Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness / 中国中药杂志

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Establishment and clinical application of ibrutinib blood concentration assay / 中国药房

OBJECTIVE To establish a method to detect the blood concentration of ibrutinib and apply it to the clinic. METHODS Using zanubrutinib as internal standard， the concentration of ibrutinib was detected by high performance liquid chromatography （HPLC） after plasma samples were processed by solid-phase extraction. The separation was performed on an Agilent 5 TC-C18（2） column with acetonitrile-0.5% potassium dihydrogen phosphate solution （43∶57， V/V） as the mobile phase at a flow rate of 1 mL/min， a detection wavelength of 260 nm， a column temperature of 40 ℃ ， a sample size of 20 μL， and a run time of 25 min. The concentration of ibrutinib was measured in the plasma of 9 patients with non-Hodgkin’s lymphoma 2 h after drug administration on the 30th day by the above method. RESULTS The linear range of the assayed mass concentration of ibrutinib was 10-500 ng/mL （R 2＝0.998 9）， the lower limit of quantification was 10 ng/mL， and the RSDs of the intra-batch and inter-batch precision tests were not higher than 12.77%. The recoveries of the extraction were 74.80% and 97.70%， with both RSDs＜2.90%， and the RSDs of the stability tests were not higher than 7.10%. The peak plasma concentrations of 9 patients were 15.341-279.628 ng/mL. CONCLUSIONS The established HPLC method is simple and rapid， and can be used for the determination of ibrutinib concentration in plasma samples.

Optimization of the simultaneous extraction technology of dietary fiber and flavonoids from the peel of Prunus armeniaca / 中国药房

OBJEC TIVE To optimize the simultaneous extraction technology of dietary fiber （DF）and flavonoids from the peel of Prunus armeniaca . METHODS The content of DF was calculated with enzyme-gravimetric method ，and the content of flavonoids was determined by ultraviolet spectrophotometry. The orthogonal design and single factor test were used to optimize the extraction technology ，with the factors of liquid-solid ratio ，pH，papain concentration ，α-amylase concentration ，temperature of enzymatic hydrolysis and time of enzymatic hydrolysis as factors ，using the contents of DF and flavonoids as indexes. RESULTS The optimal extraction technology included the solid-liquid ratio of 1 ∶ 10（g/mL），pH5，0.5％ papain and 0.5％ α-amylase， enzymatic hydrolysis at 50 ℃ for 1 h. After three times of validation ，the average content of DF was 0.801 g/g（RSD＝1.95％）， and the average content of flavonoids was 2.135 mg/g（RSD＝2.44％）. The average comprehensive score was 0.988（RSD＝ 0.81％）. CONCLUSIONS The optimal extraction technology is stable and feasible.

Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).@*METHODS@#In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.@*RESULTS@#In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).@*CONCLUSION@#HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.

Hematologic Phenotype and Genotype Analysis of Patients with Hemoglobin Variants / 中国实验血液学杂志

OBJECTIVE@#To study the hematologic and molecular features of 14 patients with hemoglobin (Hb) variants, so as to provide reference data for its laboratory screening.@*METHODS@#A total of 1 029 samples were screened by high performance liquid chromatography (HPLC) on the Bio-Rad VariantⅡHPLC system. GAP-PCR and reverse dot blot (RDB) were used to detect common mutation of α and β globin gene in Chinese. DNA sequencing for α and β globin gene was simultaneously performed in samples with abnormal spectrum peak and negative thalassemia gene.@*RESULTS@#In 1 029 samples, 10 types of structural Hb variants were detected in14 cases (1.36%), including 1 case of Hb E / β- thalassemia, 1 case of Hb E /α- thalassemia (HbH disease), 2 cases of HbG-Taipei, 2 cases of Hb Q-Thailand, 2 cases of Hb Youngstown, 1 case of Hb Guangzhou-Hangzhou, 1 case of Hb M-Boston, 1 case of Hb G-Siriraj, 1 case of Hb J-Baltimore, 1 case of Hb J-Sicilia and 1 case of Hb Tamano.@*CONCLUSION@#The occurrence of abnormal structural Hb variants with many genotypes in Shanghai is unique. Except for Hb E, Hb Youngstown, and Hb M-Boston, other types of heterozygous are normal in phenotypes, and symptoms such as hemolysis and anemia often occur when other diseases are combined.

Rapid Health Technology Assessment of Albumin-bound Paclitaxel in the Treatment of Breast Cancer / 中国药房

OBJECTIVE：To evaluate th e effectiveness ，safety and economy of albu min-bound paclitaxel （nab-PTX）in the treatment of breast cancer by using rapid health technology assessment （HTA），and to provide evidence-based reference for drug selection. METHODS ：Retrieved from PubMed ，the Cochrane Library ，CNKI，Wangfang database and other databases ，systematic evaluation/Meta-analysis，HTA and pharmacoeconomic studies about nab-PTX in the treatment of breast cancer were included ；the conclusions were classified and analyzed by using descriptive analysis. RESULTS ：A total of 5 systematic reviews/Meta-analysis ， 8 pharmacoeconomic studies were included in this study. Compared with conventional taxanes ，nab-PTX increased pathological complete response （pCR）rate [OR ＝1.39，95％CI（1.16，1.67），P＜0.001] and event-free survival （EFS）[HR＝0.69，95％CI（0.57， 0.85），P＜0.001] in neoadjuvant chemotherapy （NAC）-treated breast cancer patients. However ，there were no significant differences in overall survival （OS），progression-free survival （PFS），objective response rate （ORR）and disease control rate （DCR）in metastatic breast cancer （MBC）patients between 2 groups. In the terms of safety ，nab-PTX increased the incidence of grade 3-4 sensory neuropathy [OR ＝1.89，95％CI（1.36，2.61），P＜0.001] in MBC patients ，and increased the incidence of neutropenia [OR ＝ 1.52，95％CI（1.23，1.88，P＜0.001]，sensory neuropathy [OR ＝ 2.17，95％CI（1.38，3.40），P＜0.001]，rash [OR ＝1.46，95％CI mei1213@163.com （1.18，1.80），P＜0.001] and fatigue [OR ＝1.28，95％CI（1.04， 1.56）， P＝0.02] in NAC -treated breast cancer patients.Pharmacoeconomic studies showed that nab-PTX could improve the quality adjusted lif e years of MBC patients compared with traditional taxanes ，and it was a economical option. CONCLUSIONS：Nab-PTX enhances pCR in NAC-treated breast cancer patients ，but has no significant advantage in the effectiveness of MBC patients ，and increases the occurrence of ADR. Nab-PTX may have a cost-utility advantage over conventional taxanes for MBC.

Effects of Gene Polymorphism on the Increasing of Tacrolimus Blood Concentration Induced by Wuzhi Capsules in Renal Transplantation Patients / 中国药房

OBJECTIVE：To inve stigate the effects of polymorphism of CYP3A4，CYP3A5 and other genes on the increasing of tacrolimus blood concentration by Wuzhi capsules in renal transplantation patients. METHODS ：Totally 194 patients in Han nationality underwent renal transplantation and rece ived outpatient follow-up after surgery were selected from the First Affiliated Hospital of Anhui Medical University during Aug. 2015-Nov. 2018，and then divided into single drug group （107 cases）and combination group （87 cases）according to using of Wuzhi capsules or not. Single drug group was given Tacrolimus capsules 0.1-0.15 mg/kg，po，bid+Mycophenolate mofetil capsule s 0.5-0.75 g，bid or Mycophenolate sodium enteric-coated tablets 360-540 mg，bid+Prednisone acetate tablets 10 mg，qd；combination group was additionally given two Wuzhi capsules ，bid，on the basis of single drug group. Two groups were treated at least 7 d. The clinical data （such as patients ’sex and age ）were collected ，and enzyme amplification immunoassay was used to detect steady-state valley concentration of tacrolimus ，and calculate valley concentration/daily dose （C/D）value. PCR was adopted to detect patient genotyping of CYP3A5 gene rs 4646457，rs15524 and rs776746 locus，CYP3A4 gene rs 4646437，rs2242480 and rs 35599367 locus，ABCB1 gene rs 1128503 locus，ABCC2 gene rs3740066 locus，NR1I2 gene rs 3814055 locus，POR gene rs 1057868 locus，PPARA gene rs 4253728 locus，IL-3 gene rs 181781 locus， IL-10 gene rs 1800896 locus，CTLA4 gene rs 4553808 locus，CYP2C19 gene rs 4244285 and rs 4986893 locus，respectively. The correlation of each factor and tacrolimus C/D value was analyzed by Kruskal-Wallis test or Spearman rank test. Multivariate linear regression was conducted. RESULTS ：In 194 renal transplanation patients ，only wild type at rs 3599367 locus of CYP3A4 gene and rs4253728 locus of PPARA gene were detected ，and each genotype distribution of other genes was consistent with the Hardy-Weinberg equilibrium （P＞0.05）. Single factor analysis and multiple linear regression analysis showed that the combination of Wuzhi capsules and rs 776746 polymorphism of CYP3A5 gene were related to tacrolimus C/D value（P＜0.05）. There was statistical significance in tacrolimus C/D values among different genotypes of CYP3A5 gene in single drug group and combnation group（P＜0.05）. C/D value of GG and AG genotype in single drug group were significantly lower than combination group （P＜ 0.05），while there was no statistical significance in tacrolimus C/D value of AA genotype between 2 groups （P＞0.05）. CONCLUSIONS：Combination of Wuzhi capsules or not and polymorphism of CYP3A5 gene rs 776746 locus are associated with blood concentration of tacrolimus in renal transplantation patients in Han nationality. Combined use of Wuzhi capsules can increase blood concentration of tacrolimus in GG and AG genotype ，but have no significant effect on AA genotype.

Ater-soluble Protein Profiles of Astragalus membranaceus var. mongholicus and A. membranaceus / 中国实验方剂学杂志

Objective::Astragalus membranaceus var. mongholicus and A. membranaceus are medicinal Astragalus, which are closely related and similar in composition, but with unclear medicinal value. Water-soluble protein profiles for A. membranaceus var. mongholicus and A. membranaceus were established to explore the differences between the two kinds of Astragalus Radix. Method::The water-soluble protein components were obtained through water ultrasonic extraction and acetone precipitation. After digested with trypsin, the obtained peptides were analyzed by nano ESI-LC-MS/MS method. Proteome Discovery 1.4 software was used to identify the proteins by comparing with the legume protein database, and the different expression water-soluble proteins were analyzed by the label-free quantitative software SIEVE. Finally, relevant information for common expression proteins, including classification, molecular function, involved biological process and signaling pathway, were analyzed by bioinformatics. Result::There were 920 and 717 specific proteins identified for A. membranaceus var. mongholicus and A. membranaceus, respectively. Totally 472 proteins were found to be co-expressed, in which 21 were differentially expressed, such as PR-10 protein, NDK-1 protein, glutelin A2, and phospholipase D. There were 14 highly expressed proteins in A. membranaceus var. mongholicus and 7 highly expressed proteins in A. membranaceus. Conclusion::There are significant differences in water-soluble protein profiles for two kinds of Astragalus Radix. Specific proteins, differentially expressed proteins and common expressed proteins can provide references for the identification of A. membranaceus var. mongholicus and A. membranaceus. It also can be used to define pharmacological mechanisms and search for drug action targets.

Study on Relationship of CYP3A4，CYP2C8 and CYP3A5 Gene Polymorphism with ADR/Blood Concentration of Hydroxy- chloroquine in Patients with Autoimmune Disease / 中国药房

OBJECTIVE： To study the relationship of CYP3A4， CYP2C8 and CYP3A5 gene polymorphism with ADR/blood concentration of hydroxychloroquine in patients with autoimmune disease （AID）， and to provide reference for individual medication of hydroxychloroquine. METHODS： Totally 77 AID patients，who were treated with hydroxychloroquine （daily dose of 200 mg to 400 mg） for a long-term （＞6 months）， were selected from the department of rheumatology and immunology， the First Affiliated Hospital of Anhui Medical University during Jul. 2017 to Aug. 2018. The information， blood sample and ADR of them were collected. Those patients were divided into normal liver function group， abnormal liver function group， normal renal function group， abnormal renal function group， normal eye group and abnormal eye group according to the site of ADR. The concentration of hydroxychloroquine was determined by HPLC. Genotype of CYP3A4， CYP2C8 and CYP3A5 were detected by MassARRAY microarray system. The differences of hydroxychloroquine-induced ADR in different genotypes were analyzed by χ2 test. The blood concentration difference of hydroxychloroquine in different genotypes were analyzed by independent sample t-test and one-way ANOVA. RESULTS： There was statistical significance in the distribution of CYP3A5 rs4646453 locus between normal renal function group and abnormal renal function group（P＜0.05）. The incidence of CC genotype was higher than that of AA+AC genotype in abnormal renal function group. There was statistical significance in the distribution of CYP2C8 rs10882526 locus between normal liver function group and abnormal liver function group（P＜0.05）. The incidence of allele G was higher than that of allele A in abnormal liver function group， and the incidence of AG genotype was higher than that of AA genotype. There was no significant correlation of the gene polymorphisms of CYP3A4， CYP2C8 and CYP3A5 with blood concentration among 77 AID patients. In subgroup analysis， blood concentration of GT， GG and TT genotypes of CYP2C8 rs10882521 in 58 patients with systemic lupus erythematosus （SLE） were 514.1，735.3 and 785.9 ng/mL， respectively； GG and TT genotypes were significantly higher than GT genotype （P＜0.05）. CONCLUSIONS： AID patients with CYP3A5 rs4646453 CC genotype have a higher incidence of renal dysfunction due to taking hydroxychloroquine； patients with CYP2C8 rs10882526 locus allele G and AG have a relatively high incidence of renal dysfunction due to taking hydroxychloroquine. When SLE patients taking the same dose of hydroxychloroquine， the blood concentration of hydroxychloroquine in patients carrying CYP2C8 rs10882521 GT genotype is lower than other genotypes.

Feasibility of balloon dilation with injectable calcium sulfate cement for tibial plateau fractures / 中国组织工程研究

BACKGROUND: The balloon dilatation technique plays an important role in the correction of kyphosis. A balloon catheter can enlarge the spinal cavity in kyphoplasty followed by injection of bone cement under low pressure to lay a foundation for the stability of the spine. OBJECTIVE: To explore the feasibility of balloon dilation with injectable calcium sulfate cement for tibial plateau fractures and to analyze its clinical effect. METHODS: Twenty-four upper tibia specimens of the adults were taken to make the Schatzker Ⅲ collapsed fracture model of the tibial plateau. Then, these specimens were randomized into three groups: the standard group was subjected to poking reduction with autologus bone grafting and screw internal fixation, the bone cement group was inflated with balloon dilatation followed by calcium sulfate cement injection, and the combined group was treated with fixation with cancellous bone screws and balloon dilatation followed by injection of calcium sulfate cement. The general situation of reduction and fixation was observed and the reduction effect was measured. RESULTS AND CONCLUSION: (1) Fixation effect in the model: All three models were well reset, and the average displacement of the standard group, the simple bone cement group and the bone cement screw group was (-0.22±0.62), (-0.23±0.67), and (-0.20±0.69) mm, respectively. There was no significant difference in the displacement between the three groups (P ＞ 0.05). (2) Clinical application: One case of Schatzker type Ⅱ fracture of the left tibial plateau was treated with cancellous bone screw fixation and balloon dilatation followed by injection of calcium sulfate cement. X-ray results showed calcium sulfate cement was visible at 3 postoperative days. At 30 postoperative days, the patient presented with good joint range of motion, and the calcium sulfate was partially absorbed on the X-ray film. At 60 postoperative days, the patient appeared to have no joint extension disorder, and fracture healing and absorption of calcium sulfate as shown by X-rays. To conclude, the balloon dilation with injectable calcium sulfate cement for the treatment of tibial plateau fracture is feasible and has clinical value.

Network pharmacology of flavonoids in Sophora alopecuroides / 中国中药杂志

The aim of this paper was to investigate the potential pharmacological effect of flavonoids in Sophora alopecuroides by network pharmacology. This study predicted the potential targets of 11 flavonoids of S. alopecuroides with help of reversed pharmacophore matching target recognition service platform (PharmMapper). The pathway information was acquired from DAVID and KEGG databases. Cytoscape software was used to construct the "ingredient-target-pathway" network of flavonoids active components of S. alopecuroides. The flavonoids active components of S. alopecuroides play anti-inflammatory, blood sugar regulating and other pharmacological effects by regulating 62 targets (such as INSR，KDR，MET) and intervening 44 pathways, such as B cell receptor signaling pathway, insulin signaling pathway, neurotrophin signaling pathway, and T cell receptor signaling pathway. In this study, the mechanism of "muti components-multitargets-multiple pathway" of flavonoids was studied. It reflects the multi-components, multi-targets and multiple pathway features of traditional Chinese medicine. Meanwhile, it provides a scientific basis for the elucidation the mechanism of S. alopecuroides as a medicine, and the development and utilization resources of S. alopecuroides.

Effect of exercise on adiponectin in aged obese rats / 中国应用生理学杂志

OBJECTIVE@#To explore effects of exercise on the expression of adiponectin mRNA and protein in visceral adipose tissue, plasma adiponectin concentration, and insulin resistance of aged obese rats.@*METHODS@#Male SD rats age to 21 days old were fed with high-fat diet (fat percentage was 36.3% to 40.0%) for three stages of adolescence, maturity and old age to establish elderly obesity rats model. When the rats aged to 60 weeks old, natural growing elderly rats were randomly divided into control group (C) and aged exercise group (AE), =6; elderly obesity rats were randomly divided into obesity control group (OC) and obesity exercise group (OE), =6. The treadmill grade was 0°, the exercise speed and time were 15 m/min×15 min, 4 groups each time, between consecutive groups the rats had 5 minutes rest, the rats were exercised for 60 minutes every day, five days a week, continuous exercise for 8 weeks. Then, the expressions of adiponectin mRNA and protein in visceral adipose tissue were determined. The concentrations of blood glucose, plasma adiponectin and insulin were measured. Insulin resistance was calculated.@*RESULTS@#Comparison with control group, the expressions of adiponectin mRNA and protein were obviously decreased, the concentration of blood glucose and insulin resistance were significantly increased in obesity control group, while the expressions of adiponectin mRNA and protein were obviously increased. Comparison with obesity control group, the expressions of adiponectin mRNA and protein, the concentration of plasma adiponectin were obviously increased, the concentration of blood glucose and insulin resistance were significantly decreased in obesity exercise group.@*CONCLUSIONS@#Adiponectin mRNA and protein expression in visceral adipose tissue is decreased and accompanied by high blood glucose and insulin resistance in elderly obesity rats. Exercise can increase the adiponectin mRNA and protein expression in visceral adipose tissue, elevate levels of plasma adiponectin, and decrease the level of blood glucose and insulin resistance in elderly obesity rats.

Regulatory Effect of Liuwei Dihuang Pills on Connexin 43 Expression in Hepatocarcinoma CBRH7919 Cells in Vitro / 广州中医药大学学报

Objective To investigate the effect of Liuwei Dihuang Pills (LDP)on the expression of connexin 43 (Cx43) in rat hepatocarcinoma CBRH7919 cells. Methods LDP-containing serum was prepared by serum pharmacological method. The protein expression of Cx43 in CBRH7919 cells was determined by Western blotting method, indirect immuno-fluorescent staining labeled by fluorescein isothiocyanate (FITC)-laser scanning confocal microscope technology and flow cytometry. And the mRNA expression of Cx43 in the hepatoma cells was detected by reverse transcription real-time quantitative polymerase chain reaction(RT-qPCR). Results Compared with the blank serum control group,the protein and mRNA expression levels of Cx43 were increased by volume fraction of 2.5%, 5%, 10% LDP-containing serum (P < 0.05 or P < 0.01). Conclusion LDP play an anti-cancer role through promoting the expression of Cx43 in CBRH7919 cells, altering Cx43 membrane location, and improving the gap junctional intercellular communication(GJIC).

Effect of Serum Containing Rhizoma Chuanxiong on Proliferation and Differentiation of Mouse Embryonic Stem Cells / 广州中医药大学学报

Objective To observe the influence of serum containing Rhizoma Chuanxiong on the proliferation and differentiation of mouse embryos stem cells(ESCs).Methods Mouse ESCs were co-cultured with serum containing Rhizoma Chuanxiong.The proliferation of ESCs was detected by CCK-8 method.The expression level of specific gene beta-myosin heavy chain (β-MHC) in cardiac myoblasts was detected by reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with the blank rat serum group and the blank fetal bovine serum group,the differences of activities of ESCs in serum containing Rhizoma Chuanxiong group were in significant(P ＞0.05) and the expression level of specific gene β-MHC in cardiac myoblasts was increased (P ＜ 0.05).Conclusion Serum containing Rhizoma Chuanxiong can promote the differentiation of ESCs into cardiac myoblasts.

Determination of plasma concentration of mycophenolic acid and mycophenolic acid glucuronide by HPLC / 中国生化药物杂志

Objective To develop an HPLC method for the determination of mycophenolic acid(MPA), mycophenolic acid glucuronide(MPAG) in plasma.Methods The samples were precipitated with zinc sulphate-methanol solution before injection.Carbamazepine was selected as internal standard,ZORBAX XDB C18 (4.6 mm ×250 mm,5 μm) column was used and the flow rate was 1 mL/min.The mobile phase consisted of methanol-acetonitrile-potassium dihydrogen phosphate buffer solution(gradient elution) .The column temperature was 30℃ and the detective wave length was 254 nm.And then the MPA,MPAG concentration of 32 patients in 7-14 days after renal transplantion were determined.Results The assay was linear within 0.2-50μg/mL for MPA, 2.5-500 μg/mL for MPAG(r>0.999).Absolute recovery rates of MPA,MPAG were more than 80%, the recoveries were between 90%-110%.The intra-day and inter-day RSDs were both lower than 10%.Totally 32 cases of renal transplantion patiens were with mycophenolate mofetil at the dose of 1-1.5 g/d,and MPA in plasma was within the range of 0.32-6.19μg/mL,MPAG in plasma was within the range of 9.52-149.25μg/mL.Conclusion The method is accurate, convenient and rapid, which could be used in the quantitative determination of plasma concentration of MPA,MPAG in renal transplantion patients.

Analysis of Related Factors of Leukopenia Induced by Azathioprine in the Treatment of Inflammatory Bowel Disease / 中国药房

OBJECTIVE:To explore the clinical related factors of leucopenia induced by azathioprine in the treatment of inflam-matory bowel disease (IBD). METHODS:Clinical information of 114 IBD patients were collected from our hospital during Jan. 2013-Mar. 2015. Steady concentration of AZA metabolite 6-thioguanine(6-TGNs)in red blood cell was determined by HPLC. The correlation of patient’s gender,age,diseases,AZA daily dose and blood concentration of 6-TGNs with leucopenia induced by AZA were investigated. The optimal critical value of leucopenia could be predicted with ROC curves. RESULTS:Among 114 IBD patients,40 patients suffered from leucopenia(35.1%). There was no statistical significance in the proportion of leucopenia among patients with different age,gender,diseases and AZA daily dose(P>0.05). There was statistical significance in the proportion of leucopenia among patients with different concentrations of 6-TGNs(P291.04 pmol/(8 × 108)RBC. CONCLUSIONS:AZA induced leucopenia may be related to the concentration of 6-TGNs in red blood cell of IBD patients,and high concentration of 6-TGNs is risk factors of leucopenia. Clinicians can provide AZA individual treatment for IBD patient to reduce the occurrence of leucopenia according to routine blood test and the concentra-tion of 6-TGNs.

The proteomics research of 4-amino-2-trifluoromethyl-phenyl retinate on human leukemia K562 cells / 中国药理学通报

Aim To explore the proteomics mechanism of the differentiation induction effect of 4-amino-2-trif-luoromethyl-phenyl retinate(ATPR)on human leukemi-a K562 cells. Methods Human leukemia K562 cells were incubated with the same concentration (1 × 10 - 6 mol·L - 1 ) of ATPR or ATRA for 48 hours. The total cell proteins were collected, purified and digested by trypsin, solid phase extraction, and the peptides were detected by ESI-LC-MS / MS. The difference of the pro-tein expression between the cells treated with ATPR and ATRA was compared by using the Discoverer Pro-teome 1. 2 software, and the molecular function, the biological process and other information of those pro-teins were analyzed based on the DAVID, KEGG, STRING databases. Results 120 specific proteins were identified only in the ATPR group, 143 only in the ATRA group, and 422 other proteins in both groups. Results of DAVID analysis showed that ATPR-induced specific proteins were mainly involved in 39 biological processes of proteins and macromolecules metabolism, protein transport and localization and so on. Results of KEGG analysis revealed that ATPR-in-duced proteins participated in signal pathways, mainly metabolic pathways, PI3K-Akt signal pathway, TGF-beta signal pathway and other pathways in cancer. String protein interaction network analysis displayed that ATPR-induced proteins, like EIF3A, EIF6, RPL3, RPL8, RPL13, RPL7A, RPL21, RPS3, RPS14, NACA, BTF3, NHP2L1, PPP2CA proteins had direct interactions with more than or equal to 10 associated proteins. Conclusion The differentiation induction effect of ATPR on K562 cells might be as-cribed to the ATPR-induced proteins interaction net-work and the specific central proteins it induced, which are involved in the regulation of cell prolifera-tion, differentiation and apoptosis.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca(2+)-CaMKII-CREB pathway / 中国天然药物

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

Management and Maintenance of the Purification Air-conditioning System in PIVAS of Our Hospital / 中国药房

OBJECTIVE:To improve the system of management and maintenance for the purification air-conditioning system in PIVAS,and to further strengthen the management of cleaning environment. METHODS:The cleanness monitoring project of purifi-cation air-conditioning system in PIVAS of our hospital was introduced in terms of temperature and humidity record,pressure differ-ence record,airborne particles detection,settling microbe monitoring report. And the monitoring results were analyzed. RESULTS:The temperature and humidity,pressure difference of clean area in PIVAS of our hospital are both in line with the standard of Phar-macy Intravenous Admixture Quality Management Specification (2010 edition),i.e. temperature at 18-26 ℃,relative humidity of 40%-65%;negative pressure difference between antibiotics,hazardous drug dispensing area and second dressing room are 5-10 Pa. The number of airborne particles (average static particle/m3) at various cleanness degrees in clean area are all in line with the standard of GMP(2010 edition),i.e. maximal allowable number of airborne particles(≥0.5 μm)were 3 520/m3(100 degree);352 000/m3 (10 000 degree);3 520 000/m3 (100 000 degree). The percentage of qualified static settling microbe detection reach 100%in clean area,which is in line with the standard of Settling Microbe Detection Method in Clean Room(Area) of Pharmaceu-tical Industry,i.e. criteria for settling microbe(90 mm)CFU/0.5 h≤1(100 degree);≤3(10 000 degree);≤10(100 000 degree). The percentage of qualified dynamic settling microbe detection is in low level,especially those of dispensing room and secondary dressing room only reaches 80%. CONCLUSIONS:It’s important for effective hospital infection control in PIVAS,the quality im-provement of intravenous injection,the safety guarantee of drug use in patients to further improve standard operation procedure of purification air-conditioning system management and maintenance,and manage and maintain the purification air-conditioning sys-tem completely and scientifically.

3D dynamic research on spatial lengths of functional bundles in knee cruciate ligaments / 医用生物力学

Objective To analyze patterns of functional bundles in anterior and posterior cruciate ligaments during knee joint movement, so as to provide important references for studying injury mechanism of cruciate ligaments and implant reconstruction. Methods Five healthy knee cadavers were elaborately dissected to expose insertions of functional bundles in anterior and posterior ligaments on both the femur and tibia. CT scans and 3D finite element reconstruction with Mimics and ANSYS were conducted at 0°, 30°,60°, 90°, and 120° flexion angle of the knee joint. The center points of insertions and parallel sections of functional bundles defined by the software ANSYS and CATIA were connected to the centerlines, and at five different knee flexion angles, the lengths of centerlines, defined as the bundle lengths, were measured. Results The length of anterior medial bundle (AMB) of anterior cruciate ligament (ACL) increased gradually as the flexion angle grew from 0° to 90°, but slightly decreased at 120° flexion angle; whereas the length of posterior lateral bundle (PLB) of ACL decreased as flexion angle went from 0° to 90° and slightly increased at 120° flexion angle. In posterior cruciate ligament (PCL), both anterior lateral bundle (ALB) and posterior medial bundle (PMB) extended in length as the flexion angle went from 0° to 120°. The change of ACL and PCL bundle’s length was statistically significant (P<0.05). Conclusions ACL bundles functioned in a reciprocal manner and PCL bundles functioned in a complementary manner during knee flexion. Through establishing the finite element model of functional bundles in cruciate ligaments, the actual length of cruciate ligaments could be reflected, which provided a reasonable method for studying the changes of actual length of functional bundles in cruciate ligaments during knee flexion.