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日本科学技术振兴机构数据库(JST)
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    Hongping XIANG,Hong ZHOU,Yong HAN
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    Exosomes are nanosized vesicles which carry nucleic acids,proteins and other substances, and are specialized in intercellular communications and facilitating transfer of substances in vivo.Due to their high biological permeability and biocompatibility but low immunogenicity and toxicity,exosomes represent novel nanosized vehicles for protein encapsulation and target delivery.This paper reviews exosomes as novel protein-loaded drug delivery systems,and mainly focuses on the current researches,isolation methods,drug loading methods,target delivery methods and property evaluation.This review will contribute to promoting the fundamental researches on the usage of exosomes as protein-loaded target delivery system.

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    Hui ZHU,Chunrui LI
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    Multiple myeloma is one of the most common hematology malignancies often with multiple system involvement, poor quality of life and poor prognosis.Although the application of new drugs and autologous hematopoietic stem cell transplantation have significantly improved its prognosis, relapse/refractory multiple myeloma is still a tough problem for clinicians.More strategies are needed to improve the quality of life and prognosis of patients.Emergence of immunotherapy brings hope for patients with multiple myeloma.Monoclonal antibodies, including elotuzumab, daratumumab, pembrolizumab and others, have undergone clinical trials and the results demonstrate that monoclonal antibodies in combination with other drugs show some efficacy for the treatment of multiple myeloma.Adoptive immunotherapy of genetically engineered T cells, including chimeric antigen receptor T cells and TCR-engineered T cells, shows the potential of different targets for the treatment of multiple myeloma with minimal adverse reactions.Dendritic cell vaccines exert anti-multiple myeloma effects by enhancing cytotoxic T cells and can be used in combination with immunomodulators.These immunotherapies may offer more options for patients with multiple myeloma in the future.

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    Xuan GONG,Sisi LIU,Liang YIN,Chuyue TU,Zhinan MEI,Hui XIONG
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    Objective To investigate the antipruritic effect of Tibetan medicine Qingpeng ointment in treating histamine-induced acute itch in mice as well as its possible mechanisms. Methods A total of 42 male C57BL/6 mice were randomly divided into blank control group,model control group,low-,medium- and high-dose Qingpeng ointment groups(0.625 g·kg-1,1.25 g·kg-1 and 2.5 g·kg-1),diphenhydramine group( 10 mg·kg-1).Mice in Qingpeng ointment group and diphenhydramine group,Qingpeng ointmen and diphenhydramine were applied to pically to the neck of mice for 4 consecutive days, respectively, and then all the mice except blank control group were intradermically injected with 500 μg(50 μL) histamine.The scratching times in 30 min after histamine injection was recorded.IL-4 and TSLP mRNA levels in the skin and the levels of IgE,histamine,TNF-α, IFN-γ,IL-1β and IL-4 in serum were detected. Results Compared with model control group, scratching times in mice of low-,medium- and high-close Qingpeng ointment group were significantly lower(P<0.05).TSLP mRNA and IL-4 mRNA levels in the skin,and the levels of IgE,Histamine,TNF-α,IFN-γ,IL-1β and IL-4 in the serum were also significantly lower(P<0.05). Conclusion The topical application of Qingpeng ointment has a dramatic therapeutic effect on histamine-induced acute itch in mice.

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    Na DENG,Jintang WANG
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    Objective To investigate interference of chlorogenic acid(CGA) on TLR2 signal pathway in herpes simplex virus(HSV)-1-induced responses in BV2 microglia. Methods The cellular model was established with BV2 cells stimulated by HSV-1 and then treated with CGA at different concentrations.The mRNA expression of Toll-like receptor(TLR)-2 and Myd88 was assayed by real-time quantitative PCR(RT-PCR),and the protein expression was assayed by Western blotting.IL-6 levels in the serum were tested by ELISA and RT-PCR. Results TLR2,Myd88 and IL-6 were significantly higher in the model control group than in the normal control group(P<0.05).After CGA treatment,TLR2,Myd88,IL-6 were significantly lower than those in the model control group(P<0.05). Conclusion In HSV-1 infected microglia cellular model,CGA inhibits the inflammatory reaction via suppressing TLR2,Myd88,IL-6 in TLR2 signal pathway and inhibiting IL-6 release.

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    Xubo LI,Guangyu JIANG,Xu ZHAO
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    Objective To investigate effect of ligustrazine on expression of TLR7/NF-κB in human THP-1 cells. Methods The THP-1 cells were inoculated in 6 plates with 2×106 per hole.Experiment was divided into blank control group,high-dose,medium-dose and low-dose ligustrazine group.Cell proliferation was determined by MTT method.The cell apoptosis was determined by TUNEL method;mRNA expression of TLR7 and NF-κB was determined by RT-PCR method;the expression of protein of TLR7 and NF-κB was determined by Western blotting. Results Compared with the blank control group,the cell activity was not significantly changed when ligustrazine was less than 2.5 μg·L-1(P>0.05),but significantly changed when ligustrazine was higher than 2.5 μg·L-1(P<0.01).TLR7 and NF-κB mRNA and protein expression of THP-1 cells in high,middle dose group significanlty increased(P<0.01).TLR7 and NF-κB mRNA and protein expression of THP-1 cells in low dose group was not significantly changed(P>0.05). Conclusion Ligustrazine can significantly improve cell apoptosis rate,and its mechanism may be related to the increase of TLR7 and NF-κB gene and protein expression.

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    Jing HE,Min CHEN,Yonggang CHEN,Jinhu WU
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    Objective To study amylase activity and the effect on gastrointestinal motility function in mice during malt germination,and compare the effect of malt with different bud length in promoting digestion to optimize the bud length. Methods The amylase activity in different-length bud of malt was determined by DNS colorimetry.A total of 80 KM mice were randomly divided into ten groups, normal control group, domperidone group (6 mg·kg-1), different-length bud group (0.25,0.50,0.75,1.00,1.25,1.50,1.75,2.00 cm) (2.28 g·kg-1), 8 mice in each group. Small intestinal propelling rate and gastric emptying rate in different-length bud of maltdecoctiongroup were determined by the charcoal propulsion experiment.The content of pepsin and gastrin in serum of mice in all groups were determined by enzyme-linked immunosorbent assay(ELISA). Results With the increase bud length of malt,the amylase activity increased at first and then leveled off.Compared with the normal control group,small intestinal propelling rate and gastric emptying rate were significantly increased in domperidone group(P<0.01).Different-length bud of malt decoction could increasesmall intestinal propelling rate and gastric emptying rate(P<0.01 or P<0.05),and the effect of malt was the strongest with bud length of 0.75 cm.The contents of serum pepsin and gastrin were increased in all the malt groups without obvious regularity. Conclusion Different-length bud of malt can enhance gastrointestinal motility function,and it’s most obvious with the bud length of malt reaching 0.75 cm.It is suggested that the sprout bud length of malt should be from 0.75cm to 1.25cm.

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    Xiaojun PANG,Ling GAO
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    Objective To investigate effect of water-soluble and low-relative molecular-mass part of Angelica sinensis on hemorheology and hemodynamics of sepsis rat model. Methods ts were randomly divide into blank control group,model control group,hydrocortisone group(or aspirin group),high-,low-dose of Angelica sinensi group(water-soluble and low-relative molecular-mass part of Angelica sinensis 1.8,0.9 mL·kg-1)(n=10).Rats were given 1 mg·kg-1 of LPS to prepare sepsismodel.Carotid artery intubation was performed to record mean arterial pressure(MAP).Heart rate(HR),left ventricular pressure(LVDP),maximum increasing/decreasing rate of left intraventricular pressure(±dp/dtmax) was determined through intracardiac catheterization.Whole blood viscosity,activated partial thromboplastin time(APTT),prothrombin time (PT) and fibrin degradation products (PDP) were determined from blood of carotid artery/vein. Results As compared with model control group,MAP,LVDP,±dp/dtmax and HR were significantly increased in high-,low-dose of Angelica sinensi group(P<0.01 or P<0.05).Whole blood viscosity,plasma viscosity,APTT,PT and FDP were significantly decreased(P<0.01). Conclusion Water-soluble and low-relative molecular-mass part of Angelica sinensis can improve hemorheology and hemodynamics of sepsis rat model.

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    Bin LI,Lin HUANG,Jianguo ZHAO,Jian RUAN
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    Objective To explore the effect of methimazole combined with rehmannia glutinosaon thyroid hormone levels iodothyronine deiodinases in mice with Graves' diseases(GD). Methods Injection with sinistral thyroxine sodium to establish GD mouse model.After the model established,the mice were divided into model control group,methimazole group and methimazole combined with rehmannia glutinosaon group, 12 mice in blank control group.The methimazole group and themethimazole combined with rehmannia glutinosaon group were respectively treated with methimazole and themethimazole combined with rehmannia glutinosaon,and then the body weight and food intake were measure.After treatment,the heart rate,and the levels of total triiodothyronine(T3),free triiodothyronine(FT3),thyroxine(T4),free thyroxine(FT4),and the activity of type Ⅰ deiodinases(ID1),type Ⅱ deiodinases(ID2),and type Ⅲ deiodinases (ID3) in mice were detected. Results Compared with the blank control group,the weight and the activity of ID3 in the model control group were significantly reduced(P<0.05),and the levels of T3,T4,FT3,FT4,and the activity of ID1,food intake,and heart rate were significantly increased(P<0.05).Compared with the methimazole group,the levels of T3,T4,FT3,FT4,the activity of ID1 were significantly decreased in the methimazole combined with rehmannia glutinosaon group,the activity of ID3 was significantly increased(P<0.05).There was no significant difference in the activity of ID2 between the two treatment groups(P>0.05).But compared with model control group,the activity of ID2 in two treated group were significantly decreased(P<0.05). Conclusion The methimazole combined with rehmannia glutinosaon effectively changes the activity of iodine enzyme,and decreases the level of thyroid hormone.The therapeutic effect of methimazole combined with rehmannia glutinosaon in GD is significantly better than that of the methimazole.

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    Xue TIAN,Baili ZHOU
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    Objective To investigate effects of erythropoietin(EPO) on mitochondrial respiratory chain in rats with hypoxia injury. Methods The rats were divided into EPO group,model control group and normal control group.Mice in the EPO group were introperitoneally injected with 3000 U·kg-1 EPO.Model control group and normal control group were introperitoneally injected with equal volume of 0.9% sodium chloride soution.Acute myocardial ischemia and hypoxia was induced by 85 mg·kg-1isoproterenol hydrochloride,acute poisoning induced by 400 mg·kg-1 nitrite and hypoxia and anoxia induced by simulation of condition at altitude of 5000 m.Rats’ survival time was recorded.Activity of ATP ase and mitochondrial respiratory chain complex enzyme Ⅰ,Ⅱ,Ⅲ were detected by ATPase detection kit and mitochondrial respiratory chain complex enzyme detection kit,respectively. Results EPO significanlty prolonged survival time of isoproterenol hydrochloride-induced myocardial anoxia rats,sodium nitrite-induced acute poisoning rats and anoxia rats(P<0.05),and increased activity of ATPase,enzyme Ⅰ,Ⅱ,Ⅲ and Ⅳ in mitochondrial respiratory chain complex(P<0.05). Conclusion EPO can protect hypoxic injury by affecting the mitochondrial respiratory chain enzymes.

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    Shan GONG,Longfei WANG,Guolong YU
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    Incidence rate of depression and/or anxiety is high in patients with cardiovascular disease(CVD).Depression and anxiety increased risks of adverse cardiovascular events including all-cause mortality and cardiovascular disease mortality in patients with CVD.There were significant differences in the safety and effectiveness in different types of antidepressant drugs used in different types of CVD patients.This paper,based on recent clinical researches about antidepressant and anxiolytic drugs in patients with hypertension,coronary heart disease,arrhythmia,chronic heart failure,focus on the benefits and risks of the new antidepressant and anxiolytic drugs commonly used in patients with CVD,and reviews the clinical curative effect,drug adverse reactions and interaction of commonly used antidepressant and anxiolytic drugs.The purpose is to help clinicians correctly choose antidepressant and anxiolytic drugs for patients with CVD combined with depression and/or anxiety.

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    Zilei GUO,Yong LIN
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    Objective To study clinical application and safety of quetiapine fumarate in treating Alzheimer’s disease (AD). Methods A total of 74 patients with AD were randomly divided into treatment group(n=48)and control group(n=26).Patients in the control group were given 5 mg·d-1 of donepezil chloride,patients in the treatment group were given 5 mg·d-1 of donepezil chloride and 12.5 mg·d-1 of quetiapine fumarate.Before and 1,2,4,8 and 12 weeks after the treatment,the patients were evaluated by mini-mental state examination(MMSE),the brief psychiatric rating scale(BPRS),neuropsychiatric inventory(NPI),NPI distress factor and activity of daily life(ADL). Results After 1 week of treatment,total NPI score of treatment group and control group was(72.830±10.45) and(78.057±10.97),respectively;NPI distress factor was(30.532±5.82) and(34.208±6.50),respectively(all P<0.05).After 4 weeks of treatment,BPRS scores of treatment group and control group was(30.277±6.43) and(35.01±7.38),respectively(P<0.05).After 8 weeks of treatment,NPI distress factor of treatment group and control group was(23.021±5.74) and(28.618±6.08)(P<0.05).After 12 weeks,MMSE score of treatment group and control group was(7.83±3.02) and(7.116±2.67),which was increased compared with that before treatment(all P>0.05). Conclusion Short-term use of quetiapine fumarate can reduce anguish of AD tender,and relieve psychological and behavioral symptoms of AD patients,and may have positive effects on cognitive function.

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    Jiangen SHEN,Yong LIN,Yu’e FEI,Zhengping PU,Qingfeng WU
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    Objective To discuss the long-term efficacy of quetiapine combined with donepezil on Alzheimer’s disease(AD) with behavioral and psychological symptoms. Methods A total of 122 AD patients with behavioral and psychological symptoms were randomly divided into control group and treatment group(n=61).Patients in the treatment group were given 25-300 mg·d-1 of quetiapine combined with 5 mg·d-1 of donepezil.Patients in the control group were given 5-10 mg·d-1 of olanzapine combined with 5 mg·d-1 of donepezil.The observation lasted 52 weeks for each group.The activities of daily living(ADL),mini-mental state examination(MMSE),neuropsychiatric inventory(NPI,including distress factor) and the brief psychiatric rating scale(BPRS) were used to assess patients’ cognitive function,daily life ability and mental status before treatment,at the 16th and 52nd weekend after treatment. Results The NPI scores,distress factor scores of NPI,BPRS scores in both groups after treatment were significantly lower than those before treatment(all P<0.05);The MMSE score of both groups were significantly increased after treatment(P<0.05).The total score of NPI,NPI distress score and BPRS score in the treatment group were significantly lower than those in the control group at the end of the 52nd week after treatment,and the MMSE score was significantly higher than that in the control group(P<0.05). Conclusion Donepezil combined with olanzapine and donepezil combined with quetiapine could improve AD patients’ behavioral and psychiatric symptoms,and long-term efficacy of donepezil combined with quetiapine is better than that of donepezil combined with olanzapine.

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    Qin ZHOU,Runfeng YANG,Sha LI,Yan LI
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    Objective To investigate preventive recurrence effect of GnRH-a on multiple hysteromyoma after laparoscopic myomectomy. Methods A total of 148 patients of multiple hysteromyoma were randomly divided into control group (n=79)and treatment group(n=69). Patients were given laparoscopic myomectomy ,and patients in the treatment group were given 3.75 mg of goserelin acetate,triptorelin or leuprorelin for 3 to 6 times with an 28 d interval. Therapeutic effect was followed for 2 years and recurrence rate was compared between two groups. Results The uterine volume was significantly smaller in treatment group than control group (P<0.05) at 12th, 18th and 24 th month after laparoscopic myomectomy(P<0.05). Recurrence rate was significantly lower in treatment group than control group at 18th and 24th months after laparoscopic myomectomy (P<0.05). Conclusion GnRH-a treatment is effective for reducing recurrence rate in multiple hysteromyoma patients after laparoscopic myomectomy.

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    Wei CHEN,Jing GAO,Hui ZHU,Shiliang LIU,Jianbin CHEN
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    Objective To compare with efficacy of 30% verteporfin photodynamic therapy(PDT)combined with spironolactone vs.the half dose verteporfin PDT on chronic central serous retinopathy(CSC). Methods A total of 27 cases of chronic CSC were randomly divided into two groups: treatment group,13 cases with 15 eyes treated by oral spironolactone combined with 30% verteporfin PDT;control group,14 patients with 17 eyes treated by 50% verteporfin PDT.In about 2 months and 6 months after PDT treatment,eyes were detected by optical coherence tomography(OCT) imaging and best corrected visual acuity(BCVA) was determined.Statistical comparison was performed in BCVA,central macular thickness(CMT),subfoveal choroidal thickness(SFCT),subretinal fluid(SRF) absorptionand the recurrence rate between the two groups at the corresponding time point. Results The comparison of BCVA,CMT,SFCT and SRF absorption and recurrence rates at all time points between the two groups showed no statistically significant differences(P>0.05).The subretinal fluid absorption in treatment group and control group were 12 eyes and 15 eyes,respectively.The difference was statistically significant(P<0.01) when BCVA,CMT and SFCT were compared with baseline 6 months after treatment in each group.The changes of BCVA in treatment group were greater than those in control group,indicating faster visual improvement. Conclusion Spironolactone combined with 30% vitipofen photodynamic therapy and half dose verteporfin photodynamic therapy for chronic CSC has similar good effect.

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    Tongshuai LI,Wanpu WANG,Tingfu DU,Shuaiyao LU,Tianxing CHEN,Kaili MA
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    Objective Parkinson’s disease is a degenerative disease of the central nervous system.Despite the rapid development of Parkinson’s desease research, traditional drug therapy can only alleviate the symptoms, but not prevent the disease from progressing.On the other side, surgical treatments are relatively dangerous and have side effects.Bone marrow mesenchymal stem cell transplantation treatment of Parkinson’s disease has become one of the main research topics in this field, because bone marrow mesenchymal stem cells not only have the ability to diversify and self-renewal ability, but also can be used as a gene carrier to treat Parkinson’s desease.It is one of the hotspots in neurobiology research which has broad application prospects.This paper reviews the progress of bone marrow mesenchymal stem cell transplantation in the treatment of Parkinson’s disease.

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    Genghuan WANG,Heping SHEN,Chengsheng JIN,Xuan HUANG,Xiaohong JIANG,Zhengmin CHU
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    Objective To explore quality of the podophyllotoxin conjugated stearic acid grafted chitosan oligosaccharide micelles(PPT-CSO-SA) and the preparation process. Methods Stearic acid grafted chitosan oligosaccharide(CSO-SA) was synthesized by the EDC-mediated coupling reaction between carboxyl group of stearic acid(SA) and amine groupsof chitosan oligosaccharide(CSO).The substitution degree of amino groups were determined by TNBS method.PPT-CSO-SA was prepared using a dialysis method.The quality of PPT-CSO-SA through micellar size and the zeta potential, the drug encapsulation efficiency, drug release profiles was evaluated . Results PPT-CSO-SA size was from 30.8 nm to 48.3 nm.The micellar size and the zeta potential increased with increasing charged amounts of drug.The drug encapsulation efficiency could reach a higher level.The highest drug entrapment efficiency could reach 69.31% when the drug feeding ratio was 10%.The cumulative release percentage of PPT from micelles enhanced with decreasing PPT content in the micelles. Conclusion PPT-CSO-SA can be prepared in a simple way and has a good quality.

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    Tianqian JIA,Mei WANG,Chunli CUI,Xinghuan LI,Li REN,Yajun SHI,Jing SUN
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    Objective To established fingerprint of compound Danshen and measure five active components in compound Danshen tables and compound Danshen dripping pills. Methods Acquity ODS C18(50 mm × 2.6 mm,1.7 μm) column was used.The mobile phase was 0.02% phosphoric acid of 80% acetonitrile-water containing 0.02% phosphoric acid with gradient elution mode at a flow rate of 0.42 mL·min-1.The column temperature was 40 ℃.The detection wavelength was 203 nm. Results Danshinolic acid B had good linear relationship when the sample size was 13-1300 μg(r=0.9995),and the average recoveries of dripping pills and tablets were 97.76% and 99.13%,RSD were 1.72% and 1.74%,respectively(n=6).Notoginsenoside R1 had good linear relationship when the sample size was 10-200 μg(r=0.9992),the average recoveries of dropping pills and tablets were 95.83% and 97.57%,RSD were 1.91% and 1.75%,respectively(n=6).Ginsenoside Rg1 had good linear relationship when the sample size was 22-220 μg(r=0.9999),and the average recoveries of dripping pills and tablets were 97.33% and 96.45%,respectively,and RSD were 1.13% and 2.28%,respectively(n=6).Ginsenoside Rb1 had good linear relationship when the sample size was 12.2-244 μg(r=0.9999),and the average recoveries of dripping pills and tablets were 98.00% and 98.78%,respectively,and RSD was 1.47% and 2.03%,respectively(n=6).Tanshinone IIA had good linear relationship when the sample size was 11.2-112 μg(r=0.9995),and the average recovery of tablets was 97.48%, and RSD was 1.69%(n=6)。The similarity of 5 batches of compound Danshen tablets and dripping pills were in the range of 0.913-0.982 and 0.907-0.989,respectively. Conclusion A method for the determination of the content of compound Danshen tablet and dropping pills is established.The method is efficient,reproducible,stable,and can provide valuable information for the quality control of the two preparations.

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    Xuewei YU,Rongmin DING,Zhiyuan WU
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    Objective To establish a content determination method of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, and rosmarinic acid in Yinpujiedu tablets by HPLC. Methods A ZORBAX SB-C18 chromatographic column(250 mm×4.6 mm,5 μm) was used;mobile phase was acetonitrile(A)-0.8% phosphoric acid solution(B),the eluting gradient was as follows: 0-10 min, 5%A →10%A;>10-20 min,10%A;>20-30 min, 10%A →20%A;>30-45 min, 20%A → 30%A;flow rate was 1.0 mL·min-1;column temperature was 35 ℃, and wavelength was 327 nm. Results Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, and rosmarinic acid samples were in the ranges of 0.203-4.06, 0.328-6.56, 0.318-6.36, 0.219-4.38, 0.122-2.44, 0.239-4.78, 0.179-3.58 μg, respectively, and linearly corresponds well with the AUC of peaks;The average recovery rates(n=6) were 99.04%, 100.10%, 101.99%, 101.65%, 99.82%, 100.13% and 100.25%, respectively,with RSD were 1.07%,1.24%,0.60%,0.97%,0.89%,1.67% and 0.69%, respectively. Conclusion The method determines seven components simultaneously with high accuracy and reproducibility, and can be used for quality control of Yinpujiedu tablets.

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    Ting LIU,Kaiyong HE,Jing LAN,Danqing SONG
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    Objective To establish an RP-HPLC method forsimultaneous determination of ferulic acid,calycosin-7-glucosid,liquiritin and glycyrrhizic acid in Codonopsis Radix Colla Corii Asini Pill(CCP). Methods The experiments were performed on a Inert Sustain C18 column(4.6 mm×250 mm,5 μm) with a gradient mobile phase of 0.5% formic acid(A) and acetonitrile(B).The detection wavelength was 237 nm,the column temperature was 30 ℃,the flow rate was 1.0 mL·min-1 and the injection volume was 20 μL. Results The 4 constituents showed a good linear relationship within the range of of 1.25-62.47 μg·mL-1(r=1.0000) for ferulic acid,4.84-241.85 μg·mL-1(r=1.0000) for calycosin-7-glucosid,1.95-97.66 μg·mL-1(r=0.9999) for liquiritin,18.82-941.16 μg·mL-1(r=0.9999) for glycyrrhizic acid.The average recovery was 103.5%,88.73%,93.77%,100.2% with the RSDs of 5.9%,9.5%,7.8% and 9.5%(n=6),respectively. Conclusion The experiment establishes an RP-HPLC method for simultaneous determination of ferulic acid,calycosin-7-glucosid,liquiritin and glycyrrhizic acid in CCP.It also provides a simple and effective methodto further revise the quality standard of CCP.

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    Yin HUANG,Cheng CHEN,Jiao YANG,Yong YANG
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    Objective To explore the relationship between intrapulmonary concentration and blood concentration of polymyxin in patients with ventilator-associated pneumonia. Methods The pharmacological effects of polymyxins were reviewed.Detection and calculation methods for the polymyxin concentration in lung tissue were introduced.The intrapulmonary concentration,blood concentration and lung tissue penetration of polymyxins in patients with ventilator-associated pneumonia were summarized.The relationship between intrapulmonary concentration and blood concentration was analyzed. Results When polymyxin was administered intravenously,the concentration was significantly lower in epithelial lining fluid than in the blood,or even below the detection limit; however,when polymyxin was administered by inhalation,the drug concentration in the lung was increased significantly,and the drug concentration in epithelial lining fluid could reach 100 to 1000 times over blood concentration.The greater the dose of intravenous infusion or aerosol inhalation was administered,the higher the concentration of polymyxins in the blood and lung tissue. Conclusion In the treatment of ventilator-associated pneumonia,more attention should be paid to the intrapulmonary concentration of polymyxins in patients,and adjustment of the administration route can help make the clinical use of polymyxins more effective.

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    Hongqiong ZHAO,Xiaojiang TIAN,Xuewen TANG,Zhu YANG
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    To mine the adverse drug reaction signals of methimazole(MMI) and propylthiouracil(PTU), and evaluate the security to provide reference for clinical medication. Methods The reporting odds ratio(ROR) was used to mine the risk signals from the data in the Open FDA of US Food and Drug Administration(FDA) during 2004-2016, and analyze the impact of age, gender and other effects on the signal. Results MMI and PTU as the primary suspect drug ADE were 5367 copies and 2133 copies, and the relevant signals were 536,1053.The top five ADE signals of system organ class were blood and lymphatic system disorders, general disorders and administration site conditions, hepatobiliary disorders, endocrine disorders, investigations.The high intensity risk signals include acute hepatic failure(PTU,ROR=15.73;MMI,ROR=2.39), agranulocytosis(PTU,ROR=24.1;MMI,ROR=24.6), ANCA positive vasculitis(PTU,ROR=283.10;MM,ROR=54.60), aplasia cutis congenita(PTU,ROR=475.8;MMI,ROR=374.2), etc. Conclusion PTU has the risks of severe renal and hepatic damages, vasculitis and blood system damage, etc;MMI has risks of bile duct and skin injuries, drug exposure during pregnancy, etc.PTU is recommended as the first-line choice for pregnancy with hyperthyroidism.Adolescent and skin sensitive patients using MMI should be strictly observed with caution.

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    Zhou LIU,Weiguo DONG,Zhui YU,Liang ZHANG,Lan YAO,Xiaoshu ZUO,Guo HOU,Yanan LIU
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    Objective To systematically evaluate the efficacy of Xuebijing injection in treating acute paraquat poisoning(APQ). Methods The randomized controlled trials(RCTs) about Xuebijing injection for treatment of APQ was searched in PubMed,The Cochrane Library,EMbase,CNKI,CBM and WanFang Database from the date of their establishment to Oct 15th,2017.Two researchers independently screened the literature according to the inclusion and exclusion criteria,and extracted the data.Then,Meta-analysis was performed using RevMan 5.3 software. Results A total of 20 RCTs(1240 patients) were included.The results of meta-analysis showed that compared with control groups,Xuebijing groups had lower ALT [MD=-115.53,95%CI: -182.50,-48.56],lower Crea [MD=-180.31,95%CI(-240.48,-120.14)],lower WBC [MD=-6.89,95%CI(-9.54,-4.24)],lower CRP [MD=-7.65,95%CI(-8.75,-6.55)],and higher SpO2[MD=17.65,95%CI(13.45,21.85)],meanwhile recent and long-term survival rate was much higher [RR=1.42,95%CI(1.30,1.55)].However,there were no significant statistical differences in PaO2,PaCO2 and the incidence of multiple organ dysfunction syndrome(MODS). Conclusion Xuebijing injection can protect APQ patients kidney and liver function,reduce inflammatory response,improve oxygenation level as well as recent and long-term survival rate.

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    Lian TANG
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    Objective To analyze the role of clinical pharmacists in the management of antimicrobial drugs in the United States,and to provide reference for antimicrobial drug management in China. Methods On the basis of the 6 months of clinical pharmacist training at the University of Illinois Medical Center at Chicago,one case was taken as example to analyze the role of clinical pharmacists in the management of antimicrobial drugs. Results In the United States,clinical pharmacists can prescribe initial or adjusted doses,participate in the management of the use of restricted antimicrobial drugs.Clinical pharmacists have played an important role in the individual vancomycin administration,antimicrobial drug regimes adjustment,drug optimization,monitoring adverse effects and treatment duration.In addition,anti-infection clinical pharmacists also participate in antimicrobial stewardship,such as prescription review,feedback and intervention,the establishment and updating of infection and antimicrobial agents guidelines,data support and drug optimization,etc. Conclusion The work of clinical pharmacists in the management of antimicrobial drugs in the United States is a meaningful guidance for our antimicrobial drug management.

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    Mingyu MENG,Dongmei YE,Jiaxi XI,Huijing SUN
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    Objective To investigate pharmaceutical care of clinical pharmacist in antifungal drug treatment of disseminated histoplasmosis. Methods One clinical pharmacist participated in drug therapy process for a patient with disseminated histoplasmosis.The clinical pharmacist provided pharmaceutical care in following aspects: assisting doctor to develop and optimize treatment strategies of antifungal drugs,providing pharmaceutical monitoring,dealing with adverse drug reaction and medication education,etc.Amphotericin B liposome was suggested by the clinical pharmacist instead of itraconzole to the patient,who was seriously ill with kidney injury and had been treated with itraconzole for 4 days without good curative effect.During the treatment of amphotericin B liposome,the adverse effects were noted such as increased serum creatinine levels,peripheral neuropathy and hypokalemia.Proper hydration,Neurotrophic and daily oral potassium supplement were suggested. Results The physicians adopted the suggestions of clinical pharmacists.After 14 days of systematic antifungal treatment,the patient’s condition was controlled. Conclusion The pharmaceutical practice for medication management of antifungal drug treatment of disseminated histoplasmosis by clinical pharmacists is proper and effective,and can help strengthen management of application of antibiotics in the special patients.

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    Mengxian ZHANG,Ling GUI,Dong LIU,Na HAN
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    Objective To explore the method for the training of oncological clinical pharmacist, and improve the teaching quality of clinical pharmacist. Methods Lecture-based learning(LBL) and Problem-based learning(PBL) teaching methods were used in teaching of theoretical knowledge and clinical skill during the training process in clinical pharmacist training base in our hospital. Standardized teaching mode was explored and established. Results LBL-PBL teaching mode could not only improve the students’ clinical knowledge and practical skill, but also enhance their learning enthusiasm. Conclusion An integrated teaching mode of LBL and PBL is feasible and effective for oncological clinical pharmacist training.

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    Shuyong FU,Yue YANG,Jinran YU
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    Objective To compare the laws and regulations on the modification of drug instructions between China and the United States of America, and to put forward some laws and regulations to improve the drug instructions in China. Methods The reasons why our enterprises are reluctant to modify the drug instructions in time were analysed by using game theory and other economic methods. Results Due to the lack of explicit and compulsory drug instruction modification procedures in our country''s relevant laws and regulations, enterprises are reluctant to modify the drug instructions based on cost.However, the legal revision procedure of the drug instructions in the United States of America is relatively clear and complete, and the pharmaceutical enterprises will take the initiative to modify the drug instructions and avoid the relevant punishment. Conclusion The drug regulatory departments in China should improve the relevant laws and regulations, formulate specific operational drug instructions to modify the program, and reduce the cost of enterprises to take the initiative to modify the drug instructions, and increase penalties for not actively modifying the behavior of drug instructions, and promot the pharmaceutical companies to timely and actively modify instructions.