Table of Content

Volume 23 Issue 3
26 March 2018

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Application of target-mediated drug disposition (TMDD) models in the development of monoclonal antibody

JI Shuangmin, ZHU Xiao

2018, 23(3):  241-246.  doi:10.12092/j.issn.1009-2501.2018.03.001

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In recent years, monoclonal antibodies have become the area of interest in industry. Unlike small molecules, monoclonal antibodies exhibit unique structural and physiological properties, alongside with differences in absorption, distribution, metabolism and excretion. These unique properties of monoclonal antibodies［e.g. target-mediated drug disposition (TMDD), nonlinear pharmacokinetics, time-dependence and long half-life］ pose several challenges in drug development. Appropriate application of modeling and simulation techniques can help researchers with data mining, predicting clinical trial outcomes, guiding clinical trial designs and optimizing dosing schemes. Among these, the application of the TMDD model in the monoclonal antibody development is growing. In this review, a brief introduction on the pharmacokinetic properties of monoclonal antibodies is provided, followed by a discussion on the feasibility and necessity of applying the TMDD model to monoclonal antibody drug development. The aim of current work is to provide a reference for researchers to scientifically and efficiently conduct studies on the monoclonal antibodies.

Effects of steroidal saponin RCE-4 from Reineckia Carnea (Andr.) Kunth on Ras/Erk and p16/cyclinD1/ CDK4 signaling pathways in the human cervix cancer Caski cells

YAN Weihong, ZOU Kun, HE Haibo, ZHANG Yongfeng, LI Xiaomei, LI Xiaoqin, YANG Xiaojiao, WANG Junzhi, DENG Zhangshuang

2018, 23(3):  247-254.  doi:10.12092/j.issn.1009-2501.2018.03.002

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AIM: To investigate the effects of steroidal saponin RCE-4 from Reineckia Carnea (Andr.) Kunth on Ras/Erk and p16/cyclinD1/CDK4 signaling pathways in the human cervix cancer Caski cells, and to explore its possible mechanism. METHODS: The Caski cell line was cultured in vitro, the cell viability and the distribution of cell cycle was detected by MTT and flow cytometry, respectively; the quantitative real-time PCR was used to evaluate the mRNA expressions of p16, cell cycle-related cyclinD1 and CDK4；Western blot was used to determine the total protein and phosphorylated protein of Ras/Erk signaling pathway. RESULTS:RCE-4 could significantly inhibit the growth of Caski cells compared with the control group, the IC50 was 12.33 μmol/L in the 24 h, and it increased the percentage of G0/G1 phase cells, decreased the percentage of S phase cells, inhibited the proteins levels of Ras, p-Raf, p-Mek1/2 and p-Erk1/2, decreased the p-Raf:Raf,p-Mek1/2:Mek1/2 and p-Erk1/2:Erk1/2 ratios, up-regulated the mRNA expression of p16, down-regulated the expressions level of cyclinD1 and CDK4. CONCLUSION: RCE-4 could significantly inhibit the proliferation of Caski cells and induce the cells to block in G0/G1 phase, and the mechanism is related to inhibiting the Ras/Erk and p16/cyclinD1/CDK4 signaling pathways.

Protective effects of Astragaloside Ⅳ on early kidney damage in diabetes mellitus rats and its mechanisms

LI Zhuqing, JU Yinghui, CHEN Qingqing, MA Keke, LI Weiping

2018, 23(3):  255-262.  doi:10.12092/j.issn.1009-2501.2018.03.003

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AIM: To study the effects of Astragaloside Ⅳ (AS-Ⅳ) on early kidney damage and the mechanisms in diabetes mellitus rats induced by Streptozotocin (STZ).  METHODS: The diabetic rats model was established by intraperitoneal injection with STZ (55 mg/kg) and the model rats were randomly divided into model group，AS-Ⅳ (20, 40, 80 mg/kg) group. After 8 weeks of administration, body weight, blood glucose, 24 hours urinary protein excretion rate (24 h UAER), the level of serum creatinine (Scr), urea nitrogen (BUN) , serum SOD, GSH-Px activity and MDA content were measured. HE and PAS staining were used to observe renal histopathology and Western blot was used to detect the expression of TGF-β1, Nrf2 and HO-1.RESULTS:Compared with control group, the blood glucose, kidney index, MDA content and the level of Scr, BUN, 24 h UAER and expression of TGF-β1, total protein of Nrf2 and nucleus protein of Nrf2 increased significantly and the serum SOD and GSH-Px activity decreased significantly in diabetes mellitus model group. Compared with model group, AS-Ⅳ(40, 80 mg/kg) group could decrease MDA content , the level of Scr, BUN, 24 h UAER and increase serum SOD and GSH-Px activities, expression of TGF-β1 was decreased by AS-Ⅳ(80 mg/kg) group, expression of total Nrf2, nucleus Nrf2 and HO-1 were increased by AS-Ⅳ(80 mg/kg) group.CONCLUSION:AS-Ⅳ can inhibit renal oxidative stress injury. The meachanism may be related to increasing the serum antioxidant activity and reducing the expression of TGF-β1, activation of Nrf2 pathway, upregulating the expression of antioxidative protein in HO-1.

Effects of activated carbon N-acetylcysteine sustained-release microcapsule on miRNA of non-alcoholic fatty liver disease in young rats

ZHOU Hongping, YANG Xingxin, ZHUANG Rangxiao, SHAO Yidan, XI Jianjun, LIAO Li, REN Bailu, WANG Pingping, YU Shuying, SHI Tingting

2018, 23(3):  263-270.  doi:10.12092/j.issn.1009-2501.2018.03.004

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AIM: To primarily investigate the protective effect of active carbon N-acetylcysteine sustained-release microcapsules (ACNAC) on non-alcoholic fatty liver disease (NAFLD) in young rats and explore its effect on miRNA and corresponding target genes.  METHODS: The models of NAFLD in young rats were produced by high-fat diets; the degree of fatty degeneration in the liver tissue of young rats was observed by HE staining; the miRNA expression spectra of liver tissues was detected by microRNA microarray. The miRNA was verified by fluorescence quantitative PCR. The target gene prediction and validation were performed for target miRNA by fluorescence quantitative PCR and Western blot. RESULTS:miRNA199a-5p and miRNA-378-5p were the key miRNA of NAFLD, Lpl was the target gene of miR199a-5p, and srebp1 and C/EBP-α were the target genes of miR-378-5p. CONCLUSION:ACNAC can up regulate the expression of Lpl and down regulate the expressions of srebp1 and C/EBP-α,which are closely associated with fatty liver, so they may have a protective effect on NAFLD in young rats.

Immune response elicited in HBV-transgenic mice by cytoplasmic transduction peptide-HBcAg18-27-Tapasin adjuvanted with CpG ODN

WU Shanshan, TANG Yuyan, CHEN Xiaohua, ZHANG Yi, WANG Jieling, TANG Zhenghao, ZANG Guoqing, YU Yongsheng

2018, 23(3):  271-276.  doi:10.12092/j.issn.1009-2501.2018.03.005

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AIM: To investigate the effects of fusion protein of cytoplasmic transduction peptide (CTP) -HBcAg18-27-Tapasin adjuvanted with CpG ODN on immune response and anti-viral response in HBV transgenic mice.  METHODS: HBV-transgenic mice were randomly divided into 5 groups: experimental group: CTP-HBcAg18-27-Tapasin+CpG ODN, control group: CpG ODN, IFN-α and CTP-HBcAg18-27-Tapasin, vehicle group: normal saline. Serum samples were collected at various times before and after immunization. Intracellular cytokine in T lymphocytes was analyzed by flow cytometry, and the levels of IL-2 and IFN-γ secreted by T lymphocytes were detected by ELISA. The expression of HBsAg in liver sections was detected by immunohistochemistry. Sera levels of HBV DNA and HBsAg were examined by qRT-PCR and automatic enzyme-linked immunosorbent assay, respectively. RESULTS:An increased percentage of IFN-γ+CD8+ T cells was detected in CTP-HBcAg18-27-Tapasin+CpG ODN group and predominantly Th1 cellular immune response. In addition, the expression levels of serum HBsAg and HBV DNA were significantly inhibited, along with evident down-regulation of HBsAg in liver samples than CTP-HBcAg18-27-Tapasin alone group. CONCLUSION: CpG ODN acts as adjuvant could enhance anti-virus immune responses in HBV transgenic mice immunized with fusion protein CTP-HBcAg18-27-Tapasin.

Effects of elemene injected in multiple ways on liver histology changes in rabbits

LIU Wengui, WANG Youjin, MA Kun, DAI Guoliang, SHEN Xianglei, WANG Wei, SI Haipeng

2018, 23(3):  277-282.  doi:10.12092/j.issn.1009-2501.2018.03.006

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AIM: To explore the effects of elemene injected in multiple ways on liver histology changes in rabbits.  METHODS: Thirty New Zealand White rabbits were randomly divided into 5 groups: transauricular vein group (n=6), transarterial perfusion group (n=6), transarterial lipiodol group (n=6), transarterial gelfoam group (n=6) and transhepatic puncture group (n=6). Each rabbit was administrated elemene (20 mg/kg) via different access in 6 minutes. The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) concentrations were measured and 2 rabbits were euthanized for histological analysis at 6 hours and 1 week after administration. RESULTS: The AST concentration in plasma 6 hours after administration was（414.7±235.2） μmol/L in transarterial lipiodol group,（333.3±250.6） μmol/L in transhepatic puncture group, （92.3±73.6）μmol/L in transarterial gelfoam group and ALT concentration was （209.0±116.5）μmol/L in transarterial lipiodol group, （118.7±50.0）μmol/L in transhepatic puncture group, （68.3±21.4） μmol/L in transarterial gelfoam group, respectively, which were significantly higher than those of transauricular vein group or transarterial perfusion group (P<0.01). Under optical microscope, different degree of coagulation necrosis was seen easily in the transarterial lipiodol group, transhepatic puncture group and transarterial gelfoam group, concurrent with small bile duct hyperplasia, infiltration of a lot of inflammatory cells around bile duct, fatty degeneration of liver cells. However, only mild or moderate hydropic degeneration of liver cells was seen in transauricular vein group or transarterial perfusion group. CONCLUSION: Compared with transauricular vein or transarterial perfusion administration, the effects of elemene injected transarterial with lipiodol or gelfoam and transhepatic puncture may be more efficient.

Effects of platelet activation on renal tubular epithelial cells in sepsis

FANG Jingjing, TAO Jing, HUANG Qin, SHI Chaolu, YAN Biqing, GAI Lei, LI Xuguang

2018, 23(3):  283-289.  doi:10.12092/j.issn.1009-2501.2018.03.007

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AIM: To investigate the effect of platelet activation on renal tubular epithelial cells in sepsis. METHODS: ELISA was used to detect the inflammatory cytokines IL-1β and IL-6 secreted by platelets. Renal tubular epithelial cells and platelets were co-cultured in the co-culture system. Western blot was used to test p65 and p-p65 protein in renal tubular epithelial cells in the lower chamber. IL-1β and IL-6 mRNA expression level was measured by qRT-PCR. Cecal ligation and puncture(CLP) were used to construct the sepsis model, and TLR4 inhibitor TAK-242 was injected in caudal vein. In order to observe injury degree of renal tissue, EdU experiment and serum creatinine detection were carried out. RESULTS: IL-1β and IL-6 cytokines secreted by active platelets were increased in the presence of different concentrations of LPS. In the platelet and renal tubular epithelial cells co-culture system, p-p65 protein was increased in the tubular epithelial cells. TAK-242 could inhibit platelet activation, and reduce the renal tubular epithelial cell inflammatory cytokines secretion.The proliferation and pathological status were improved, and serum creatinine was decreased. CONCLUSION: The platelets in septic patients are aggregated and activated. inflammatory cytokines are increased. These cytokines activate NF-κB signaling pathway of renal tubular epithelial cells, leading to renal injury. TLR4 inhibitors have potential clinical value to improve the renal injury in sepsis. 

Effects of coenzyme Q10 chaperone drinks on femur and ulna in the mild aging mice

LV Simin, HUANG Zhirong, YU Qiong, SUN Jinying, CUI Liao, WU Tie

2018, 23(3):  290-295.  doi:10.12092/j.issn.1009-2501.2018.03.008

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AIM: To investigate the effect of coenzyme Q10 chaperone drinks on femur and ulna in the mild aging mice with Micro CT technology and bone composition analysis method.  METHODS: Eight-month-old SPF grade Kunming mice, both male and female, were randomly into normal saline group (NS), coenzyme Q10 Group (Q10), coenzyme Q10 chaperone drinks group (QC). After 10 weeks, the right femur was performed on Micro CT, and the left ulna bone was collected for detecting the content of Ca, Mg and Hyp. RESULTS: After giving coenzyme Q10 chaperone drinks, the body weight decreased in mice. Compared with NS group, QC group had a significant decrease in the Hyp content, SMI, and increased significantly in Ca, Mg content, BV/TV, Density and Conn-Dens. Compared with Q10 group, QC group had a significant decrease in the Hyp content, and increased significantly in Ca, Mg content. Micro CT three-dimensional image showed that the trabecular bone increased significanty, the number increased, and the degree of tightness was better, the continuity was restored in QC group, while compared with the NS group, the trabecular bone quantity, thickness, and distribution were significantly improved. CONCLUSION: Coenzyme Q10 chaperone drinks can improve the bone mass in the mild aging mice, suggesting a good prospects of the components in anti-osteoporosis application.

Expression and clinical significance of matrix metalloproteinase-9 and endothelial cells in patients undergoing cardiac transplantation

DAI Beijun, WENG Jianfeng, HU Zhibin

2018, 23(3):  296-300.  doi:10.12092/j.issn.1009-2501.2018.03.009

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AIM: To investigate the expression and clinical significance of matrix metalloproteinase-9 (MMP-9) and endothelial cell (EPCs) in patients undergoing cardiac transplantation.  METHODS: From January 2012 to January 2016, 120 patients undergoing cardiac transplantation in our hospital were selected as the study group. At the same time, 120 healthy people were selected as the control group according to age and sex matching. The level of MMP-9 in plasma was detected by enzyme linked immunosorbent assay (ELISA). The level of EPCs was detected by Flow cytometry, the difference and correlation between MMP-9 and EPCs in two groups were compared and analyzed. RESULTS:The levels of MMP-9 and EPCs in plasma of patients after heart transplantation were significantly increased, compared with those before transplantation, the difference was statistically significant (P<0.05). The levels of MMP-9 and EPCs before and after heart transplantation in the study group were significantly higher than those in the control group, the difference was statistically significant (P<0.05). The levels of MMP-9 and EPCs in the patients plasma with heart transplantation complication were（128.46±7.32） mg/L and 166.84±14.82, which were significantly higher than those in the normal group（94.25±7.14） mg/L and 134.68±13.68（P< 0.05）. The levels of MMP-9 and EPCs in the patients plasma with heart transplantation death cases were（137.36±8.13） mg/L and 168.24±14.62, which were significantly higher than those in the survival cases (92.85±7.06） mg/L and 98.41±13.24（P <0.05）.The expression of MMP-9 was positively correlated with the expression of EPCs (r=0.686, P=0.000) in patients undergoing heart transplantation. CONCLUSION: The levels of MMP-9 and EPCs in plasma is closely related to early pathologic changes of allograft vasculopathy after heart transplantation; monitoring the dynamic changes of plasma MMP-9 and EPCs of high-risk patients may contribute to observe the early after cardiac allograft vasculopathy tendency after heart transplantation, and timely adjust the treatment plan.

Effects of gray drugs in patients with coronary heart disease: A network Meta-analysis

WANG Weiyu, YU Hao

2018, 23(3):  301-307.  doi:10.12092/j.issn.1009-2501.2018.03.010

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AIM: To evaluate the clinical effect of gray drugs such as clopidogrel, prasugrel and ticagrelor combined aspirin using network Meta-analysis by comparing major adverse cardiac events.  METHODS: Database Pubmed, Cochrane Central Register of Controlled Trials, CBM, CNKI, VIP, Wanfang Data in both English and Chinese were retrieved. RCTs using gray drugs such as clopidogrel, prasugrel, ticagrelor, cangrelor, sarpogrelate in coronary patients were then collected. Indirect step-by-step comparison was adopted for Meta-Analysis on Stata. RESULTS: A total of 33 trials entered into the study. There was significant difference between ticagrel and clopidogrel (OR=0.70, 95% CI: 0.64-0.77, P<0.001). There was no significant difference between prasugrel and clopidogrel (OR=0.92, 95% CI: 0.84-1.01, P=0.487). There was significant difference between ticagrel and prasugrel (OR=0.76, 95% CI: 0.67-0.86, P<0.001). CONCLUSION: Ticagrelor combined aspirin therapy showed best curative effect in preventing major adverse cardiovascular events of coronary heart disease, prasugrel the second, and clopidogrel the last.

Effects of different hemodilution on hepatorenal coagulation and liver function of eldly patients underwent hepatectomy

YU Jun, JIN Xiaoju, GUO Jianrong, LU Meijing, CAO Ya, CHANG Yan

2018, 23(3):  308-312.  doi:10.12092/j.issn.1009-2501.2018.03.011

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AIM: To observe the effects of preoperative acute normal volemic hemodilution (ANH) and acute hypervolemic hemodilution (AHH) on coagulation and liver function in the elderly patients undergoing hepatic carcinectomy. METHODS: Forty-five ASA Ⅱ liver cancer patients (sixty to seventy years old) undergoing scheduled elective hepatic carcinectomy were randomly divided into ANH group(group A, n=15), AHH group (group B, n=15) and the control group (group C, n=15). After tracheal intubation, ANH was performed by letting blood from the jugular vein at the rate of 200-300 mL/10 min and infusing the same volume Voluven (130/0.4) in group A，AHH was performed by infusing 15-20 mL/kg Voluven (130/0.4) at a rate of 30 mL/min in group B，and group C were infused lactated Ringer's solution routinely. Blood routine(Hb, Hct), liver function（TP, ALB, AST, ALT）and coagulation function(PT, APTT, TT, DD) were observed and compared before anesthesia (T1)，30 minutes after ANH/AHH (T2) ，end of operation (T3) and 24 hours after operation (T4) in group A and B, and the corresponding time in group C. RESULTS: The blood loss volume was similar in the three groups during operations．There was significant difference in the allogeneic blood transfusions between both of the hemodilution groups and the control group（P<0.05）．Compared with T1，the Hb and Hct decreased significantly after hemodilution in group A and B．The plasma protein also significantly decreased after ANH and AHH in group A and B as compared with T1．ALT，AST in each group increased significantly during operation（P<0.05），in T3 and T4 there was significant difference between the group A and C. PT and APTT in group A and B after hemodilution were significantly prolonged (P>0.05), but none of them shifted outside the normal range．No significant changes were found in D-dimer and TT in group A and B．CONCLUSION: ANH or AHH is relatively safe during hepatic carcinectomy for elderly liver cancer patients without cardiac and pulmonary disease．ANH or AHH with 6% hydroxyethyl starch could be well applied to the elderly patients and also decrease allogeneic blood transfusions, with no apparently impact on the blood routine, liver and coagulation function．

Security observation of intraperitoneal perfusion chemotherapy with Raltitrexed in laparoscopic radical operation for colorectal cancer

ZHANG Yang, CHEN Zhikang, GUO Xiong, WANG Wen

2018, 23(3):  313-318.  doi:10.12092/j.issn.1009-2501.2018.03.012

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AIM: To observe and evaluate the postoperative complication and adverse reaction, postoperative recovery and systemic toxicity of intraperitoneal perfusion chemotherapy with raltitrexed in laparoscopic radical operation for colorectal cancer. METHODS: The clinical data of 81 patients with colorectal cancer were analyzed. Group A underwent laparoscopic radical operation+intraperitoneal perfusion with Raltitrexed; Group B just underwent laparoscopic radical operation. General information, operative time, postoperative complication and adverse reaction, the recovery time of the bowel function, routine blood tests as well as liver and kidney functions before and 3 days after operation between the two groups were evaluated and compared. RESULTS: No statistically significant difference were observed with general information (P>0.05). No statistically significant difference were observed with postoperative complication and adverse reaction, the recovery time of the bowel function and operative time (P>0.05); No statistically significant difference were observed with WBC, PLT, AST, ALT, Cr and BUN before and 3 days after operation (P>0.05). CONCLUSION: Intraperitoneal perfusion chemotherapy with Raltitrexed in laparoscopic radical operation for colorectal cancer is safe and well tolerated to patient.

Effects of Shenlingbaizhu powder combined with mesalazine in the treatment of ulcerative colitis and the influence of NLRP3 inflammasome

ZHOU Taomei, YANG Shangwen, WANG Jianbo

2018, 23(3):  319-324.  doi:10.12092/j.issn.1009-2501.2018.03.013

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AIM: To investigate the clinical effect of Shenlingbaizhu powder combined with mesalazine in the treatment of ulcerative colitis (UC) and the influence of Nod-like receptor pyrin domain 3 (NLRP3) inflammasome.  METHODS: One hundred patients with UC were randomly divided into control group and observation group, fifty cases in each group. The control group was given mesalazine 1.0 g qid, while the observation group was given Shenlingbaizhu powder 6.0 g tid combined with mesalazine 1.0 g qid. The course of treatment was eight weeks. The clinical efficacy of the two groups was compared; the expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1mRNA were detected; The levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) in serum was detected. RESULTS: After treatment, the total effective rate of the clinical symptoms of observation group (86%) was significantly better than that of control group (73%), the difference was statistically significant (P<0.05). The expression of NLRP3, ASC, caspase-1 mRNA in observation group (4.08±0.85, 3.75±0.91, 3.86±0.93) were more lower than those of control group (5.26±0.96, 4.66±0.95, 4.97±0.99), and the difference was statistically significant (P<0.05). The levels of CRP, ESR, IL-1 beta and IL-18 in observation group (6.74±2.45,11.63±4.58,44.27±8.58, 263.37±60.34) were more lower than those of control group (15.32±5.68,18.45±5.12,51.11±9.26, 371.18±61.25), and the difference was statistically significant (P<0.05). CONCLUSION: Shenlingbaizhu powder combined with mesalazine in the treatment of UC has good clinical curative effect, the mechanism may be related with the inhibition of NLRP3 inflammasome and inflammation.

Synergistic effect of Addie injection on pemetrexed combined with nedaplatin in the treatment of advanced non-small cell lung cancer

LI Weiwen, LI Yuan, SUN Lei, HUANG Gongcai, ZHAO Zhongwei

2018, 23(3):  325-328.  doi:10.12092/j.issn.1009-2501.2018.03.014

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 AIM: To investigate whether Addie injection can improve the efficacy of pemetrexed combined with nedaplatin in the treatment of advanced non-small cell lung cancer.  METHODS: Eighty-six cases of advanced non-small cell lung cancer patients were divided into the study group and the control group, 43 cases in each group. The control group was treated with pemetrexed combined with nedaplatin. The study group was treated with Addie injection on the basis of the control group. The clinical efficacy of the two groups was compared. The changes of serum immune indexes before and after treatment in two groups were detected. The immune indexes included CD3+, CD4+, CD4+/CD8+, IgM, IgA, IgG. Adverse reactions of two groups in the course of treatment  were observed. RESULTS:The control rate and effective rate of the study group were higher than those of the control group. But the difference was not statistically significant (P>0.05). The levels of CD3+, CD4+, CD4+/CD8+, IgA and IgG in the control group were significantly decreased after treatment (P<0.05). The levels of CD3+, CD4+, CD4+/CD8+, IgA and IgG after treatment in the study group were significantly higher than those in the control group. The difference was statistically significant (P<0.05). The incidence of gastrointestinal reaction, white blood cell reduction, abnormal liver and kidney function in the study group was significantly lower than that in the control group. The difference was statistically significant (P<0.05). CONCLUSION: Addie injection has a synergistic and attenuated effect on pemetrexed combined with nedaplatin in the treatment of advanced non-small cell lung cancer.

Number of regulatory B cells in peripheral blood of patients with autoimmune hemolytic anemia and its clinical signifcance

HE Hesheng, JIN Xiaoke, XU Youhai, YANG Yuqiong, LIU Shanhao, QI Jing

2018, 23(3):  329-332.  doi:10.12092/j.issn.1009-2501.2018.03.015

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AIM: To explore the number of regulatory B cells (Bregs) in peripheral blood of patients with autoimmune hemolytic anemia (AIHA) and its significance in the incidence of AIHA.  METHODS: A total of 16 AIHA patients and 14 healthy controls were enrolled. The expressions of CD19+IL-10+ Bregs and CD19+CD24hiCD27+ Bregs in peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry. And levels of IL-10 were measured in the culture supermatants by ELISA. RESULTS: The expression of CD19+IL-10+ Bregs in PBMCs of AIHA patients was (1.27±0.39)%, which was lower than that in healthy controls (2.92±0.71)% (P<0.05). The number of CD19+CD24hiCD27+ Bregs in AIHA patients was (9.85±2.18)%, which was lower than that in healthy controls (26.47±4.31)% (P<0.05). The level of IL-10 significantly decreased in culture supermatants of autoimmune hemolytic anemia patient as compared with healthy controls (P<0.05). CONCLUSION: The expression of Bregs significantly decreases in PBMCs of AIHA patients. Bregs may play some role in the pathogenesis of AIHA.

Effects of oxycodone hydrochloride controlled release tablets plus NB-UVB in the treatment of herpes zoster neuralgia

XU Lili, WANG Yunfu, QUAN Bianrui

2018, 23(3):  333-336.  doi:10.12092/j.issn.1009-2501.2018.03.016

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AIM: To evaluate the curative effects of oxycodone hydrochloride controlled-release tablets plus NB-UVB in the treatment of herpes zoster neuralgia.  METHODS: A prospective study method was adopted; one hundred and twenty cases of patients with herpes zoster treated by our hospital from September 2013 to February 2016 were selected and were equally divided into the observation group and control group according to the random-envelope principles. Both groups received antiviral treatment, and the control group was given NB-UVB therapy, while the observation group received oxycodone hydrochloride controlled release tablets combined with NB-UVB therapy; the treatment cycle was 14 days. RESULTS: The skin lesion regression time of the observation group was (6.18±1.05) d, which was significantly shorter than (7.93±1.36) d in the control group (P<0.05). The pain and skin lesions scores in the observation group after treatment were (2.33±1.38) points and (1.26±0.76) points, which were significantly lower than (4.46±1.93) points and (3.56±1.18) points of the control group (P<0.05), and that before treatment (P<0.05). There were no severe adverse reactions in the two groups during the treatment, and the nausea and vomiting, constipation, drowsiness, dizziness and other adverse reactions compared between the two groups showed no significant difference (P>0.05). CONCLUSION: Oxycodone hydrochloride controlled release tablets combined with NB-UVB in the treatment of herpes zoster neuralgia can effectively and safely relieve the pain and skin lesions so as to promote the patient's rehabilitation.

Effects of rivaroxaban combined with Xuesaitong injection on deep venous thrombosis of lower extremity after spinal trauma surgery

ZHENG Qiluan, SHEN Qi, YU Jincong, YUAN Yao, CHEN Bo

2018, 23(3):  337-341.  doi:10.12092/j.issn.1009-2501.2018.03.017

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AIM: To explore the effects of rivaroxaban combined with Xuesaitong injection on deep venous thrombosis (DVT) formation of lower extremity after spinal trauma surgery and its effects on blood coagulation function, blood rheology and other blood biochemical indexes.  METHODS: One hundred and five patients undergone spinal surgery in our hospital were divided into the treatment group and control group 1, control group 2 according to the different treatment methods after surgery, with 35 cases in each. After surgery, the control group 1 was given Xuesaitong injection therapy; the control group 2 was given rivaroxaban, while the treatment group was treated with rivaroxaban intervention and Xuesaitong injection therapy. The changes of coagulation function, hemorheology index and other blood biochemical indexes were detected and compared among the three groups. The incidence of DVT in three groups was evaluated and compared among three groups five days after surgery. RESULTS: After treatment, the PT, APTT and TT of the three groups were significantly prolonged compared with those before treatment; the FIB level was significantly lower than that before treatment (P<0.05 or P<0.01), and the difference among the three groups was significant (P<0.05 or P<0.01). After treatment, the whole blood viscosity, hematocrit, erythrocyte rigidity index of three groups were significantly lower than those before treatment; erythrocyte deformation index was significantly higher than that before treatment (P<0.05 or P<0.01), and the difference among three groups was significant (P<0.05 or P<0.01). After treatment, the levels of PLT and ET in the two groups were significantly higher than those before treatment, the D-D level was significantly lower than that before treatment (P<0.01), and there was significant difference among the three groups (P<0.05 or P<0.01). There was no significant difference in Hb level before and after treatment and among three groups (P>0.05). The incidence of DVT in the treatment group was 2.86%, which was significantly lower than 14.28% in control group 1 and 11.42% in control group 2 (P<0.05). CONCLUSION: Rivaroxaban combined with Xuesaitong injection can safely improve the coagulation function, blood rheology and other blood biochemical indexes, and effectively prevent the formation of DVT after spinal surgery.

Research and development progress of the novel acid suppression drugs potassium-competitive acid blockers

ZHAO Shifeng, WANG Ronghua

2018, 23(3):  352-360.  doi:10.12092/j.issn.1009-2501.2018.03.019

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The advent of proton pump inhibitors represents an important milestone in the treatment of acid related diseases. However, these drugs have some deficiencies in pharmacokinetics and pharmacodynamics. Potassium-competitive acid blockers reversibly bind to proton pumps in a competitive manner with potassium ions, thereby inhibiting gastric acid secretion and having multiple advantages. In order to provide a new reference for the treatment of acid related diseases, the research and development experience and pharmacological characteristics and clinical research of these drugs are reviewed, and the focuses are on the already listed revaprazan and vonoprazan.