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In vivo pharmacokinetics of silymarin phospholipid complex microporous osmotic pump-controlled release tablets in beagle dogs and evaluation of in vitro-in vivo correlation
ZENG Qiping, YANG Lina, LIU Jianqing, SONG Hongtao
In Press  doi: 10.12206/j.issn.2097-2024.202206052
Abstract(11) HTML(7) PDF (1181KB)(1)
  Objective  To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets(SM-PC MPOP).  Methods  The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon(30 mg/kg). The concentration of silybin in plasma was determined by HPLC and the data were processed by software.   Results  The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:(3.2±0.4)and(0.9±0.1)h, Cmax:(0.298 6±0.068 9)and(0.629 9±0.076 5)μg/ml, AUC0→24:(2.996 8±0.583 3)and(2.268 9±0.432 8)h·μg /ml. The relative bioavailability of SM-PC MPOP was(162.21 ± 30.82)%.   Conclusion  SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine(r = 0.839 0).
Effects of metformin hydrochloride tablets on clinical efficacy and number of dominant follicles in polycystic ovary syndrome
LI Hui, TANG Huaiyun, GUAN Huijuan, ZHANG Shuai
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202208080
Abstract(1) HTML(1) PDF (855KB)(0)
  Objective  To explore the effect of metformin hydrochloride tablets on the clinical efficacy, number of dominant follicles and ovarian volume of polycystic ovary syndrome.   Methods  150 patients diagnosed with polycystic ovary syndrome who were diagnosed and treated in our hospital from January 2019 to March 2021 were selected .The patients were divided into observation group and control group by random number table. The control group was treated with letrozole + gonadotropin, and the observation group was treated with letrozole + gonadotropin + hydrochloric acid + Metformin tablets. The clinical efficacy, endometrial thickness, number of high-quality follicles, sex hormone levels, blood lipid levels, and adverse reactions were compared between the two groups.   Results  ① The effective rate of treatment in the observation group was 90.67%, which was significantly higher than that in the control group, 78.67% (P<0.05). ② After treatment, the endometrial thickness of the observation group was lower than that of the control group, and the number of high-quality follicles was more than that of the control group. (P<0.05). ③ After treatment, the levels of Luteinizing Hormone-LH, Follicle Stimulating Hormone-FSH and Testosterone (T) in the observation group were lower than those in the control group (P<0.05). ④ After treatment, the total cholesterol (TC) and triglyceride (TG) in the observation group were lower than those in the control group (P<0.05). ⑤ The incidence of adverse reactions in the observation group was 8.00%, which was significantly lower than 20.00% in the control group (P<0.05).   Conclusion  Letrozole + gonadotropin + metformin hydrochloride tablets could significantly improve the sex hormone and blood lipid levels in patients with polycystic ovary syndrome, relieve the symptoms of the patients, and improve their uterine condition, which had a good clinical effect.
Exploration on the potential therapeutic mechanism of artemisinin in polycystic ovary syndrome based on network pharmacology and molecular docking technology
YU Weili, WEI Yifang, YE Zishao, LIU Aifen, WANG Chengniu, ZHANG Lei
In Press  doi: 10.12206/j.issn.2097-2024.202209051
Abstract(295) HTML(155) PDF (3568KB)(16)
  Objective  To explore the potential mechanism of artemisinin in the treatment of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking technology.   Methods  The corresponding targets of natural product artemisinin were obtained from PubChem, Swiss Target Prediction and PharmMapper databases, targets related to PCOS were obtained through GeneCards and DisGeNET databases; the intersection target genes of Artemisinin and PCOS were screened by Draw Venn diagram. Then the protein-protein interaction network (PPI) was constructed according to the intersection target genes through the STRING Database, and the core targets were screened by Cytoscape. Besides, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was performed by DAVID Database, and finally the data were analyzed visually by the online platform. Molecular docking of artemisinin and core targets were performed by Chemdraw, Pymol, Auto Dock Tools and RCSB PDB database.   Results  A total of 229 targets of artemisinin and 1292 targets of PCOS were screened out, 90 overlapping targets were obtained by Draw Venn diagram, and 5 potential core targets, AKT1, ESR1, MMP9, PPARG, MMP2, were mainly act on PI3K Akt, MAPK, RAS, endocrine resistance and other signal pathways. Molecular docking results showed that there were molecular binding sites between artemisinin and core targets.   Conclusion  It is preliminarily analyzed that artemisinin may play a therapeutic role in PCOS through multiple targets and mechanisms.
Design, synthesis and biological evaluation of 8-hydroxyquinoline derivatives as potential clostridium difficile antibiotics
YE Tengfei, CHENG Tao, SONG Ping, JI Weili, BIAN Xiaolan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202303021
Abstract(97) HTML(36) PDF (1321KB)(6)
  Objective  To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate.  Methods  A series of 8-hydroxyquinoline derivatives were designed and synthesized based on the hit molecule within the research group.   Results  The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compounds 8 and 9f showed attractive anti-C. difficile activity.   Conclusion  A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development.
Study on the treatment compliance and influencing factors of inhalation therapy in patients with stable chronic obstructive pulmonary disease
DUAN Hu, ZHOU Yanqing, QIAN Yulin, ZHAO Liang
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202204094
Abstract(7) HTML(4) PDF (840KB)(0)
  Objective  To study the compliance and influencing factors of inhalation therapy in patients with stable chronic obstructive pulmonary disease (COPD),and carry out patient education and management accordingly.   Methods  COPD patients were selected from Respiratory Clinic of our hospital from June to December in 2021. Compliance and inhalation techniques were assessed with the Morisky Medication Adherence Scale and the ten-step inhalation technique, and the factors influencing compliance were analyzed.   Results  A total of 58 outpatients with COPD were included, in which 25 cases (43.1%) with moderate or above compliance. Univariate analysis showed that the patients with course of disease ≥5 years, CAT≥10 points, used 2 inhalation devices and inhalation technique score ≥8 points had better compliance (P<0.05).   Conclusion  Patient education and management should be carried out actively, The patients with course of disease<5 years, CAT<10 points should be highly concerned. The patients' ability to use inhalation devices and personal preference should be fully considered. Training on the use of device should be strengthened and regularly follow-up evaluation should be carried out.
Study on the usual practices of traditional Chinese medicine in treatment of postembolization syndrome after TACE based on data mining
ZHONG Zhipeng, GUO Bingjie, XIAO Chulan, YIN Zifei, LI Bai
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202208101
Abstract(7) HTML(5) PDF (1399KB)(0)
  Objective  To explore the usual practices of traditional Chinese medicine (TCM) in the treatment of postembolization syndrome (PES) after transcatheter arterial chemoembolization (TACE).   Methods  CNKI, WANFANG and VIP were used as data sources to search the journals and literatures related to TCM treatment from January 2000 to December 2021. Then, relevant TCM formula or Chinese patent medicines preparations were screened out. The Chinese medicinal materials contained were entered into Excel2019 table database, and the data were analyzed by SPSS Statistics 21.0 and SPSS Modeler 18.0 statistical software.   Results  86 qualified prescriptions were included, containing 181 Chinese medicinal materials, with a total frequency of 942 times. Of the 181 Chinese herbs included, there were 28 herbs with frequency≥10%, with a total frequency of 587. The top 5 Chinese medicinal materials of frequency were licorice, Poria, Atractylodes, Bupleurum and Astragalus. Among the efficacy classifications, tonifying deficiency drugs, heat-clearing drugs and diuretics are most used. In four properties and five tastes, the top three of four properties were warm, flat and cold, and the top three of five tastes were sweet, bitter and pungent. In the classification of meridians, the first three meridians are spleen meridian, lung meridian and liver meridian. 30 association rules were obtained in association rules analysis, 11 common factors were obtained by factor analysis, 6 clustering combinations were obtained by cluster analysis, and 4 commonly used drug combinations were obtained.   Conclusion  The prescription drugs for the treatment of PES after TACE are mainly tonic drugs, heat-clearing drugs and diuresis and dampness-draining drugs. The treatment methods are mainly invigorating spleen and replenishing qi, clearing heat and dampness and detoxification.
Advances in metabolomics of cholangiocarcinoma
HE Yongping, JIAO Yang, LIU Yue
In Press  doi: 10.12206/j.issn.2097-2024.202211025
Abstract(348) HTML(113) PDF (886KB)(7)
As a highly malignant tumor, the diagnosis of cholangiocarcinoma (CCA) is often late and the prognosis is poor for which the early symptoms are atypical and the lack of accurate biomarkers. Metabolomics is an emerging science that researches the alterations of all endogenous small molecule metabolites in an organism under the influence of pathological, physiological or genetic modification. The development and progress of CCA is closely related to metabolism. Metabolomic is characterized by global analysis, high throughput and reflects real-time alterations in biology system, providing a new avenue for biomarker screening and diseases diagnosis and treatment. The advances of metabolomics studies on CCA in the recent years were reviewed in this paper which could provide the reference for further research.
Research progress on transcription factor ZNF24 in Tumors
TIAN Shuo, LI Jianzhong
In Press  doi: 10.12206/j.issn.2097-2024.202204043
Abstract(832) HTML(372) PDF (1181KB)(10)
The transcription factor ZNF24 (also known as ZNF191 or KOX17) is a member of the Krüppel-like zinc finger transcription factor family, with a leucine-rich (Leu) SCAN domain (also known as LeR domain) at the N-terminus and four consecutive typical Kruppel-like zinc finger modities at the C-terminus. ZNF24 is a multifunctional transcription factor involved in the regulation of kinase transcriptional activity, vascular proliferation and development, especially in tumorigenesis and tumor progression. ZNF24 plays an important and complex dual-directional regulation role (promoting and inhibiting) in tumor development, invasion and metastasis by regulating the transcriptional expression of different target genes (such as VEGF, Wnt8B, Twist1, β-catenin and DGL1, etc.) and the competitive binding with protein factors (such as β-catenin). Therefore, elucidating the mechanism of ZNF24 in tumors would provide clues and ideas for the treatment of tumors. The researches status of ZNF24 in tumors were summarized in this paper.
Pharmaceutical care in a case of myocardial infarction complicated with antithrombotic therapy after tricuspid valve repair
LIU Yulan, LIU Mei, LU Yi, BI Hui, XU Guili
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202204122
Abstract(125) HTML(53) PDF (796KB)(6)
  Objective  To investigate the antithrombotic therapy for acute myocardial infarction patients after PCI stenting combined with tricuspid valve repair.   Methods  The risk of bleeding and embolization was evaluated, relevant data were reviewed, professional knowledges of pharmacy were utilized through the whole treatment process, individualized medication plan for patients was designed and used.   Results  A better therapeutic effect was achieved through the implementation of pharmaceutical care and medication education to the patients.   Conclusion  Clinical pharmacists carry out pharmaceutical care in antithrombotic drugs utilities to improve the safety level of drug use and provide basis for clinical rational drug use.
Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles
XU Ziyi, SUN Yuhan, FAN Li, LU Guangzhao, ZHANG He
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202308043
Abstract(101) HTML(140) PDF (1154KB)(61)
  Objective  Construction of methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX to reduce the toxicity and side effects of DOX.   Methods  AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay.   Results  AuNPs-mPEG@DOX was successfully prepared with Z-Average of 46.12±0.49 nm, Zeta potential of 18.60±1.51 nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L.   Conclusion  AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.
Mechanism of Qizhen Ziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking
PAN Yujiong, HE Zhigao, CHEN Shixiu, ZHOU Gui, ZHOU Xin, YU Chao
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202208111
Abstract(217) HTML(69) PDF (3499KB)(10)
  Objective  To investigate the mechanism of Qizhen Ziyin mixture in the treatment of hypogonadism by using the network pharmacology approach.   Methods  The active components of Qizhen Ziyin mixture were obtained by searching TCMSP , TCMID and HIT databases; The related targets of candidate compounds were obtained by searching STITCH databases. The potential targets of Qizhen Ziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction (PPI) network was constructed by introducing Cytoscape software. The mechanism of Qizhen Ziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO, KEGG and molecular docking technology.   Results  a total of 148 drug-disease chemical compound, 96 drug-disease intersection targets,1085 disease targets were obtained; the components for treating diseases are: quercetin, kaempferol, luteolin, etc.; go enrichment analysis revealed 1792 biological processes (BP), 31 cellular components (CC) and 79 molecular functions (MF); the results of KEGG pathway enrichment analysis indicate such as FOXO signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc.; The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy.   Conclusion  The active components of Qizhen Ziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.
Effects of light regulation on the synthesis of secondary metabolites in medicinal plants
ZHANG Wei, MENG Xiangqing, SU Xiaohui, WANG Jinyi, LI Lihua, JIA Min
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202305027
Abstract(265) HTML(163) PDF (1286KB)(18)
Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are an adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we will review the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.
Network pharmacology study on the treatment of cerebral infarction with Chinese medicine Shenmajingfu granule
XU Yi, HE Ruihua, HUANG Jin
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202303013
Abstract(297) HTML(123) PDF (5133KB)(9)
  Objective  To explore the material basis and mechanism of the Chinese medicine Shenmajingfu granules in the treatment of cerebral infarction.   Methods  The potential active ingredients and targets of Shenmajingfu granules were retrieved through TCMSP, ETCM database and TCM Database. The related target genes of cerebral infarction were searched from OMIM database. The common targets of Shenmajingfu granules and cerebral infarction were obtained by the intersection method. Cytoscape was used to construct active components of Shenmajingfu granules-targets network. Protein-protein interaction network was constructed by STRING software. By using DAVID database was used for GO and KEGG enrichment analysis.   Results  The 183 potential active ingredients of Shenmajingfu granules were screened out. 1785 potential targets were screened in the TCMSP database, including 30 targets related to cerebral infarction. These target genes were mainly involved in the inflammatory response and apoptosis process, involving the TNF signaling pathway, HIF-1 signaling pathway and NF-κB signaling pathway.   Conclusion  The therapeutic effect of Shenmajingfu granules on cerebral infarction may be related to the regulation of inflammatory response, improvement of impaired neurological function and protection of cerebral ischemia-reperfusion injury.
Study on the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway
MENG Panpan, SONG Muge, YANG Shichao, CHEN Keming, YANG Zhongduo, MA Huiping
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202303006
Abstract(252) HTML(77) PDF (2083KB)(6)
  Objective  Study on the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway.   Methods  Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group: 400 mg/kg, low, medium and high dose groups of Lishukang capsule: 400 mg/kg, 600 mg/kg, 800 mg/kg, with 10 mice in each group. The normal control group was fed at the local altitude (1500m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500 m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given normal saline once a day, and 1 hour after the last administration, the eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice.   Results  Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased (P<0.01). Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased (P<0.01).   Conclusion  High altitude hypoxia can lead to oxidative stress injury in mice and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment in mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.
Progress on the relationship of aldehyde dehydrogenase 2 with human diseases and its small-molecule activators
SUN Xiangpei, GAO Xing, ZHAO Fengping, WANG Wentao, ZHANG Tianyi, TIAN Wei, ZHENG Canhui, CHEN Xin
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202302038
Abstract(343) HTML(125) PDF (1987KB)(20)
Aldehyde dehydrogenase 2 (ALDH2) is an important shield from the damage occurring under oxidative stress in human body, and a high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value for clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.
The improvement of gefitinib-resistance of PC9/GR by thapsigargin combined with gefitinib
DU Jiangyuan, ZHANG Lanlin, CAI Tongkai, CAO Yongbing
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202209018
Abstract(283) HTML(94) PDF (1568KB)(7)
  Objective  To study the effect and mechanism of the thapsigargin combined with gefitinib on the proliferation of human lung adenocarcinoma gefitinib resistance cell line PC9/GR.   Methods  The cell viability of PC9/GR treated with gefitinib alone or gefitinib combined with thapsigargin was evaluated by CCK8 assay; The flow cytometry was used to analyze the PC9/GR cell apoptosis indued by the two group drugs; The ATF-6 and IRE1α protein expression of PC9/GR cells treated with the two group drugs were detected by Western blotting.   Results  The group of drug combination exhibited enhanced ability to inhibit cell proliferation, promote cell apoptosis and upregulate the ATF-6 and IRE1α protein expression of the PC9/GR compared with the group gefitinib used alone.   Conclusion  The sensitivity of PC9/GR to gefitinib was increased when the cells were treated by thapsigargin, which may be related with the state of endoplasmic reticulum stress(ERS) induced by thapsigargin.
Anti-fatigue activity of selenium nanoparticles functionalized by polysaccharides from Pleurotus tuber-regium sclerotium
ZOU Si, WU Yanbin, WU Jinzhong, WU Jianguo, WONG Kahing
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202206072
Abstract(252) HTML(127) PDF (1745KB)(6)
  Objective  To investigate the anti-fatigue effect of PTR-SeNPs in vivo by measuring the muscle relative length of hindlimb, load-bearing swimming time as well as serum and liver indexes of mice.   Methods  48 Male C57/BL6 mice were randomly assigned into 4 groups with 12 mice in each group, including vehicle control group (Control group), swimming training exercise group (EC group) with vehicle treatment, swimming training exercise with low dose of PTR-SeNPs group (LPTR-SeNPs) and high dose of PTR-SeNPs group (HPTR-SeNPs). The mice were intragastrically administrated with normal saline in both Control group and EC group, as well as 2.5 and 10 μmol/kg·bw PTR-SeNPs in L/HPTR-SeNPs group, respectively, once per day for consecutively 21 days. After swimming training exercise, the muscle structures in the hind limb of mice were examined by magnetic resonance imaging. Furthermore, the burdened swimming time was measured, the serum content of blood lactic acid (BLA), urea nitrogen (BUN), alanine aminotransferase (ALT), glutamic oxalate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as the hepatic level of glycogen (HG), malondialdehyde (MDA) and activity of catalase (CAT) and superoxide dismutase (SOD) were determined.   Results  Compared with the Control group, the serum contents of BLA, BUN, ALT, AST and LDH in EC group (P<0.05 or 0.01) and hepatic CAT in HPTR-SeNPs group (P<0.01) were significantly increased. The muscle relative length of hind limbs and the burdened swimming time were extended by HPTR-SeNPs markedly (P<0.05). There was no significant difference in MDA level in L/HPTR-SeNPs group. Compared with EC group, the burdened swimming time of mice was significantly prolonged (P<0.01), the contents of BLA and BUN were obviously decreased in the HPTR-SeNPs group(P<0.05 or 0.01), the level of HG was significantly increased in the L/HPTR-SeNPs groups (P<0.05 or 0.01), the serum content of ALT, AST and LDH were markedly decreased in the HPTR-SeNPs group (P<0.05 or 0.01). Hepatic SOD activity was remarkably increased in LPTR-SeNPs group (P<0.05), the level of CAT was evidently increased (P<0.01) and AST was decreased (P<0.05) in the HPTR-SeNPs group.   Conclusion  PTR-SeNPs could improve the liver physiological function, increase glycogen storage, reduce the accumulation of metabolites and enhance the body’s antioxidant capacity to ameliorate fatigue significantly, which could present the potential to be developed into health care products or drugs.
Determination and effect of five alkaloids from extracts of Piper longum on rats with experimental myocardial ischemia induced by injection of pituitrin
YI Bowen, LIU Huining, ZHENG Rui, REN Jiawei, LIU Yang
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202112011
Abstract(611) HTML(268) PDF (999KB)(7)
  Objective  To determine the content of five alkaloids from extracts of piper longum and test the pharmacodynamic effect of them on rats with experimental myocardial ischemia induced by injection of pituitrin.   Methods  The content of five alkaloids was determined simultaneously by HPLC. The experimental myocardial ischemia in rats was induced by injection of pituitrin, and the absolute value of T wave change and change of heart rate before and after model establishment were chosen to be the observation index. The effects of large, medium and small dose groups were evaluated.   Results  Three batches of samples were analyzed, with the contents of piperine for 56.1%, 49.7%, 51.6%; N-isobutyl-(2E,4E)octadecatrienamide for 4.5%, 4.2%, 4.3%; guineensine for 0.46%, 0.38%, 0.40%; piplartine for 1.73%, 1.67%, 1.70% and piperamide for 0.55%, 0.46%, 0.49%, respectively. All dose groups from extracts of piper longum had significantly reduced the absolute value of T wave and almost have no effect on the change of heart rate, except the high dose group showed the effect of reducing heart rate at some time .  Conclusion  The HPLC method was suitable for the simultaneous determination of five alkaloids from extracts of piper longum. It was shown that extracts of piper longum had good bioactivity in anti-myocardial ischemia.
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Research progress on therapeutic DC vaccine against melanoma
ZHANG Xinyue, TAI Zongguang, ZHU Quangang, CHEN Zhongjian, BAO Leilei
2023, 41(11): 643-647.   doi: 10.12206/j.issn.2097-2024.202211043
Abstract(69) HTML(24) PDF (853KB)(6)
Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected.
Progress on factors affecting gastrointestinal function and drug protection in high altitude hypoxia environment
CHENG Junfei, ZHAO Anpeng, ZHAO Yilan, WANG Zihan, LI Wenbin, WANG Rong
2023, 41(11): 648-653.   doi: 10.12206/j.issn.2097-2024.202111018
Abstract(410) HTML(168) PDF (1243KB)(41)
Due to factors such as low pressure, low oxygen and cold in the plateau environment, people who enter the plateau rapidly are susceptible to digestive system diseases, such as upper abdominal pain, loss of appetite, nausea and vomiting and other gastrointestinal dysfunction, which seriously affect the health and work ability of people who enter the plateau rapidly. The gastrointestinal dysfunction caused by the rapid advance to the plateau is mainly reflected in three aspects: gastrointestinal motility dysfunction, impaired mucosal barrier function, and intestinal flora imbalance. At present, the pathogenesis of gastrointestinal dysfunction is still not very clear, and there are fewer drugs for targeted prevention and treatment. Gastrointestinal hormones, oxygen free radicals, inflammatory factors, intestinal flora and other factors, as well as the protective effects of related drugs were reviewed in this paper to provide treatment options and theoretical basis for the prevention and treatment of the gastrointestinal emergency response caused by entering the plateau.
Effect of intestinal Metrnl gene knockout on intestinal microbiota and ulcerative colitis
CHEN Simin, LING Qisheng, ZHANG Sailong, MIAO Chaoyu
2023, 41(11): 654-661.   doi: 10.12206/j.issn.2097-2024.202211050
Abstract(76) HTML(27) PDF (2729KB)(5)
  Objective  To investigate the effect of intestinal Metrnl on dextran sodium sulfate (DSS)-induced ulcerative colitis mouse model and the regulation mechanism of intestinal microbiota.   Methods  Different concentrations of DSS (3% DSS and 1% DSS) were used to induce ulcerative colitis on C57 mice to determine the experimental conditions. Intestinal epithelial Metrnl specific knockout mice (Metrnl(-/-)) and its control mice (Metrnl(+/+)) were administrated with 3% DSS for 5 d. Then the survival time, body weight, DAI (disease activity index), colon length and pathological changes in colon tissues were observed. 16S ribosomal RNA gene sequencing was used to detect the composition of intestinal microbiota.   Results  Compared with 1% DSS, 3% DSS could significantly aggravate ulcerative colitis on C57 mice, such as lower survival rate (P<0.05), more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). After administrated to 3% DSS for 5 d, comparing with Metrnl(+/+) mice, Metrnl(-/-) mice showed more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). The 16S ribosomal RNA results showed that the diversity of intestinal microbiota in Metrnl(-/-) mice significantly decreased. Furthermore, Bacteroidetes and Proteobacteria significantly decreased, while Firmicutes increased.   Conclusion  Metrnl could protect the DSS-induced ulcerative colitis mouse through regulating intestinal microbiota.
TLC identification and quantitative determination of Shipi Xiaoshui gel plaster
MA Bingzhi, LIANG Yingying, WANG Haiyang, TANG Yonghe, LI Dong, HE Jun
2023, 41(11): 662-665, 679.   doi: 10.12206/j.issn.2097-2024.202205054
Abstract(317) HTML(108) PDF (1780KB)(7)
  Objective   To establish the method of thin layer chromatography (TLC) for identification and quantitative determination of Shipi Xiaoshui gel plaster.   Methods  TLC was adopted to qualitatively identify astragalus radix, plantaginis semen, curcumae rhizome, cinnamomi ramulus, polyporus umbellatus and akebia quinata. UPLC-MS was used to determine the content of astragaloside Ⅳ.   Results  TLC spots were clear and well-separated; RSDs of precision, reproducibility and stability tests were all lower than 3%, the linear range of astragaloside Ⅳ was 2.75-33 μg/ml (r=0.999 9, n=6), and the average recovery was 100.49% (RSD=1.98%, n=6).   Conclusion  The established method in this study is accurate, reliable and specific, which could be used for the quality control of Shipi Xiaoshui gel plaster.
Protective effect of Shenmajing formula on ischemic brain injury in mice
LIU Jingxue, HE Ruihua, TAO Xia, HUANG Jin
2023, 41(11): 666-671, 685.   doi: 10.12206/j.issn.2097-2024.202208066
Abstract(66) HTML(21) PDF (2968KB)(3)
  Objective   To observe the protective effect of Shenmajing formula on brain tissue of mice with cerebral ischemic injury and explore the possible mechanism.   Methods  Thirty SPF-grade C57 BL/6 male mice were randomly divided into model control group, Shenmajing group and nimodipine group, and the animal models of cerebral ischemic injury in mice were prepared by electrocoagulation. The protein expression level in endothelial progenitor cells were detected by Western blot.   Results  Compared with the model control group, the infarct volume of mice in the Shenmajing group was significantly reduced, and the migration, adhesion and tubule formation ability of endothelial progenitor cells were significantly improved, and the expression level of BDNF protein in endothelial progenitor cells was significantly increased.   Conclusion  The protective effect of Shenmajing granules on brain tissue of mice with cerebral ischemic injury could be closely related to the regulation of BDNF expression in endothelial progenitor cells and improvement of endothelial progenitor cell function of bone marrow origin.
Mechanism of Artemisia annua L. in GIOP with kidney-yin deficiency based on network pharmacology
LAI Liyong, XIA Tianshuang, YUE Xiaoqiang, XIN Hailiang
2023, 41(11): 672-679.   doi: 10.12206/j.issn.2097-2024.202204115
Abstract(103) HTML(60) PDF (3112KB)(7)
  Objective  To predict and preliminarily verify the potential targets and related signaling pathways of Artemisia annua L. in treating glucocorticoid-induced osteoporosis (GIOP) with kidney-yin deficiency by network pharmacology and in vitro experiments.   Methods  The pharmacological targets of Artemisia annua L. were obtained from TCMSP database and were converted to gene names through Uniprot database. The target genes of GIOP with kidney-yin deficiency were obtained from GeneCards database, OMIM database and Drugbank database, and the common target genes were obtained by cross analysis with drug target gene. Protein-protein interaction (PPI) network was constructed by String database, and visualization analysis and core targets screening were performed by Cytoscape 3.9.0. All common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis through Metascape database. Finally, the prediction results were verified by in vitro experiments.   Results  Ninety-eight targets of Artemisia annua L. to GIOP with kidney-yin deficiency were screened, including 17 core genes. The results of GO and KEGG functional enrichment analysis indicated that Artemisia annua L. treating GIOP with kidney-yin deficiency was related to biological processes such as hormonal response, positive regulation of cell death and extracellular stimulation response, et al, as well as signaling pathways such as PI3K/AKT, AGE/RAGE, MAPK and IL-17 et al. The number of genes enriched in PI3K/AKT signaling pathway was the largest. In vitro experiment results showed that Artemisia annua L. promoted the proliferation of osteoblasts damaged by dexamethasone (DEX), increased alkaline phosphatase activity, activated PI3K/AKT pathway, and promoted the phosphorylation of AKT.   Conclusion  Artemisia annua L. treating GIOP with kidney-yin deficiency has the characteristics of multi-targets and multi-pathway, which could promote the proliferation and differentiation of osteoblasts through multiple pathways. The PI3K/AKT signaling pathway is an important pathway. Artemisia annua L. treating GIOP with kidney-yin deficiency might be related to its ability to promote the PI3K/AKT signaling pathway and promote the phosphorylation of AKT.
Review of clinical use of Dingqing Tablets in a Tertiary A Hospital of Integrated Traditional Chinese and Western Medicine
XU Yi, YANG Yuehong, HUANG Jin, WANG Jie, LIU Jing, WU Tiejun
2023, 41(11): 680-685.   doi: 10.12206/j.issn.2097-2024.202208034
Abstract(60) HTML(27) PDF (1110KB)(2)
  Objective  To improve the quality of prescriptions and promote the rational drug application of Dingqing Tablets by investigating the outpatient prescriptions in a tertiary A hospital.   Methods  A total of 4 796 prescriptions of outpatient pharmacy patients from August 1, 2020 to August 1, 2021 were extracted from the hospital information system by the hospital information software, focusing on the analysis of indications, usage and dosage, drug interaction, etc.   Results  10 departments including hematology department and geriatrics department were used Dingqing Tablets, and the irrationality was mainly manifested in the superposition of drug flavors and drug interactions.   Conclusion  Dingqing tablets were widely used in clinic and had remarkable curative effect. However, there are certain risks in the use of Dingqing tablets. It is necessary to add medication education and supervision to promote the safe and rational use of drugs in clinic.
Effect evaluation of the clinical pharmacists participating in the treatment of patients with diabetic foot
YANG Zhihui, ZHANG Lili, ZHAO Yan, HUANG Jinghui, LIU Yuan, YUAN Hailong
2023, 41(11): 686-688, 699.   doi: 10.12206/j.issn.2097-2024.202209087
Abstract(133) HTML(53) PDF (1185KB)(5)
  Objective  To evaluate the effect of clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot by antibiotics management index and health economics index.   Methods  40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department of Air Force Medical Center from April to September 2017 were selected as control group, and 40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department from April to September 2019 were selected as interventional group. No clinical pharmacists were involved in drug treatment of patients in the control group, while the clinical pharmacists in the interventional group participated in drug treatment, and implemented antimicrobial stewardship, medication reconciliation, pharmaceutical care and medication education. Antibiotics management indexes (use intensity of antibiotics, use rate of special class antibiotics) and health economics indexes (medicine expenses, hospitalization expenses) of the two groups were compared.   Results  The efficacy of the two groups was similar. The use intensity of antibiotics and use rate of special class antibiotics of the interventional group in which clinical pharmacists participated were significantly lower than the control group (P<0.01), so were the medicine expenses and hospitalization expenses (P<0.01).   Conclusion  Clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot could reduce antibiotics administration index and health economics index, promote rational medicine use and save medical expenses.
Practice and exploration of physician-pharmacist joint outpatient service mode of chronic obstructive pulmonary disease (COPD) and asthma
CHEN Dan, LIU Guodong, LIU Yu, TONG Shaohua, LIU Shengjun
2023, 41(11): 689-693.   doi: 10.12206/j.issn.2097-2024.202209034
Abstract(140) HTML(59) PDF (1016KB)(6)
  Objective   To explore the physician-pharmacist joint outpatient service mode of chronic obstructive pulmonary disease ( COPD) and asthma.   Methods  Cases of COPD or asthma patients who visited the joint outpatient department from June 2021 to December 2021 were collected in our hospital, the inhaler usage score, compliance ( MMAS-8) score, clinical control efficacy, incidence of adverse reactions and patient satisfaction were evaluated before and after pharmaceutical care intervention and statistically analyzed.  Results  The inhaler usage score, MMAS-8 score, and the Asthma Control Test(ACT)/COPD Assessment Test(CAT) score had been changed significantly after the intervention (P<0.05). Patient satisfaction with pharmaceutical care was basically above 94.75%.  Conclusion  Pharmaceutical care provided by joint outpatient department in our hospital could help COPD and asthma patients to use inhaler device correctly, resulting in improving compliance of inhaler usage, better disease control, and reducing the occurrence of adverse drug reactions, which could be a positive attempt and exploration of standardized pharmaceutical care model for patients with COPD and asthma.
Risk factors of linezolid-related thrombocytopenia in patients in the department of hepatobiliary surgery
SHAN Xuechun, LI Xu, DU Hongli, BAO Leilei, WANG Hui
2023, 41(11): 694-699.   doi: 10.12206/j.issn.2097-2024.202210061
Abstract(257) HTML(79) PDF (957KB)(4)
  Objective  To provide the evidence for clinical medication safety by the investigation of the risk factors of linezolid-related thrombocytopenia in cancer patients in the department of hepatobiliary surgery.   Methods  Patients who received linezolid for anti-infective treatment from January 2017 to December 2021 were selected. The patients were divided into thrombocytopenia group and non-thrombocytopenia group according to whether thrombocytopenia occurred or not after administration of linezolid. The general data and laboratory indicators of the two groups were compared, and the risk factors of linezolid-related thrombocytopenia were screened by multivariate logistic regression analysis.   Results  A total of 104 patients were included in the study, including 84 patients who underwent surgery and 20 patients who did not. The incidence of linezolid-related thrombocytopenia was 24.0%. There were significant differences in gender, age, duration of linezolid use, platelet count, white blood cell count, alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin, creatinine, estimated glomerular filtration rate between the two groups (P<0.05); logistic regression analysis suggested that age ≥60 years (OR=7.093; P=0.017), duration of linezolid use ≥12 days (OR=4.399; P=0.035), baseline platelet count ≤200×109/L (OR=8.470; P=0.004), baseline AST≥50 U/L (OR=15.465; P<0.001), and baseline white blood cell count ≥11×109/L (OR=11.436; P=0.001) were the risk factors for linezolid-related thrombocytopenia in cancer patients.   Conclusion  During the treatment of linezolid in cancer patients, attention should be paid to the adverse reactions of thrombocytopenia in the patients, especially those with old age, long-term treatment, low baseline platelets, poor baseline liver function, and high baseline white blood cell counts.
Risk factors of poor early prognosis in the treatment of COVID-19 with nematevir and ritonavir tablets and the establishment of prediction model
HUANG Wenhui, XU Yanyu, HAO Xiaowei, LIN Guan, OUYANG Shandan, WANG Jiakun, CHEN Jinshan
2023, 41(11): 700-704.   doi: 10.12206/j.issn.2097-2024.202303038
Abstract(176) HTML(73) PDF (971KB)(8)
  Objective  To explore risk factors of poor early prognosis in the treatment of COVID-19 by nematevir and ritonavir tablets Paxlovid and establish the prediction model to provide reference for improving the effect of such patients.   Methods  92 inpatients of COVID-19 treated with Paxlovid in three military tertiary hospital in southern Fujian from January 2023 to March 2023 were retrospectively analyzed. The clinical indicators of 92 inpatients were collected for univariate and multivariate analysis by single factor and multiple factors and the independent risk factors of poor early prognosis in Paxlovid were screened out. Logistic model equation was transformed to construct the combined predictors, and ROC curve was used to determine the area under the curve (AUC) and the optimal critical value of the combined predictors.   Results  Among 92 patients, 31 (33.70%) developed poor early prognosis, including 11 deaths (35.48%), 17 critical cases (54.84%) and 3 severe cases (9.68%). Multi-factor Logistic regression analysis showed that the disease days, lymphocyte count, aspartate aminotransferase(AST), C reactive protein(CRP) and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. A formula for calculating the combined predictors (Y) was established as Ycombinedpredictors=7.875Xdisease days+126.188Xlymphocyte count+1.438XAST+XCRP+220.500Xventilator-assisted ventilation based on the above independent risk factors, and the ROC curve was drawn. With the maximum area under the ROC curve of the combined predictors being 0.939, the prediction value was best, and the optimal critical value of the ROC curve corresponding to the maximum Youden index (0.756) was 447.920.Theoretical accuracy of the model was 89.10%.  Conclusion  The disease days, lymphocyte count, AST, CRP and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. Combined predictors could be calculated by the above risk factors before medication. The efficiency should be improved by taking more active treatment, including combining with other anti-COVID-19 drugs when the prediction result exceeds 447.920.

Chief Editor: LI Jie Wei

Publication Number:

ISSN 2097-2024   CN  31-2185/R

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