Table of Content

Volume 23 Issue 10
26 October 2018

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Screening and bioinformatics analysis of differential microRNA in nitroglycerin-tolerant rat aorta

ZENG Zhenhua, LIU Jianxin, CAO Chunya, WU Weihua

2018, 23(10):  1081-1087.  doi:10.12092/j.issn.1009-2501.2018.10.001

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AIM: To screen the differential expression of microRNA (miRNA) in nitroglycerin-tolerant rat aorta and to analyze their target genes and function. METHODS: Sprague Dawley (SD) rats were treated with nitroglycerin (100 mg·kg^-1·time^-1 for 3 days, three times a day, s.c). Then, miRNA sequencing technology and qRT-PCR were used to find differential miRNAs involved in nitroglycerin-tolerant rats. Furthermore, bioinformatics analysis was performed to predict target genes regulated by these differential miRNAs, and to analyze the enriched gene ontology (GO) and signaling pathway. RESULTS: Compared with control group, the expression of 28 miRNAs changed significantly in nitroglycerin-tolerant group, of which 16 were known. 12 up-regulated and 4 down-regulated were obtained among the 16 miRNAs. The expression of miR-487b-3p and miR-503-5p were detected by qRT-PCR showed the similar trend as well as the sequencing results. Bioinformatics analysis showed that the target genes of differential miRNAs were mainly enriched in protein binding and metabolic pathways. CONCLUSION: The expression of miRNA in nitroglycerin-tolerant rat aorta changes significantly, and these differential miRNAs are involved in the development of nitroglycerin tolerance by regulating their target genes.

Therapeutic effect and mechanism of Yipi Yangwei decoction in treating ulcerative colitis-related cancerous mice

LOU Chaosheng, WU Xian, WANG Haibo, ZHANG Yin, YE Lechi

2018, 23(10):  1088-1096.  doi:10.12092/j.issn.1009-2501.2018.10.002

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AIM: To observe the therapeutic effect of Yipi Yangwei decoction in treating ulcerative colitis-related cancerous mice and its effect on toll-like receptor 4/mitogen-activated protein kinase (TLR4/MAPKS) signaling pathway. METHODS: Eighty BALB/c male mice were randomly divided into the normal group, the model group, the high-dose and low-dose groups of Yipi Yangwei decoction. Each group contains 20 cases. AOM/DSS (azoxymethane/dextran sodium sulfate) method was used to establish murine mouse models of ulcerative colitis-associated cancer. After modeling, the corresponding dosage of Yipi Yangwei decoction was given to the models at the same time. The general condition, colon crypt changes, and colon histopathology changes of the mice in each group were observed. ELISA method was used to detect the levels of inflammatory cytokines IFN-γ, IL-4 and IL-12 in serum of each group. Real-time PCR was used to detect the expression of IFN-γ, IL-4, IL-12 and NF-κBp65 mRNA. The relative expression levels of TLR4, p-JNK1/2 and p proteins were detected by Western blot. RESULTS:Compared with the model group, the body mass and colon length of the mice in each medication administration group were significantly increased, while the colon weight, colon weight length ratio, and colonic mucosal histological damage score were remarkably decreased; the levels of serum IFN-γ and IL-12, as well as the expression levels of IFN-γ and IL-12 mRNA in colon tissues were all significantly decreased, while IL-4 level was significantly increased; the mRNA and protein expression levels of TLR4, p-JNK1/2, p-p38 and p-ERK1/2 in colon tissues and the protein expression levels of p-NF-κBp65, PCNA, COX-2, Bcl-xl were significantly decreased (P<0.05). Compared with the low-dose group of Yipi Yangwei decoction, the histological injury score of colonic mucosa in the high-dose group of Yipi Yangwei decoction decreased significantly, and the levels of any other elements were all higher (P<0.05). The difference of protein expression levels of p-NF-κB(p65) in all groups was without statistical significance（P＞0.05）. CONCLUSION: Yipi Yangwei decoction can relieve the inflammatory injury of colonic mucosa and reduce the risk of cancer. The mechanism may be related to the down-regulation of TLR4/MAPKS signaling pathway.

Inhibitory effect and mechanism of cinobufotalin on lung cancer NCI-A549 xenograft in nude mice

XIONG Fei, SHI Yanyan, SHEN Jiucheng, CHENG Honglan, HANG Yongfu

2018, 23(10):  1103-1108.  doi:10.12092/j.issn.1009-2501.2018.10.004

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AIM: To investigate the anti-tumor effect and mechanism of cinobufotalin on lung cancer cells NCI-A549.  METHODS: Forty BALB/c nude mice were randomly divided into the normal group, the mock group, the cinobufotalin group and the DDP (cisplatin) group. Body weight change, tumor inhibition rate, blood function, liver and kidney function of the mice in each group were detected. Western blot was used to investigate the expression of apoptosis-associated proteins.RESULTS:Cinobufotalin significantly inhibited the growth of A549 xenograft, but had no significant effect on the blood, liver and kidney function of the mice. The tumor-inhibition rate of the cinobufotalin group and the DDP group was 58.0% and 82.3%, respectively. Western blot results showed that cinobufotalin significantly up-regulated the expression of Bax/Bcl-2, promoted the expression of cleaved-caspase-3, cleaved-PARP, and inhibited the expression of p-AKT(ser473). CONCLUSION: Cinobufotalin can significantly inhibit the growth of lung cancer A549 xenograft. Its molecular mechanism might be related to the inhibition of PI3K/AKT pathway activation. Based on this mechanism, cinobufotalin can accelerate cell apoptosis.

Study on the protective mechanism of anti-platelet thrombolysin against cerebral ischemia reperfusion injury in rats

LUO Shengyong, JIA Dewu, LI Xiaoyi, DAI Xiangrong

2018, 23(10):  1109-1115.  doi:10.12092/j.issn.1009-2501.2018.10.005

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AIM: To investigate the protective mechanism of anti-platelet thrombolysin (APT) on cerebral ischemia reperfusion injury in rats. METHODS: The TLR4 siRNA in vivo transfection technique was used to reduce the TLR4 expression in the brain of rat. Wild-type and TLR4 down-regulated rats were randomly divided into six groups: sham group, model group, TAK-242 (Toll-like receprot 4 blocker) 2 mg/kg group, APT 0.02 mg/kg, 0.01 mg/kg, 0.005 mg/kg group respectively with eight rats in each group. The rat focal ischemia-reperfusion injury model was established by ligation of middle cerebral artery occlusion(MCAO). RhoA activity was measured using absorbance based G-LISA RhoA activation assay and the expression of TLR4, ROCK1/2 and p-JNK were determined by Western blot. RESULTS: The expression of TLR4 protein in TLR4 siRNA transfected rats brain tissue decreased significantly compared with that in control group rats. Compared with model group, APT could obviously decrease the TLR4, ROCK1/2 and p-JNK protein expression, inhibit the RhoA activity in wild rat brain; however, APT had no significant effect on RhoA activity, ROCK1/2 and p-JNK protein expression in brain compared with model group in TLR4 siRNA transfected rats. CONCLUSION: The protective mechanism of APT on cerebral ischemia reperfusion injury in rats is mainly related to the inhibition of TLR4/RhoA/ROCK signaling pathway.

Clinical trial of multiple compound Chinese medicine injections in the treatment of mice with chemotherapy-related leukopenia

ZHANG Xiping, ZHANG Xiang, YANG Hongjian, ZOU Dehong, QIAO Enqi, WANG Zhun, HE Xiangming, YU Xingfei, ZHANG Ying, TANG Binbin

2018, 23(10):  1116-1125.  doi:10.12092/j.issn.1009-2501.2018.10.006

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AIM: To investigate the effects of 5 commonly-used compound traditional Chinese medicine (TCM) injections and granulocyte-colony stimulating factor (G-CSF) in the treatment of chemotherapy-related leukopenia mice, as well as their effects on multiple organs and thymus of the mice.  METHODS: Cyclophosphamide intraperitoneal injection was used to prepare mice model with Chemotherapy-related leukopenia. The mice treated with G-CSF were taken as positive control, while the mice in each treatment group were given intraperitoneal injection of kang'ai, kushen, shenfu, shenmai and shengmai, respectively. The mice were killed the next day after drawing peripheral blood for routine blood test. Cardiac blood was taken to measure serum liver and kidney function indexes (ALT, AST, BUN and CR), while important organs (heart, liver, spleen, lung, kidney) and thymus were taken to calculate the corresponding organ index. RESULTS:Compared with the model group, the white blood cell (WBC) count of the mice in the five TCM-treated groups was significantly increased (P<0.01), which was lower than that of the G-CSF-treated group (P<0.05, P<0.01). In addition, G-CSF and 5 kinds of TCM injections can promote platelet at different levels (P<0.05, P<0.01). Compared with the model group, the level of serum AST was slightly increased in the kushen-treated group (P=0.036) and the shenfu-treated group (P=0.008). Serum ALT and renal function index were not significantly increased in each TCM-treated group, while the spleen index decreased (P<0.05 or P<0.01) and the lung index increased (P<0.01). In 5 TCM-treated groups, the liver cells of the mice showed different degrees of cellular degeneration, spot-like necrosis and inflammatory response, but the difference between the groups was not significant. Expect for the kushen-treated group, the liver pathology score of the other TCM-treated groups was significantly lower than that of the model group (P<0.05, P<0.01), among which the most significant was in the shengmai-treated group (P<0.01). CONCLUSION: All the 5 TCM injections can effectively treat chemotherapy-related leukopenia, which is weaker than G-CSF. Five TMC injections and G-CSF also have a certain platelet effect. In addition to kushen, the other 4 TMC injections may all have protective effects on liver. The effects of 5 TMC injections on other organs and thymus are not significant.

Healing effect of Xianling Gubao plus probiotics on osteoporotic fracture rats

DENG Zuyue, HUANG Junjun

2018, 23(10):  1126-1131.  doi:10.12092/j.issn.1009-2501.2018.10.007

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AIM: To study the healing effect of Xianling GuBao (XLGB) plus probiotics on osteoporotic fracture rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into five groups: fracture control group, osteoporotic fracture model group, XLGB treatment group, probiotics treatment group and XLGB combined probiotics treatment group, 10 rats in each group. In addition to the conventional fracture control group, the other groups were treated with bilateral ovaries to prepare osteoporosis model. After 6 weeks, each group was prepared for right middle femoral fracture model. Then, Saline, XLGB (250 mg·kg^-1·d^-1) or probiotics (12.5 g·kg^-1·d^-1) were intragastrically administered separately. The right femur specimens of each group were taken 5 weeks after surgery. The bone mineral density was measured bone mineral density scanner, CR and Micro-CT were used to observe femur related parameters in rats. The bone alkaline phosphatase（BALP）, tartrate resistant acid phosphatase (TRACP) contents were measured by ELISA kit, calcium（Ca）concentration was measured by biochemical analyzer. HE staining was used to observe the pathological changes of periosteum in fractures. RESULTS: Compared with the osteoporotic fracture group, the BALP level was increased, the TRACP level was decreased, the bone density and the amount of callus were increased, the fracture line was blurred, the number and thickness of the trabecular bone were increased, and the trabecular space was decreased in XLGB and probiotic group, and XLGB combined probiotic group expressed the most obvious effect of treatment (P<0.05, P<0.01). CONCLUSION: Both XLGB and probiotics showed the therapeutic effect on osteoporotic fractures, and the combination of drugs has a better effect on osteoporotic fracture.

Efficacy and safety of iguratimod combined with methotrexate in rheumatoid arthritis: A systematic review and Meta-analysis

WU Jiaqi, YANG Qiaowen, CHEN Xiumin, HUANG Runyue, HUANG Qingchun, ZHAO Yue, WU Xiaodong

2018, 23(10):  1132-1140.  doi:10.12092/j.issn.1009-2501.2018.10.008

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AIM: To evaluate the efficacy and the safety of the combination therapy of iguratimod (IGU) and methotrexate (MTX) as compared with MTX monotherapy in adults with rheumatoid arthritis (RA) through a Meta-analysis on randomized controlled trials (RCTs). METHODS: A systematic review was conducted by searching multiple databases including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), VIP, the Chinese Biomedical Literature Database, Wanfang Data, the Chinese Scientific and Technological Journals Database. The systematic literature search was carried out up to June 2017. RCTs related the efficacy and/or safety of IGU combined with MTX to treat RA were selected. The quality of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions and Jadad scoring, and Meta-analysis was performed using Rev2Man5.3 software. RESULTS: Six RCTs involving 553 patients were included. Compared with MTX, IGU combined with MTX showed better effects in ACR20 ［RR:1.53, 95%CI(1.13,2.06), P=0.006］, ACR50［RR:2.15, 95%CI(1.64,2.81), P<0.001］, ACR70［RR:2.93, 95%CI(1.54,3.72), P<0.001］, and had a better result in lowering ESR, physician VAS and DAS28 level with the similar adverse effects (AEs) ［RR:1.06, 95%CI(0.91,1.24), P=0.46］. Meanwhile, the systematic review shows that IGU combined with MTX was no less effective than MTX monotherapy in reducing CRP, TJC28, SJC28, Pain VAS, Patient VAS and HAQ after treatment. CONCLUSION: For RA, IGU combined with MTX has a better clinical efficacy than MTX monotherapy, and adverse drug reactions remain stable of the combination therapy, which is referential for clinical application.

Bioequivalence of high variation drug abiraterone acetate tablets in healthy subjects

LIU Yanan, YANG Guoping, PEI Qi, WANG Yiya, JIAO Feifei, YANG Xiaoyan, YANG Shuang, GUO Can, HUANG Jie

2018, 23(10):  1141-1146.  doi:10.12092/j.issn.1009-2501.2018.10.009

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AIM: To evaluate the bioequivalence of the experimental preparation and reference preparation of the high-variation drug abiraterone acetate tablets administered once orally in the healthy Chinese volunteers after taking fatty food. METHODS: It was a randomized, open-label, double- sequence, four-period, repeated cross-test and 32 healthy volunteers were given a single oral 250 mg dose of test or reference abiraterone acetate tablets with a high-fat meal. The blood concentrations of abiraterone in plasma were determined by LC-MS/MS. The major pharmacokinetic parameters were calculated with the aid of WinNonlin 7 and the bioequivalence was evaluated. RESULTS:The abiraterone's major pharmacokinetic parameters of test and reference were as follows: C _max were（238.0±108.6）and（220.1±96.9）ng/mL; T _max were 2.0 (1.0-4.0) and 2.0 (1.0-5.0) h; t _1/2 were (13.1±2.6) and (13.0±2.9) h; AUC _0-t were (615.2±226.3) and (589.4±210.1) h·ng·mL^-1， AUC _0-∞ were (618.7±227.7) and (592.8±211.6) h·ng·mL^-1, respectively. The 90% confidence interval, the geometric mean ratio（T/R）of the AUC _0-t ,AUC _0-∞ and C _max, all ranged from 80.00% to 125.00%. CONCLUSION: The test preparation of acetabone acetate tablets is bioequivalent to the reference preparation after diet.

Pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced NSCLC in a single and multiple dose group

WANG Lu, ZHENG Xin, WANG Weicong, ZHAO Hongyun, MA Yuxiang, ZHANG Li, HU Pei, JIANG Ji

2018, 23(10):  1147-1152.  doi:10.12092/j.issn.1009-2501.2018.10.010

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AIM: To evaluate the pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced nonsmall-cell lung cancer (NSCLC) after single and multiple dose of abivertinib maleate capsules. METHODS: Seven Chinese patients with advanced NSCLC were administered a single oral dose of 350 mg of abivertinib maleate capsule. After a washout period, three of them were administered 350 mg of abivertinib QD for 28 days, four were administered 175 mg of abivertinib twice a day for 28 days. The plasma concentrations of five metabolites of abivertinib were assayed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated with WinNonlin ver. 6.4. RESULTS: Among these five metabolites, the exposure of MII-2, a cysteine conjugate, was the highest, which was 3.32%-5.57% of the exposure of the parent drug. The exposures of M1 (N-demethylation) and M2 (N-oxidation) were 2.14%-4.24% and 0.56%-1.00% of the exposure of the parent drug, respectively. The exposures of M4 (N-dealkylation) and MII-1 (acetylcysteine conjugate) were low, most of the concentrations of MII-1 were blow the lower limit of quantitation (0.1 ng/mL). CONCLUSION: The exposures of the five metabolites monitored were no more than 10% of the exposure of the parent drug.

Effects of fasudil combined with rosuvastatin in the treatment of vascular dementia on patients' cognitive function, C-reactive protein and oxidative stress

CHEN Juanyan, SONG Shuijiang, XU Dongjuan, XU Qiong, LI Hongfei

2018, 23(10):  1153-1158.  doi:10.12092/j.issn.1009-2501.2018.10.011

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AIM: To investigate the effects of fasudil combined with rosuvastatin in the treatment of vascular dementia (VD) on patients' cognitive function, C-reactive protein and oxidative stress.  METHODS: One hundred and eighty-four VD patients were selected as study subjects. They were divided into the rosuvastatin group and the combined drug group (fasudil + rosuvastatin) according to the random number table method. Each group contains 92 cases. MMSE (Mini-Mental State Examination), MoCA (Montreal Cognitive Assessment) and ADL (Activities of Daily Living) scores, the level of CRP (C-reactive protein), MDA (malondialdehyde), Hcy (serum homocysteine) and SOD (superoxide dismutase), as well as blood lipid index (TC, TG, LDL-C, HDL-C) levels, clinical efficacy and incidence of adverse reaction were compared between the two groups before and after treatment. RESULTS:The total effective rate of the combined drug group (93.48%) was significantly higher than that of the rosuvastatin group (82.61%), and the difference was statistically significant (P<0.05). After treatment, the MMSE, MoCA and ADL scores of the combined drug group were significantly higher than that of the rosuvastatin group, while the level of CRP, MDA, Hcy, TC, TG and LDL-C was significantly lower than that of the rosuvastatin group, and the SOD level was significantly higher than that of the rosuvastatin group, which were of statistically significant difference (P<0.05). There was no significant difference in the incidence of adverse reaction (P>0.05). CONCLUSION: Fasudil combined with rosuvastatin in the treatment of VD can improve patients' cognitive function and daily living ability, reduce oxidative stress response and the level of C-reactive protein, and improve patients' blood lipid index. This method is of significant clinical efficacy and high safety.

Effects of Shenfu injection on the quality of life and immune function on patients with breast cancer after chemotherapy

CHEN Zhou, HUANG He, CHEN Qiyu

2018, 23(10):  1159-1164.  doi:10.12092/j.issn.1009-2501.2018.10.012

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AIM: To study the effect of Shenfu injection on the quality of life and immune function in patients with breast cancer after chemotherapy.  METHODS: A total of 150 patients with breast cancer who received chemotherapy in our hospital from Dec.2016 to Dec.2017 were selected and randomly divided into the study group and the control group according to the random number table method. The control group was given conventional chemotherapy; the study group received extra Shenfu injection treatment on the basis of the control group. After 6 courses of chemotherapy, the clinical efficacy of the two groups was compared. The T cell subgroup, NK cell level, immunoglobulin level and the quality of life of the two groups were analyzed before and after chemotherapy and the occurrence of adverse reactions was observed. RESULTS: The total effective rate of the study group was 96%, which was significantly higher than that of the control group (86.67%) (P<0.05). Before chemotherapy, there was no significant difference in the levels of CD3+, CD4+, CD8+, CD4+/CD8+ and NK cells between the two groups (P>0.05). After chemotherapy, the level of CD3+, CD4+, CD4+/CD8+ and NK cells in the two groups increased, and the increase of the study group was higher than that of the control group. The level of CD8+ decreased and the decrease of the study group was lower than the control group. The two groups were significantly different (P<0.05). After chemotherapy, the lgG, lgA and lgM level of the two groups decreased, and the study group decreased more than the control group (P<0.05). After chemotherapy, the score of somatic function in the functional subscale of the study group was significantly higher than that of the control group. The scores of fatigue, nausea, vomiting and pain in the symptom subscale were significantly lower than those of the control group (P<0.05). The total adverse reaction rate in the study group was 4%, which was significantly lower than that in the control group (14.67%). There was a significant difference between the two groups (P<0.05). CONCLUSION: Shenfu injection can effectively improve the immune function of patients with breast cancer after chemotherapy, and improve the quality of life after operation. The clinical effect is remarkable and worthy of clinical application.

Effects of Muguasantie combined with mesalazine on the clinical efficacy, inflammatory and intestinal barrier protective factors of ulcerative colitis

ZHANG Jihong, LI Xiaomei, SHI Mengiong, XIONG Xiinjun, LI Xiaoqin, FENG Minlu, XU Haiyan, YANG Wenyan, QIN Huilin, LUO Tao

2018, 23(10):  1165-1173.  doi:10.12092/j.issn.1009-2501.2018.10.013

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Clinical pharmacists' pharmaceutical care and practice in the department of nephrology

ZHU Xuting, HANG Yongfu

2018, 23(10):  1174-1178.  doi:10.12092/j.issn.1009-2501.2018.10.014

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AIM: To explore the content of clinical pharmacists participating in the clinical rational drug use in the department of nephrology. METHODS: Clinical pharmacists conducted pharmacy services for physicians, nurses, and patients, provided pharmaceutical care for key patients, and promoted the clinical rational drug use. RESULTS: Through pharmaceutical care and service in the department of nephrology, the patients' compliance with medication was improved, which also encouraged pharmacists to integrate into the medical team. CONCLUSION: Clinical pharmacists should improve their professional knowledge and strengthen clinical cogitation in practice constantly, thus to provide safe, effective, and satisfactory pharmacy services for the department of nephrology.

Progress of proton pump inhibitors using in cancer patients

HUANG Qiong, DU Jie, CHENG Shuqiao, GONG Zhicheng

2018, 23(10):  1179-1187.  doi:10.12092/j.issn.1009-2501.2018.10.015

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Proton pump inhibitors (PPIs) are a class of drugs that inhibit gastric acid secretion. They are used in the treatment of acute and chronic digestive diseases. They are also commonly used in chemical therapy, radiation therapy, stress ulcers and prophylactic administration of steroids. In clinical research, it is found that most of the preventive administrations of PPIs are unreasonable. This article reviews the clinical trials and adverse reactions of PPIs in cancer patients, providing a reference for rational use of PPIs.

Hepatic macrophages in liver injury and repair

WANG Lu, LI Liping, XING Xin, XU Dengqiu, XIAO Li, JIANG Zhenzhou, ZHANG Luyong, SUN Lixin

2018, 23(10):  1188-1195.  doi:10.12092/j.issn.1009-2501.2018.10.016

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Hepatic macrophages play a critical role in the pathogenesis of liver injury and repair. It is noted that, based on the distinct origins and phenotypes, hepatic macrophages can clear bacterial pathogens, antigens, promote or inhibit the liver inflammation, which directly participate in the liver disease development and repair. This article reviews the functions and phenotypes of hepatic macrophages, and their roles in the different stages of liver injury and repair. Also, the potential macrophage-targeted therapies against liver diseases were also summarized.

Advance in linezolid-induced thrombocytopenia

ZHONG Ling, SHAO Hua, CHEN Yan, HU Linlin, YU Feng

2018, 23(10):  1196-1200.  doi:10.12092/j.issn.1009-2501.2018.10.017

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Linezolid (LZD) has good antibacterial activity against methicillin-resistant staphylococcus aureus,penicillin-resistant pneumococcus and vancomycin-resistant enterococci. However, platelet toxicity greatly limits its clinical application. In recent years,significant progress has been acheived in studies of the pathogenesis and clinical risk factors of linezolid-induced thrombocytopenia（LIT）. LZD has been found to be closely related to bone marrow suppression, inhibition of platelet release,oxidative stress and immune destruction to result in low platelet count.In addition,a large number of clinical studies had also summarized the risk factors of LIT,and explored the dose adjustment methods of LZD,which became the breakthrough of prevention and treatment for LIT.However,there are many different kinds of opinoins in these literatures.This article reviews the pathogenesis,risk factors,and dose adjustment of LIT,with a view to providing ideas for clinical prevention and treatment of LIT.