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  • Table of Content
      , Volume 41 Issue 9 Previous Issue   
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    Bibliometric Analysis of Literatures Published in Herald of Medicine from 2011 to 2021
    Chen CHEN,Qi WANG,Chengyu ZHANG,Xinyi XU,Ziyan JIN,Bin WU,Ting XU
    Herald of Medicine. 2022, 41 (9): 1251-1260.   DOI: 10.3870/j.issn.1004-0781.2022.09.001
    Abstract   HTML   PDF (3901KB) ( 0 )

    Objective To investigate the dynamic changes of article published in Herald of Medicine in the past ten years through bibliometrics and visual analysis,providing data for authors' submission and the high-quality development of Herald of Medicine. Methods We searched and gathered relevant articles from Chinese Biomedical Literature Database from 2011 to 2021 published in Herald of Medicine.We used bibliometrics method to analyze the annual number of articles published,foundation papers,publication regions,authors,authors' organization,keywords and citations.CiteSpace(5.8.R3) software was used for visualization analysis. Results A total of 5365 articles were included,involving 13 477 authors.The article source covered various districts.The proportion of funded articles was steadily increasing.High-quality author teams were prominent.The degree of cooperation was improved.The articles had a wide range of topics,keeping up with the development trend of the pharmaceutical era. Conclusion The popularity and academic level of Herald of Medicine were steadily increasing,and its academic influence was gradually expanding,making it a first-class academic journal in China and an internationally influential journal.

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    Interpretation of the Consensus Document from Working Groups of European Society of Cardiology on Antithrombotic Therapies in Aortic and Peripheral Arterial Diseases in 2021
    Qinan YIN,Lizhu HAN,Yuan BIAN,Xuefei HUANG,Yang LEI,Yujie SONG,Rongsheng TONG
    Herald of Medicine. 2022, 41 (9): 1264-1269.   DOI: 10.3870/j.issn.1004-0781.2022.09.003
    Abstract   HTML   PDF (1344KB) ( 0 )

    In July 2021,the working groups of European Society of Cardiology(ESC) in aortic and peripheral vascular disease,thrombosis,and cardiovascular drug therapy published a consensus on antithrombotic therapy for aortic and peripheral artery disease.Antithrombotic therapy is the backbone of the best pharmacological treatment for these patients with very high cardiovascular risk.This paper introduced antithrombotic schemes of the carotid artery,vertebral artery and subclavian artery disease,aortic disease,lower limb arterial diseases,and kidney and intestine arterial disease. In addition the antithrombotic plan of patients with peripheral disease who needed oral anticoagulant drugs was analyzed in detail.This paper aimed to provide an update of optimal antithrombotic strategies for patients with aorta and/or peripheral arterial disease.

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    Structure-activity Relationships Between Three Small-molecule Antagonists and C-X-C Chemokine Receptor 4
    Kun WANG,Lu HE,Xinyu LIAO,Xu WANG,Zhengliang SHI,Guang YANG,Yanlin LI
    Herald of Medicine. 2022, 41 (9): 1270-1275.   DOI: 10.3870/j.issn.1004-0781.2022.09.004
    Abstract   HTML   PDF (4189KB) ( 0 )

    Objective To explore the structure-activity relationships and its mechanism of small-molecule antagonists(TN14003,T140,AMD3100) against CXC chemokine receptor 4(CXCR4), and to lay a foundation for developing an efficient anti-osteoarthritic drug. Methods Interaction models between the three small-molecular drugs with CXCR4 were clarified by molecular docking,and their antagonistic efficiency were then verified by cell experiments.The process included the following steps:① the crystal structure of CXCR4 was searched in the protein data bank(PDB) database;② the structures of three small-molecule antagonists were constructed using ChemDraw 15.0 software;③ their interaction were analyzed and assessed antagonistic efficiency by GOLD5.2.2 software;④ Passage 1(P1) human osteoarthritis(OA) chondrocytes were randomly divided into four groups,the A,B and C groups corresponding to TN14003,T140,and AMD3100,respectively; and the D group as a control group.Finally,the contents of matrix metalloprotein 13(MMP-13) secreted by OA chondrocytes in four groups were verified through ELISA to verify their antagonistic efficiency. Results Pharmacophores of these three small-molecule antagonists were obtained and their antagonistic efficiency were TN14003>T140>AMD3100.Cell experiments had also found that MMP-13 content in A,B,C,and D group gradually increased and they had statistically significance comparison between groups(P<0.01),which was consistent with the molecule prediction. Conclusion This study predicted the pharmacophore groups and mechanism of three small molecular drugs by using molecule docking technology.We also found that TN14003 could better reduce the MMP-13 level secreted by OA chondrocytes and it would be expected to become a highly efficient anti-osteoarthritic drug.

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    Effects of Spermine on Attenuating Myocardial Collagen Deposition and Oxidative Stress via Inhibiting SHH Signaling Pathway
    Li WANG,Min LIU
    Herald of Medicine. 2022, 41 (9): 1276-1281.   DOI: 10.3870/j.issn.1004-0781.2022.09.005
    Abstract   HTML   PDF (1682KB) ( 0 )

    Objective To investigate the effects and mechanisms of spermidine on attenuating myocardial collagen deposition and oxidative stress. Methods The collagen deposition and oxidative stress of rats cardiomyocytes H9c2 were induced by 50 mol·L-1 D-galactose.The cells were divided into D-galactose model control group,20 μmol·L-1 and 50 μmol·L-1 spermidine groups,as well as 50 μmol·L-1 spermidine + 3 nmol·L-1 sonic hedgehog(SHH)signaling pathway agonist group(SAG group).Additionally,a vehicle control group was set.The collagen deposition was evaluated by measuring the levels of hydroxyproline and the mRNA levels of collagens.The oxidative stress was evaluated by measuring the level total antioxidant capacity,the activities of antioxidant enzymes,the contents of malondialdehyde and reactive oxygen species.The activity of SHH signaling pathway was evaluated by measuring the expression of node proteins,and the mRNA level of downstream target transforming growth factor(TGF)-β1.The epithelial-mesenchymal transition(EMT) was evaluated by measuring the mRNA levels of EMT markers. Results When compared to the vehicle control,D-galactose significantly(P<0.01) increased the content of hydroxyproline and mRNA levels of collagens,enhanced the expression of SHH signaling pathway node proteins,promoted oxidative stress and EMT in H9c2 cells.When compared to the D-galactose model control group,both 20 μmol·L-1 and 50 μmol·L-1 spermidine significantly(P<0.01) inhibited the collagen deposition,oxidative stress,EMT and SHH signaling pathway in H9c2.When compared to the 50 μmol·L-1 spermidine group,co-treated with SAG alleviated these protective effects of spermidine. Conclusion Spermidine can attenuate D-galactose-induced myocardial collagen deposition and oxidative stress via inhibiting SHH signaling pathway,and thus has the potential application value in alleviating heart aging.

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    Protective Effect and Mechanism of Amygdalin on Renal Fibrosis in Rats
    Xiang LI,Qing LIU,Chen GAO,Hongbing ZHOU,Hong CHANG,Jia WANG,Wanfu BAI,Songli SHI
    Herald of Medicine. 2022, 41 (9): 1282-1288.   DOI: 10.3870/j.issn.1004-0781.2022.09.006
    Abstract   HTML   PDF (2210KB) ( 0 )

    Objective To investigate the effect and its possible mechanism of amygdalin(AMY) on renal fibrosis rats. Methods A total of 60 male SD rats were randomly divided into sham operated group(SDG),model control group(MOD),benazepril hydrochloride tablets group(BHT),and amygdalin low-,medium-,high-dose groups(AMY-L,AMY-M,AMY-H).Renal fibrosis model was prepared by unilateral ureteral obstruction.After 21 days of continuous intragastric administration,the rats were sacrificed,the 24 h urine output was recorded,and the renal viscera coefficients were calculated;Blood urea nitrogen(BUN),serum creatinine(Scr),albumin(ALB),superoxide dismutase(SOD),malondialdehyde(MDA) in serum and the content of SOD,MDA,and hydroxyproline(HYP) in the tissue were detected.Quantitative polymerase chain reaction(qPCR) method was used to detect transforming growth factor β1(TGF-β1),Smad3,Smad7 mRNA expression level in the kidney.The hematoxylin-eosin(HE) and Masson staining was used to observe the histopathological changes in the kidney tissue. Results Compared with the SDG,the urine output was significantly reduced(P<0.01),the SOD activity of serum and tissue was significantly reduced(P<0.01),the renal viscera coefficients,the levels of BUN,Scr,ALB,and the MDA content of serum and tissue,and the HYP content of tissue increased significantly(P<0.01) in the MOD group. The expressions levels of TGF-β1,Smad3 mRNA in the tissue were significantly increased,and Smad7 mRNA was significantly reduced(P<0.01).Compared with the MOD group,the renal interstitial and renal tubular injury were alleviated significantly,the degree of fibrosis was significantly reduced(P<0.01),24-hour urine output was significantly increased(P<0.01),and renal viscera coefficients were significantly reduced(P<0.01) by the AMY,among which the AMY-L has the most significant effect. The BUN,Scr,ALB levels,MDA content of serum and tissue and HYP content were significantly reduced(P<0.01),SOD activity of serum was significantly increased(P<0.01),and the expressions of TGF-β1 and Smad3 mRNA were significantly down-regulated(P<0.01),the expressions of Smad7 mRNA was significantly up-regulated(P<0.01) in the AMY-L group. The Scr and ALB levels were significantly reduced(P<0.01),MDA content of serum and tissue and HYP content were significantly reduced(P<0.01),and SOD activity of tissue was significantly increased(P<0.01) in the AMY-M group. The MDA content of serum and tissue was significantly reduced(P<0.01) in the AMY-H group. Conclusion AMY has a good protective effect on the kidneys of renal fibrosis rats,and it can improve the body's antioxidant capacity.The effect of low dose AMY is better.The mechanism may be through the intervention of TGF-β1/Smad signaling.

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    Effects and Mechanism of Adenanthin on Acute Lung Injury Model in Mice
    Jie SITU,Cheng ZENG
    Herald of Medicine. 2022, 41 (9): 1289-1296.   DOI: 10.3870/j.issn.1004-0781.2022.09.007
    Abstract   HTML   PDF (3274KB) ( 0 )

    Objective To investigate the therapeutic effect and mechanism of adenanthin(Ade) on acute lung injury(ALI). Methods Thirty male C57BL/6 mice were randomly divided into 6 groups: normal control group(n=5 in each group),model control group(10 mg·kg-1 lipopolysaccharide),dexamethasone group(5 mg·kg-1 dexamethasone),and 3 different dose groups of Ade(5,10 and 20 mg·kg-1 Ade). After 6 hours of modeling,therapeutic drugs were given.After 18 hours,mass changes were recorded.The contents of TNF-α,IL-1β and IL-6 in lung tissue homogenate were determined by ELISA.The concentration of total protein,the numbers of macrophages and neutrophils were determined by BCA colorimetry and Ray-Giamsa staining in alveolar lavage fluid,respectively.The histopathological changes of lung were observed by H & E staining in lung tissue.MTT assay was used to detect the effect of different concentrations of Ade on the viability of RAW264.7 cells.AnnexinV-FITC/PI double staining was used to detect the effect of Ade on the apoptosis of RAW 264.7 cells.The expressions of TLR4,MyD88,p-NF-кB,NF-κB,Bcl-2,Bax and β-tubulin were detected by Western blotting in RAW 264.7 cells and lung tissues. Results Ade significantly inhibited the TNF-α,IL-1β and IL-6 generation,and decreased the concentration of total protein as well as the percentage of macrophages and neutrophils in alveolar lavage fluid,and significantly improved the LPS-induced lung injury.Ade had no effect on the viability of RAW264.7 cells in the concentration range from 0 to 12 μmol·L-1.Ade significantly inhibited LPS-induced apoptosis of RAW 264.7 cells and the expression of TLR4,MyD88,p-NF-κB and Bax along with increased expression of Bcl-2.Ade significantly inhibited the expressions of TLR4,MyD88,p-NF-кB,Bax and promoted the expression of Bcl-2 in lung tissues of ALI mice. Conclusion Ade alleviates macrophage apoptosis and improves ALI by inhibiting TLR4/MyD88/p-NF-кB inflammatory pathway.

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    The Protective Effect and Mechanism of Ilex rotunda Thunb. in Rat Model of Small Intestinal Mucosal Injury
    Xinyi LIANG,Ruliu LI,Yiting LIU,Wanxia CHEN,Xinping ZENG,Ling HU
    Herald of Medicine. 2022, 41 (9): 1297-1303.   DOI: 10.3870/j.issn.1004-0781.2022.09.008
    Abstract   HTML   PDF (3942KB) ( 0 )

    Objective To explore the protective effect and mechanisms of Ilex rotunda Thunb.in preventing and treating small intestinal mucosal injury of rat. Methods Male SD rats were randomly divided into each groups as followed: 6 rats in normal control group,and 10 rats in model control group,and 8 or 16 g·kg-1 of Ilex rotunda Thunb. aqueous extract(ILTA)groups,respectively.The test drug groups were given ILTA by gavage.The normal control group and model control group were perfused with equal capacity of water at the same time.An hour later,rats of model control group and the test drug groups were injected subcutaneously with 5 mg·kg-1 indomethacin once daily and rats of normal control group were injected subcutaneously with normal saline daily,which last for 4 days in each group.At fifth day,animals were sacrificed by anesthesia,the gross appearance of intestinal mucosal injury was scored.HE staining was performed for pathological score of intestinal mucosal injury.The D-lactate(effective index of intestinal permeability) in plasma was detected by Amplite fluorescence method.Immunohistochemical(IHC) and Western blotting(WB)was adopted to evaluate the expression of related proteins(ZO-1,Occludin,Claudin-1,E-cadherin,α-catenin,and β-catenin) in the small intestinal mucosal. Results Compared with the normal control group,the gross score and pathological score of the model control group were significantly increased(P< 0.01).Compared with the model control group,ILTA 8 or 16 g·kg-1decreased the gross scores and pathological scores of its small intestinal mucosal injury(P<0.05 or P<0.01). In groups of ILTA 8 and 16 g·kg-1, the expression of ZO-1,Occludin,Claudin-1,E-cadherin,α-catenin,β-catenin and CDX-2 increased comparing to those in the model rats(P<0.05 or P<0.01). In ILTA 8 and 16 g·kg-1 groups,the D-lactate in plasma reduced comparing to that of the model rats(P<0.05 or P<0.01). Conclusion The prevention and the therapeutic effects of the ILTA on indomethacin-induced small intestinal mucosal injury might be related to regulating the expression of tight junction proteins,adherens junction proteins and transcription factors,and alleviating intestinal permeability in order to improve the structure and function of intestinal barrier.

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    Effect of Mahuang Shengma Decoction on Microbial Diversity and Carbohydrate Enzyme Spectrum in Rat Model of Acute Lung Injury
    Mingran LIU,Bo SONG,Lin WANG,Xianglong MENG,Biwang LIU,Li GAO,Tao PENG,Yanmiao MA
    Herald of Medicine. 2022, 41 (9): 1304-1311.   DOI: 10.3870/j.issn.1004-0781.2022.09.009
    Abstract   HTML   PDF (4428KB) ( 0 )

    Objective To investigate the effects of Mahuang Shengma decoction on microbial composition and carbohydrate enzyme(CAZy) function spectrum in rat model of acute lung injury induced by intestinal ischemia-reperfusion based on metagenomic method. Methods A total of 32 Wistar rats were divided into sham group,model control group,Mahuang Shengma decoction group and dexamethasone group(n=8 in each group).The infiltration of macrophages in alveolar lavage fluid of rats was detected,and the morphological changes of lung and intestine tissues were observed by HE staining.Colon contents were collected and DNA was extracted for metagenomic analysis. Results Ephedra shengma decoction could improve bronchiole and alveolar dilatation and congestion and alveolar macrophage infiltration.Metagenomic analysis showed that the abundance of Prevotella,Bacteroides,Lactobacillus and Ruminococcus in Mahuang Shengma decoction group was higher than that in model control group,and it could activate and promote the utilization rate of CAZy.In order to degrade and digest the plant cell wall polysaccharide components in Traditional Chinese Medicine. Conclusion From the perspective of pharmacomicrobiome,increasing the abundance of CAZy or glucosidase activity in certain intestinal microorganisms and enhancing the bioavailability of the active components of Traditional Chinese Medicine may be the mechanism of Mahuang Shengma decoction inhibiting the inflammatory response of intestinal ischemia-reperfusion.

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    Effects of Jinlida Granules on Proliferation and Apoptosis of Mouse Islet β Cells Under High Glucose Environment
    Wei CHEN,Zhiyang WANG,Youjuan FU,Ziwei LIU,Ling YUE
    Herald of Medicine. 2022, 41 (9): 1312-1317.   DOI: 10.3870/j.issn.1004-0781.2022.09.010
    Abstract   HTML   PDF (3175KB) ( 0 )

    Objective To investigate the effects of Jinlida granules on the proliferation and apoptosis of pancreatic islet β cells in mice induced by high glucose. Methods MIN6 cells were divided into normal control(NC) group,Jinlida(JLD) group,high glucose(HG) group and high glucose and JLD(HG+JLD) group.After culture for 48 h,the cells were treated with KRBH medium for 0.5 h as glucose stimulation(2.8 or 16.7 mmol·L-1).The insulin content of supernatant was detected by ELISA;cell proliferation rate was detected by MTT assay;cell apoptosis rate was detected by flow cytometry;and expression of Caspase-3,Bax,Bcl-2 and Smad2/3 protein were detected by Western blotting. Results Compared with 2.8 mmol·L-1 glucose stimulation,the glucose-stimulated insulin secretion(GSIS) of each group increased at 16.7 mmol·L-1 glucose stimulation(all P<0.01).The GSIS of HG+JLD group was higher than that of HG group at 16.7 mmol·L-1 glucose stimulation(P<0.01).Compared with HG group,HG+JLD group had higher proliferation rate(P<0.01),lower in early and late apoptosis rate(all P<0.01),down-regulated Caspase-3-2,Bax protein expression(P<0.01,P<0.05),up-regulated Bcl-2 protein expression(P<0.01) and down-regulated p-Smad2/3 protein expression(P<0.01). Conclusion Under high glucose environment,Jinlida granules can improve insulin secretion,promote the proliferation,regulate apoptosis protein expression,and inhibit apoptosis of mouse pancreatic β cells,which may be related to inhibition of Smad2/3 phosphorylation.

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    Effect of Guishao Formula on Dibutyl Phthalate Induced Ocular Apoptosis of Zebrafish
    Mengyu LI,Yongqing HUA,Tianyi HUANG,Yunfeng ZHENG,Guojun YAN,Jianming CHENG,Xiaolin YUAN
    Herald of Medicine. 2022, 41 (9): 1318-1323.   DOI: 10.3870/j.issn.1004-0781.2022.09.011
    Abstract   HTML   PDF (1626KB) ( 0 )

    Objective To investigate the effect of Guishao formula on ocular apoptosis of zebrafish,to evaluate the relationship between different extraction methods and pharmacological effects, and to explore the possible mechanisms for its anti-ocular apoptosis effect. Methods At 30 hours post fertilization(30 hpf),zebrafish were divided into normal control group and different preparation process groups including Chinese material medicine extract of Guishao formula(ME) group,Chinese material medicine extract alcohol precipitation treatment(MEA) group and Chinese medicine extract powder solution(PS) group.The survival rate of zebrafish was observed at 24 and 48 h after administration.Acridine orange staining was used to investigate the effect of extracts on ocular apoptosis of zebrafish.The 30 hpf zebrafish were divided into normal control group,model control group,and different dose groups(low,medium,high concentration) of ME,MEA and PS.The model control group was given 10 μmol·L-1 dibutyl phthalate(DBP),and each administration group was given 1 μmol·L-1 ginsenoside Rg1 and 10,50,100 μg·mL-1 ME,MEA and PS.After cultured for 18 h,the number of ocular apoptosis in zebrafish was observed.Western blotting was used to detect the expression of apoptosis-related protein Bcl-2,and real-time quantitative PCR was used to explore the change of number in mitochondrial mtDNA copy. Results In 100 μg·mL-1 and lower dose groups of Guishao formula, extracts had no significant effect on the survival rate of zebrafish.1 μmol·L-1 positive drug, ginsenoside Rg1 could significantly reduce the number of apoptotic cells in the eyes of model zebrafish. In high concentrations(100 μg·mL-1) of ME,MEA and PS groups and low,medium concentrations(10,50 μg·mL-1) of MEA and PS groups, the extracts significantly reduced the number of ocular apoptosis in zebrafish(P<0.05).Low and medium concentrations of ME had no significant effect on the number of ocular apoptosis.Guishao formula significantly increased the expression of Bcl-2 protein,and the number of mtDNA copy in mitochondrial in model of zebrafish(P<0.01). Conclusion Guishao formula has protective effect on ocular apoptosis in model of zebrafish.The anti-apoptotic effects of MEA and PS are comparable,and both are better than that of ME.The anti-apoptotic effects of Guishao formula may be related to increasing the expression of Bcl-2 protein and protecting mitochondria in model of zebrafish.

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    Pharmacodynamic Study of Liangfu Pill in the Treatment of Functional Dyspepsia of Stomach-cold Type
    Jiangbo FU,Bei GUI,Kunping LI,Chaoyan YANG,Ling WEI,Jinru LIANG,Jiang MA,Mengyue REN,Yanfen CHEN
    Herald of Medicine. 2022, 41 (9): 1324-1330.   DOI: 10.3870/j.issn.1004-0781.2022.09.012
    Abstract   HTML   PDF (2148KB) ( 0 )

    Objective To investigate the pharmacodynamics and mechanism of action of Liangfu pill in the treatment of functional dyspepsia(FD) of stomach-cold type. Methods The effect of Liangfu pill on gastrointestinal motility was studied by gastrointestinal emptying test in mice.The analgesic effect of Liangfu pill was investigated by acetic acid writhing test and formaldehyde-induced pain test in mice.A total of 72 SPF rats were randomly divided into normal control group,model control group,low-,medium- and high-dose group of Liangfu pill,and mosapride group.Despite of the normal control group,all the rats were constructed with FD model of stomach cold.After the end of modeling,the drugs was given to each group for 7 days.The general conditions of the rats were recorded,two-bottle choice test and the open field test were performed,the gastrointestinal emptying test was performed,the contents of serotonin(5-HT),motilin(MTL),vasoactive intestinal peptide(VIP),substance P(SP) were measured by ELISA,the levels of chromaffin cells in the gastric antrum and colon tissues were observed by transmission electron microscopy,and the expression of 5-HT in the gastric antrum and jejunum tissues was observed by immunohistochemistry(IHC). Results Compared with the normal control group,the Liangfu pill group significantly relieved pain and promoted gastric emptying and small intestine propulsion in mice. Compared with the model control group,the general condition of the Liangfu pill group was significantly better,with a clear upward trend in food intake and water intake,a significant increase in the percentage of two-bottle choice test and the score for the open field test,a significant increase in the content of MTL and SP,a significant decrease in VIP,an increase in chromaffin cells in the gastrointestinal tissue,and a significant increase in the positive expression of 5-HT. Conclusion Liangfu pill has potential therapeutic effects on FD,and the mechanism may be related to the regulation of brain-gut peptide,especially 5-HT levels.

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    Research Progress of Teriparatide in the Treatment of Osteoporosis
    Yingying GU,Wei DONG
    Herald of Medicine. 2022, 41 (9): 1331-1334.   DOI: 10.3870/j.issn.1004-0781.2022.09.013
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    Osteoporosis is a systemic degenerative bone disease caused by imbalance of bone metabolism,which is mainly treated by drugs such as bone resorption inhibitors,bone formation promoters and Traditional Chinese Medicine.In recent years,the number of osteoporosis patients is increasing both in domestic and abroad, and how to improve its therapeutic effect efficiently and quickly without side effects has become the focus of current research.Teriparatide is the only bone formation-promoting drug approved for the treatment of osteoporosis in several countries,and research shows that it has a significant effect on the treatment of osteoporosis,and it is gradually becoming a research hot spot in the direction of increasing bone density and preventing osteoporotic fractures.Therefore,this paper reviewed the results of teriparatide in animal model of glucocorticoid osteoporosis and diabetic osteoporosis. The clinical effects of teriparatide in the treatment of postmenopausal osteoporosis,osteoporosis in the elderly,osteoporosis in men,and glucocorticoid osteoporosis are summarized in order to provide some theoretical basis for the clinical treatment of various primary and secondary osteoporosis.

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    Research Progress of Nanomedicines in Treatment of Bone Metastasis of Malignant Tumors
    Yaze WANG,Mingyang QIN,Rong XU
    Herald of Medicine. 2022, 41 (9): 1335-1340.   DOI: 10.3870/j.issn.1004-0781.2022.09.014
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    Bone metastasis tumor is a secondary tumor caused by the hematogenous metastasis of some primary malignant tumors outside bone tissue.The incidence of bone metastases is higher in breast and prostate cancer.Patients with bone metastases have a worse prognosis than others. They frequently got complications such as bone pain,pathologic fracture,spinal cord compression.Unfortunately,current therapeutic options in most cases are only palliative, although not curative.Most anti-tumor drugs are rarely distributed to the bone and are hence pharmacologically ineffective in treating bone metastases.In order to effectively treat bone metastasis,bone-targeted technology needs to be developed.In recent years,nanomedicines showed a prospective role in cancer treatment.This review summarized the latest advances in bone-targeted nanomedicines for bone metastases based on the current status of treatment of bone metastases,with a view to providing a safer and more effective strategy for the treatment of bone metastases.

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    Research Progress of Population Pharmacokinetic Model of Lamotrigine Based on Nonlinear Mixed Effect Model
    Yilin LIU,Shenghui MEI,Jiping HUO,Zhigang ZHAO
    Herald of Medicine. 2022, 41 (9): 1341-1345.   DOI: 10.3870/j.issn.1004-0781.2022.09.015
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    Objective To summarize the population pharmacokinetic characteristics and influencing factors of lamotrigine(LTG) in different age groups,and to provide a reference basis for the establishment of a more accurate population pharmacokinetic model in the future. Methods Five databases including PubMed,Embase,Web of Science,Cochrane Library,and Science Direct were systematically searched from January 1995 to July 2021.Population pharmacokinetic studies of LTG conducted in human using a nonlinear-mixed effect model(NONMEM) approach were included for a systematic review. Results A total of 20 studies were included in this review.In most studies,the pharmacokinetics of LTG was described as an one-compartment model.The three most common significant covariates that affect LTG clearance include concomitant antiepileptic drugs,body weight and gene polymorphism.There are a few studies on other significant covariates. Conclusion When establishing a new population pharmacokinetic model of LTG,important covariates such as the use of other antiepileptic drugs,body weight and genotypes should be considered.For pregnant women and other special groups,the physiological and pathological characteristics of the special population should be included as covariates to establish the population pharmacokinetic model of the special population.At the same time,internal and external verification should be carried out to increase the universality of the model.

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    Preparation and the Quality Standard of Compound Feiduqing Granules
    Congzi ZHANG,Jinling ZHANG,Guang DU,Weiwu WANG,Qiong JIANG,Songbai XIA,Hui CHEN,Luzhen GAN,Jinjun XU,Dengzheng ZHANG,Bo FU,Zhiwei RAO
    Herald of Medicine. 2022, 41 (9): 1346-1350.   DOI: 10.3870/j.issn.1004-0781.2022.09.016
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    Objective To establish the preparation method and quality standard of compound Feiduqing granules. Methods According to the requirements of small-scale production,30 times the prescription amount of medicinal materials were used to prepare compound Feiduqing granules.The qualitative identification of bupleurum in the prescription was carried out by thin-layer chromatography,and the content of saikosaponin A in the prescription was determined by high performance liquid chromatography. Results The molding ratio of compound Feiduqing granules was 96.31%,and the relevant inspections of the granules are in compliance with the regulations.Characteristic spots could be detected in the thin layer chromatography of bupleurum.Saikosaponin A in 0.06—0.98 mg·mL-1 has a good linear relationship. Conclusion The extraction process of compound Feiduqing granules is reasonable and feasible,and the quality standard of this preparation has been formulated.

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    Determination of Three Anions in Sodium Dihydrogen Phosphate by Ion Chromatography
    Ziyu SONG,Dazhong DING,Lei ZHANG,Longhua YANG,Chengzhang LUAN,Zhao YANG
    Herald of Medicine. 2022, 41 (9): 1351-1353.   DOI: 10.3870/j.issn.1004-0781.2022.09.017
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    Objective To establish a method for simultaneous determination of chloride,nitrate and sulfate in sodium dihydrogen phosphate by ion chromatography(IC). Methods The separation was performed on Thermo ICS-2100 ion chromatograph and potassium hydroxide eluent generator cartridge with gradient elution.The separation column was Thermo Scientific Dionex IonPac AS19 IC analytical column(4 mm×250 mm) with the column temperature at 45 ℃ and the flow rate of 1 mL·min-1.The injection volume was 100 μL. Results When the concentration of chloride ion,nitrate ion and sulfate radical ion were 10.00—400.00 μg·L-1,33.33—1 333.33 μg·L-1 and 50.00—2 000.00 μg·L-1, the linear relationship were good with correlation coefficient of 0.999 2,0.998 8 and 0.999 0, respectively. The average recovery rates of chloride ion,nitrate ion and sulfate radical ion were 101.77%,98.29% and 99.63%,respectively. RSD were 3.64%,4.25% and 2.77%,respectively.The determination results of 6 batches of samples determined by the proposed method were consistent with the regulation of Chinese Pharmacopoeia(2020). Conclusion The method is simple,sensitive and reproducible.The peak patterns of the three components are good and the resolution is high. Therefore, it can be used for the quality assessment of anions in sodium dihydrogen phosphate.

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    Variation Law of Characteristic Components and Optimal Harvest Time of Belladonna by Multi-stage Sampling
    Yanyan FENG,Weizheng XIONG,Lei LI,Li GUO,Junxia GUO
    Herald of Medicine. 2022, 41 (9): 1354-1359.   DOI: 10.3870/j.issn.1004-0781.2022.09.018
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    Objective To investigate the effects of different harvesting time and different parts of autumn planting belladonna in Henan province on the quality of the whole plant. To compare hyoscyamine sulfate and scopoletin content with other parts of belladonna. Methods The high-performance liquid chromatograph(HPLC) method was used to determine the content of hyoscyamine sulfate and scopoletin in belladonna at different harvest time,different parts and different origins.To compare the contribution of each part of autumn planting belladonna in Henan to the two characteristic components of the whole plant.To predict the suitable harvest time of autumn planting belladonna in Henan,and conduct cluster analysis on belladonna from different origins. Results The linear relationships between hyoscyamine sulfate and scopoletin were 0.25-8.00 mg·mL-1 and 18.764-600.44 μg·mL-1,respectively.The average recovery rates were 97.07% and 94.76%.And the RSD values were 1.30% and 1.04%.The content of the two components was the highest in mid-June;the contribution of different parts of autumn planting belladonna in Henan to the two components of the whole plant:leaf>stem>fruit>root;20 samples from different origins can be divided into 4 categories.Among them,the quality of autumn planting belladonna in Henan is better. Conclusion The quality of autumn planting belladonna in Henan is better,and it is the most suitable to be harvested in mid-June.

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    Correlation Between Pathogenic Bacteria Types,Case Characteristics,and Prognosis in Patients with Diabetic Foot Infection
    Jiaqi ZHANG,Xiaorui JIANG,Kai WANG,Chuanchong ZONG,Huiyuan ZHANG,Quan ZHAO
    Herald of Medicine. 2022, 41 (9): 1360-1365.   DOI: 10.3870/j.issn.1004-0781.2022.09.019
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    Objective To analyze the case characteristics of different pathogenic bacteria types of diabetic foot infection(DFI) patients,and to explore the correlation between different pathogenic bacteria types and short-term prognosis. Methods A total of 224 hospitalized DFI patients with pathologic results from January 2017 to June 2021 were selected as the study subjects.General data,laboratory test indicators,ulcer type,severity of foot ulcer,severity of foot infection and prognosis of patients were collected.Patients were divided into gram-positive bacteria(G+ bacteria) infection group(n=97),gram-negative bacteria(G- bacteria) infection group(n=65) and mixed bacteria infection group(n=62) according to the type of pathogenic bacteria,and the case characteristics and prognosis of each group were compared.Multivariate logistic regression was used to analyze the risk factors affecting prognosis. Results Compared with G+infection group,patients with G-infection had significantly higher age.Patients infected with G-bacteria and mixed bacteria had a high proportion of previous use of antibiotics,the proportion of neurotic ulcers was lower and the proportion of mixed and deficient blood groups was significantly higher and the proportion of Wagner grade 3—5 was large.The infection prognosis was biased,and the healing rate was significantly lower,and the unhealed rate was significantly higher and the time in hospital was longer.Logistic regression analysis showed that G-infection,mixed or ischemic ulcer,HbA1c>9% and age>65 years were the risk factors that were closely related to the uncured patients.Wagner grade 3 and above,G-infection,mixed or ischemic ulcers,and HbA1c>9% were risk factors strongly associated with amputation. Conclusion The case characteristics of DFI patients with different pathogenic bacteria types,and the short-term prognosis of G-bacteria and mixed bacteria was poor,the prognostic risk factors included G-infection and case characteristics. In order to improve the prognosis, a comprehensive evaluation of cases for judgment may be pathogens,choose reasonable antimicrobial agents for empiric treatment as soon as possible.

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    Clinical Characteristics of 31 Children with Acute Lymphoblastic Leukemia Accompanied with Acute Pancreatitis Treated with Polyethylene Glycol Conjugated Asparaginase
    Wen YU,Qun HU,Aiguo LIU,Dong LIU,Jianxin DUN,Yaqin WANG,Ai ZHANG,Hao XIONG,Wei TANG,Zhuo WANG,Yan HOU,Pingping XUE
    Herald of Medicine. 2022, 41 (9): 1374-1377.   DOI: 10.3870/j.issn.1004-0781.2022.09.022
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    Objective To investigate the occurrence and clinical characteristics of acute lymphoblastic leukemia(ALL) accompanied with acute pancreatitis(AP) after treatment with polyethylene glycol conjugated asparaginase(PEG-ASP) in children. Methods From January 2016 to October 2021,31 children with ALL accompanied with AP and treated with chemotherapy regimens containing PEG-ASP were collected.The age,gender,chemotherapy regimen,risk stratification,immune type,treatment stage,and cumulative PEG-ASP dosage of the children were collated to analyze their correlation with AP severity.The clinical treatments and outcomes of these children were also described and analyzed. Results The 31 children consisted of 21 males(67.74%) and 10 females(32.26%),with an age range of 3 months to 14 years and 3 months.There were 27 cases of acute B lymphoblastic leukemia and 4 cases of acute T lymphoblastic leukemia.In 15 cases of severe AP,these children had no significant differences in gender,age,chemotherapy regimen,risk stratification,immune type,treatment stage and cumulative PEG-ASP dosage when compared to mild AP(P>0.05). Conclusion Childhood leukemia accompanied with AP usually appears in the remission induction therapy.There are no significant correlations between severity of pancreatitis and gender,age,chemotherapy regimen,risk stratification,immune type,treatment stage and cumulative PEG-ASP dosage.Close monitoring of pancreatic enzymes and imaging changes is helpful for early detection and evaluation of AP,and for guiding the subsequent medical treatment.

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    Establishment of Audit Prescription Rules of Rational Drug Use Management System
    Xiaoyan WU,Haixia ZHANG,Xiaojie BIAN,Jie PENG,Weihong GE
    Herald of Medicine. 2022, 41 (9): 1387-1392.   DOI: 10.3870/j.issn.1004-0781.2022.09.027
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    Objective To discuss the principles of setting drug rules in our hospital’s rational drug use review system,and to introduce the system’s handling process of problematic prescriptions. Methods The problematic prescriptions were divided into different levels according to the degree of risk,and different treatment procedures were set up according to the level.Drug rules were set based on drug instructions,and supplemented by other clinical evidence. Results The rules were established for the rational use of various drugs,according to usage,dosage,indications,contraindications,medications for special populations,interactions,compatibility,and high-risk drugs,medical insurance/hospital management regulations,total parenteral nutrition programs,etc.The problematic prescriptions were labeled into grades 4,5,7 and 8,and the prescriptions adopt different treatment procedures according to the grades.Grade 4 prescriptions were only for reminders without intervention.Grade 5 and 7 prescriptions would be further reviewed by the reviewing pharmacist to confirm whether intervention and grade 8 prescriptions are directly intercepted by the system. Conclusion The information technology is a powerful tool for pharmacists to review prescriptions.Reasonable review procedures and drug use rules are the core content of ensuring the efficient operation of the system.

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    Practice and Establishment of Smart Outpatient Pharmacy
    Jingquan CHEN,Yan LIU
    Herald of Medicine. 2022, 41 (9): 1393-1396.   DOI: 10.3870/j.issn.1004-0781.2022.09.028
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    Objective To improve the dispensing efficiency and accuracy of the outpatient pharmacy and to ensure the safety of patients' medication use. Methods By sorting out the outpatient pharmacy workflow,the problems of traditional outpatient pharmacy in drug storage,prescription dispensing and dispensing at the window were summarized as low informatization, low automation and heavy workload.To solve these problems,we introduced a smart outpatient pharmacy. Results The smart outpatient pharmacy uses intelligent robots,deep learning and other technologies to realize drug storage automation management,automatic replenishment and intelligent window prescription check,which reduces the labor intensity of pharmacists, and improves the accuracy of dispensing to 100% and the efficiency to 2,500 boxes per hour. Conclusion The smart outpatient pharmacy has led to more scientific,standardized and efficient in outpatient pharmacy management and services.

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