Table of Content

Volume 24 Issue 5
26 May 2019

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Transcriptomic analysis of neonatal mammalian vestibular after hair cell injury by neomycin

HAN Jinghong, LIU Yuchen, NIE Guohui

2019, 24(5):  481-489.  doi:10.12092/j.issn.1009-2501.2019.05.001

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AIM: Vestibular hair cell damage is an important cause of vestibular dysfunction. This study tried to explore the changes of gene expression, signal pathway and biological process in the process of hair cell damage, so as to provide new ideas for hair cell regeneration and vestibular function recovery. METHODS: In the present study, RNA from the newborn mouse utricles was collected for RNA-seq immediately after the damage of neomycin, in order to investigate gene expression changes. RESULTS:There were 172 and 232 genes that were found to be up-regulated and down-regulated in neomycin-treated utricles. GO and KEGG pathway analyses of these genes revealed many deregulated cellular components, molecular functions, biological processes and signaling pathways that may be related to hair cell development.CONCLUSION: These results provide valuable reference and preliminary basis for future studies, and find that Wnt, Notch TGFβ and other signaling pathways that may be closely related to vestibular hair cell injury and regeneration, which may provide important signaling pathways and gene targets for vestibular hair cell regeneration research and clinical vertigo prevention.

Hepatic toxicity and pharmacodynamic effects of paracetamol and chlorphenamine maleate with three herb extracts capsules

ZHANG Shengpeng, MIU Dongdong, LIU Dingfeng, ZHU Xiaohong, ZHANG Chao, CHEN Yunyu, LIU Xiaoping

2019, 24(5):  489-495.  doi:10.12092/j.issn.1009-2501.2019.05.002

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AIM: To investigate the hepatic toxicity and pharmacodynamic effects of paracetamol and chlorphenamine maleate with three herb extracts capsules. METHODS: Fixed dose toxicity test and two-week feeding toxicity test were applied to observe the degree of toxic injury in rats; the analgesic effect was investigated by hot plate method, and the fever model in rats was induced by yeast, and the body temperature of the rats was measured to investigate the antipyretie effects of the products. RESULTS:There was no death within one week after oral administration of 10 000 mg/kg; In the two-week feeding toxicity test, edial and high dose group (equivalent to the human maximum daily dose of 3, 9 times) increased the serum levels of AST, ALT, ALP, total bile acid levels, decrease CYP1A2, CYP3A4 expression of mRNA in rat liver tissues, a week after stopping, the above indexes were improved. Each three herb extracts capsules group (124.81, 249.62, 499.24 mg/kg) could lower the body temperature of yeast-induced febrile rats; hot-plate test results showed that 1.75 g/kg, 3.50 g/kg and 7.00 g/kg of herb extracts capsules increased the pain thresholds for 1 and 2 hour. CONCLUSION: The drug has no severe acute toxic risk in human, the human maximum daily dose of medication for two weeks cause no obvious toxicity to the animal body; the human maximum daily dose of 9 times two weeks have influence on animal liver function, mainly caused by acetaminophen, but it can be recovered after stopping medication for a week. And the products have better effects on relieving fever and analgesia.

Effect of interleukin 12A on proliferation and differentiation of CD4+CD25+Foxp3+Treg

ZHANG Xiaoling，GUAN Qiaobin，YANG Yi, GUO Li，HAN Chenyang

2019, 24(5):  496-502.  doi:10.12092/j.issn.1009-2501.2019.05.003

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AIM: To study the role of interleukin 12A (IL-12A) in promoting proliferation and differentiation of CD4+CD25-T cells into CD4+CD25+Foxp3+Treg（iTreg）. METHODS: CD4+CD25-T cells in umbilical cord blood were selected by immunomagnetic beads. Both the experimental group and the control group were activated by anti-CD3 and anti-CD28 monoclonal antibodies, and induced by adding 10 ng/mL of TGF-1, while the experimental group was simultaneously induced by adding 5 ng/mL of IL-12A.After the cells were cultured for 72 h, the ratio of CD4+CD25+Foxp3+Treg (iTreg) cells was detected by flow cytometry (FACS). The expression of Foxp3, Smad2, Smad3 and Smad6 in the cells was detected by protein immunoblotting (Western-Blot), and the expression of TGF-β1 was detected by real time fluorescence quantitative PCR.iTreg and CD4+CD25-T cells were induced by co-culture in vitro, and lymphocyte activity was assessed by CCK-8.The co-culture of 5 ng/mL IL-12A with iTreg and CD4+CD25-T cells in vitro was used to detect the effect of IL-12A and iTreg on the activity of CD4+CD25-T cells.RESULTS:IL-12A could promote the differentiation of CD4+CD25-T into iTreg by FACS detection. CCK-8 showed that iTreg could inhibit the activity of CD4+CD25-T cells in a concentration-dependent manner. IL-12A can synergize the inhibitory effect of iTreg on CD4+CD25-T cell activity.Western-Blot and RT-QPCR results showed that Foxp3, Smad2, Smad3 and Smad6 expression levels were increased during iTreg differentiation, and related mRNA levels also was increased. CONCLUSION: IL-12A can promote the differentiation of iTreg and synergistic effect on the inhibition of effector T cells.

Effects of ginsenoside-induced bone marrow mesenchymal stem cells on liver regeneration and Wnt/β-catenin signaling in rats with acute liver failure

MAO Yun, ZHANG Zhaorui

2019, 24(5):  503-510.  doi:10.12092/j.issn.1009-2501.2019.05.004

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AIM:To analyze the effects of ginsenoside-induced bone marrow mesenchymal stem cells (BMSC) on liver regeneration and Wnt/β-catenin signaling in rats with acute liver failure (ALF).  METHODS:Sixty-six Wistar male rats of SPF grade were selected. One of them was cultured with BMSCs. Fifty rats were randomly selected to prepare ALF model.After 24 hours,5 of them were randomly selected and sacrificed.The success of the rat model was judged by liver function and histopathology.The remaining 15 rats were intraperitoneally injected with an equal dose of 0.9% sodium chloride solution as a normal group.Forty-five rats were randomly divided into three groups:BMSCs group,model group and ginsenoside-induced BMSCs group,with 15 rats in each group.The model group and the normal group were injected with 1 mL of cell culture medium from the tail vein and the BMSCs group was injected with 1 mL of BMSCs suspension (cell concentration:2.0×109/L).The ginsenoside-induced BMSCs group was injected with 1 mL of ginsenoside to induce differentiation of BMSCs (cell concentration 2.0×109/L).The solution was administered continuously for 10 days.The pathological conditions of liver tissue were observed, serum TBil,AST,ALT,TNF-α,IL-6 levels,Wnt7b,Wnt7a and Wnt2 gene expression in liver tissue.RESULTS:The normal group of rats had no necrosis,degeneration,neatly arranged,the structure of hepatic lobule was clear,and there was no inflammatory cell infiltration in the portal area.The hepatocytes in the model group were characterized by extensive necrosis,and all hepatocytes in the hepatic lobules were necrotic.The stent collapsed, and there were a large number of granulocytes, monocytes and lymphocytes infiltrated in the portal area and surrounding areas.The residual hepatocytes were degenerated,swollen and accompanied by cholestasis.The BMSCs group and ginsenoside-induced BMSCs group showed that the hepatic lobule structure became more intact.The number of hepatocyte necrosis and degeneration was reduced,and there was a little inflammatory cell infiltration in the portal area. The ginsenoside-induced BMSCs group was superior to BMSCs.Compared with the normal group,serum TBil,AST,ALT,IL-6 and TNF-α level in the model group increased. Compared with the model group, serum TBil,AST,ALT,IL-6 and TNF-α level in the BMSCs group and ginsenoside-induced BMSCs group decreased.Compared with BMSCs group,the levels of serum TBil,AST,ALT,IL-6 and TNF-α in ginsenoside-induced BMSCs group were significantly lower (P<0.05).Compared with the normal group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the liver tissue of the model group was decreased.Compared with the model group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the BMSCs group and ginsenoside-induced BMSCs group increased.Compared with BMSCs group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the liver tissues of rats in ginsenoside-induced BMSCs group increased,the difference was statistically significant (P<0.05). CONCLUSION:Ginsenoside-induced BMSCs can significantly improve liver function in ALF rats,and its mechanism may be related to activating Wnt/β-catenin signaling pathway to accelerate liver regeneration.

Interventional effect of low molecular weight heparin on mice with experimental hepatic fibrosis

ZHENG Qiongna, WU Qiaoqiao, MA Zhele, ZHANG Xianfei, GAN Fangmin, KONG Qingming

2019, 24(5):  511-516.  doi:10.12092/j.issn.1009-2501.2019.05.005

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AIM: To investigate the interventional effect of low molecular weight heparin on mice with hepatic fibrosis caused by carbon tetrachloride (CCl4). METHODS: Thirty mice were randomly divided into three groups: normal control group (intraperitoneally injection of olive oil for 8 weeks, n=10), model group (intraperitoneally injection of CCl4 for 8 weeks, n=10) and interventional group (intraperitoneally injection of CCl4 and subcutaneous injection of low molecular weight heparin for 8 weeks, n=10). All animals were sacrificed at the end of week 8, and blood samples and liver tissue samples were obtained. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL) and hyaluronicacid (HA) were detected. Liver pathology morphology and collagen deposition were observed by HE staining, masson-trichrome staining and PCR staining. The expression of α-smooth muscle actin (α-SMA) in hepatic tissue was detected by immunohistochemistry. The expression of α-SMA and collagen type Ⅰ(COL-Ⅰ) mRNA in the hepatic tissue was quantified by real time PCR. RESULTS:Compared with control group, the serum level of ALT, AST, TBIL, DBIL and HA, the liver collagen deposition, the hepatic tissue expression of α-SMA and the hepatic tissue expression of α-SMA and COL-Ⅰ mRNA in both model group and interventional group were all significantly higher(all P＜0.05). Compared with model group, the serum level of ALT, AST, TBIL, DBIL and HA, the liver collagen deposition, the hepatic tissue expression of α-SMA and the hepatic tissue expression of α-SMA and COL-Ⅰ mRNA in interventional group were all significantly decreased (all P＜0.05).CONCLUSION: Low molecular weight heparin can attenuate the progression of mice hepatic damage and fibrosis caused by CCl4. The mechanism may be related with the anticoagulation of low molecular weight heparin.

Protective effects of Butylphthalide on S-nitrosoglutathione-induced brain microvascular endothelial cells injury and potential mechanisms

YAN Jieping，ZHANG Shuijun，ZHANG Guobing，HU Ying，LUO Dan，JIANG Hongjuan，LI Minjing

2019, 24(5):  517-522.  doi:10.12092/j.issn.1009-2501.2019.05.006

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AIM: To investigate the protection of Butylphthalide (dL-NBP) on oxidative damage in brain microvascular endothelial cells, and to further find the potential mechanisms of dL-NBP effects. METHODS: The brain microvascular endothelial cells were injured by GSNO. The cell viability was measured by MTT assay. ROS was observed by DCFH staining. ERK, p-ERK，cleaved caspase 9，pro-caspase 9，cleaved caspase 3 and pro-caspase 3 were detected by Western blot. The gene expressions of GR, SGK and MKP-1 were detected by RT-PCR assay. RESULTS:dL-NBP (10,20 μmol/L) protected endothelial cells against GSNO-induced injury and ROS release. dL-NBP increased SGK and MKP-1 gene expression. dL-NBP up-regulated ERK phosphorylation. dL-NBP inhibited cleaved caspase 9 and cleaved caspase 3. CONCLUSION: dL-NBP attunates bEnd.3 cells GSNO-induced injury, and its mechanism is related with activating GR relative SGK and MKP-1. dL-NBP increases ERK phosphorylation and down-regulates caspase decades.

Correlation between phosphorylation of PEA-15-Ser104 site and prognosis of epithelial ovarian cancer

FANG Chuanchuan, NI Guantai, JIN Lan, LIU Ji, LIU Xiaoqing, QIAO Chun, LUO Yonghong

2019, 24(5):  523-528.  doi:10.12092/j.issn.1009-2501.2019.05.007

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AIM: To detect the expression level of pPEA-15-Ser104 in epithelial ovarian carcinoma and to explore its clinical significance, and the correlation with the prognosis of epithelial ovarian carcinoma. METHODS: From January 2009 to June 2013, 95 cases of primary ovarian epithelial carcinoma who were admitted to the First Affiliated Hospital of Wannan Medical College Yijishan Hospital for gynecology and obstetrics surgery and pathologically confirmed were selected. All the patients were not treated with chemotherapy before surgery. The expression levels of pPEA-15-Ser104 in 95 cases of primary ovarian epithelial carcinoma were detected by immunohistochemical method.Chi-square test was used to analyze the difference of pPEA-15-Ser104 expression in patients with ovarian cancer with different clinical characteristics. Survival status of patients with ovarian epithelial carcinoma was closely followed up after surgery . Kaplan-Meier (K-M) method was used to analyze the difference of survival rate in patients with ovarian epithelial carcinoma with different clinical characteristics. Multivariate Cox proportional risk regression model was used to analyze prognostic factors in patients with epithelial ovarian carcinoma.RESULTS:There were significant differences in the expression levels of pPEA-15-Ser104 in different histological grades, surgical and pathological stages, types and distant metastasis of ovarian epithelial carcinoma.There was no significant difference in age, tumor location, tumor maximum diameter and lymph node metastasis.K-M survival analysis and Cox regression analysis showed that the prognosis of ovarian cancer patients with high expression of pPEA-15-Ser104 was poor and the survival time was short, which could be used as an independent risk factor for poor prognosis of ovarian cancer (P<0.05).CONCLUSION: Phosphorylated PEA-15 plays an important role in the development of ovarian epithelial carcinoma.The prognosis of the patients with high expression is poor. It may become a new target to predict the prognosis of ovarian cancer patients, and it is expected to provide an important target for the treatment of ovarian cancer patients.

Expression and function of transmembrane protein 106A in lung cancer

PAN Huan, ZHOU Yuling, QI Weibo, SHEN Hui, JIN Jing, SHEN Jianfen, MA Xingjie, XU Yufen

2019, 24(5):  529-534.  doi:10.12092/j.issn.1009-2501.2019.05.008

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AIM: To investigate the expression of transmembrane protein 106A (TMEM106A) in lung cancer and its relationship with clinicopathological features, and the effect of this molecule on the proliferation of lung cancer cells. METHODS: Thirty-one cases of lung cancer tissues were collected from patients with early stage lung cancer. Tissue RNA was extracted and real-time quantitative PCR was used to detect the relative expression of TMEM106A mRNA in lung cancer tissues and para-cancer tissues. TMEM106A lentiviral expression vector Plenti-UBI/TMEM106A was constructed and transfected into H1299 cells to overexpress TMEM106A. Cell proliferation assay and colony formation assay were used to observe the effect of TMEM106A overexpression on the proliferation of lung cancer H1299 cells.RESULTS:Real-time quantitative PCR (qRT- PCR) showed that the relative expression of TMEM106A gene mRNA in lung cancer tissues was lower than that in the control para-cancer tissues. H1299-TMEM106A，the cell line overexpressed TMEM106A, was successfully constructed. Compared with H1299-control, the expression of TMEM106A in cell line H1299-TMEM106A was significantly increased. The proliferation experiment showed that the high expression of TMEM106A significantly inhibited the proliferation of lung cancer cells. The colony formation assay showed that the colony forming ability of lung cancer cells with high expression of TMEM106A in cell line H1299-TMEM106A was significantly lower than that of H1299-control lung cancer cells (P<0.01). CONCLUSION: TMEM106A can inhibit the proliferation of lung cancer cells.

Effects of PicrosideII on autophagy of MCF-7 breast cancer cells and its mechanism

YANG Hong, ZHOU Jie, YANG Xiaoqing

2019, 24(5):  535-540.  doi:10.12092/j.issn.1009-2501.2019.05.009

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AIM: To investigate the effects of PicrosideII on autophagy and PI3K/AKT/mTOR pathway in MCF-7 breast cancer cells. METHODS: Fifty nude mice were randomly divided into five groups, ten in each group, divided into model group, 3-MA group, high dose (100 mg/kg), medium dose (10 mg/kg), low dose (1 mg/kg). Human breast cancer cells MCF-7 were cultured in vitro, and then transplanted into nude mice to establish a subcutaneous transplantation model of MCF-7 breast cancer. The weight of each group of nude mice and the breast tumor volume were measured, the tumor inhibition rate was calculated. Tumor cell morphology was observed by HE staining, and the apoptosis of MCF-7 cells by TUNEL assay.Western blot was used to detect the expression of Beclin1, PI3K, p-PI3K, AKT, p-AKT, mTOR and p-mTOR proteins. RESULTS:PicrosideII significantly inhibited the weight loss of breast cancer nude mice (P<0.01), increased the tumor inhibition rate (P<0.01), improved the pathological tissue results; promoted the apoptosis of MCF-7 cells, increased the expression of Beclin1 protein, and reduced PI3K expression of p-PI3K, AKT, p-AKT, mTOR, p-mTOR protein (P<0.01). CONCLUSION: PicrosideII has a significant inhibitory effect on MCF-7 breast cancer cells, and its mechanism is related to inhibition of PI3K/AKT/mTOR pathway and enhancement of autophagy in MCF-7 cells.

miR-106 b expression in breast cancer tissues and mechanism of enhancing cisplatin sensitivity in breast cancer cells

ZHENG Zhongqiu, XIE Bojian, CUI Binbin, KE Yichen, LIN Yi

2019, 24(5):  541-545.  doi:10.12092/j.issn.1009-2501.2019.05.010

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AIM: To explore miR-106 b expression in breast cancer tissues and mechanism of enhancing cisplatin sensitivity in breast cancer cells. METHODS: Fifty-eight cases of breast cancer patients diagnosed and treated in our hospital from October 2015 to May 2015 were randomly selected. Breast cancer tissue and paracancer tissue were taken. Cellular DNA was extracted from breast cancer tissues and adjacent tissues, and the expression level of miR-106 b was detected by real-time PCR. MCF-7 cell lines of breast cancer were purchased to construct the high-expression group promoting the expression of mir-106 b and the low-expression group inhibiting the expression of miR-106 b. After 48 h treatment with cisplatin at different concentrations, the inhibition of tumors in vitro and subcutaneous in nude mice was observed. Fluorescence quantitative PCR was used to detect the expression of PTEN/PI3K/AKT signaling pathway related genes.RESULTS:Real-time PCR showed that the relative expression of miR-106 b in breast cancer tissues was higher than that in adjacent tissues (P<0.05). At 20, 30 and 40 μmol/L concentrations, the cell inhibition rates of the control group and the high expression group were significantly higher than those of the low expression group, and the cell inhibition rate of the control group was significantly higher than that of the low expression group (P<0.05). At the concentrations of 20, 30 and 40 μmol/L, the fluorescence intensity at the corresponding concentrations in the control group and the high expression group was lower than that in the low expression group, and the high expression group was significantly lower than the control group (P<0.05). The relative expression of PTEN in the low expression group was significantly lower than that in the control group, while the relative expression of PTEN in the high expression group was significantly higher than that in the control group (P<0.05). The relative expression levels of PI3K and AKT in the low expression group were significantly higher than those in the control group, and the relative expression levels of PI3K and AKT in the high expression group were significantly lower than those in the control group (P<0.05). CONCLUSION: miR-106 b is highly expressed in breast cancer, and the higher the expression, the more sensitive breast cancer cells are to cisplatin chemotherapy.

Intervention effect of modified Ganmaidazao Tang combined with cognitive behavioral intervention on ultra-high risk for developing psychosis and the effects on cognitive function, quality of life and serum levels of 5-HT, MT and TSH

HU Defeng, WANG Yihu, LONG Xiaoyu, WANG Guangshui

2019, 24(5):  546-553.  doi:10.12092/j.issn.1009-2501.2019.05.011

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AIM: To investigate the intervention effect of modified Ganmaidazao Tang combined with cognitive behavioral intervention(CBT) on ultra-high risk for developing psychosis and the effects on cognitive function, quality of life and serum levels of 5-HT, MT and TSH. METHODS:A total of 110 patients of first-degree relatives of schizophrenia patients or who met the UHR criteria in our hospital from January 2015 to December 2016 were selected as the study subjects.All subjects were randomly divided into study group (35 cases), control group 1 (35 cases) and control group 2 (40 cases).The study group was given modified Ganmaidazao Tang combined with CBT, the control group 1 was given CBT, the control group 2 did not intervene, only questionnaire follow-up.The scale of prodromal symptoms (SOPS) was used to evaluate the prodromal symptoms,the Continuous perfomance test (CPT) and Wisconsin Card Sorting Test (WCST) was used to evaluate the cognitive function,the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) was used to evaluate the quality of life.Precursor symptoms, mental disease conversion rate, cognitive function, quality of life, and serum 5-HT, MT, and TSH levels were compared at different time points.RESULTS:At the 3th, 6th, 12th, and 18th months, the SOPS positive symptom score, SOPS disintegration symptom score, SOPS general symptom score, and SOPS total score of the study group were significantly lower than those of the control group 1 and the control group 2, the SOPS positive symptom score, the SOPS disintegration symptom score, the SOPS general symptom score, and the SOPS total score of the control group 1 were significantly lower than those of the control group 2 (P<0.05).The conversion rate of mental illness in the study group and the control group 1 was lower than that in the control group 2 at the 6th months, and the conversion rate of mental illness in the study group was lower than that in the control group 2 at the 12th and 18th months (P<0.05).At the 3rd, 6th, 12th, and 18th months, the CPT (reaction time) and WCST (number of persistent errors) in the study group and the control group 1 were lower than those in the control group 2 (P<0.05).At the 3th, 6th, 12th, and 18th months, the Q-LES-Q score of the study group was higher than that of the control group 1 and the control group 2, and the Q-LES-Q score of the control group 1 was higher than that of the control 2 groups (P<0.05);at the 3th, 6th, 12th, and 18th months, the serum 5-HT, MT, and TSH levels of the study group were higher than those of the control group 1 and the control group 2, and at the 3rd, 6th, 12th, and 18th months, the serum MT level of the control group 1 was higher than that of the control group 2, at the 6th, 12th, and 18th months. Serum 5-HT and TSH levels in control group 1 were higher than those in control group 2 (P<0.05).CONCLUSION:Modified Gan Mai Da Zao Tang combined with CBT can effectively improve the positive symptoms, disintegration symptoms, general symptoms and cognitive function of UHR, reduce the conversion rate of mental illness,improve quality of life,and regulate the levels of serum 5-HT, MT and TSH.

Effects of metformin on patients with polycystic ovary syndrome and its effect on adipose tissue miR-25 level

GUO Liangtang, LIN Chao, SUN Yun, DAI Shengfeng, ZHANG Bingcai, CHEN Shu

2019, 24(5):  554-560.  doi:10.12092/j.issn.1009-2501.2019.05.012

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AIM: To analyze the effect of metformin on patients with polycystic ovary syndrome (PCOS) and its effect on adipose tissue miR-25 level. METHODS: From March 2018 to January 2019, 76 patients with PCOS were enrolled in the department of endocrinology and gynecology in our hospital. The simple randomization method was used to divide them into two groups, 38 cases in each group. The control group was given ethinyl estradiol progesterone tablets. The observation group was given metformin on the basis of this, and the total effective rate, sex hormone binding protein (SHBG), luteinizing hormone (LH), testosterone (T), follicle stimulating hormone (FSH), and female two were compared after treatment for 6 courses. Alcohol (E2), fasting insulin (FINS), insulin resistance index (HOMA-IR), waist-to-hip ratio (WHR), body mass index (BMI), adipose tissue miR-25 mRNA level were counted. RESULTS:After treatment for 6 courses, the total effective rate was 94.74% higher than that of the control group (76.32%) (P<0.05). After 6 courses of treatment, SHBG in the observation group increased more significantly than that in the control group, while LH, T, FINS, HOMA-IR, WHR and BMI decreased more significantly than that in the control group (P<0.05). There was no significant difference in FSH and E2 between the two groups after 6 courses of treatment (P>0.05); after 6 courses of treatment, the expression of microRNA-25 in the observation group decreased more significantly than that in the control group (P<0.05).CONCLUSION:Metformin treatment of PCOS can improve the level of sex hormones and central obesity, correct endocrine abnormalities and increase insulin sensitivity. The mechanism may be related to the inhibition of miR-25 expression in adipose tissue. miR-25 targeting inhibitor provides new idea for treating PCOS.

Analysis of the efficacy, safety and economics of prophylactic antibiotics in high-risk neonates guided by C reaction protein and procalcitonin

HUA Xudan, XIE Hongyi, YU Shufang

2019, 24(5):  561-566.  doi:10.12092/j.issn.1009-2501.2019.05.013

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AIM: To evaluate the efficacy, safety and economics of C reaction protein (CRP) and procalcitonin (PCT) in the prevention of the use of antibiotics in high-risk newborns.  METHODS:One hundred and twenty-four cases of high risk neonates treated in our hospital from July 2015 to January 2018 were selected as the research subjects and were divided into the control group (62 cases) and the experimental group (62 cases) by random digital tables. The children in the control group were treated with prophylactic antibiotic treatment. The experimental group was treated with selective antibiotics according to the level of CRP and PCT. The positive rate of bacterial culture, the incidence of sepsis and the incidence of adverse reactions were compared between the two groups. RESULTS:There was no statistical difference between the levels of CRP and PCT and the positive rate in the two groups (t/χ2=0.299, -0.461, 0.292, 0.544, 0.186, P=0.766, 0.646, 0.589, 0.461, 0.666). There was no statistical difference in the positive rates of bacteria culture before and after treatment in the two groups (χ2=0.040, 0.287, P=0.842, 0.592), and the positive rate of bacteria culture in the two groups was significantly lower than that before treatment (χ2=47.825, 40.367, P=0.000, 0.000), and the incidence of sepsis in two groups was 12.90% and 14.52%, respectively, which have no statistical significance (χ2=0.068, P=0.794). The NICU treatment in the experimental group was significantly lower than that in the control group (t=2.904, 2.729, 2.152, 5.337, P=0.004, 0.007, 0.033, 0.000), and there was no statistical difference between the two groups (χ2=0.372, P=0.542). The incidence of adverse reactions in the control group was 19.35%, which was significantly higher than that in the experimental group (6.46%, χ2=4.593, P=0.032). CONCLUSION:The effect of preventive use of antibiotics under the guidance of CRP and PCT in high-risk newborns show similar efficay of universal application, which can significantly reduce treatment time and treatment costs, obviously reduce treatment-related adverse reactions and improve the short-term prognosis.

Efficacy and safety of third-line treatment with mesylate apatinib in patients with advanced non-small cell lung cancer

WANG Haili, GONG Tianxiao, ZHOU Shixia, MEI Jiazhuan, ZHANG Zhongmian

2019, 24(5):  567-572.  doi:10.12092/j.issn.1009-2501.2019.05.014

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AIM: To investigate and explore the efficacy and safety of third line treatment of mesylate apatinib in patients with advanced non-small cell lung cancer. METHODS: Designed as a retrospective study, a total of 96 patients with advanced non-small cell lung cancer from March 2015 to June 2018 were included in this study, and the clinical data and clinical outcomes were retrospectively analyzed. The 96 patients with advanced non-small cell lung cancer were treated with mesylate apatinib until the disease progress. The clinical efficacy and changes of MMP-9, VEGF and CEA were observed after two cycles treatment. The objective remission rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated and safety data were recorded. RESULTS:All of the 96 patients were available for efficacy evaluation, among them, complete remission (CR) 0 cases, partial remission (PR) 16 cases, stable disease (SD) 54 cases and progression disease (PD) 26 cases. The objective remission rate (ORR) was 16.67%, and the disease control rate (DCR) was 72.92%. There were significant differences in MMP-9, VEGF and CEA between before treatment group and after treatment group (P<0.05). The median progression-free survival (mPFS) was 4.65 months. The median overall survival (mOS) was 8.90 months. In terms of safety analysis, grade 3 and above adverse reactions with high incidence were hypertension (13.54%), hand-foot syndrome (9.75%), proteinuria (7.29%), hemoptysis (7.29%), fatigue (6.25%) and hypertriglyceridemia (4.17%). CONCLUSION:Mesylate apatinib is effective and safe in the treatment of advanced non-small cell lung cancer.

Prospective of a natural remedy, silymarin from milk thistle, for treating chronic hepatitis

ZHAI Shuo，LI Na，CHEN Beining，KOU Junping，XING Weifan，ZHANG Pinghu

2019, 24(5):  573-579.  doi:10.12092/j.issn.1009-2501.2019.05.015

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Silybum marianum is a plant of the genus salicaceae,and its flavonoid natural product silymarin has many pharmacological activities such as anti-oxidation,anti-inflammatory,anti-cancer,liver-protecting,lipid-lowering,etc.It has significant effects on liver diseases such as viral hepatitis,drug-induced hepatitis,alcoholic hepatitis,and autoimmune hepatitis.This article reviews the research progress and mechanism of classic hepatoprotectant-silymarin in the treatment of various liver diseases,in order to provide reference for the re-development and application of silymarin in the field of anti-hepatitis.

Effect and mechanism of endogenous metabolism on drug metabolism and disposition

CHEN Hongzhu, LIU Jianming, ZHOU Fang, JIA Yuanwei, WANG Guangji, ZHANG Jingwei

2019, 24(5):  580-588.  doi:10.12092/j.issn.1009-2501.2019.05.016

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Endogenous substance metabolism is the response process of the body to internal and external factors at the level of cells, molecules, etc. It is the feedback of the body's own components on health, disease and foreign substances. Drug metabolism and disposition is a prerequisite for drugs to exert their effects and produce adverse reactions. Under different physiological or disease states, changes in the metabolism of endogenous substances will inevitably affect the drug metabolism, which will affect the efficacy and adverse reactions. Studies at home and abroad have shown that changes in the metabolism of endogenous substances can lead to changes in the content of certain intermediates or end products in the metabolic pathway, leading to changes in drug metabolizing enzymes and transporters. This article reviews the effects of endogenous glucose metabolism, lipid metabolism, nucleotide metabolism, amino acid metabolism and hormones on drug metabolism and its mechanisms, in order to provide reference and ideas for clinical safe medication and individualized treatment under different physiological and disease states.

Research progress on drug therapy of hyperuricemia

SUN Shanshan, QU Lianyue, DU Rongrong, LIN Jianyang

2019, 24(5):  589-594.  doi:10.12092/j.issn.1009-2501.2019.05.017

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Hyperuricemia (HUA) is a metabolic disease resulting from either the overproduction of uric acid or reduced uric acid excretion. Chronic hyperuricemia and gout are associated with comorbidities such as hypertension, cardiovascular disease and chronic kidney disease (CKD). Timely and effective urate lowering therapy (ULT) is the key to reducing urate deposition, preventing gout attacks, reducing kidney damage, and reducing the incidence of other accompanying diseases. According to the different targets of drugs, uric acid lowering drugs can be divided into four categories: drugs that inhibit the production of uric acid, drugs that promote the excretion of uric acid, drugs that promote the dissolution of uric acid, and newly discovered drugs that can simultaneously inhibit the production of uric acid and promote the excretion of uric acid. Recently the development of the promising drugs, the introduction of drugs and the combination therapy have become the research focus.This paper reviews the research progress of uric acid-lowering drugs in recent years.

Research progress of pharmacokinetic evaluation methods on inhalable formulations

KONG Ying, LI Ning, LU Yang, ZHAO Di, REN Chang, XING Han, CHEN Xijing

2019, 24(5):  595-600.  doi:10.12092/j.issn.1009-2501.2019.05.018

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Inhalable formulations have attracted increasing attentions due to the superiority in both local and systemic therapy. Thorough evaluation system is related to the quality of formulations, but the reported papers concerning inhalable formulations mainly focused on the evaluation of physicochemical properties. Pharmacokinetic evaluation is relatively ignored and the evaluation system is unsound. This paper reviews the pharmacokinetic evaluation methods in recent years, including the pharmacokinetic studies in animals, enzymes and cells, to further provide information for the establishment and improvement of pharmacokinetic evaluation system.