperlipidemia-related disease targets were obtained. Finally, 48 intersections of active ingredient targets and disease targets were obtained. The network of "drug-active ingredient-target-disease" of Polygonum cuspidatum showed that the average degree of compounds in the network was 16.67, and 8 of 12 compounds could interact with 15 or more disease targets. Through the analysis of GO function and KEGG pathway enrichment, the 48 intersecting targets were mainly involved in regulating insulin resistance, PPAR signaling pathway, non-alcoholic fatty liver disease (NAFLD), HIF-1 signaling pathway and Regulation of lipolysis in adipocytes. Molecular docking results showed that all four active components could be spontaneously bind with TNFRSF1A, and rhein had the lowest binding energy with TNFRSF1A, which was -10.08 kcal/mol. Among the seven active components of Polygonum cuspidatum, physovenine has the lowest binding energy with PPARG, which was -13.45 kcal/mol. The binding mode was mainly based on hydrogen bonding, electrostatic force and hydrophobic interaction. CONCLUSION: The active ingredients of Polygonum cuspidatum may regulate lipid metabolism by regulating insulin resistance, PPAR signaling pathway and lipid decomposition, thus realizing the anti-hyperlipidemia effects.

Effects of N-acetylcysteine on regulation of EGFR/MAPK signaling pathway in airway mucus hypersecretion in chronic obstructive pulmonary disease

BAI Xuemin, ZOU Likao, JIN Zhenmu, JIANG Lijia

2019, 24(10):  1120-1127.  doi:10.12092/j.issn.1009-2501.2019.10.006

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AIM: To investigate the role of N-acetylcysteine (NAC) in the regulation of epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signaling pathway in airway mucus hypersecretion in chronic obstructive pulmonary disease (COPD) effect. METHODS: Thirty male clean Wistar rats were randomly divided into 3 groups, 10 in each group. The control group was healthy rats. The model group was COPD airway mucus hypersecretion rats. The NAC group was given 3 mmol/ from the modeling. NAC group received 3 mmol/kg 100 μL NAC for 30 days. The pathological results of lung tissue, airway resistance (RL) and dynamic compliance (Cdyn), blood gas results［arterial blood carbon dioxide partial pressure (PaCO2), arterial oxygen partial pressure (PaO2)］, mucosal thickness / bronchial wall thickness (Reid index), airway epithelial positive goblet cells / total epithelial cell number, EGFR/MAPK signaling pathway protein［EGFR, phosphorylation stress activated protein kinase (p-JNK) /Total JNK, phosphorylation-mitogen-activated protein kinase p38 (p-P38MAPK)/total P38, phosphorylated extracellular regulated protein kinase (p-ERK)/total ERK, mucin 5AC (MUC5AC)］ expression were observed and compared.RESULTS:There were no abnormalities in the epithelial cells, airway mucosa epithelium, submucosal glands, and bronchial wall of the control group. There was no secretion in the lumen. The model group showed pulmonary interstitial vascular congestion, thinning and rupture of the alveolar space, and the formation of adjacent alveolar fusion. Polycystic cavity, epithelial cells have obvious thickening, hyperplasia, necrosis, submucosal gland hypertrophy, goblet cell hyperplasia, inflammatory cell infiltration around the bronchi, atrophy and rupture of smooth muscle bundle; compared with control group tube in NAC showed no abnormalities, but compared with the model group, the pathological features were alleviated; Cdyn and PaO2 in the model group were lower than those in the control group, RL and PaCO2 were higher than those in the control group (P＜0.05); Cdyn and PaO2 in the NAC group were higher than those in the model group. RL and PaCO2 were lower than those in the model group (P＜0.05); the Reid index, positive goblet cells/total epithelial cells in the model group were higher than those in the control group (P＜0.05); Reid index, positive goblet cells/total epithelial cells in the NAC group were lower than those in the model group, but the difference was statistically significant compared with those in the control group (P＜0.05). p-JNK/JNK, p-P38/P38, p-ERK/ERK, MUC5AC of the model group were higher than those in the control group. (P＜0.05); p-JNK/JNK, p-P38/P38 p-ERK / ERK, MUC5AC of NAC group were lower than those in the model group as compared with the control group(P＜0.05). CONCLUSION: N-acetylcysteine can inhibit the expression of EGFR/MAPK signaling pathway, improve bronchial mucosal gland hyperplasia, goblet cell hyperplasia, inhibit airway mucus hypersecretion and improve rat lung features.

Effects of artesunate on oxidative stress in cultured retinal ganglion cells and its protective mechanism

QIN Hui, LAI Li

2019, 24(10):  1128-1133.  doi:10.12092/j.issn.1009-2501.2019.10.007

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AIM: To study the effects of artesunate on oxidative stress in cultured retinal ganglion cells (RGC-5) and to investigate its possible mechanism. METHODS: RGC-5 cells were cultured in vitro and were divided into five groups, including control group, H2O2 group, low-, middle-, high-dose artesunate groups. CCK8 assay was used to measure the relative survival rate of RGC-5 cells. Cell apoptotic rate was determined by flow cytometry. Related kits were used to determine the levels of MDA, NO and SOD1. Western bot method was used to analyze the expression levels of HO-1, SOD1, PI3K, p-Akt and Akt. RESULTS:Compared with H2O2 group, the relative survival rates were significantly increased and cell apoptotic rates were greatly decreased in varying concentrations of artesunate groups (P<0.05). The contents of MDA, NO were greatly decreased, while the activity of SOD1 was strongly increased in artesunate groups compared with H2O2 group (P<0.05). The expression levels of HO-1, SOD1, PI3K and p-Akt were greatly increased in artesunate groups compared with H2O2 group (P<0.05). Moreover, PI3K inhibitor decreased the protective effect of artesunate on the injury of RGC-5 cells. CONCLUSION: Artesunate significantly inhibit the oxidative stress injury of RGC-5 cells and its underlying mechanism maybe related with inducing the activation of PI3K/Akt signaling pathway.

Effects of circadian clock gene Period2 on Warburg effect and metastasis in hepatocellular carcinoma cells

ZHAO Qiaosu，YE Hua，SUN Qinxue

2019, 24(10):  1134-1141.  doi:10.12092/j.issn.1009-2501.2019.10.008

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AIM: To study the effects of circadian clock gene Period2 on Warburg effect and metastasis in hepatocellular carcinoma cells. METHODS: Real-time fluorescence quantitative PCR (RT-QPCR) was used to detect the expression of Period2 in tissues and 4 hepatocellular carcinoma cells,up-regulated the expression of Period2 in hepatocellular carcinoma cell line MHCC97L.silenced the expression of Period2 in hepatocellular carcinoma cell line HepG2.The glucose uptake level,lactic acid level，cell oxygen consumption level，cell viability，migration,and cell invasion were detected.Western-Blot was used to detect the expression of the key metabolic enzymes.RESULTS:The expression level of Period2 in MHCC97L was low,while HepG2 level was high.After Period2 silencing, the relative glucose uptake and lactate production of HepG2 cells were down-regulated compared with control group, and the oxygen consumption of HepG2 cells was increased compared with control,and the cell viability, migration and invasion ability were decreased.The expression level of key enzymes of glycometabolism was down-regulated.After overexpression of Period2,the glucose uptake level of MHCC97L cells was increased,the lactate production level was increased,the oxygen consumption was decreased compared with control, and the cell viability, migration and invasiveness were increased.The expression level of key enzymes of glucose metabolism was up-regulated.CONCLUSION: The clock gene Period2 is highly expressed in HCC, and its role is related to the promotion of Warburg effect and metastasis and invasion of HCC cells.

Role of macrophages in LPS-induced apoptosis of intestinal epithelial cells

CAO Yingya, CHEN Qun, WANG Zhen, WU Jingyi, JIANG Xiaogan, JIN Xiaoju, LU Weihua

2019, 24(10):  1142-1146.  doi:10.12092/j.issn.1009-2501.2019.10.009

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AIM: To evaluate the role and mechanism of macrophages on lipopolysaccharide (LPS)-induced apoptosis of intestinal epithelial cells. METHODS: NCM460 intestinal epithelial cells were incubated in regular culture medium (group R) or macrophage conditioned medium (group M) in 6-well plates. Different concentrations (0, 0.1, 10, 30 μg/mL) of LPS was added to the medium of NCM460 cells for 24 hours, then the cells were collected for Annexin V/7AAD staining, following with flow cytometry analysis. The cell culture supernatant was also collected to detect the TNF-α and IL-6 levels by enzyme-linked immunosorbent assay. Western blot was used to measure the activity of NF-κB signaling pathway. RESULTS:In the same culture medium, with the increase of LPS concentration, the levels of inflammatory factors TNF-α, IL-6 and apoptotic rate in the supernatant of cell culture medium increased gradually (P<0.05). Compared with group R, the percentage of apoptotic cells were significantly increased in group M when cells were treated with equal concentrations of LPS. Compared with NCM460 cells stimulated by LPS at the same dose, the apoptotic rate and the levels of inflammatory factors TNF-α and IL-6 in supernatant of M group were higher than those of R group (P<0.05). Compared with group R, the expression levels of IκB-α protein was down-regulated.CONCLUSION: Macrophages play an important role in LPS-induced apoptosis of intestinal epithelial cells. The mechanism may be related to the release of inflammatory cytokines by activation of NF-κB signaling pathway.

Role of MSX2 in melanoma cells for trametinib resistance

WANG Xiaoli, LU Shuping, DAI Jiale

2019, 24(10):  1147-1154.  doi:10.12092/j.issn.1009-2501.2019.10.010

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AIM: To study the role of homeobox gene MSX2 in the melanoma cell line A375 of trametinib resistance.  METHODS: To construct trametinib resistant A375 cell line (A375-AR). After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate was detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. Small interfering RNA (siRNA) was used to silence MSX2 gene in A375-AR. After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate was detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. To construct MSX2 over-expressing A375 cell line (A375-OE), and A375, A375-OE and A375-AR groups were set up. After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. RESULTS:A375-AR was resistant to trametinib of 1.8 nmol/L, the activity of A375 cells and the rate of cell apoptosis were significantly higher than that of A375-AR, and the expression level of Bcl-2 gene in A375 cells was lower than that of A375-AR, while the expression level of Bax, Caspase-3 and Caspase-9 was higher than that of A375-AR. After A375-AR silenced of MSX2, the cells were significantly increased to the sensibility of trametinib, the apoptosis rate was up-regulated, the expression of Bcl-2 in the cells was down-regulated, and the expression of Bax, Caspase-3 and Caspase-9 was up-regulated. After A375 overexpression of MSX2, the cells were down regulated to the sensibility of trametinib, the cell viability was up-regulated, the apoptosis rate was down-regulated, the expression of Bcl-2 in the cells was up-regulated, and the expression of Bax, Caspase-3 and Caspase-9 was down regulated. CONCLUSION: MSX2 gene can induce the resistance of melanoma cells to trametinib. It is a potential target for the treatment of melanoma resistance.

Blinded analysis of double-blind randomized controlled trial for unequal integer ratio grouping

LIU Yaqi, LU Mengjie, LIU Yuxiu, CHEN Yu, YUAN Yangdan, ZHOU Chongchong, LIU Man

2019, 24(10):  1155-1160.  doi:10.12092/j.issn.1009-2501.2019.10.011

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AIM: The blinded data analysis under the conventional equal ratio grouping is easy to be realized in the double-blind randomized controlled trial.However, there is no effective blinded analysis method for the trial of unequal integer ratio grouping.To develop a blinded analysis under the unequal integer ratio grouping to avoid the bias during data analysis due to knowledge of grouping information in the double-blind randomized controlled clinical trials. METHODS: In the design phase, according to the sum of unequal integer ratios, the samples were divided into several equal split groups.The random allocation sequence was generated by means of the new split groups.The drug labeling was conducted by a third party independent of the study based on the split groups.In the statistical analysis phase, all possible combinations of the split groups were analyzed and reported.RESULTS:The implementation of blind analysis was illustrated with a clinical trial in which two groups were grouped in 2∶1 ratio. In this method, only the codes of each subgroup were known after the first level unblinding, and the corresponding real group could not be identified, so it could keep blinded to treatment allocation in the statistical analysis.The final reporting of statistical analysis could be determined after the second level unblinding.CONCLUSION: The method we proposed is simple in principle, easy to implement and in line with the regulatory requirements.In spite of increasing workload during the random allocation sequence generating, drugs labeling,and statistical analysis,it could maintain the blindness of data analysis under the unequal integer ratio grouping and effectively avoid the possible analysis bias caused by unblinding.It has unique practical value in ensuring objectivity and science of clinical trial analysis.

Effects of neoadjuvant chemotherapy on the pharmacodynamics of rocuronium bromide in patients undergoing gastric cancer surgery

LIAN Yanhong, JIANG Huifang, YUAN Xiaohong, ZHOU Huidan, XIE Kangjie, FANG Jun, JIN Xiaoju

2019, 24(10):  1161-1164.  doi:10.12092/j.issn.1009-2501.2019.10.012

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AIM: To evaluate the effect of neoadjuvant chemotherapy on neuromuscular block induced by rocuronium in the patients undergoing radical gastrectomy. METHODS:Fifty patients with open gastric cancer, ASA Ⅰ or Ⅱ, aged 40 to 68 years old, 56-79 kg, scheduled for elective radical gastrectomy, were divided into 2 groups (n=25 each) according to whether the patient received neoadjuvant chemotherapy before operation or not: non-chemotherapy group (group N) and neoadjuvent chemotherapy group (group C). Anesthesia was induced with rocuronium 0.9 mg/kg injected intravenous. When T1 recovered to 25% of control height, IV infusion of rocuronium 0.15 mg/kg was used. The onset time, time for T1 to recover to 25%, recovery index and time for train of four ratios to recover to 90%, and the total amount of rocuronium were recorded. RESULTS:Compared with the group N, time for T1 to recover to 25%, recovery index and time for train of four ratios to recover to 90% were significantly prolonged, and the consumption of rocuronium was decreased in group C. There was no significant difference of onset time between the two groups. CONCLUSION:Neoadjuvant chemotherapy can reduce the usage of muscle relaxant in the patients undergoing radical gastrectomy.

Metabolism- and transporter-mediated drug-drug interaction-overview of in vitro study and cases analysis

SHAN Xiaolei, FU Shujun, GAO Guanghua, SUN Tao, WANG Qingli, YU Shanshan

2019, 24(10):  1165-1171.  doi:10.12092/j.issn.1009-2501.2019.10.013

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Evaluation of drug-drug interaction (DDI) risk is vital to establish benefit risk profiles of investigational new drugs during drug development. In vitro experiments are routinely conducted as an important first step to assess metabolism- and transporter-mediated DDI potential of investigational new drugs. Results from these experiments are interpreted, often with the aid of in vitro-in vivo extrapolation methods, to determine whether and how DDI should be evaluated clinically to provide the basis for proper DDI management strategies, including dosing recommendations, alternative therapies, or contraindications under various DDI scenarios and in different patient population. This article summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and introduces two cases at the end to demonstrate how the in vitro and in vivo study results affect the drug labeling.

Correlation between PGC-1α gene polymorphism and metabolic diseases

FAN Zhipeng, LI Ling, ZHAO Huijia, CHEN Binyao, LIU Xiaohong, HAO Zhuowen, SUN Gongpeng, DONG Li, YUE Jiang, WU Jianguo, YE Qifa

2019, 24(10):  1172-1180.  doi:10.12092/j.issn.1009-2501.2019.10.014

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Peroxisome proliferator-activated receptor gamma coactivator 1-alpha（PGC-1α）is an important nuclear transcriptional coactivator in human body. Nuclear receptors and transcription factors interact to regulate the expression of their target genes. PGC1-α plays an important role in human energy metabolism, which is involved in fatty acid oxidation, hepatic gluconeogenesis and regulation of mitochondrial ATP biosynthesis.Studies have shown that PGC-1α gene polymorphism is closely related to the occurrence of metabolic diseases such as type 2 diabetes, diabetic nephropathy, obesity and coronary heart disease. Exploring the correlation between PGC-1α gene polymorphism and metabolic diseases is beneficial to detect and evaluate the risk of metabolic diseases from the genetic level, so as to realize early detection and prevention of the disease, improve the quality of life of metabolic diseases, and prolong Survival period. This article reviews the research progress of the metabolic pathways involved in PGC-1α and the correlation between its genetic polymorphisms and metabolic diseases in the recent five years.

Progress in drug therapy for multidrug-resistant Acinetobacter baumannii infection

FU Peishu, SUN Fengjun, FENG Wei, XIONG Lirong, LI Xiaoyu, XIA Peiyuan

2019, 24(10):  1181-1187.  doi:10.12092/j.issn.1009-2501.2019.10.015

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Acinetobacter baumannii is a common pathogen that causes infections in the respiratory tract, blood flow, urinary tract and abdominal cavity. In recent years, the drug resistance rate of Acinetobacter baumannii to commonly used clinical drugs has increased year by year. It has been reported that multidrug-resistant, extensively drug-resistance and even pandrug-resistance strains are widely spread all over the world, which brings great challenges to clinical treatment. Therefore, the purpose of this paper is to review the drug treatment and the latest progress of multi-drug-resistant Acinetobacter baumannii.

Common narrow therapeutic index drugs and the current status of bioequivalence evaluation

CHEN Xiaoping, HU Chaoying, ZHANG Lan

2019, 24(10):  1188-1193.  doi:10.12092/j.issn.1009-2501.2019.10.016

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There are still some blind areas in bioequivalence evaluation of narrow therapeutic index (NTI) drugs so far and no relevant guideline is issued in China. The bioequivalence requirements of NTI drugs are variable among the main international regulations, and there is no global unified NTI drugs list. In addition, for some particular NTI drugs, different equivalence limits are accepted in different regulatory regions. Based on domestic and foreign regulations, guidelines and related literature, through analyzing the status of several fundamental NTI drugs and the bioequivalence studies, we hope to contribute to the conduction of bioequivalence study in the future and to help the development of bioequivalence guideline of NTI drugs in China.

Progress of apatinib in the treatment of advanced gastric cancer

JING Qindong, LIU Haipeng, WANG Binru, CHEN Kang, CHEN Xiao

2019, 24(10):  1194-1200.  doi:10.12092/j.issn.1009-2501.2019.10.017

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Gastric cancer is one of the most common malignant tumors in the world. Early diagnosis is difficult and most patients have missed the best timing of surgery when diagnosed. Therefore, systemic comprehensive therapy should be the best treatment option for advanced gastric cancer. Recent years, the standard chemotherapy regimen, such as platinum and fluorouracil-based regimen has been proven poor efficacy. However, with continuous research and development, the role of targeted drugs has become increasingly important in the treatment of advanced gastric cancer. Apatinib is a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptor developed and applied in China, which highly selectively competes with the binding site of adenosine triphosphate (ATP) of VEGF-2 in cells, inhibits the formation of new blood vessels in tumor tissues, and then inhibits the occurrence and development of tumor tissues. This article systematically reviewed the current research status and progress of apatinib in the treatment of advanced gastric cancer in order to provide a reference for further clinical application.