Table of Content

Volume 27 Issue 5
26 May 2022

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Investigation of potential pharmacodynamic substances and mechanism of Qingxin-zishen prescription decoction in treatment of menopause syndrome based on HPLC-Q-TOF-MS/MS and network pharmacology

YAO Qian, CHEN Yun, SHANG Juan, XI Xiaoyun, CHEN Ying, GU Xiao, JU Wenzheng, ZOU Jiandong, LU Su, XU Meijuan

2022, 27(5):  481-497.  doi:10.12092/j.issn.1009-2501.2022.05.001

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AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD.

Role of Nrf2 pathway in flutamide-induced mitochondrial biogenesis

ZHANG Li, WANG Jin, LI Huizi, PENG Hui, HE Jun, PENG Shuangqing, GUO Jiabin

2022, 27(5):  498-504.  doi:10.12092/j.issn.1009-2501.2022.05.002

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AIM: To investigate the effect of flutamide on mitochondrial biogenesis and the regulating effect of anoxidative pathway Nrf2 on it.  METHODS: Human hepatocyte HepG2 cells were treated with flutamide (0-50 μmol/L) for 24 h, then mtDNA copy number and protein expression of mitochondrial biogenesis were detected by RT-PCR and WB. The effects of ERK1/2 and the role of Nrf2 pathway in mitochondrial biogenesis were further observed by gene knockdown and protein activation/inhibition methods. RESULTS: Flutamide interfered mitochondrial biogenesis concentration-dependently, the mtDNA copy number, ERK1/2 and PGC-1α proteins increased with the dose. ERK1/2 inhibition and activation regulated flutamide-induced mtDNA copy number and PGC-1α expression, and inhibition of Nrf2 pathway also affected flutamide-induced mtDNA copy number and expression of PGC-1α, as well as ERK1/2 expression. CONCLUSION: Flutamide affects mitochondrial biogenesis, and the antioxidant pathway Nrf2 may be involved in the regulation of flutamine-induced mitochondrial biogenesis by regulating ERK1/2.

Study on the screening of active constituents of Taohong Siwu Decoction and the protective effect of ferulic acid on myocardial injury

LIU Yizhen, REN Lingxuan, YANG Jianjun, HE Jianyu, LIU Xiaojun, WANG Long, LIN Rong

2022, 27(5):  505-515.  doi:10.12092/j.issn.1009-2501.2022.05.003

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AIM: To screen the active constituents in Taohong Siwu Decoction(THSWD) by Systems Pharmacology and to study its protective effect on myocardial injury through cell experiments.  METHODS: The TCMSP database and Pharmmaper database were used to retrieve the constituents and active constituent targets of THSWD. The Genecards database was used to retrieve the myocardial injury related targets gene. Then construct and analyze the constituents-disease intersection target network and the contribution value of constituents, and screen out the main active constituents of THSWD acting on the myocardium. Furthermore, CoCl2 was used to induce H9c2 to establish a hypoxic injury model, and the effects of the selected active constituents on cell viability were detected. The level of myocardial enzyme and energy metabolism were detected to investigate whether the active constituents in THSWD play a protective effect on myocardial injury by affecting energy metabolism. RESULTS: The screening found that THSWD contained 73 active constituents, which corresponded to 340 targets, while 1 544 disease targets related to myocardial injury. According to the network diagrams of constituents-disease intersection targets, quercetin, ferulic acid and paeoniflorin were screened out as the main active constituents of THSWD against myocardial injury. Further experiments found that ferulic acid can significantly increase the viability of H9c2 induced by CoCl2 (P<0.05), and significantly reduce the levels of CK, CK-MB and LDH after CoCl2 stimulation (P<0.01). In addition, ferulic acid can inhibit the increase of LD level and the decrease of ATP level after CoCl2 stimulation (P<0.01). CONCLUSION: Ferulic acid in THSWD is the main active constituent against myocardial injury and it can protect the myocardium by inhibiting myocardial enzyme levels and improving energy metabolism disorders.

Pharmacokinetics of methotrexate mediated by organic anion transporter 3 in adjuvant induced arthritis rats

PAN Shu, WU Yijin, ZHANG Sasa, WANG Qihai, LUO Tingting, YIN Qin

2022, 27(5):  516-525.  doi:10.12092/j.issn.1009-2501.2022.05.004

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AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms.  METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX.

Study on the inhibition of compound salvia miltiorrhiza on the proliferation of ovarian cancer cells and its preliminary mechanism

DENG Zhaoya, LI Yan, LIU Jian, HUANG Yinjiu

2022, 27(5):  526-534.  doi:10.12092/j.issn.1009-2501.2022.05.005

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AIM: To explore the inhibitory effect and mechanism of compound salvia miltiorrhiza on ovarian cancer by using network pharmacology and molecular docking knowledge. METHODS: The core components of compound salvia miltiorrhiza and the inhibitory effect of compound salvia miltiorrhiza on ovarian cancer cell cycle were studied by combining the methods of MTT cell cycle inhibition and MTT signal network of compound salvia miltiorrhiza. RESULTS: Based on network pharmacology, the core components of compound salvia miltiorrhiza were luteolin and quercetin, and the core target of the disease was VEGFA, SRC, EGFR, hsp90aa1. The docking mode between the core component and the core target EGFR was verified and analyzed by molecular docking. Finally, MTT colorimetry was used to verify that luteolin, one of the core components, significantly inhibited the proliferation of ovarian cancer cells. The results of flow cytometry showed that luteolin induced ovarian cancer A2780 cell cycle arrest in G1/S phase.CONCLUSION: Compound salvia miltiorrhiza preparation can inhibit the proliferation of ovarian cancer cells, which may be related to PI3K Akt signal pathway mediated by EGFR; Network pharmacology and molecular docking technology have important predictability and possibility for the treatment of tumor by compound salvia miltiorrhiza, and have guiding significance for the role and mechanism of compound salvia miltiorrhiza against ovarian cancer cells.

Study of TPA on enhancing the anti-tumor effects of cisplatin and reducing its renal toxicity

WANG Xinli, XU Xiaqing, FANG Hanbing, GUO Yuzhong

2022, 27(5):  535-543.  doi:10.12092/j.issn.1009-2501.2022.05.006

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AIM: To investigate the effects of phorbol ester (TPA) on the anti-tumor effect and renal toxicity of cisplatin (CP).  METHODS: MTT assay was used to examine the effect of TPA on the proliferation inhibition of CP in A549 and SPC-A-1 lung cancer cells. Also the effect of TPA on acute toxicity of CP was observed by once injection of high dose CP through caudal vein; The tumor-bearing mice model was explored to investigate the effect of TPA on tumor inhibition ratio and renal toxicity of CP in vivo. And the effect of TPA on renal oxidative stress induced by CP was detected. RESULTS: 1 ng/mL TPA could significantly enhance the inhibitory effect of CP on cell proliferation. In acute toxicity test, TPA could significantly reduce the toxicity of CP and prolong the survival time of animals. And the tumor weight (P<0.05), serum creatinine (P<0.05) and urea nitrogen levels (P<0.01) in TPA combined with CP group were significantly lower than those in CP group. Meanwhile, the results of HE staining showed that the renal tissue damage was significantly reduced in the combined group compared with CP group. The contents of MDA in renal tissue were decreased (P<0.01). However, the contents of GSH and the activity of SOD were increased (P<0.05) in TPA and CP combined group. CONCLUSION: TPA can enhance the inhibitory effect of CP on cell proliferation and inhibit tumor growth in tumor-bearing mice. At the same time, TPA can reduce the renal toxicity of CP, which may be related to the inhibition of renal oxidative stress induced by CP.

Effects of Rho kinase inhibitors on septic liver injury

XING Bomin, GUO Na, NING Haihui, DING Xinyun, MA Yuqing

2022, 27(5):  544-550.  doi:10.12092/j.issn.1009-2501.2022.05.007

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AIM: To investigate the effect of Rho kinase inhibitor Y-27632 on acute liver injury in sepsis. METHODS: Thirty-two healthy adult male SD rats were randomly divided into sham operation group (Sham group), sham operation+Y-27632 group (Sham+Y group), cecal ligation and perforation group (CLP group) and CLP+Y-27632 group (CLP+Y-27632 group), 8 animals in each group. The rat sepsis model was established by the CLP method, and the rat was euthanized 24 hours after the model was established, and the serum and liver tissue were collected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the liver tissue of the rats in each group; Western Blot was used to detect the expressions of ROCK1 and downstream NF-κB proteins in the liver tissue of the rats in each group; immunohistochemical method The expression of ROCK1 protein in liver tissue of rats was detected; enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of serum liver function indexes ALT and AST, and the changes of IL-18, IL-10 and GSH contents in liver tissue homogenate. RESULTS: Compared with the Sham group, there was no significant change in the histopathology of the liver in the Sham+Y group. In the CLP group, the arrangement of hepatocytes was disordered, with a large number of inflammatory cells infiltrating. Compared with the Sham group, the expression of ROCK1 protein in the CLP and CLP+Y groups was increased (P<0.05); compared with the CLP group, the ROCK1 protein expression in the CLP+Y group was decreased (P<0.05). Compared with the Sham group, the expression of NF-κB protein in the CLP and CLP+Y groups increased (P<0.05); compared with the CLP group, the NF-κB protein expression in the CLP+Y group decreased (P<0.05); A small amount of expression was found in the liver Sham group, and a large amount was expressed in the CLP group and CLP+Y group; compared with the Sham group, the serum ALT and AST levels in the CLP and CLP+Y groups were increased (P<0.05). The levels of ALT and AST in +Y group decreased (P<0.05). Compared with the Sham group, the contents of IL-18 in the liver tissue homogenate of the CLP and CLP+Y groups increased (P<0.05), while the contents of IL-10 and GSH in the liver tissue homogenate of the CLP group decreased (P<0.05). The changes of IL-10 and GSH in the group were similar (P>0.05); compared with the CLP group, the content of IL-18 in the CLP+Y group was decreased (P<0.05), and the content of IL-10 and GSH was increased (P<0.05). CONCLUSION: Rho kinase inhibitor can alleviate acute liver injury in septic rats, which may be related to inhibiting the expression of ROCK1 and NF-κB proteins, reducing the inflammatory response of liver tissue, and reducing the level of liver oxidative stress.

Comparison on the efficacy and safety of ultrasound-guided and X-ray guided for needle approach of percutaneous vertebroplasty

YE Sen, CHEN Yanzhen, LAI Liping, ZHONG Lingjian, YU Changzhang

2022, 27(5):  551-557.  doi:10.12092/j.issn.1009-2501.2022.05.008

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AIM: To compare ultrasound-guided vertebroplasty (percutaneous vertebroplasty, PVP) with X-ray guided vertebroplasty (PVP) to confirm the success rate of puncture point, X-ray radiation dose, operation time and postoperative outcome to explore the clinical application value of ultrasound-guided vertebroplasty.  METHODS: Patients with thoracolumbar vertebral compression fractures treated by PVP in our hospital from November 2018 to October 2021 were divided into ultrasound-guided group and X-ray guided group. The success rate of puncture, the X-ray radiation dose, operation time and postoperative outcome were compared between the two groups. RESULTS: A total of 97 patients were included in this study, with an average follow-up time of (14.412±10.261) months. The success rate of one-time puncture was 60.4% in the ultrasound-guided group and 30.6% in the X-ray guided group (P<0.05). The X-ray radiation dose, fluoroscopy times and operation time in the ultrasound-guided group were significantly lower than those in the X-ray-guided group (P<0.05). The difference was statistically significant (P<0.05). The VAS of low back pain was significantly relieved in the two groups, but there was no significant difference between the two groups. There were no postoperative complications such as infection, puncture site hematoma and fracture nonunion between the two groups. CONCLUSION: Ultrasound guidance is a safe and effective method to determine the needle entry point of PVP. Skillful operation can improve the success rate of one-time puncture. Compared with traditional X-ray guidance, it can shorten the operation time, reduce the number of X-ray fluoroscopy and radiation during PVP operation.

Analysis of the outcome of graduate students of master's degree in hematology under the new "dual track integration" policy

HUANG Dongping, HE Hesheng, WEI Zhongling

2022, 27(5):  558-561.  doi:10.12092/j.issn.1009-2501.2022.05.009

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AIM: To analyze the effect of the new "dual track integration" training policy on graduate students of master's degree in hematology.  METHODS: The graduate students of master's degree majoring in hematology from January, 2013, to September, 2018 at the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. They were divided into the "dual track integration" training group and "non-dual track integration" training group. Their health care ethics, basic knowledge in hematology, clinical skills, medical research capabilities, and employment were compared and analyzed. RESULTS: There were no significant differences with regard to the health care ethics, and employment by class A tertiary referral hospitals of the dual track group relative to those from the non-dual track group (P>0.05); However, the dual track training group scored much higher on their basic medical knowledge, clinical skills and reasoning than that of the non-dual track training group (P<0.05); The dual track training group published fewer papers than the non-dual track group (P<0.05). CONCLUSION: The dual track training system enhances significantly clinical skills and basic medical knowledge of graduate students of master's degree. However, more attention needs to be paid to improve their research capabilities.

Research progress on interaction between tumor microenvironment and breast cancer cells leading to tumor metastasis

SHI Jingbin, XIONG Yang

2022, 27(5):  562-574.  doi:10.12092/j.issn.1009-2501.2022.05.010

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Breast cancer is a malignant tumor with strong invasiveness, strong metastasis and high recurrence rate. Breast cancer cells can be transferred to different tissues in a variety of ways. Breast cancer cells can spread because of the tumor microenvironment created by tumor interaction with surrounding cells. This review examines the role and mechanisms of the tumor microenvironment in breast cancer cell metastasis in recent years, including adipocytes, fibroblasts, neuroendocrine cells, immune and inflammatory cells, blood and lymphatic network, and extracellular matrix, as well as how to treat breast cancer metastasis. 

Colorectal cancer and microRNA: research progress

ZHOU Guangchen, LIU Yixi, ZHENG Yun

2022, 27(5):  575-587.  doi:10.12092/j.issn.1009-2501.2022.05.011

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Colorectal cancer (CRC) has a high incidence and mortality rate worldwide. Its lesions are associated to gene mutation, epigenetic changes and activation of related signaling pathways. microRNAs (miRNAs) are a class of non-coding RNAs of 20-24 nt in length that can regulate the expression of target mRNAs and control various cellular mechanisms. As a novel marker for the treatment and prognosis of colorectal cancer, miRNAs are closely related to the occurrence and progression of colorectal cancer. In this review, we summarize the miRNAs dysregulated in CRC tissues, analyze the relationship between specific miRNAs and CRC proliferation, metastasis, apoptosis, and chemotherapy, and present the clinical applications of miRNAs in CRC treatment and prognosis.

Mechanism of vascular endothelial cells ferroptosis in cervical spondylosis of vertebral artery type

WANG Kai, SONG Min, SONG Zhijing, LI Jinyi

2022, 27(5):  588-594.  doi:10.12092/j.issn.1009-2501.2022.05.012

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Ferroptosis is a novel type of cell death, characterized by iron overload and lipid metabolism disorders, and is closely related to the occurrence of cardiovascular and cerebrovascular diseases, tumors, and acute injuries. When tissues and organs of the body are in a state of ischemia and hypoxia, iron ions initiate lipid peroxidation and produce a large number of oxygen free radicals. A series of oxidative stress reactions are more likely to trigger ferroptosis. In the process of cervical spondylosis of vertebral artery type, insufficient blood supply to the vertebral artery caused by degenerative changes of the cervical spine leads to imbalance of iron homeostasis and abnormal amino acid metabolism. Then ferroptosis is induced and plays an important role in the development of cervical spondylosis of vertebral artery type. This paper reviewed the mechanism of ferroptosis in the occurrence of cervical spondylosis of vertebral artery type, in order to provide new ideas and perspectives for the study of related problems of the disease.

Advances in new fast-acting antidepressants

YU Zefang, FAN Liju, YIN Xiaoyu, GAO Lili, DONG Zhanjun

2022, 27(5):  595-600.  doi:10.12092/j.issn.1009-2501.2022.05.013

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Antidepressants are mainly used to treat mental illnesses. Traditional antidepressants mainly target monoamine neurotransmitters, but these drugs are slow to be effective and cannot meet clinical needs. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis and focus on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in clinical practice. This article mainly summarizes the research mechanisms and treatment programs of new antidepressants, and briefly reviews common rapid-acting antidepressants.