Table of Content

Volume 22 Issue 10
26 October 2017

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Effects of vasoactive drugs on crystalloid fluid kinetics in septic sheep

YI Shenghua, LI Yuhong, ZHENG Xiaozhu, AN Manli, DING Qiannan, RU Guomei, ZHANG Lin

2017, 22(10):  1081-1089. 

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AIM: To explore how vasoactive drugs influence the distribution and clearance of lactated Ringer's solution(RL) in septic sheep. METHODS: This was a prospective randomized double-blinded study. Twenty-five experimental sheep were randomized into five groups: no drug (Control group), norepinephrine (Nor group), phenylephrine (Phe group), dopamine (Dop group), or esmolol (Esm group), with five animals for each group. After general anesthesia and tracheostomy tube for all sheep, septic model was established through cecal ligation puncture (CLP) method and a short infusion of lipopolysaccharide (LPS). Then a continuous intravenous administration of saline or corresponding vasoactive drugs were given to five groups respectively. 10 min later 20 mL/kg of RL solution over 30 min was given. The kinetics of RL and the effects of covariates were calculated by plasma dilution based on dilution of hemoglobin-time curve, urinary excretion by using Phoenix software for mixed effects modeling.RESULTS:Compared with Control group, Nor group and Dop group accelerated the distribution rate from plasma to peripheral tissue (k12); while decreased the distribution rate opposite direction (k21). Adrenergic α1-receprtor accelerated, while β1-receptors retarded, the distribution and elimination of the fluid. The pharmacodynamics Emax model showed that RL increased stroke volume by 13 mL/beat, α1-receptors but not β1-receptors further increased stroke volume, while both raised the mean arterial pressure, modulation of the β1-receptors limited the acidosis. CONCLUSION: The distribution and elimination of RL is slow in septic sheep. The tendency to peripheral accumulation of fluid is pronounced, in particular when phenylephrine and dopamine are given, and norepinephrine can alleviate acidosis.

Effects of compound Baihe shugan anshen on stucture and expressions of GR, BDNF and NPY on prefrontal cortex-edge structure in anxious depression model rats

YANG Qin, DU Qing, ZHAO Hongqing, WANG Yuhong, HAN Yuanshan, YANG Hui, MENG Pan

2017, 22(10):  1090-1098. 

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AIM: To investigate the effects of compound Baihe shugan anshen on anxiety depression model rat prefrontal cortex-edge(hippocampus and amygdala) structure and expression of GR/BDNF/NPY.  METHODS: SD rats were randomly divided into 7 groups according to body weight: the anxious depression model group, the positive drug (venlafaxine 6.75 mg/kg) group, the compound Baihe shugan anshen-high, -middle, -low (24.28 g/kg, 12.24 g/kg, 6.12 g/kg) group, the control group and the vehicle group. Chronic restraint stress plus solitary feeding and subcutaneous injection of CORT (30 mg/kg) for 21 d were administered to build the animal model of anxiety depression. At the same time, the positive drug group and compound Baihe shugan anshen group received intragastric administration. The vehicle group received subcutaneous injection of physiological saline plus 5%DMSO. The control group was fed normally. Morphological changes of prefrontal cortex (PFC), hippocampus and amygdala were analyzed by HE staining, and determination of GR, BDNF and NPY by Western blotting.  RESULTS: Compared with the blank control group, glial cells were increased while the neurons were decreased; vertebral neurons were physalides, and nucleus were wither in PFC of anxiety-depression rats. Neurons in hippocampal DG and CA3 area were lost, and the nucleus of neurons in CA3 area was deeply stained. The nucleus of amygdala neurons was fuzzy, the cells were scattered, and the number of cells were decreased significantly. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly decreased (P<0.05 or P<0.01). Compared with the model group, prefrontal cortex glial cell proliferation was obviously relieved; cells were arranged in order in the Baihe shugan anshen high dose group. Neurons in hippocampus DG and CA3 were increased and CA3 neurons recovered. The damage of neurons in the amygdala was also reduced. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly increased (P<0.05 or P<0.01). CONCLUSION: The anti-anxiety and depression effect of Baihe shugan anshen may be related to the cascade of regulation of GR/BDNF/NPY signal to protect the prefrontal-marginal(hippocampus,amygdala) structural injury. 

Effects of Rutin combined with oxaliplatin on the proliferation and apoptosis of human gastric cancer SGC-7901 Cells

LI Qi, REN Liqun, WANG Yadi, CHEN Suxian

2017, 22(10):  1099-1105. 

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AIM: To study the effect of rutin combined with oxaliplatin on the proliferation and apoptosis of human gastric cancer SGC-7901 cells.  METHODS: Human gastric cancer SGC-7901 cells in logarithmic growth phase were selected as the research object.Hoechst33258 nuclear staining was used to observe the morphological changes. Cell cycle and cell apoptosis were detected by flow cytometry. The expression of caspase-3, Bax and Bcl-2 protein in SGC-7901 cells were analyzed by Western-blot. RESULTS: Rutin (100,200,300 μmol/L) and oxaliplatin inhibited the proliferation of SGC-7901 in a dose-dependent manner. Rutin combined with oxaliplatin, compared with the same concentration of oxaliplatin SGC-7901 cells, was significantly more effective on SGC-7901 cells (P<0.05). Compared with oxaliplatin, SGC-7901 cells treated with different concentrations of rutin and oxaliplatin significantly increased the apoptosis rate of SGC-7901 cells (P<0.05).The ratio of bcl-2/bax protein expression was significantly decreased (P<0.05). CONCLUSION: Both curcumin and oxaliplatin can inhibit the proliferation of gastric carcer cells SGC-7901 and induce apoptosis. The mechanism may be related to up-regulation of caspase-3 and down-regulation of apoptosis-related protein such as bcl-2/bax. And the joint application of rutin and oxaliplatin presents some synergistic effect.

Influence of dopamine D1 receptor Ala229Thr polymorphism on receptor signal transduction

PENG Juan, LI Cuilin, LIU Jianqiu, LI Zhi

2017, 22(10):  1106-1111. 

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AIM: To construct the eukaryotic expression vector carrying human dopamine D1 receptor (DRD1) gene in order to determine the influence of Ala229Thr polymorphism on the receptor signal transduction. METHODS: Site-directed mutagenesis and gene recombination techniques were used to construct the recombinant eukaryotic expression vectors containing different genotypes of DRD1 gene. The coding sequence of DRD1 gene was cloned from human genome DNA by polymerase chain reaction (PCR). Purified PCR product was ligated to pMD19-T vector. Mutant DRD1-pMD19-T vector by site-directed mutagenesis was established based on wild DRD1-pMD19-T vector. After using Kpn I and EcoR I double endonucleases to excise DRD1-pMD19-T vector and pcDNA3.1(+) empty vecor, both wild and mutant DRD1 gene CDS were then ligated to pcDNA3.1(+) vectors to construct wild and mutant DRD1-pcDNA3.1(+) recombinant eukaryotic expression vectors. pcDNA3.1(+) empty vector, wild and mutant DRD1-pcDNA3.1(+) vectors were transiently transfected into COS-7 cells. 48 h after transfection, short-term exposure of cells to 100 μmol/L forskolin, dopamine and (±)-SKF38393 with various concentrations, intracellular cAMP accumulations were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: DRD1-pcDNA3.1(+) recombinant eukaryotic expression vectors were verified correctly by enzyme digestion as well as sequence analysis. The cAMP accumulations induced by 100μmol/L forskolin were (0.40±0.14) pmol/well for pcDNA3.1(+) empty vector group and (0.78±0.24) pmol/well for mock-transfected group (P=0.082). The cAMP accumulations in response to forskolin treatment for the wild-type receptor (WT) group and mutant receptor (MT) group were (2.06±0.35) and (1.37±0.12) pmol/well, respectively. The WT group presented markedly higher cAMP accumulations than pcDNA3.1(+) empty vector group (P<0.001) and the MT group (P=0.007). The agonist-induced cAMP accumulations both increased in a concentration-dependent manner in COS-7 cells transfected WT and MT. Moreover, the MT group had a remarkable reduction in agonist-induced cAMP accumulations compared with the WT group (all P<0.001 for dopamine and SKF38393). In addition, intracellular cAMP maximal accumulation and EC50 value were investigated to evaluate the influence of MT on the efficacy and potency of agonists. Our data demonstrated that agonist-induced intracellular cAMP maximal accumulations of the MT group were significantly lower than those of the WT group (dopamine, P<0.001; SKF38393, P<0.001). The EC50 value for dopamine at the WT group was 625 nmol/L and at the MT group was 9612 nmol/L, a 15-fold increase over that obtained at the WT group. However, the EC50 value for SKF38393 at the WT group was 421 nmol/L and at the MT group was 417 nmol/L, which was similar to that obtained at the WT group. CONCLUSION: DRD1-pcDNA3.1(+) recombinant eukaryotic expression vectors were constructed successfully; Ala229Thr polymorphism affect the activation and signal transduction of DRD1, with the 229Thr receptor exert a lower signal transduction effect than wild type receptor.

Alternate dosing of ezetimibe and colestipol on regulating lipid metabolism in hyperlipidemia rats

YANG Yi, GUAN Qiaobing, GUO Li, LI Wenyan, ZHANG Hui, HAN Chenyang

2017, 22(10):  1112-1116. 

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AIM: To explore alternate dosing of ezetimibe and colestipol on regulating for lipid metabolism in hyperlipidemia rats.  METHODS:Fifty rats of clean grade, half male and female were modeling through feeding high fat diet; the rats were randomly divided into normal group, model group, and experimental groups (including ezetimibe group, colestipol group, ezetimibe+colestipol group); experimental groups received gavage administration, while the normal group and model group were given normal saline for 8 weeks; TG, TC, HDL-C, LDL-C and ACC, FAS, HMGR, CPT-I expression of mRNA in serum were thereafter detected. RESULTS: The levels of TC, TG, LDL-C and AAC, FAS, HMGR mRNA in serum were decreased, and levels of ezetimibe+colestipol group were significantly lower than those of single drug group (P<0.05). CONCLUSION: Alternate dosing of ezetimibe and colestipol was better than single medication in regulating lipid metabolism in hyperlipidemia rats, but the effect on human body still needs further clinical validation.

Effects of obatoclax plus 5-Fluorouracil on the epithelial mesenchymal transition of pancreatic cancer cells under hypoxia

HOU Xinfang, SONG Haiyan, ZHOU Zhixin, DENG XiaoHui, ZHANG Yimin, CHENG Huixin

2017, 22(10):  1117-1122. 

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AIM: To explore the effect of obatoclax combined with 5-Fluorouracil (5-FU) in epithelial mesenchymal transition(EMT) of pancreatic cancer BxPC-3 cells and its possible mechanism. METHODS: MTT assay was performed to detect cell viability in hypoxic group, 5-FU group and obatoclax combined with 5-FU group. RT-qPCR and Western blotting were used to detect EMT-related genes and proteins expression in BxPC-3 cells of hypoxic group, 5-FU group and obatoclax combined with 5-FU group. RESULTS: Under hypoxia condition, obatoclax combined with 5-FU time-dependently inhibited BxPC-3 cell proliferation activity. Obatoclax combined with 5-FU further down-regulated the expression of transcription factors Snail and Slug, as well as mesenchymal markers N-Cadherin, Fibronectin, Collagen I and Vimentin. Obatoclax combined with 5-FU up-regulated the expression of epithelial marker E-Cadherin. CONCLUSION: Under hypoxia condition, obatoclax combined with 5-FU inhibit the viability of BxPC-3 cells. Obatoclax combined with 5-FU can up-regulate E-Cadherin and down-regulate N-Cadherin, Fibronectin, Collagen I and Vimentin through inhibiting Snail and Slug, thus inhibiting EMT, reducing migration and invasion ability of BxPC-3 cells.

Radix tetrastigma hemsleyani flavone suppresses human lung carcinoma A549 cell via proteasome inhibition

ZHONG Liangrui, CHEN Hua, JING Jing, QIAO Hongli, WEI Kemin, WANG Weidong

2017, 22(10):  1123-1126. 

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AIM: To study the effect of radix tetrastigma hemsleyani flavone (RTHF) on the growth in human lung carcinoma A549 cells as well as its mechanisms. METHODS: A549 cells were treated with the RTHF in different concentrations. The proliferation of A549 cell was detected by MTT assay in vitro. Enzyme proteasome assay was used to detect the activity of proteasome and DUB. Expressions of ubiquitin proteasome pathway associated proteins were detected by Real-time PCR and Western blot. RESULTS: MTT showed that RTHF had obvious anti-proliferation effect on A549 cells in a dose-dependent manner. Enzyme proteasome assay showed that the treatment of activity of proteasome and DUB was significantly lower than the proportion in the control group (P<0.05). Real-time PCR and Western blot showed the protein expression of ub-prs and was up-regulated significantly and that of USP14, UCHL5, POH1 were down- regulated in RTHF group when compared with the control group. CONCLUSION: Radix tetrastigma hemsleyani flavone may inhibit the proliferation of lung cancer A549 cells through the ubiquitin proteasome pathway.

Statistical performance comparison of different simultaneous global development designs for targeted drugs

WANG Yafei, CHEN Feng, BAI Jianling, HUANG Lihong, YU Hao

2017, 22(10):  1127-1132. 

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AIM: To evaluate the statistical performance of all-randomized design and enrichment design in simultaneous global development program for targeted drugs, and to provide a framework for the clinical practice. METHODS: Monte Carlo techniques were applied to simulate clinical data of simultaneous global development design for targeted drugs, and the power of all-randomized design and enrichment design was compared with different parameter settings.RESULTS:When the efficacy of non-targeted ethnic (NTE) patients and targeted ethnic (TE) patients, target positive and negative patients were equal, the power of all-randomized design and enrichment design with allocation was the highest, and the power of the enrichment design with screening was lower. When the target negative population had lower efficacy than the positive population, the enrichment design with allocation had the highest power, the second was all-randomized design, and the enrichment design with screening was the lowest. The power rose with the ratio of target positive population increased. When the efficacy of TE patients was lower than that of NTE patients, the results of power were almost the same with those in above, and the power was slightly lower. CONCLUSION: When there is sufficient evidence of a better effect on targeted positive patients than negative patients, the enrichment design is recommended. When researchers can't make sure that target drug is effective for marker-negative patients or not or there is not a reliable target diagnosis method, all-randomized design is recommended. And weighted Z test can provide enough power to verify the hypothesis when the sample size of local clinical trials is small.

Determination of caspofungin in human plasma by UPLC-MS/MS

SHAO Hua, HE Zijian, HU Linlin, ZHAN Ying, HU Rongrong, HE Jie

2017, 22(10):  1133-1137. 

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AIM: To establish a method to determine the concentration of caspofungin in human plasma by UPLC-MS/MS. METHODS: Plasma samples were spiked with roxioxithromycin as the internal standard and precipitated by methanol. The column was Ultimate AQ C₁₈ (100 mm×2.1 mm,3 μm) with the column temperature of 40 ℃. The mobile phase was acetonitrile and aqueous solution (5 mmol/L ammonium acetate, 0.2% formic acid), and the pump flow rate was 0.4 mL/min. The ion transitions were performed under ESI positive MRM model at m/z 547.5→538.2 for caspofungin and m/z 838.6→157.9 for internal standard. The analysis time was 6.5 min. RESULTS: Calibration curves of caspofungin showed good linear regression in the range of 0.1-25 μg/mL (R ²=0.999 5). The lowest quantification limit of caspofungin was 0.1 μg/mL. The extraction recovery was about 59.08%. The intra-day and inter-day relative standard deviation (RSD) were less than 15%. CONCLUSION: The established method is simple, accurate, sensitive and had good reproducibility, which can be used for the blood concentration determination of caspofungin.

Association of synergistic effects of Wuzhi capsules on tacrolimus and PXR polymorphisms

XIN Huawen, YANG Yan

2017, 22(10):  1138-1144. 

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AIM: To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus and PXR polymorphisms. METHODS: A total of 74 patients were continually administered with Wuzhi capsules for 24 months as Wuzhi capsules (+) group. A total of 96 patients took tacrolimus alone as Wuzhi capsules (－) group. The PXR 7635 A>G (rs6785049) and PXR 24381 A>C (rs1523127) genotypes were determined by PCR-direct sequencing. PXR 6bp deletions (rs3842689) genotype was determined by Allelic Special-Touch down PCR. The tacrolimus whole blood levels of renal transplant recipients were measured by chemiluminescent microparticle immunoassay.Analysis of covariance (ANCOVA) was performed to determine the difference of tacrolimus C0/D among various groups. RESULTS: Tacrolimus C0/D of patients with PXR 7635 A>G GG was significantly higher than that with GA/AA in Wuzhi capsules (+) group from 3 months to 24 months (P=0.005, 0.049, 0.001, 0.031, 0.035) and there was no significant difference in Wuzhi capsule (－) group. Whether co-administration of Wuzhi capsules and tacrolimus or not, PXR 6bp deletions, PXR 24381 A>C genotype were not associated with tacrolimus C0/D.CONCLUSION:When combined with Wuzhi capsules, PXR 7635 G>A mutation might associate with tacrolimus C0/D.

Therapeutic effect of amtiriptyline combined with opioids for moderate to severe cancer pain patients with depression

XU Xiangwei, CHEN Yanqiao, ZHU Peizhen

2017, 22(10):  1145-1151. 

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AIM: To investigate the effect and safety of amitriptyline combined with opioid for moderate to severe cancer pain patients with depression. METHODS: Forty-two patients with moderate to severe cancer pain and depression were randomly divided into two groups. The control group was given strong opioids (n=21), the treatment group was given opioids combined with amitriptyline (n=21). The digital classification method (NRS), depression self rating scale (SDS) and Hamilton depression scale (HAMD 17), quality of life questionnaire (SF-36) were used to assess the clinical effect of pain, depression and quality of life. In addition, the opioids dose and adverse drug reactions were recorded. RESULTS: Pain was significantly alleviated in each group (P<0.01) after two or four weeks, and the NRS of the treatment group was better than that of the control group after two or four weeks (P<0.05); depression was relieved in each group (P<0.01), and the depression score of the treatment group was better than that of the control group (P<0.05); after the treatment, the quality of life had improved to a certain extent in both groups, and the emotional function, energy, mental health, social functioning and body pain in the treatment group were better than those of the control group (P<0.05); the average daily dosage of opioids for treatment group was significantly lower than that of the control group after four weeks (P<0.01); the total incidence of adverse of the treatment group was slight higher than that of the control gtoup (P>0.05), but the dizziness, sleepiness and urinary retention were obviously more than those of the control group (P<0.05). CONCLUSION: Amitriptyline combined with opioids can effectively control severe cancer pain, relieve depressive symptoms, and improve the quality of life for cancer pain patients, which is referential for clinical application.

Efficacy and safety of amisulpride for schizophrenia

ZHOU Yong, Chen Xuefang, HUANG Hanjin

2017, 22(10):  1152-1157. 

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AIM: To explore the efficacy and safety of amisulpride in treating patients with schizophrenia. METHODS: Ninety patients with schizophrenia were randomly divided into the experimental group (received amisulpride) and the control group (received risperidone) with forty-five cases in each group. The Positive and Negative Syndrome Scale (PANSS) was used to assess the patients' mental symptoms and the Clinical Global Impressions-Severity of Illness Scale (CGI-S) for the degree of severity; the efficacy was assessed through the changes of scores, the improvement rate and effective rate of symptoms. The Treatment Emergent Symptom Scale (TESS) was assessed to evaluate the adverse reactions. All scales were assessed before treatment and at the 2nd, 4th, 8th weekend after treatment. RESULTS:The scores of PANSS and all its factor scores at every time interval were significantly lower than those at baseline (P<0.05). The scores of negative symptoms in the experimental group were much lower than those in the control group at the 2nd, 4th, 8th weekend after treatment (P<0.05). There's no difference in total scores of PANSS, scores of positive symptoms and psychopathological symptoms between the two groups at every time interval (P>0.05). Scores of CGI-S in the experimental group was obviously lower than those at baseline in comparison with the control group (P<0.01). There's no difference in scores of CGI-S between the two groups (P>0.05). Both of two groups presents no severe adverse reactions after treatment, and no significant difference was observed between the two groups either (P>0.05). CONCLUSION: Both amisulpride and risperidone can obviously improve patiens' positive, negative and psychopathological symptoms. However, the efficacy on negative symptoms of amisulpride is better than that of risperidone. Amisulpride also exhibit better tolerance with no severe adverse reaction in treating schizophrenia.

Curative effect of LNG-IUS in the treatment of adenomyosis

MAO Jingjing, ZHENG Mengnv, HU Bingzhen

2017, 22(10):  1158-1161. 

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AIM: To research the effect of LNG-IUS on adenomyosis with moderate to severe dysmenorrhea patients. METHODS: 160 cases of adenomyosis with moderate to severe dysmenorrhea patients treated in our hospital were selected, they were divided into control group and treatment group randomly, each group had 80 cases.Patients in the control group were treated with Mifepristone Tablets 12.5 mg, once a day, orally for 6 months. Patients in the treatment group were placed LNG-IUS in menstrual 5-7 d, 52 mg containing levonorgestrel, release rate was 20 g/d. Compared with the dysmenorrhea score, PBAC score, the situation of the uterus and hemoglobin, CA125 levels between the two groups.RESULTS:The score of the two groups of patients before treatment of dysmenorrhea was similar (P>0.05), 1 months after the treatment in the test group, after 3 months and 6 months after the dysmenorrhea scores were (1.71±0.46), (1.03±0.27) and (0.68±0.47), control group were respectively (2.06±0.51), (1.43±0.50) and (1.08±0.35), the difference had statistical significance (P<0.05). Two groups of patients before treatment PBAC score were similar (P>0.05).The PBAC score of 1 months,3 months and 6 months after the treatment in the test group were (108.36±23.10), (71.83±19.51) and (42.98±16.19), those of patients in the control group were (131.96±26.43), (95.60±22.56) and (69.76±17.71),respectively.The difference had statistical significance (P<0.05). Two groups of patients before treatment of endometrium, uterine volume and hemoglobin, close to the level of CA125 (P>0.05), after 6 months of treatment, the test group of patients with endometrial and uterine volume, the level of CA125 and hemoglobin levels were (4.72±1.24) mm, (134.53±22.09) cm3, (23.85±11.31) U/mL and (127.04±12.90) g/L, the control group were respectively (6.55±2.95) mm, (158.45±26.96) cm3, (36.35±15.19) U/mL and (108.63±12.01) g/L, the difference had statistical significance (P<0.05). CONCLUSION: LNG-IUS can significantly reduce the pain of adenomyosis with severe dysmenorrhea patients, reduce menstrual flow, control endometrial hyperplasia, reduce the level of CA125, improve the level of hemoglobin, it is worthy of clinical application.

A comparison of clinical applications of transdermal estradiol and estradiol valerate on endometrial receptivity in frozen-thawed embryo transfer cycles

JIN Congcong, WANG Peiyu, LIN Jia, ZHOU Wei, YANG Haiyan

2017, 22(10):  1162-1166. 

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AIM: To compare the clinical outcome of two endometrial preparation protocols (oral estradiol vs 17β-estradiol transdermal gel) in frozen-thawed blastocyst transfer.  METHODS: One hundred and twenty FET cycles were analyzed from July 2016 to December 2016. All cases were divided into two groups: group A (n=60) received transdermal gel application for 60 cycles, while group B received (n=60) oral estradiol valerate for 60 cycles. Patient's age, basic endocrine, endometrial thickness on the day of progesterone initiation, high quality embryo rate, mean number of embryo transferred per patient, implantation rate, clinical pregnancy rate, early abortion rate and ectopic pregnancy rate were compared between the two groups. RESULTS: Clinical pregnancy rate and implantation rate of group A （63.63% and 52.72%） were higher than those of group B（61.11% and 46.29%, respectively）, but there were no statistically significant difference (P>0.05). The total amount of estradiol used［(102.6.8±34.10 vs 85.52±17.18) mg］ in group A was significantly higher than that in group B(P<0.05), and the total duration of estradiol used［(16.80±4.02) vs (12.64±2.52) d］ in group A was significantly higher than that in group B (P<0.05)．No significant differences of other indicators were observed between the two groups. CONCLUSION: In frozen-thawed embryo transfer, estradiol transdermal gel endometrial preparation protocol can obtain the similar pregnancy rate compared with taking estradiol valerate . Estradiol transdermal gel can be used as an effective clinical method for patients with abnormal liver function and hyperlipidaemia. Yet, the dosage and span time increased, estradiol transdermal gel as a regular recommendation still need further discussion.

Effects of MCT/LCT and LCT fatty acid on parenteral nutrition-associated cholestasis in premature infants

CAI Ruihong, YANG Changyi, XIU Wenlong, CAI Wenhong, LIN Yunfeng

2017, 22(10):  1167-1171. 

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AIM: To investigate the effect of MCT/LCT and LCT fat emulsion on the incidence of parenteral nutrition-associated cholestasis (PNAC) in preterm infants that accept long-term parenteral nutrition (PN) so as to provide a reference for the choice of neonatal PN fat emulsion, and to explore the protective factors of PNAC.  METHODS: This retrospective analysis was conducted on hospitalization data of preterm infants (gestational age 29-34 weeks) that received PN for more than 14 days in March 2015 and March 2016 in NICU. Different types of fat emulsion were used in these two periods; the occurrence of PNAC was compared. Then the patients with the same condition were collected from March 2016 to September 2016, and these patients were divided into two groups (≥3 g·kg-1·d-1 group and ≤2 g·kg-1·d-1 group) according to the daily maximum dosage of LCT fat emulsion. The occurrence of cholestasis was compared in the two groups.RESULTS:Compared with MCT/LCT, the incidence of PNAC was significantly increased in LCT group.The patients that received ≥3 g·kg-1·d-1 daily maximum dosage of LCT has a higher incidence of PNAC and lipid accumulative amount; and the time to reach the whole gastrointestinal nutrition was longer as well as the hospital stay. CONCLUSION: LCT is more likely to cause cholestasis. Reducing the accumulative amount of fat emulsion and daily maximum dosage, achieving total gastrointestinal nutrition as soon as possible are protective factors of PNAC.

Effects of gender difference on response to sertraline and imipramine in patients with chronic depression

FANG Guodong, ZHANG Lihua, TANG Weiting

2017, 22(10):  1172-1179. 

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AIM: To examine the gender difference on response to sertraline, a selective serotonin reuptake inhibitor, and to imipramine, a tricyclic antidepressant, for chronic depression.  METHODS: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or bipolar depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout.RESULTS:Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSION: Men and women with chronic depression show differential responsivity and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women were observed primarily in pre-menopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.

Farnesoid X receptor gene polymorphisms and metabolic disease

XU Qian, LI Ling, WEI Wanhui, ZHAO Huijia, SHI Yuying, YUE Jiang, WANG Yanfeng, YE Qifa

2017, 22(10):  1180-1188. 

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Farnesoid X receptor (FXR)is a ligand-activated transcription factor that maintains homeostasis. In the nucleus, FXR forms a heterodimer with RXR and binds to inverted repeat elements separated by one nucleotide (IR-1) to regulate the expression of target genes. Highly expressed in the human liver, intestine, kidneys and adrenals, FXR is an important regulator of bile acid, lipid and glucose metabolism. This makes FXR a potential therapeutic target in metabolic disease. What's more, FXR SNPs (single-nucleotide polymorphisms) are proved to be associated with cholelithiasis, glucose homeostasis, intrahepatic cholestasis and obesity. This review focuses on the metabolic pathway and the gene polymorphism of FXR, which can bring the results of early identification and prevention of some metabolic diseases.

Circular RNA: function and role in colorectal cancer

PENG Xiangdong，FANG Weijin，HE Yang，GUO Ren

2017, 22(10):  1189-1194. 

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Colorectal cancer (CRC) is a common human digestive system malignant tumor, and its morbidity and mortality are in the third place among different diseases. Many factors including age, life style, obesity, and smoking are involved in the morbidity of CRC. Recent studies have demonstrated the abnormal expressions of non-coding RNAs, including circular RNA, participate in the development and progression of CRC. CircRNAs are a novel type of endogenous long noncoding RNAs, unlike the better known linear RNA, forms a covalently closed continuous loop. Recent studies indicate that circRNAs can function as sponges of miRNA and regulators of splicing and transcription. CircRNAs can also modulate protein-protein interaction and affect the maturation of ribosomal. Emerging evidence indicates that circRNAs play a vital role in controlling the proliferation, metastasis and invasion of tumor cells. This review focuses on the function of circRNAs and discusses its role in colorectal cancer.

Progress in application of humanized hemato-lymphoid system mice in human acute leukemia model

CHENG Liyan，TU Linglan，YAN Dongmei，WANG Xiaoju，ZHENG Xiaoliang

2017, 22(10):  1195-1200. 

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Despite a continuous improvement in xenograft models, engraftment of human malignant cells remains challenging in research of human hematopoiesis.In order to investigate the molecular mechanism involved in human leukemia and to improve therapy, establishing xenograft models that faithfully replicated the disease is critically important. Humanized mice are generated by transplanting human hematopoietic cells into recipient mice. An ideal model would be a humanized mouse in which the human graft fully replaces the endogenous mouse hematopoietic and immune systems. For this purpose, there are three basic requirements: tolerance by the mouse host, correct spatial location and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules.Here we review the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology, which closely resembling the human situation in the xenogeneic mouse environment.