Table of Content

Volume 22 Issue 8
26 August 2017

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Changes of signal protein HMGB1 and RAGE expression in neurons damaged by Aβ _25-35

YANG Fanghua, NAN Ke, XIANG Fangfang, LIU Xuhua, HAN Yuan, CAO Hong, LI Jun

2017, 22(8):  841-845. 

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 AIM: To investigate the changes of high mobility group box 1 protein (HMGB1) and receptor of advanced glycation (RAGE) in neurons damaged by β-amyloid 25-35 (Aβ _25-35).  METHODS: Primary hippocampal neurons were chosen and cultured 7 days with different concentrations of Aβ _25-35. CCK-8 test was used to detect cell viability for determining drug concentration and reaction time. Primary hippocampal neurons were then divided into two groups, i.e. the normal cell group (group C) and the injury group (group I). Neuronal morphology and Western blot technique were applied to detect the expression level of HMGB1 in cytoplasm and nucleus as well as RAGE and NF-κB in the cytoplasm. The quantity of HMGB1, IL-1β and TNF-α in supernatant of neurons was detected by ELISA.RESULTS:Neuron injured model was determined with Aβ25-35 concentration at 25 μmol/L and reaction time for 24 h by CCK-8 test. Morphology showed neurons decreased significantly and most of them in aggregation state in group I. Western blot showed the expression level of HMGB1 in cytoplasm was significantly lower than that in group C (1.596±0.189 vs. 0.146±0.043, P<0.05), while HMGB1 in cell nucleus was higher than that in group C (0.934±0.145 vs. 1.370±0.354, P<0.05), the expression level of RAGE and NF-κB in cytoplasm were higher in group I than those in group C (0.962±0.180 vs. 1.253±0.254, 0.825±0.116 vs. 1.023±0.150, P<0.05). ELISA showed the quantity of HMGB1, IL-1β and TNF-α in supernatant were significantly higher in group I than those in group C (P<0.05). CONCLUSION:Signal proteins of HMGB1, RAGE and inflammatory factors such as IL-1β and TNF-α were obviously increased in Aβ25-35 injured neurons; HMGB1 might be involved in Aβ _25-35 injured neuronal inflammation through RAGE/ NF-κB inflammatory pathway.

Effects of tetramethylpyrazine on the down-regulation of HMGB1 expression and reducing contents of RAGEs in diabetic nephropathy rats

FU Yongjin, XIA Xueyi, ZHANG Xiaomu, LIU Yanbo, PAN Jingqiang, LV Junhua

2017, 22(8):  846-851. 

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AIM: To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP) on streptozocin(STZ)-induced-nephropathy in type 2 diabetic rats.  METHODS: Fifty SD rats were randomly divided into control group (n=10) and model group (n=40). All model rats were fed with high-fat diet for 4 weeks and then injected with streptozotocin (STZ, 40 mg/kg, ip). Fasting blood glucose (FBG) was measured by One-Touch glucometer after 72 h. Rats with fasting blood glucose above 16.67 mmol/L were then randomly divided into four groups: model, metformin (250 mg/kg), low-TMP (80 mg/kg) and high-TMP (160 mg/kg) groups, and the later three received respective drug for 8 weeks, while control and model groups were given equal amount of distilled water by intragastric administration. At the end of the experiment, blood glucose, urine protein, blood urea nitrogen, creatinine, insulin, HOMA-IRI and receptor for advanced glycationend-products (RAGEs) were measured. The expression of high mobility group box 1 (HMGB1) in kidney tissue of rats was determined by immunohistochemistry. Pathological damages of kidney were observed under light microscope. RESULTS:After 8 weeks' administration, compared with the model group, metformin group, low-TMP and high-TMP group showed significant decrease in the dynamic fasting blood glucose (P<0.01) and urinary protein excretion of total dynamic (P<0.05 or P<0.01); Metformin and high-TMP can significantly reduce the level of Cr, BUN and RAGEs; the protein expressions of HMGB1 in metformin group and high-TMP group were significantly lower than that in model group (P<0.05); pathological damages of kidney tissue were significantly reduced.CONCLUSION: TMP exhibited protective effect on STZ induced nephropathy in type 2 diabetic rats and its mechanism may be related to the down-regulation of HGMB1 expression and reducing contents of RAGEs.

Comparison of pharmacodynamics of Fufang lujiao rutongning capsule and its original formula

LENG Xiaowei, Rita, LI Min, ZHANG Tong, REN Liqun, FAN Zhimin

2017, 22(8):  852-858. 

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AIM: To compare the therapeutic and analgesic effect of improved Fufang lujiao rutongning capsule and its original formula on hyperplasia of mammary glands in rats.  METHODS: The model of mammary glands hyperplasia was induced by intramuscular injection of estradiol and progesterone so as to evaluate the action receptors in breast issues and the serum levels of hormone and to compare the therapeutic effect of both formulas. In the analgesic experiment, glacial acetic acid was used to induce writhing to compare the time of latency, number of writhing and of analgesic rate of the two formulas. RESULTS: Both formulas of Rutongning capsule could alleviate the breast hyperplasia, while the improved formula presented better therapeutic and analgesic effect. CONCLUSION: Fufang lujiao rutongning capsule is better than Rutongning capsule for controlling hyperplasia pain.

Different expression of FoxO3/Keap1/Nrf2 pathway in tumor cells and drug resistant tumor cells

YE Haizhu, CHEN Yajuan, ZHAO Wenying, LIU Xiaoping

2017, 22(8):  859-865. 

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AIM: To detect the different expression of FoxO3/Keap1/Nrf2 pathway in normal and drug resistant tumor cells so as to investigate the effect of FoxO3/Keap1/Nrf2 signal on drug resistance of tumor cell. METHODS: Cell lines of A549 (resistant to cisplatin) and HCT-8 (resistant to 5-FU) were constructed and verified by the MTT assay. The mRNA and protein expressions of FoxO3/Keap1/Nrf2 pathway members in drug-resistant tumor cells and non- drug-resistant tumor cells were evaluated by QRT-PCR and Western blot. RESULTS:The drug resistance of A549/DDP was significantly stronger than A549 cell (P<0.05), the resistance index was 5.25 times; the drug resistance of HCT-8/5-FU was significantly stronger than HCT-8 cell (P<0.05), the resistance index was 31.67 times; the mRNA expressions of FoxO3, Keap1 and Akt in A549/DDP and HCT-8/5-FU cells were decreased compared with normal control cells, while mRNA expression levels of Nqo1 and Nrf2 were increased; the protein expression of FoxO3 and Keap1 in A549 DDP and HCT-8/5-FU cells were decreased compared with normal control cells, while protein expression levels of p-Akt, Nqo1 and Nrf2 were increased. CONCLUSION: FoxO3/Keap1/Nrf2 signaling pathway is related with tumor resistance, which was referential for further study of this pathway and for exploring therapeutic strategies to reduce drug resistance of cancer.

Effects of Jiawei Zengye decoction on diphenoxylate-induced constipation in mice

ZHAO Tianwen, TANG Hanxiao, HUANG Wenjing, BAO Yishu, CHEN Congcong, CHEN Dongsheng, SHENG Yunjie, ZHANG Yongsheng

2017, 22(8):  866-869. 

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AIM: To study the effect of dendrobii officmalis caulis (DOC) and/or atractylodismacrocephalaerhizoma (AMR) based on Zengyedecoction (ZYD), including scrophulariaeradix, rehmanniaeradix, ophiopogonisradix on diphenoxylate-induced constipation in mice.  METHODS: Diphenoxylate was used to establish the mouse model of constipation, the decoction of DOC+AMR+ZYD, AMR+ZYD and ZYD, the dissolving liquid of Maren capsule (MRC) were prepared, after the gavage administration of them respectively, the defecation, small intestine propulsion and serum SOD activity in constipated mice were detected.RESULTS:The efficacy of promoting defecation and small intestine propulsion by DOC+AMR+ZYD and AMR+ZYD was better than that of ZYD and MRC; DOC+AMR+ZYD significantly increased serum SOD activity in constipated mice and the efficacywas superior to ZYD and MRC. CONCLUSION:DOC+AMR and AMR enhanced ZYD efficacy on diphenoxylate-induced constipation in mice,DOC+AMR+ZYD elevated the constipated mice serum SOD activity. 

Effects and mechanism of deep-sea fish oil on blood lipid in hyperlipidemia rats

XIE Zhen, KANG Hua, HE Licheng, KUANG Rong

2017, 22(8):  870-874. 

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AIM: To investigate the regulation effect of deep-sea fish oil for blood lipid of rat models with hyperlipidemia and its possible mechanism. METHODS: Rats models with mixed hyperlipidemia were established by feeding high-fat diet and were divided into control group, model group and three deep-sea fish oil treatment groups (250, 500, 1 500 mg/kg), with 12 rats in each. The control group and model group received equal volume of soybean oil, while the treatment groups were administered with deep-sea fish oil for 40 days. Changes in TC,TG,HDL-C,LDL-C of serum were compared, and atherosclerosis index（AI1, AI2）,R-CHR indexes were calculated. Activities of SOD,MDA,GSH-Px in serum and liver tissue were measured by kits. Protein expression levels of SIRT1,PPAR-α were detected by Western blot. RESULTS: Compared with model group, levels of TC,TG,LDL-C in treatment groups were significantly decreased, and AI1,AI2 and R-CHR indexes in middle and high dose groups were significantly decreased. Oxidative stress was increased in hyperlipidemia rats of its serum and liver. In serum, the SOD,GSH-Px levels in high and middle dose groups were significantly increased, while the level of MDA decreased remarkably. In liver, the SOD,GSH-Px levels in middle and high dose groups were significantly increased, the level of MDA in three treatment groups decreased remarkably. Middle and high dose of deep-sea fish oil increased the protein expressions of SIRT1 and PPAR-α in liver. CONCLUSION: Deep-sea fish oil can moderate blood lipid in hyperlipidemia rats, which is probably associated with the regulation of the response level to oxidative stress in serum and liver and improving expression level of the SIRT1 and PPAR-α proteins.

Protective effect of Naoxintong capsule on kidney injury in spontaneously hypertensive rats

YANG Xiaohu, LIAN Hong, YU Yang, YUE Yingxing, ZHANG Yong

2017, 22(8):  875-880. 

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AIM: To investigate the protective effect of Naoxintong capsule (NXTC) on kidney injury in spontaneously hypertensive rats.  METHODS: Twenty-four female spontaneously hypertensive rats (SHR) were randomly divided into model group, Irbesartan group and NXTC group, while eight female normotensive Wistar-Kyoto rats (WKY) were blank group. Rats in each group were intragastricly administrated with corresponding drugs and saline in eight weeks. Non-invasive blood pressure (BP) measuring instrument monitored BP of each group rats in every two weeks. The serum levels of total creatinine (Cre), uric acid (UA), urea (Urea) and microalbumin (MALB) were measured. Kidney injury was evaluated with histopathologic examination by hematoxylin eosin (H&E) staining. Real-time RT-PCR was used to test the gene expression changes of Mb, Nox1 and Duox2 in each group. And the expression of Mb in kidney tissue was measured by Western blot. RESULTS:NXTC significantly decreased mean BP in SHR group. Serum levels of Cre, UA and MALB in NXTC group were significantly lower than those in the model group (All P<0.01). Kidney injure in NXTC group was decreased as compared with model group (P<0.01). NXTC significantly reversed not only the down-regulation expression of Mb, Nox1 and Duox2 genes (All P<0.01), but also Mb protein (P<0.01) in SHR group. CONCLUSION: NXTC can protect SHR rats from kidney injury  at least partly via regulating Mb overexpression.

Serum C4/C3 ratio in predicting the adverse prognosis of IgA nephropathy

ZHOU Qiongxiu, ZHANG Jianna, YOU Xiaohan, LV Yinqiu, CHEN Bo, ZHANG Ji

2017, 22(8):  881-886. 

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AIM: To investigate the relationship between serum complement levels and prognosis of IgA nephropathy.  METHODS: Patients diagnosed through renal biopsy as primary IgA nephropathy from 2009 to 2013 in our hospital were recruited into this retrospective study. Baseline demographic, clinical laboratory examination, renal biopsy and histopathology examination, as well as the follow-up results were reviewed. The ratio of serum complement C4 to C3 (C4/C3 ratio, marked as C. ratio) was calculated. Multiple statistical methods were used to investigate the relationship between C. ratio and nephropathy prognosis. All statistics were calculated using R software and related software packages. RESULTS:A total of 206 patients were enrolled in the present study, and the median follow-up time was (37.2±6.5) months. There were 88 (42.8%) male patients. The comparison of different pathological changes of nephropathy with C.ratio showed that the C.ratio levels were significantly higher in mesangial hypercellularity, segmental fibrosis/adhesion, and interstitial fibrosis/tubular atrophy. ROC curve showed that C.ratio could effectively identify the adverse prognosis of IgA nephropathy, the area under the ROC curves was 0.735 for C.ratio, with a cut-off value of 0.25 (sensitivity: 70.9%, specificity: 72.2%). In addition, higher C.ratio (>0.25) was associated with higher diastolic blood pressure, and greater proteinuria. Kaplan-meier survival analysis also confirmed that patients with higher level of C.ratio had significantly poorer nephropathy prognosis after adjusted by age, gender, blood pressure and urine protein, the Hazard Ratio was 5.1(95%CI, 1.9-13.9, P=0.001). CONCLUSION: High level of serum C4 to C3 ratio was significantly associated with poor prognosis of IgA nephropathy; this could be used as a clinical prognosis predictor in IgA nephropathy patients.

Effect of obatoclax in combination with 5-fluorouracil on the apoptosis of pancreatic cancer cells under hypoxic

SONG Haiyan, ZHANG Yimin, ZHOU Zhixin, CHENG Huixin, FU Shengqi

2017, 22(8):  887-891. 

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AIM: To explore the effects of OBX combined with 5-FU on pancreatic cancer cell apoptosis (HPAC), and its possible mechanism. METHODS: Hypoxic condition was established. Western blot method was used to detect the expression of HIF-1α in HPAC cells under normal oxygen and hypoxia condition. Hoechest33258 staining was applied to analyze the effects of OBX on apoptosis of HPAC cells under normal oxygen and hypoxia condition. MTT assay was used to detect cell viability in hypoxic group, 5-FU group and OBX combined with 5-FU group. Western blot was applied to detect HIF-1α, Bcl-2 and Bax proteins expression in HPAC cells of hypoxic group, 5-FU group and OBX combined with 5-FU group. RESULTS:Under hypoxia condition, the expression of HIF-1α in HPAC cells was much higher than its expression under normal oxygen. The effect of OBX on HPAC cells apoptosis enhanced with dose-dependent in a certain range of concentrations. Under hypoxia condition, 5-FU decreased pancreatic cancer cells viability and reduced the expressions of HIF-1α, Bcl-2 proteins, but promoted the expression of Bax protein in HPAC cells. OBX combined with 5-FU enhanced the inhibitive effects on cells viability. The expressions of HIF-1α, Bcl-2 proteins reduced further, but the expression of Bax protein increased significantly. CONCLUSION: Under hypoxia condition, OBX combined with 5-FU can enhance the inhibition on HPAC cells viability, and the induction on HPAC cells apoptosis, the mechanism maybe related to reduce the expressions of HIF-1α, Bcl-2 proteins and increasing Bax expression.

Protective effect of omega-3 fatty acids on hepatic fibrosis of rats induced by thioacetamide

ZENG Xi, HUYANG Liuzi, WU Yamin, CHEN Zhiheng

2017, 22(8):  892-898. 

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AIM: To investigate the possible protective effect of omega-3 fatty acids (n-3 FAs) from fish oil on hepatic fibrosis induced by thioacetamide (TAA) in rats. METHODS: Sixty experimental animals were divided into four groups. The control group received normal saline solution. The TAA group was given 250 mg/kg body weight of TAA. The omega-3 fatty acids group was given saline solution and supplemented with n-3 FAs. The n-3 FAs + TAA group was treated with n-3 FAs and TAA. At the end of TAA treatment for three weeks and six weeks, body weight, liver weight, and biochemical indexes were detected. HE staining was used to observe liver morphology and organizational structure. RESULTS:Treatment of rats with TAA for three and six weeks resulted in a significant decrease in body weight, while the value of liver/body weight ratio was statistically increased. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and total bilirubin were significantly increased. After three weeks of exposure to only TAA, liver sections showed an abnormal morphology characterized by noticeable fibrosis with the extracellular matrix collagen contents and damage of liver cells' structure. Liver sections from rats treated with only TAA for six weeks revealed an obvious increase in extracellular matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with n-3 FAs significantly attenuated the severe physiological and histopathological changes.CONCLUSION: n-3 FAs have the antioxidation ability and can act against hepatic fibrosis induced by TAA, thus supporting its use in hepatic fibrosis therapy.

Effect of gimeracil capsules combined with radiotherapy on breast cancer and on tumor markers, human epidermal growth factor receptor-2 and midkine levels

YAN Jianqiang,NIE Gaihong

2017, 22(8):  899-903. 

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 AIM: To explore the effect of gimeracil capsules combined with radiotherapy on breast cancer, and on tumor marker, human epidermal growth factor receptor-2 (HER-2) and level of midkine (MK).  METHODS: Sixty-four breast cancer patients were selected by random number table method from January 2010 to May 2016 in our hospital, sixty-two cases in each group. The control group was treated with three-dimensional conformal radiotherapy; the study group was treated with three-dimensional conformal radiotherapy and gimeracil capsule; the therapy continued for 2 courses of treatment. Clinical efficacy and adverse reaction incidence rate were compared between two groups; tumor markers (CEA, CA125, CA153) and changes of MK, HER-2 level were analyzed. RESULTS:The effective rate (50%) and tumor control rate (81.25%) of the study group were higher than those of the control group (25%, 53.13%), the difference were statistically significant (P<0.05); Before treatment, no significant difference of CEA, CA125, CA153 was observed between groups (P>0.05), while all the indexes decreased after treatment, and the study group presented more significant change than the control group (P<0.05); Before treatment, no significant difference of HER-2 and MK level was observed between groups (P>0.05), while all the indexes decreased after treatment, and the study group presented more significant change than the control group (P<0.05). Both groups presented no IV degrees of adverse reactions, and compared with control group (31.24%, 37.51%, 34.37%), the incidence of leucopenia, diarrhea, nausea and vomiting (34.38%, 34.38%, 37.51%) of the study group presented no statistically significance (P>0.05). CONCLUSION: Gimeracil capsules combined with radiotherapy exhibited remarkable effect on breast cancer, and on the serum tumor markers, human epidermal growth factor receptor-2 and midkine expression level. With high safety, it is worthy of promotion.

Correlation analysis between the detection rate of CR-KP and the utilization of antibacterial drugs based on PLSR algorithm

JIANG Cheng, LI Fangqiong, YE Zuowu, SUN Yunfeng, ZHANG Meiling, LI Gonghua

2017, 22(8):  904-909. 

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AIM: To provide guidance for the reasonable clinical usage of antibacterial drugs by employing the partial least squares regression (PLSR) algorithm to analyze the correlation between the detection rate of carbapenem-resistant Klebsiella pneumoniae (CR-KP) and the utilization of antibacterial drugs.  METHODS: Different PLSR models were established with the defined daily doses (DDDs) of antibacterial drugs in different quarters as independent variables and the detection rate of CR-KP with same and different periods (lagged 1-4 quarters) as dependent variables. The lag time between the detection rate of CR-KP and the utilization of antibacterial drugs was investigated. The antibacterial drugs, which were highly correlated to the detection rate of CR-KP were screened. The influences of the antibacterial drugs on the detection rate of CR-KP were then investigated according to the regression coefficients. RESULTS:The detection rate of CR-KP lagged about two quarters behind the utilization of antibacterial drugs. It was significantly positively correlated with the DDDs of amoxicillin-clavulanic acid and sulbenicillin, while negatively correlated with the DDDs of itraconazole. The regression coefficients of amoxicillin-clavulanic acid, itraconazole and sulbenicillin were 0.085 2, -0.083 9 and 0.076 3, respectively. CONCLUSION: It is effective to employ PLSR algorithm to simultaneously analyze the correlation between the detection rate of CR-KP and the utilization of multiple antibacterial drugs, which provides a new scientific tool for controlling the detection rate of CR-KP.

Association of leptin and leptin receptor gene polymorphisms with hypertension: a Meta-analysis

ZHANG Xiaoyu, FANG Zhengmei, YAO Yingshui

2017, 22(8):  910-916. 

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AIM: To evaluate the association between leptin gene and leptin receptor gene polymorphisms with hypertension.  METHODS: CNKI, Wanfang database, Chongqing VIP network, Pubmed database and EMBASE database were researched. The data on the relationship between leptin/its receptor gene and hypertension were extracted and evaluated by software STATA11.0. RESULTS: Twenty-one studies involving 4 736 patients and 3 096 healthy people were included. The meta-analysis showed the II/I polymorphism of LEP gene was associated with hypertension in recessive genetic model and additive genetic model (recessive genetic model: OR=2.16, 95%CI=1.08-4.31, P=0.029, additive genetic model: OR=2.27, 95%CI=1.08-4.79, P=0.031); the Gln223Arg polymorphism of LEPR gene was associated with hypertension in dominant model and allelic model (dominant model: OR=1.55, 95%CI=1.14-2.11, P=0.005; allelic model: OR=1.36，95%CI=1.09-1.71, P=0.007). No statistically significant correlation was found between the Lys109Arg polymorphism of LEPR gene and hypertension (dominant model: OR=0.87, 95%CI=0.67-1.14, P=0.307, recessive genetic model: OR=0.91, 95%CI=0.70-1.20, P=0.099, additive genetic model: OR=0.92, 95%CI=0.70-1.21, P=0.071, allelic model: OR=1.04, 95%CI=0.80-1.35, P=0.830). CONCLUSION: There is no significant correlation between Lys109Arg polymorphism of LEPR gene and hypertension, but the II/I polymorphism of LEP gene and Gln223Arg polymorphism of LEPR gene are associated with hypertension.

Sample size calculation for single-arm OPC trials with multi endpoints

LU Mengjie, LIU Yuxiu, LU Guangming, ZHANG Longjiang, HUANG Wei, GE Aichen

2017, 22(8):  917-921. 

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AIM: To explore the sample size calculation by control global power for multiple rates as multi endpoints in single-arm Objective Performance Criteria (OPC) trials. METHODS: Based on the sample size calculations for single-arm OPC with single endpoint, we illustrated the statistical principle of sample size calculations with multi endpoints in theory and proposed a method by control global power. According to the pre-determined level of OPC, target value, type I error and total type II error, the power of each endpoint could be evaluated under the given sample sizes and the multiplication of all powers was the actual global power. The sample size reached objective global power was evaluated by the stepwise search method. RESULTS: We compared the sample sizes using the conventional direct power correction and stepwise search method through an example of one-sample clinical trial with four proportions based on normal approximation method and exact method. The results showed that the latter could more accurately control the global power and reduced the sample sizes. CONCLUSION: We proposed a solution to correct sample sizes for single-arm OPC trials with multi endpoints, which could control global power and reduce sample sizes significantly.

Inhibition of CYP450 activity by honokiol and other four components of Chinese traditionalmedicine in vitro

ZHANG Peiyu, REN Jing, ZHI Wenqian, LIU Chengming, GAO Na

2017, 22(8):  922-926. 

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AIM: To explore the inhibition of honokiol and other four components of Chinese traditional medicine on four kinds of cytochrome P450 activity in human liver microsomes (HLM) and rat liver microsomes (RLM) in vitro, and to provide foundation for further research of clinical combination of Chinese medicine with western medicine. METHODS: Paclitaxel, tolbutamide, chlorzoxazone and coumarin were incubated in vitro as probe drugs of CYP2C8, CYP2C9/CYP2C11, CYP2E1 and CYP2A6/CYP2A1/2 respectively. HPLC was used to detect the amounts of metabolites of the probe drug. The inhibition ratio and the IC50 of the five kinds of effective components of Chinese traditional medicine were calculated and analyzed to find out whether they can affect the enzyme activity. RESULTS:IC50 of honokiol and magnolol on CYP2C9 in HLM were 7.7 μmol/L and 7.6 μmol/L, while IC50 of honokiol and magnolol on CYP2C11 in RLM were 13.0 μmol/L and 3.8 μmol/L separately. IC50 of honokiol and magnolol on CYP2C8 in HLM were 19.2 μmol/L and 84.5 μmol/L, while IC50 of honokiol and magnolol on CYP2C8, CYP2E1, CYP2A1/2 in RLM and CYP2E1, CYP2A6 in HLM were all above 100 μmol/L. IC50 of geniposide, chlorogenic acid and astragaloside on four kinds of CYP enzymes were all above 100 μmol/L. CONCLUSION: Honokiol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and CYP2C8 in HLM. Magnolol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and has slightly inhibition on CYP2C8 in HLM.

Relationship of Syndecan-1 and EGFR expression, K-Ras gene mutations and response to FOLFOX in advanced colorectal carcinoma

YUAN Shaofei, ZHU Linjia, ZHENG Weie, LIANG Meizhen

2017, 22(8):  927-932. 

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AIM: To investigate the relationship of Syndecan-1 and EGFR expression, K-Ras gene mutations and response to FOLFOX in advanced colorectal carcinoma.  METHODS: 160 surgical specimens of advanced colorectal carcinoma from patients consecutively treated between June 2009 and December 2014 at our hospital were collected. Immunohistochemistry method was used to screen for Syndecan-1 expression. The relationship between Syndecan-1 expression and various clinicopathological parameters, molecular markers, curative effect of FOLFOX was analyzed.RESULTS:Syndecan-1 expression was identified in the cancer cells of 41 (25.6%) colorectal cancer cases, epidermal growth factor receptor expression in 111(69.4%) colorectal cancer cases. The expression of syndecan-1 was statistically correlated with the expression of epidermal growth factor receptor (P<0.05). However, it was not significantly correlated with K-Ras mutation (P>0.05). Patients with over-expressed Syndecan-1 exhibited better efficacy on FOLFOX solution than patients presented negative Syndecan-1 expression (56.1% vs. 40.3%, P<0.05);  Patients with over-expressed Syndecan-1 also presented longer median time to progress (8.8 month vs. 7.2 month, P<0.05). CONCLUSION: The expression of Syndecan-1 is referential for evaluating the progress and the prognosis of colorectal cancer. And the expression of Syndecan-1 is statistically correlated with curative effect of FOLFOX regimens.

Influence of proton pump inhibitors on clinical efficacy of chemotherapy for advanced gastric cancer

ZHAI Mengmeng, LI Zhigang, SHEN Jie, WANG Fengli, GU Ning, YANG Na

2017, 22(8):  933-936. 

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AIM: Oxaliplatin combined with capecitabine (XELOX program) is the preferred chemotherapy regimen for patients with advanced gastric cancer. But, it remains uncertain whether extra administration of proton pump inhibitors (PPI) will influence the effect of capecitabine. This study investigates the influence of PPI on clinical efficacy of chemotherapy for advanced gastric cancer. METHODS: Fifty-four patients with advanced gastric cancer of the second affiliated hospital of Zhengzhou University from January 2014 to January 2016 were reviewed and analyzed. They were treated with XELOX regimen, i.e., oxaliplatin 130 mg/m2, continuous intravenous drip infusion for 2 h; capecitabine 1 000 mg/m2,po.,taking in the morning and evening within half an hour after a meal, D1-14. 21 d constitutes a cycle. Patients treated with proton pump inhibitor were observed as the observation group (24 cases) and without as the control group (30 cases). All patients received maximally eight cycles of chemotherapy. RESULTS:Twenty-three cases from the observation group were evaluable.The mean follow-up was 10.3 months;the median time to progression was 5.7 months (95% confidence interval,4.6-7.1 months); the median survival time was 10.2 months (95% confidence interval, 7.7-12.8 months). While twenty-eight cases from the control group 28 cases were evaluable.The median follow-up time was 11.0 months; the median time to progression was 6.1 months (95% confidence interval, 4.8-7.3 months); the median survival time was 11.1 months (95% confidence interval 8.3-13.1 months). CONCLUSION: Proton pump inhibitors increase the pH of gastric juice and affect the dissolution and absorption of capecitabine, which may further influence the therapeutic effect of XELOX on advanced gastric cancer.

Effect of ambroxol hydrochloride combined with high-dose methylprednisolone therapy on the recovery of neurological function after spinal cord injury in patients with thoracolumbar fractures

ZHANG Peng, CHEN Yongzhong, WANG Jinxing, ZHANG Jinfeng, WENG Chaoqun, YE Zhongxing

2017, 22(8):  937-942. 

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AIM: To discuss the therapeutic effect of ambroxol hydrochloride combined with high-dose methylprednisolone (MP) on the recovery of neurological function after spinal cord injury in patients with thoracolumbar fractures.  METHODS: Forty eight patients with thoracolumbar fractures plus spinal cord injury admitted to our hospital from Feburary 2016 to August 2016 were randomly divided into the combination group and the control group according to random number table (n=24). All the patients were performed decompression and internal fixation operation, and MP was given 30 mg/kg intravenously for 15 min, another 5.4 mg·kg-1·h-1 MP was given intravenously for 23 h 45 minutes later. Based on the treatment of the control group, the combination group received extra ambroxol hydrochloride intravenously (60 mg/time, 1 time/12 h), continued for 30 days. Patients in both groups were given anti-infection, hemostatic, dehydration, and symptomatic treatment, and intravenous drip of omeprazole (30 mg/time, 1 time/12 h, 3 d) was administered to prevent gastrointestinal stress ulcer. All patients were followed up for 6 months; the clinical curative effect in two groups were determined according to Frankel classification method; ASIA sensory and motor score were evaluated and compared between two groups before and 1 month and 6 month after treatment; adverse drug reactions were recorded. RESULTS:No statistically significant difference were observed with the baseline data such as age,sex,heart rate,breathing and body mass index between the two groups(P>0.05).After 6 months' treatment,the total effective rate in the combination group was significantly higher than that of the control group (87.5% vs. 62.5%, P<0.05); ASIA sensory and motor score were significantly elevated compared with before treatment in both groups 1 month and 6 month after treatment (P<0.05), and between the two groups, the combination group presented more significant improvement (P<0.05); No statistically significant difference was observed with adverse reaction occurrence between the two groups (29.2% vs. 33.3%, P>0.05).CONCLUSION:Compared with simple MP shock treatment, ambroxol hydrochloride combined with high-dose MP can significantly alleviate the injured neurological function and improve neural functional recovery in patients with thoracolumbar fractures combined with spinal cord injury, whereas more clinical and laboratory research are needed to confirm the effect.

Study of the efficacy and safty of irinotecan combined with nedaplatin versus topotecan combined with nedaplatin in treatment of small lung cancer

ZHANG Zhaowei, FANG Tianzi, LIU Jianxia

2017, 22(8):  943-947. 

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AIM: To compare the efficacy and safety between irinotecan (CPT) and topotecan (TPT) combined with nedaplatin (NDP) in the treatment of extensive small cell lung cancer.  METHODS: Eighty-nine cases of patients who have been diagnosed as extensive small cell lung cancer were analyzed, in which 44 cases received CPT+NDP while the other 45 cases received TPT+NDP as chemotherapy. Three weeks are one treatment course, every patient in two groups accepted more than 2 periods of chemotherapy. On the first day of each course, they received intravenous drip with LBP 30 mg/m2. In addition, CPT+NDP group was given intravenous drip with NDP 80 mg/m2 on the first day and CPT 60 mg/m2 on the first eighth, fifteenth day, while TPT+NDP group was given intravenous drip with NDP 80 mg/m2 on the first day and TPT 1.2 mg/m2 on the first to fifth day. Comparison was made between the clinical response rate (RR), disease control rate (DCR), median overall survival, median progression-free survival and adverse reactions between the two groups. RESULTS:The RR of the two groups were 36.36% and 37.78%, the CDR of the two groups were 72.73%and 66.67%. There was no significant differences between the two groups (P>0.05). The median overall survival of the two groups were 12.0 months and 11.2 months, the median progression-free survival were 6.5 months and 5.8 months weeks, there are also no differences between the two groups (P>0.05). The CPT+NDP group was milder than the TPT+NDP group in the leukopenia and the thrombopenia (P<0.05), while more severe than the TPT group in the diarrhea and neutrophilic (P<0.05). CONCLUSION: The curative effect of CPT combined with NDP is similar with the TPT combined with NDP on the treatment of extensive small cell lung cancer patients. The main adverse reaction of the former one is diarrhea and neukopenia, while the latter one is leukopenia and thrombopenia. Therapeutic regimen should be chosen according to the patients' physical condition.

Research progress of surface modified albumin nanoparticles in tumor targeting therapy

XU Lihua, XU Xiaoyang, XU Junjun, YU Wenying

2017, 22(8):  948-954. 

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At present, most drugs for clinical cancer therapy are non-selective, with the inhibition of tumor cell proliferation, they also have significant side effects on normal tissues, thereby improving the tumor-selective capacity, reducing their gathering in non-targeted areas are the keys to enhance the effectiveness of anti-cancer drugs. As drug carriers, albumin nanoparticles exhibit various outstanding biological properties, and now have been used in targeted delivery systems. The paper reviews the albumin's tumor aggregation features, the latest researches in the targeted therapy of tumor and clinical applications when they are modified with RGD peptides, monoclonal antibodies, folic acid, hyaluronic acid, transferrin and other targeted material，in order to provide advices for developing safe and effective tumor targeting drugs.

Research progress on risk-based management in clinical trials

XIAO Liang, ZHENG Gaozhe, HUANG Yumin

2017, 22(8):  955-960. 

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With the evolutions of information technology, the application and development of data management and statistical methods, and onsite tasks resolved by remote approaches, human work replaced by computer automation, a new project management model of risk based management gradually evolved out in clinical research industry. Now, twenty years later, ICH issued a new version of the GCP, and the European and American regulators also issued new guidelines for quality management in clinical trials. These policies and regulations will result in great changes in clinical research industry. In the risk based management model of clinical trials, information technology and professional implementation personnel will both play the important roles.