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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 24 Issue 1
    26 January 2019
    Inhibitory effect of MicroRNA-136 targeting CD163 on the polarization of CD68+CD163+M2 macrophages
    HAN Chenyang, YANG Yi, LI Wenyang, WANG Jin, GUO Li
    2019, 24(1):  1-8.  doi:10.12092/j.issn.1009-2501.2019.01.001
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    AIM: To study the mechanism of MicroRNA (miR-136) inhibiting the polarization of CD68+M0 macrophages to CD68+CD163+M2 macrophages by targeting CD163. METHODS: The ratio of CD68+CD163+M2 macrophages in the tumor tissues and adjacent tissues of 20 patients with hepatocellular carcinoma was detected by flow cytometry, and the level of miR-136 in the tumor and adjacent tissues was detected by real-time fluorescence quantitative PCR (RT-qPCR). CD68+M0 macrophages were separated from the spleen, and the cells were divided into the control group (Control), the miRNA analogue group (miRNA mimic) and the miRNA inhibitor group (miRNA inhibitor). IL-4 and IL-13 10 ng/mL were used to induce M2 polarization. Western blot was used to detect the expression of CD163, TNF-α, iNOS and Arg1 in M2 macrophage. In the mechanism study, the levels of JAK1, STAT1 and STAT6 in the JAK/STAT signal were detected, and the expressions of PI3K and AKT1 in the PI3K/AKT signal were detected also. Luciferase reporter gene method was used to determine the target relationship between miR-136 and CD163. RESULTS: The proportion of M2 macrophages in HCC tissues was significantly higher than that of adjacent tissues, while the expression of miR-136 was significantly lower than that of adjacent tissues, and the expression of the two was negatively correlated. Luciferase reporter gene results showed that CD163 was the target gene of miR-136. The percentage of CD68+CD163+M2 macrophages in miRNA mimic was significantly lower than that in miRNA inhibitor, and there was no significant difference compared with control group. The low expression of JAK1, STAT6, PI3K, AKT1 in miRNA mimic showed that miR-136 could inhibit the expression of JAK1-STAT6 and PI3K-AKT1 to inhibit the polarization of M2 macrophage. CONCLUSION: miR-136 can target CD163 to inhibit the M2 polarization of macrophage, and its mechanism is related to the inhibition of JAK1-STAT6 and PI3K-AKT1, which is one of the regulatory mechanisms of M2 macrophages in the immunization of liver cancer.

    PDCD4 enhances the sensitivity mechanism of nasopharyngeal carcinoma cell line CNE1 to cisplatin chemotherapy
    LI Lin, WANG Wenhong, WANG Hongmei
    2019, 24(1):  9-13.  doi:10.12092/j.issn.1009-2501.2019.01.002
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    AIM: To investigate the roles of PDCD4 involved in promoting cisplatin (CDDP) induced tumor cell apoptosis. METHODS: CCK8 method was used to detect the cytotoxicity induced by CDDP in human nasopharyngeal carcinoma cell line(CNE1) before and after PDCD4 transfection. The rate of apoptosis for CDDP-induced nasopharyngeal carcinoma cells was investigated using flow cytometry before and after transfection of PDCD4. Western blot method was used to probe the molecular mechanisms involved in the chemosensitivity. RESULTS: PDCD4 enhanced the killing effect of CDDP on human nasopharyngeal carcinoma cell line CNE1; PDCD4 increased CDDP-induced apoptotic rate of human nasopharyngeal carcinoma cell line CNE1; mechanism study found that PDCD4 significantly decreased the expression of Twist and MDR1 protein, thereby promoting the cell chemosensitivity. CONCLUSION: PDCD4 enhances the sensitivity of chemotherapy drugs by inhibiting Twist protein, suggesting that PDCD4 might serve as a chemotherapy target in nasopharyngeal carcinoma treatment.

    Effect of paeonol on the expression of cytokines production and maturation of DCs co-stimulated by FSL-1 and IL-4
    HU Yuping, ZHOU Haiyun, HUANG Qiaoling, YAO Yimin
    2019, 24(1):  14-19.  doi:10.12092/j.issn.1009-2501.2019.01.003
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    AIM: To study the molecular mechanism of natural paeonol induced by TLR2 signal transduction pathway of inflammation of the skin, developing new ideas for prevention and treatment of atopic dermatitis and provide a theoretical basis. METHODS: Bone marrow-derived dendritic cells (BMDCs) were divided into three groups: control group, FSL-1 stimulated group, paeonol treatment group with different concentrations (25, 50, 100 g/mL). The DC surface molecules such as CD40, CD86 and MHC-II were detected by flow cytometry. The cytokine levels of IL-10, IL-12 in culture supernatant were detected by ELISA. RESULTS: The expression of CD40, CD86 and MHC-II on the surface of dendritic cell surface molecules were significantly increased after stimulated with FSL-1 as compared to control group (P<0.05). After treated with paeonol (50, 100 g/mL), expressions of CD40, CD86 and MHC-II were all decreased, only in the high and middle dose groups, the difference was statistically significant (P<0.05). Compared with the control group, FSL-1 stimulated group significantly enhanced the secretion of pro-inflammatory cytokines IL-12(P<0.05), while the anti-inflammatory cytokine IL-10 was decreased significantly (P<0.05). Meanwhile, compared with FSL-1 stimulated group, the levels of IL-12 were found significantly decreased in the middle and high dose of paeonol treatment group(P<0.05), but the low dose treatment group did not show significant effect(P>0.05). The above results showed that FSL-1 can change the differentiation of lymphocyte subset through affecting the secretion of DC cytokines, which can promote the pro-inflammatory cytokines such as IL-12 secretion, while the secretion of anti-inflammatory cytokines such as IL-10 were decreased. But paeonol reversed these effects. CONCLUSION: FSL-1, the TLR2 ligands, can promote the development of chronic dermatitis and chronic inflammation of the development through influencing the expression of cytokines production and maturation of DCs. The level of IL-12 is increased while level of IL-10 is decreased by activating the TLR2 signaling pathway. Furthermore, the primitive Th cells are promoted to transform to Th1 thereby resulting in Th1/Th2 polarization. However, paeonol can reverse FSL-1 induced cellular processes, and shows potential in the prevention and treatment of chronic dermatitis.

    Effects of Yiqi Yangyinshengji recipe on rats with recurrent oral ulcer and its effect on mucosal inflammatory factors and immune function
    XIE Fangying, CHEN Zheli, GAO Yuelan
    2019, 24(1):  20-26.  doi:10.12092/j.issn.1009-2501.2019.01.004
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    AIM: To analyze the therapeutic effect of Yiqi Yangyinshengji recipe on rats with recurrent oral ulcer (ROU) and its effect on mucosal inflammatory factors and immune function. METHODS: Sixty Wistar male rats of SPF grade were randomly divided into six groups, namely, low-, medium-, and high-dose groups of Yiqi Yangyinshengji receipe, normal group, model group and positive control group. Each of the 10 rats, except the normal group, was prepared for the ROU model. After successful modeling, the low-, medium-, and high-dose groups of Yiqi Yangyinshengji group was administered with 0.17 mg/kg, 0.34 mg/kg and 0.68 mg/kg Yiqi Yangyinshengji liquid, respectively; positive control group was treated with ibuprofen solution, normal group and model group were given normal saline, once a day, for a continuous gavage of 10 days. The number, duration, interval and ulcer area of rats in each group were observed. Serum interleukin-2R (IL-2R), IL-1β, IL-17 and γ-interferon (IFN-γ) were detected in each group, as well as IL-2, transforming growth factor-β1 (TGF-β1), epidermal growth factor, vascular endothelial growth factor (VEGF) and T lymphocyte content, and relative expression of NLRP3 mRNA and matrix metalloproteinase in ulcer tissue 9 (MMP-9), MMP-2 protein expression. RESULTS: At 2, 6 and 10 days after administration, the area of ulcer in the positive control group, the middle- and high-dose groups of Yiqi Yangyinshengji receipe was lower than that in the model group, and the ulcer area of the middle- and high-dose groups of Yiqi Yangyinshengji receipe was lower than that of the positive control group (P<0.05). Compared with the normal group, the serum IL-2R, IL-17, IL-1β and IFN-γ levels in the model group increased, serum IL-2 content deceased (P<0.05); compared with the model group, the serum levels of IL-2R, IL-17 and IFN-γ in the positive control group, Yiqi Yangyinshengjifang middle and high dose group decreased, serum IL-2 content increased (P<0.05). Compared with the normal group, the serum levels of TGF-β1 and EGF in the model group decreased, serum VEGF content, relative expression of NLRP3 mRNA in ulcer tissues, and MMP-9 and MMP-2 protein expression increased (P<0.05). Compared with the model group, the serum levels of TGF-β1, EGF and VEGF in the positive control group, Yiqi Yangyinshengjifang middle and high dose group increased, and the relative expression of NLRP3 mRNA in ulcer tissue, level of MMP-9 and MMP-2 protein decreased (P<0.05). CONCLUSION: Yiqi Yangyinshengji can improve the immune dysfunction of ROU rats and reduce the serum inflammatory factor content.

    Increased expression of lncFOXC1 promotes liver cancer formation
    ZHOU Yuling, LIU Jiyang, YAO Hongwei, XU Yufen, ZHANG Ting, ZOU Zhuolin, PAN Huan
    2019, 24(1):  27-31.  doi:10.12092/j.issn.1009-2501.2019.01.005
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    AIM: To investigate the expression of long noncoding RNA lncFOXC1 in liver cancer and the role in liver cancer formation. METHODS: A total of 34 liver cancer and peri-tumor tissues were collected. Expression of lncFOXC1 was detected by qRT-PCR in liver cancer and peri-tumor tissues, as well as liver cancer cell spheres. LncFOXC1 deficiency cell lines were constructed by shRNA. Then, its roles in sphere formation and in vivo tumor growth assays were studied. RESULTS: lncFOXC1 was significantly highly expressed in liver cancer tissues and liver cancer cell sphere. LncFOXC1 deficiency significantly reduced sphere formation and tumor growth. CONCLUSION: LncFOXC1 is highly expressed in liver cancer tissues, and can regulate liver cancer stem cell growth.

    Inhibitory effect of juglone on proliferation and invasion of human ovarian cancer SKOV3 and IOSE80 cells and its mechanism
    SUN Hongya, YUAN Aijuan, LI Jipeng
    2019, 24(1):  32-37.  doi:10.12092/j.issn.1009-2501.2019.01.006
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    AIM: To study the effect of juglone on proliferation and invasion of human ovarian cancer SKOV3 and IOSE80 cells, and to explore its mechanism through signal pathway. METHODS: Cells were cultured in vitro and treated with different concentrations of juglone. The cell proliferation was detected by MTT colorimetry, the cell migration was detected by scratch test, the cell metastasis was detected by Transwell, and the apoptosis was detected by flow cytometry. The protein expression of AKT, ERK, NF-κB signaling pathway were detected by Western blot, and the expressions of Vimentin, MMP-2 and MMP-9 mRNA were detected by RT-PCR. RESULTS: Different concentrations of juglone could inhibit the proliferation of SKOV3 and IOSE80 cells, reduce the invasive ability of cells, and accelerate the apoptosis, with increase of concentration the effect on cell proliferation, invasion and apoptosis were more obvious, the difference was statistically significant (P<0.05). The expressions of AKT, ERK and NF-κB signaling pathway proteins in SKOV3 and IOSE80 cells were decreased by different concentrations of juglone, and the expression decreased with the increase of concentration, the difference was statistically significant (P<0.05). The expressions of Vimentin, MMP-2 and MMP-9 mRNA in SKOV3 and IOSE80 cells were decreased with the increase of concentration of juglone, and the difference was statistically significant (P<0.05). CONCLUSION: Juglone can inhibit the proliferation and metastasis of SKOV3 and IOSE80 cells in vitro and promote apoptosis. The mechanism maybe related to inhibit the expression of AKT, ERK, NF-κB signaling pathway, downregulate of the expression of Vimentin, MMP-2 and MMP-9 mRNA.

    Study on liver dysfunction related to voriconazole by automatic surveillance
    ZHAO Quanfeng, FU Peishu, MA Huan, ZHAO Suyu, GUO Daihong, TANG Min
    2019, 24(1):  43-48.  doi:10.12092/j.issn.1009-2501.2019.01.008
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    AIM: To study the real-world incidence and related factors of liver dysfunction caused by voriconazole in hospitalized patients. METHODS: The active monitoring system for adverse drug reactions was used to screened inpatients that used voriconazole from January to June 2018 in our hospital. The incidence of liver dysfunction caused by voriconazole was analyzed retrospectively. RESULTS: A total of 251 patients, liver dysfunction rate was 12.35% and mild to moderate liver dysfunction was 87.09%. Spearman correlation coefficients and binary logistic regression analysis showed that the liver dysfunction rate was positively related to voriconazole's trough concentration (P=0.000; P=0.001). The incidence of liver dysfunction was significantly increased (P=0.000) when the plasma trough concentration was greater than 5 mg /L.CONCLUSION: There is a significant correlation between voriconazole's liver dysfunction and trough concentration. In clinical application, it is essential to pay attention to the inpatient whose plasma trough concentration greater than 5 mg/L in order to reduce the risk of liver dysfunction.

    Scientific decision process and regulation requirements based on the current guidelines of data extrapolation from adult to pediatric population
    ZHANG Huimin, LIU Aiming, ZHU Wenfeng, YU Lingzhi, CHEN Fangliang
    2019, 24(1):  49-56.  doi:10.12092/j.issn.1009-2501.2019.01.009
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    AIM: To provide a general overview of the regulatory guidelines on the extrapolation from adult and other data to pediatric population, and to provide some practical advices for following these guidelines. METHODS: Literatures about the topic of "data extrapolation/and pediatric" from website of CFDA, EMA, USFDA, ICH and databases such as Wanfang,CNKI and Pubmed were searched, then the current guidelines on this topic were analyzed and compared, and the strategy for this topic was discussed. RESULTS: The current guidelines of EMA, U.S.FDA and ICH maintained consistent in critical principles. But the difference still required further improvement. The current data extrapolation guidelines laced maneuverability, and the description for some critical concepts and algorithm was not clear. CONCLUSION: Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals drug for pediatric use, and the ICH E11(R1) that may replace the current guidelines will provide a better way for the pharmaceutical manufacturers to develop drug for pediatric use.

    Clinical trial of sacubitril/valsartan in the treatment of Pulmonary hypertension (PH) due to left heart disease (LHD)
    WEI Zihan,LI Dongbo,YUAN Zheng,LU Ying, YANG Guojie
    2019, 24(1):  57-62.  doi:10.12092/j.issn.1009-2501.2019.01.010
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    AIM: To observe the clinical efficacy of sacubitril/valsartan in patients with pulmonary hypertension due to left heart disease (PH-LHD) as well as investigate the mechanism of it. METHODS: A total of 60 patients including 35 males and 25 females with PH-LHD were randomly divided into control group(n=30 cases)and observation group(n=30 cases). Observation group was treated with sacubitril/valsartan by 50 mg twice daily and control group with valsartan by 80 mg daily on the basis of routine treatment. The world health organization functional class (WHO-FC), 6-minute walking distance (6MWD) were compared before and 90 days after treatment between the two groups. The plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and endothelin-1(ET-1) as well as the serum level of sICAM-1and sCD40L were measured before and after treatment by ELISA. Concomitantly, left ventricular end diastolic diameter (LVEDD), right ventricular end diastolic diameter (RVEDD), left atrial diameter (LAD), tricuspid regurgitant velocity (TRV), ejection fraction (EF), pulmonary arterial systolic pressure (PASP) were measured before and after treatment by echocardiography. RESULTS: No significant differences of WHO-FC, 6MWD and EF between the two groups prior to administration of sacubitril/valsartan were observed (P=0.371), whereas the factors monitored above show a remarkable amelioration in observation group compared to the control group after treatment (P<0.05). In addition, utility of sacubitril/valsartan has shown more efficacy on the blood levels of NT-proBNP, ET-1, sICAM-1, sCD40L and LVEDD,RVEDD,LAD,TRV,EF and PASP in observation group. CONCLUSION: Sacubitril/valsartan can effectively reduce PASP as well as blood levels of ET-1,sICAM-1 and sCD40L in patients with pulmonary hypertension due to left heart disease,improve the cardiac function and prognosis, relieve the clinical symptoms with relatively high safety.

    Effect of ketotifen on gastrointestinal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrheal
    WANG Jing, ZHOU Haibin, GU Weigang, WANG Xia, YANG Jianfeng
    2019, 24(1):  63-70.  doi:10.12092/j.issn.1009-2501.2019.01.011
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    AIM: To investigate the effects of ketotifen on abdominal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrhea (IBS-D). METHODS: Patients with IBS-D were randomly divided into ketotifen group and placebo group, the ketotifen group were oral administration of ketotifen tablets, 1 mg, bid for 8 weeks, the control group were received oral placebo for 8 weeks. Gastrointestinal symptoms evaluation scale questionnaire, anorectal sensory function, the number and activity status of mast cell (MC) were measured before and 8 weeks after treatment in these two group. RESULTS: (1) A total of 87 IBS-D patients were included, 44 in ketotifen group and 43 in control group, there was no significant difference in age and sex between the two groups. (2) Total effective rate of improvement of gastrointestinal symptoms in ketotifen group was significantly higher than that in control group (72.7% vs. 34.9%, P<0.01). (3) Compared with before treatment, first sensation, urge to defecation, discomfort/pain sensory thresholds of ketotifen group were significantly increased after treatment (P<0.05), no significant changes were observed in the control group (P>0.05); (4) Compared with before treatment, the number of MC in terminal ileum, the proportion of MC degranulation state in the terminal ileum, ascending colon, sigmoid colon in ketotifen group were significantly decreased after treatment (P<0.05), there was no significant change in the number of MC and the proportion of degranulation state in the control group (P>0.05); (5) 5 patients (11.4%) in ketotifen group went through adverse reactions, mainly manifested as feeling of drowsiness or fatigue, which disappeared after taking the drug one week. CONCLUSION: Ketotifen can significantly relieve the gastrointestinal symptoms and improve the visceral sensitivity of patients with IBS-D, which is closely related to its effect on reducing the number and activity of MC in intestinal mucosa, especially the terminal ileum.

    Diagnostic value of thyroid function in pregnant women with pre-eclampsia
    CAI Hairui,CHENG Shuqing,LIU Xijuan,CHEN Aner
    2019, 24(1):  71-76.  doi:10.12092/j.issn.1009-2501.2019.01.012
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    AIM: To investigate the diagnostic value of thyroid function in pregnant women with pre-eclampsia (PE) so as to provide reference for the diagnosis and early treatment of pregnant women with PE.  METHODS: Forty-one patients with PE in our hospital were selected from Mar.2015 to Feb.2017 for the observation group, 29 healthy pregnant women who were participate in physical examination at the same time were selected for the control group. The levels of free thyroxine (FT4), thyroid stimulating hormone (TSH) and thyroid peroxidase autoantibody (TPOAb) were compared between groups. ROC curve was used to analyze the diagnostic value of FT4, TSH, TPOAb detection and the joint detection of three indicators for PE, and the positive and negative prediction rate, sensitivity, specific, consistency and area under curve (AUC) of the detection results were compared. RESULTS: The level of TSH and TPOAb in observation group were significantly higher than those in control group (P<0.05), and the level of FT4 in observation group was significantly lower than that in control group (P<0.05). The positive predictive value of FT4, TSH, TPOAb detection and joint detection were 0.871, 0.917, 0.848 and 0.923, the negative predictive value were 0.641, 0.765, 0.649 and 0.839, the sensitivity were 0.659, 0.805, 0.683 and 0.878, the specificity were 0.862, 0.897, 0.828 and 0.897, the value of Kappa were 0.496, 0.684, 0.491 and 0.767, the AUC were 0.620, 0.706, 0.675 and 0.775. The AUC of joint detection is significantly higher than FT4 level detection, TSH level detection and TPOAb level detection (P<0.05). CONCLUSION: Each index detection of thyroid function has high diagnostic value in pregnant women with PE, and the highest diagnostic value of PE is joint detection.

    Clinical efficacy and the effect on Hypothalamic--Pituitary--Adrenal Axis of differentdoses of methylprednisolone in the treatment of children with septic shock indecompensation stage
    LIN Hai, WANG Zijing, WANG Shibiao, GUO Xiaofeng, GUO Renming, WENG Bin
    2019, 24(1):  77-82.  doi:10.12092/j.issn.1009-2501.2019.01.013
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    AIM: To investigate the therapeutic effects of different dosages of methylprednisolone (MP) on the children with septic shock (SS) in decompensation stage, and analyse the changes of hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Eighty-one children with SS in decompensation stage were randomly divided into three groups according to the MP initial dosages: the high-dosage group (20 mg·kg-1·d-1), the middle-dosage group (5 mg·kg-1·d-1) and the low-dosage group (2 mg·kg-1·d-1). The MP dosages were reduced gradually after a week. The therapeutic effects of the three groups were recorded. The serum cortisol, adrenocorticotropic hormone (ACTH) were analyzed on day 1, 3, 8 in hospital and compared with those of 27 healthy controls. RESULTS:The fever clearance time, SS correct time and the time of vasoactive drug used in the middle-dosage group and the high-dosage group were obviously decreased compared with the low-dosage group (P<0.05). The mortality of the three groups were not statistically significant (P>0.05). The length of stay in the low-dosage group and the middle-dosage group were statistically shorter than that in the high-dosage group (P<0.05). The double infect in the high-dosage group was statistically more than that in the middle-dosage group and the low-dosage group (P<0.05). Large amplitude of glycemic excursions (LAGE) of the high-dosage group and the middle-dosage group were obviously wider than that of the low-dosage group (P<0.05). At the first day of admission, the three groups with SS in decompensation stage had statistical increase of serum cortisol and ACTH as compared with the healthy control group, but there were not significant differences among the three groups (P>0.05), the serum cortisol and ACTH in the death children were significantly higher than the survival children in the three groups (P<0.05). At the third day of admission, serum cortisol and ACTH in the middle-dosage group and the high-dosage group were obviously decreased as compared with those of the low-dosage group (P<0.05), the serum cortisol and ACTH in the death children were significantly lower than the survival children in the three groups (P<0.05). At the eighth day of admission, the serum cortisol and ACTH of the three groups were no statistical differences compared with those of the healthy control group (P>0.05). CONCLUSION: The low-dosage of MP can be used to guide the therapy of children with SS in decompensation stage, which is conductive to control inflammation, shorten the length of stay, and reduce LAGE, decrease serum cortisol and ACTH slowly. High or rapid decreasing serum cortisol and ACTH levels are indicators of mortality risk.

    Effects of low dose dexmedetomidine combined with ulinastatin on immune function and stress response in patients with lung cancer
    YUAN Jing, SUN Jingxue, HUANG Daiqiang, YUAN Lin, DING Dengfeng
    2019, 24(1):  83-88.  doi:10.12092/j.issn.1009-2501.2019.01.014
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    AIM: To observe the effect of low dose dexmedetomidine combined with ulinastatin on immune function in patients with lung cancer. METHODS:A total of 120 patients with lung cancer scheduled to undergo operation were randomly divided into group A, B, C, D with 30 cases in each group. Before anesthesia induction, the patients in group B and group D received intravenous 0.3 μg·kg-1·h-1 dexmedetomidine after 0.3 μg/kg bolus. The patients in group C and group D received intravenous 200 000 U ulinastatin. The patients in group A received intravenous equal dose of saline. The levels of CD3+, CD4+, CD4+/CD8+ were determined before anesthesia (T0), 1 h after operation began (T1), 24 h (T2) after operation. The mean arterial pressure (MAP) and HR were also observed at T0, during tracheal intubation and extubation. The consumption of sevoflurane and remifentanil and the incident of bradycardia, hypotension and hypertension during operation were recorded. RESULTS:The levels of CD3+, CD4+ and CD4+/CD8+ of T1 and T2 were lower than those of T0 in group A, B and C (P<0.05). At T1 and T2, the levels of CD3+, CD4+ and CD4+/CD8+ in group B and group C were higher than those in group A (P<0.05), while those in group D were higher than those in other groups (P<0.05). The MAP and HR of tracheal intubation and extubation were higher than those of T0 in group A and group C (P<0.05). Compared with group A and group C, the MAP and HR of tracheal intubation and extubation were lower in group B and group D (P<0.05). The consumption of sevoflurane and remifentanil and the incident of hypertension were lower in group B and group D than those in group A and group C (P<0.05). CONCLUSION:Low dose dexmedetomidine combined with ulinastatin can improve perioperative immune function, inhibit stress response during tracheal intubation and extubation, and reduce the consumption of anesthetic drugs in patients with lung cancer.

    Evaluation on drug use of systemic glucocorticoid affected by the level of eosinophils in peripheral blood of the patients with acute exacerbation of chronic obstructive pulmonary disease
    HE Xiaobin, LIN Xiaohua, LIU Shunli, OU Huanjiao
    2019, 24(1):  89-93.  doi:10.12092/j.issn.1009-2501.2019.01.015
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    AIM: To analyze the application situation of systemic glucocorticoids in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) diagnosed with different eosinophil levels in peripheral blood in order to guide clinical rational drug use. METHODS: A retrospective research method was adopted; the latest published AECOPD management recommendations issued by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) were taken as evaluation criterion. According to the percentage of eosinophils (EOS) in peripheral blood, all patients were divided into two groups: patients with EOS≥2.0% as EOS observation group and patients with EOS<2.0% as EOS control group. SPSS 19.0 statistical analysis software was used for data processing; the differences in the proportion of systemic glucocorticoids used and the length of hospital stay between the two groups were compared, so was the difference of forced expiratory volume in 1s (FEV1) between the two groups before and after treatment. RESULTS: A total of 550 AECOPD patients were included in the study, of which there were 193 patients with EOS≥2.0%, accounting for 35.10%, and there were 357 patients with EOS<2.0%, accounting for 64.90%, there were 164 patients who used systemic glucocorticoids, accounting for 29.82%, there were 386 patients who used inhaled glucocorticoids, accounting for 70.18%. There were 45 patients out of the 164 patients who used systemic glucocorticoids in the EOS observation group, accounting for 27.44%; there were 119 patients who used systemic glucocorticoids in the EOS control group, accounting for 72.56%. Compared with the EOS control group, the average length of hospital stay in the EOS observation group was shorter; so the difference between the two groups was significant (P=0.04). FEV1 in EOS observation group was improved after using systemic glucocorticoid, and there was significant difference between before and after treatment (P=0.04). CONCLUSION: According to the latest AECOPD management recommendations as an evaluation criterion, systemic glucocorticoids are overused and underused in the treatment of AECOPD; clinical pharmacists should refer to the latest recommendations recognized by international professional pharmacists when guiding clinical drug use and conducting drug utilization evaluation in order to promote rational use of drugs together with clinicians.

    Clinical efficacy of low dose risperidone combined with trazodone in the treatment of heroin addicts during detoxification
    CAI Dandan, GUI Donghui, ZHANG Jianbing, ZHOU Wenhua
    2019, 24(1):  94-98.  doi:10.12092/j.issn.1009-2501.2019.01.016
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    AIM: To investigate the clinical efficacy and safety of low dose risperidone combined with trazodone in the treatment of anxiety disorders, depression disorders and insomnia from heroin addicts after detoxification. METHODS: One hundred and fifty patients were divided into 3 groups randomly. Fifty patients of risperidone combined with trazodone group(R+T group) were given low dose risperidone and trazodone.Fifty patients of the trazodone group(T group)were only given trazodone and 50 patients of the risperidone group(R group) were only given low dose risperidone, respectively. Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the efficacy before treatment and at the end of 2, 4, 6 weeks after treatment. The safety was evaluated with Treatment Emergent Side-effect Scale (TESS) and laboratory test. RESULTS:Twenty-one patients were fallen off after 6 weeks, and 129 patients completed the course of treatment. There was significantly decrease compared with HAMA,HAMD and PSQI scores in R+T group at the end of 2,4,6 weeks after treatment, the differences were statistically significant (P<0.05); the HAMA,HAMD and PSQI scores of R group were significantly decreased compared with before treatment at the end of 4,6 week, the differences were statistically significant (P<0.05); the HAMA, HAMD scores of T group were significantly decreased compared with before treatment , the differences were statistically significant (P<0.05).PSQI scores decreased significantly only at the end of 6 week, the differences were statistically significant (P<0.05). There were significant differences in HAMA,HAMD and PSQI scores of R+T group compared with group R and group T at the end of 2,4,6 week (P<0.05). Comparison of the TESS scores in the 3 group at the end of 4,6 weeks after treatment showed no significant differences (P>0.05). CONCLUSION:Low dose risperidone combined with trazodone can significantly improve heroin addicts during detoxification of anxiety, depression and sleep quality. The effect of combined application is better than single drug use.

    Clinical application and rationality analysis of voriconazole injection
    WANG Lili
    2019, 24(1):  99-102.  doi:10.12092/j.issn.1009-2501.2019.01.017
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    AIM: To investigate the clinical application of voriconazole injection in a hospital and to analyze the rationality of drug use. METHODS: Rationality evaluation criteria were formulated according to voliconazole injection drug instructions, fungal infection treatment guidelines and references. The hospital HIS system was used to randomly select the medical records of the hospitalized patients with voriconazole from Jan.2016 to Dec.2016, and the history of the hospital and the medical advice of the hospital were consulted, and the rationality of the hospital was analyzed. RESULTS: The 50 medical records included in this study are reasonable in the way of the administration of voriconazole injection, the selection of solvent and the amount of solvent, but there are some nonstandard phenomena in the indication of drug use, the dosage, the frequency of administration and the treatment course. CONCLUSION: The irrational use of voriconazole injection in this hospital should be corrected and the implementation of the prescription review system should be further strengthened to promote the safety and rational use of voriconazole injection in clinical practice.

    Research progress in the associations of metabolic diseases and therapeutic drugs with hepatocellular carcinomas
    TIAN Jing, MENG Qiuhua, LIANG Qiuyun, DONG Min
    2019, 24(1):  103-110.  doi:10.12092/j.issn.1009-2501.2019.01.018
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    Metabolic diseases are significantly associated with the development of hepatocelluar carcinomas (HCC), and the mechanism may be related to insulin resistance, hyperglycemia, abnormal secretion of adipocyte cytokines, endoplasmic reticulum stress, gut-associated microbiota disorders, dyslipidemia and other factors. Moreover, the therapeutic drugs for metabolic diseases such as metformin and atorvastatin have been reported to reduce the incidence and recurrence risk of HCC. Therefore, we summarizes the research progress in the associations of metabolic diseases and therapeutic drugs with hepatocellular carcinomas.

    Research progress of fibroblast growth factor 1 in the treatment of diabetes and related diseases
    JIN Hui, ZHOU Ziye, LIANG Jing, WANG Chenxiang, SONG Lintao, ZHAO Longwei, GUO Kaiwen
    2019, 24(1):  111-115.  doi:10.12092/j.issn.1009-2501.2019.01.019
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    Acid fibroblast growth factor (FGF-1) as found earlier as an important member of fibroblast growth factor family, which stimulates the growth of blood vessels, accelerate wound healing and promote nerve injury repair has been widely recognized before,in recent years, research on the potential biological function of it in endocrine system has become a hot point. This article will review the FGF-1 about structure, function, receptor signaling pathway and treatment of diabetes and related diseases.

    Research and potential clinical application of adipose-derived mesenchymal stem cells
    WEI Zhaoming,JIANG Wensheng,GAO Yi,ZHANG Juanjuan
    2019, 24(1):  116-120.  doi:10.12092/j.issn.1009-2501.2019.01.020
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    Adipose-derived mesenchymal stem cells (ADSCs) are stem cells that derived from adipose. Like other adult stem cells, they have self-renewal capacity, multi-differentiation potential, plasticity, low immunogenicity, paracrine secretion of various biologically active factors and lower teratogenicity. Meanwhile they can be differentiated into osteoblasts cells, fat cells and chondrocytes cells under suitable induction conditions. Adipose-derived mesenchymal stem cells have been widely used in the repair of bone, cartilage tissue, skin damage, diabetes and immune regulation. This article reviews the clinical application of ADSCs.