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Screening and anti-colorectal activity of small molecule inhibitors against Fusobacterium nucleatum
BAI Xuexin, CHEN Yuping, SHENG Chunquan, WU Shanchao
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202405009
Abstract(3392) HTML(1135) PDF (1612KB)(10)
Abstract:
  Objective  To screen small molecule inhibitors against Fusobacterium nucleatum (Fn) based on commercially available compound libraries, and to investigate their anti-colorectal cancer activities under Fn intervention in order to obtain novel anti-colorectal cancer lead compounds.   Methods  The promotion of colorectal cancer proliferation on organoid was validated by Fn. Secondly, the effects of anti-Fn compounds on their in vitro anticancer activity under Fn’s co-incubation with colorectal cancer HCT116 cell were comparative investigated. Finally, in vivo anticancer efficacy of highly active compounds on nude mouse colon cancer HCT116 transplanted tumor under the intervention of Fn was evaluated by gavage.   Results  Fn could significantly promote the proliferation of rectal cancer organoids. 9 ant-Fn active compounds could significantly enhance their in vitro anticancer activity under Fn’s co-incubation with HCT116 cells. Methotrexate had the strongest anti-cancer activity with IC50 as 0.03 μmol/L. The combined use of methotrexate (0.5 mg/kg) and PD-1 (5.0 mg/kg) had a stronger anti-tumor effect than their standalone use.  Conclusion  As new small molecule inhibitor against Fn, methotrexate exhibited good in vitro and in vivo anti-colorectal cancer activity against HCT116 cells and nude mouse xenografts under Fn intervention, which showed the foundation for subsequent structural optimization, and could be expected to expand the new indications for methotrexate.
Quantitative evaluation on internal control of drug management in a tertiary
public hospital in Shanghai
LIAN Luying, LIU Ying, YIN Jia, ZHU Guoliang, XU Fei
In Press  doi: 10.12206/j.issn.2097-2024.202402003
Abstract(1233) HTML(1532) PDF (1014KB)(11)
Abstract:
  Objective  To establish the quantitative evaluation system on the internal control of drug management, which could reflect the improvement and optimization of the internal control of drug management and be reference for the drug management in the hospital.   Methods  Brainstorm method was used to design a quantitative evaluation table. The methods of walking test, field inspection and comparative analysis were used to carry out the internal control design and execution effectiveness evaluation.   Results  Evaluation score increased from 36.50 points in 2015 to 43.75 points in 2021 when the full score was 50 points. The proportion of drug decreased from 37.97% in 2015 to 21.62% in 2021.The drug markup rate decreased from 14.38% to 0.96%, and the intensity of antibiotic use(DDDs)decreased from 55.48 in 2018 to 39.30 in 2021. The proportion of basic drug prescriptions was higher than the national examination data.   Conclusion  The optimizing quantitative evaluation system on the internal control of drug management could improve the management specialization, the structure of income and payout and the level of rational drug use, promote the high-quality development of hospitals and safeguard the implementation of the Healthy China strategy.
The practices and implications of emergency drug authorization by the U.S. FDA
HAN Dan, GAO Wen, WANG Lunuan, SUN Rui, GUO Mingming, SHU Lixin
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309044
Abstract(307) HTML(166) PDF (851KB)(0)
Abstract:
  Objective  This study aims to provide valuable insights for improving China’s special drug approval system by conducting an in-depth analysis of the practices of the U.S. Food and Drug Administration (FDA) in granting Emergency Use Authorizations (EUAs) for drugs.   Methods  A retrospective analysis was conducted on the FDA’s EUA decision-making process for COVID-19 therapeutics between January 2020 and June 2023.   Results  During the COVID-19 pandemic, the FDA adopted a series of regulatory science approaches to facilitate rapid approval of COVID-19 therapeutic drugs. The FDA granted EUA for a total of 15 COVID-19 therapeutic drugs and 4 COVID-19 vaccines, including expanded indications for marketed drugs, EUA for investigational drugs, revocation of EUA, and marketing after EUA. The main reasons for the rapid approval of EUA drugs by the FDA included the use of existing clinical trial data, omission of animal efficacy testing, merging of phase 1 and phase 2 clinical trials, and the use of clinical outcomes as surrogate endpoints, among other regulatory science methods.   Conclusion  Suggestions were made to improve Chinese drug emergency use authorization system, apply regulatory science methods to China’s drug emergency use authorization, and establish active monitoring mechanisms for drugs authorized under emergency use.
Cost-effectiveness analysis of posaconazole versus voriconazole in the empiric or diagnostic-driven treatment of invasive mould diseases in immunocompromised patients
SHI Xiaoping, LYV Qianzhou, LI Xiaoyu, XU Qing
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202401050
Abstract(232) HTML(115) PDF (1367KB)(3)
Abstract:
  Objective  To evaluate the cost-effectiveness of posaconazole compared to voriconazole in the empiric or diagnostic-driven treatment of invasive mould diseases (IMD) in immunocompromised patients from the perspective of Chinese health system.   Methods  A decision tree model was constructed based on a phase Ⅲ clinical trial and other publicly available data to evaluate the incremental cost-effectiveness ratio (ICER) of posaconazole versus voriconazole. One-way sensitivity analysis, probability sensitivity analysis, and scenario analysis were conducted.   Results  The results of base-case analysis indicated that, at a willingness-to-pay (WTP) threshold of 3 times Chinese GDP per capita, posaconazole gained 0.0327 quality-adjusted life years (QALYs) with the cost savings of CNY 1 711.24, demonstrating a clear cost-effectiveness advantage. Sensitivity analysis revealed that the cost of voriconazole and posaconazole significantly influenced the ICER. Under different WTP thresholds, posaconazole consistently maintained its economic advantage over voriconazole. Scenario analysis showed that the incidence of mucormycosis did not impact the results, but a price reduction in voriconazole could change result.   Conclusion  In the empiric or diagnostic-driven treatment of IMD in immunocompromised patients, posaconazole was both an effective and economically viable choice when compared to voriconazole.
Discuss the role and challenges of foreign pharmacists in leading smoking cessation services
WEN Ruirui, XU Long, ZHU Wenjing, YANG Jianwei
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202408054
Abstract(118) HTML(67) PDF (938KB)(0)
Abstract:
  Objective  To investigate the global role of pharmacists in smoking cessation and to foster the dissemination and initiation of pharmacist-led smoking cessation services.   Methods  This paper conducts a search and compiles information on the value of pharmacists in offering smoking cessation services and the evolution of supportive policies through the PubMed and SCOPUS electronic databases. It examines the feasibility and barriers to pharmacists providing these services.   Results  The involvement of pharmacists in smoking cessation positively impacts public health and the economy. Endowing pharmacists with the authority to prescribe smoking cessation medications, providing training in this service, and bolstering their potential through interprofessional collaboration can effectively address the barriers to their role in smoking cessation.   Conclusion  It is advisable to consider integrating pharmacist-led smoking cessation services into healthcare and public health policy guidelines to enhance the efficacy and sustainability of smoking cessation initiatives.
Network pharmacological mechanism of Danshen Baizhu prescription on the treatment of coronary heart disease, vascular dementia and idiopathic membranous nephropathy
XU Lulu, LIU Aijun
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202312027
Abstract(95) HTML(80) PDF (6479KB)(3)
Abstract:
  Objective  To investigate the material basis and mechanism of Danshen Baizhu prescription in coronary heart disease, vascular dementia and idiopathic membranous nephropathy based on network pharmacology.   Methods  TCMSP, PubChem, UniProt, GeneCards, OMIM, and DrugBank databases were used to obtain drug and disease targets, and the TCM-compound-drug target network, compound-common target-disease network, and protein-protein interaction map were drawn by STRING database and Cytoscape software, and gene enrichment analysis was performed by Metascape database.   Results  A total of 164 active compounds, 509 potential targets, and 141 common targets were screened out. The main active ingredients are Tanshinone II A, Isorhamnetin, Quercetin, Luteolin, Kampferol, β-sitosterol, Stigmasterol, etc. The key targets are albumin, interleukin 6, Tumor necrosis factor , serine/threonine kinase 1, vascular endothelial growth factor A , mainly enriching in the positive regulation of cell migration, cell viability, protein phosphorylation, response to growth factors, oxidative stress and other biological processes and lipid and atherosclerosis, MAPK, atherosclerosis and fluid shear force, AGE-RAGE, IL-17, PI3K-Akt and other signaling pathways.   Conclusion  The mechanism of action of Danshen Baizhu prescription for coronary heart disease, vascular dementia and idiopathic membranous nephropathy may mainly play a role in multiple targets and pathways such as inhibition of inflammation, inhibition of oxidative stress, and vasodilation.
Analysis on the use of medicines in treatment of benign prostatic hyperplasia in sample hospitals under the national volume-based procurement policy
LI Rui¹, ZHANG Qianqian², WANG Ruidong³, GAO Xiaofeng¹
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202408031
Abstract(106) HTML(69) PDF (1249KB)(1)
Abstract:
  Objective  To explore the impact of national volume-based procurement policies on the use of medicines in treatment of benign prostatic hyperplasia (BPH) and provide data support for the rational clinical use of medicines in BPH treatment.   Methods  Data on the usage of BPH treatment medications from 2019 to 2023 were extracted from the Chinese Medicine Economic Information Network (CMEI), covering 892 hospitals (including 645 tertiary hospitals and 247 secondary hospitals). The changes in various indicators, including the consumption sum, Defined daily doses (DDDs), Defined daily dose cost (DDDc), and the ranking ratio (B/A) of these drugs were analyzed and compared.   Results  From 2019 to 2023, due to the influence of relevant policies, the overall consumption sums of medicines used in the sample hospitals in BPH treatment showed a trend of decreasing first and then rising steadily. The DDDs showed an overall upward trend, while the DDDc demonstrated a gradual decline. Tamsulosin and finasteride consistently ranked first and second in DDDs. The B/A value for tamsulosin was significantly higher than that of other BPH treatment medications.   Conclusion  The implementation of national centralized drug volume-based procurement policies and other policies from 2019 to 2023 had effectively reduced the economic burden of patients with benign prostatic hyperplasia. Tamsulosin and finasteride, which had the highest B/A in the two categories of α-blockers and 5α-reductase inhibitors, dominated the market for BPH treatment. The clinical use of BPH treatment medications was relatively rational.
Adverse reaction analysis of drug-induced liver injury
ZHANG Yan, LI Yanjun, LIU Jiahui, DENG Jiao, YUAN Yuan, ZHANG Jingyi
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404034
Abstract(922) HTML(457) PDF (846KB)(6)
Abstract:
  Objective  To analyze the adverse reaction reports of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use.   Methods  ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on.   Results  In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury (37.84%). The age of drug-induced liver injury was mainly over 46 years, totaling 195 (75.28%). Drugs were mainly distributed in cardiovascular system medicine (44.02%), anti-infective medicine (23.94%)and anti-tumor medicine (11.58%). Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases (46.49%). The main anti-infectious drugs were cephalosporins (29.03%), carbapenem (19.35%), antifungal (17.74%)and quinolones (11.29%). Adverse reactions occurred within 6 days (69.88%), the duration of adverse reactions was 1-2 weeks(31.66%), and most patients improved (47.88%) or cured (37.07%).   Conclusion  For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.
Retrospective analysis of the epidemic characteristics of Gram-negative bacteria in a second-class hospital in Shanghai
DAI Feifei, FU Xiang, CHEN Qiongnian, YU Suchun
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202305005
Abstract(763) HTML(608) PDF (938KB)(1)
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  Objective  To retrospectively analyze the distribution and drug resistant characteristics of isolated pathogens (especially Gram-negative bacteria) in hospital to promote the rational use of antibacterial drugs.   Methods  The pathogens and drug sensitivity test results were collected from the whole hospital every quarter from July 2018 to March 2023, and were conducted retrospective analysis.   Results  A total of 14 844 pathogens were isolated and detected, including 4 757 Gram-positive bacteria (32.05%) and 10 087 Gram-negative bacteria (67.95%). The detection rate of extended spectrum beta-lactamases Escherichia coli was 43.23%, and it maintained high sensitivity to carbapenems and enzyme inhibitors, and the sensitivity rate was about 99.00%. The drug resistance of Klebsiella pneumoniae was more serious, and carbapenem-resistant, multi-drug resistance and extensively-drug resistance appeared. In 2022, the detection rate of carbapenem-resistant Klebsiella pneumoniae was 54.82%; the detection rates of carbapenem-resistant Pseudomonas Aeruginosa and carbapenem-resistant Acinetobacter baumannii in non-fermentative bacteria were 22.02% and 74.34%, the detection rate of multi-drug resistant Acinetobacter baumannii was >70%.   Conclusion  The problem of drug resistance of Gram-negative bacteria is still serious, especially in Klebsiella pneumoniae and Acinetobacter baumannii. The problem of bacterial resistance poses great challenges to clinical treatment, and it is necessary to conduct regular monitoring and promote rational drug use.
The practice of rational drug use management in hospitals under the reform of DRGs payment methods
YANG Bin, WANG Zuojun, CHEN Han, ZHANG Jingyi
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404030
Abstract(1180) HTML(511) PDF (1007KB)(8)
Abstract:
  Objective   To establish an effective management mode, give full play to the role of DRGs in rational drug use, formulate the pharmaceutical clinical path, and intervene the prescription behavior of doctors, which could improve the level of rational drug use in the hospital through the management practice of rational drug use under the payment method of DRGs in a third-grade hospital.   Methods   A drug introduction mechanism, a rational drug use supervision mechanism and an active and rational drug use data drying mechanism based on DRGs were established, and the rational drug use indicators such as drug consumption index, average drug cost, and auxiliary drug use were accurately positioned based on the information platform, and the accurate and refined management of rational drug use was realized through the daily supervision of the office of the Pharmaceutical Affairs Committee.   Results and conclusions   Under the multi-dimensional and multi-level rational drug use management based on DRGs, the effect of rational drug use was evaluated after the reform of DRGs payment method, and all the indexes of rational drug use in our hospital were continuously improved.
Hydrogel scaffolds loaded with bone marrow mesenchymal stem cells/resveratrol liposomes for traumatic brain injury treatment
CHI Wenya, YUAN Yan, LI Weilin, WU Tongyu, YU Yuan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202406034
Abstract(1892) HTML(551) PDF (2074KB)(8)
Abstract:
  Objective  To prepare a thermosensitive hydrogel scaffold loaded with bone marrow mesenchymal stem cells(BMSCs)and resveratrol liposomes (RSV-LIP) to form a therapeutic unit and evaluate its treatment efficacy for traumatic brain injury (TBI).   Methods  BMSCs were extracted from rats, and RSV-LIP was prepared and characterized. Cell models were constructed to investigate the pharmacological effects of BMSCs combined with RSV-LIP. BMSCs and RSV-LIP were then loaded into the hydrogel, and a TBI mouse model was established to evaluate the therapeutic effects of the hydrogel.   Results  The RSV-LIP had a particle size of 127.8 nm, a Zeta potential of −4.9 mV, an encapsulation efficiency of 78.50%, and a drug loading content of 2.37%. Live-dead staining indicated good biocompatibility of the hydrogel. The combination of BMSCs and RSV-LIP significantly inhibited TNF-α and reduced ROS levels, promoting cell migration in scratch assays. Compared to the control group, the hydrogel group showed significantly lower mNSS scores (P<0.01), higher hanging scores (P<0.001), and reduced stepping errors (P<0.001).   Conclusion  The combination of BMSCs and RSV-LIP exhibited antioxidative stress, anti-inflammatory, and neurogenic cell migration-promoting effects. When loaded into a hydrogel scaffold and locally implanted, it could improve the motor and sensory functions in TBI mice.
Comparative study of pharmacodynamic experiments on compound Heishen drop pills and compound Heishen pills
HE Jing, AN Ye, ZHANG Chaoshen
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404009
Abstract(1068) HTML(444) PDF (877KB)(1)
Abstract:
Objection: To study and compare the pharmacodynamics in the treatment of chronic pharyngitis between Compound Heishen pills and Compound Heishen Drop pills.   Methods  Sixty healthy Wistar rats were randomly divided into blank group, positive control group and treatment group. The foot swelling thickness of each rat was measured at 1.0, 2.0, 3.0, 4.0, 5.0 and 6.0 h after inflammation, and the foot swelling rate of each rat was calculated. Through the experimental model of rat toe swelling, the inhibition of foot swelling induced by carrageenan was observed by two dosage forms: drop pill and pill. Sixty healthy Kunming mice were randomly divided into the blank group, positive control group and treatment group. After 4 days of continuous intragastric administration, the mice were intraperitoneally injected with 0.5% phenol red solution. After 30min, the mice were sacrificed, their trachea was dissected and washed with 0.5%NaHCO3 solution. The washing solution was put into ultraviolet spectrophotometer, and the absorbance was measured at 546 nm to calculate the corresponding concentration of phenolic red. Through the expectorant experiment of phenol red in mice, the effects of dropping pill and pill on the secretion of phenol red in experimental mice respiratory tract were compared.   Results  The experimental results of toes swelling in rats showed that compared with the blank experimental group, the five groups all had significant inhibition effect on acute foot swelling induced by carrageenan in rats. Compared with traditional form group, improved form had significant difference. The results of phenol red sputum removing experiment in mice showed that compared with the blank group the amount of phenol red secretion in mice was increased in 5 test groups could . There was no significant difference between improved form and traditional form on the amount of phenol red secretion in mice.   Conclusion  Both preparations had the function of anti-inflammatory and eliminating phlegm. There were no remarkable differences between the two preparations on pharmacologic actions.
Reasonable management and control practice of prophylactic use of antibiotics for urinary system lithotripsy
CHEN Yijun, WANG Zhuo, HE Miao, ZHANG Yu, TIAN Jing
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202402034
Abstract(2011) HTML(655) PDF (993KB)(4)
Abstract:
  Objective   To analyze the effectiveness of reasonable control measures for prophylactic use of antibiotics for urinary system lithotripsy.   Methods   By antimicrobial stewardship, strengthening special comments on antibiotics and information notification on rational use of antibiotics, adding and improving the pre-review rules for antibiotics prescriptions, conducting in-depth clinical training and consultation by clinical pharmacists, strengthening innovation in rational use of drugs, and taking various measures to actively improve rational use of prophylactic antibiotics of lithotripsy in urology department, the changes of indexes related to antibiotics in urology department from 2019 to 2022 were analyzed.   Results   After active and reasonable control, Antibiotics Use Density in urology department decreased year by year. The utilization rate of antibiotics in inpatients decreased from 94.27% in 2019 to 77.47% in 2022. Various rate of microbial inspection reached the standard in 2022; The imipenem and cilastatin sodium for injection ranking of prophylactic use of antibiotics consumption DDDs for urinary system lithotripsy decreased from the 4th place in 2019 to the 8th place in 2022. The ranking of the urology department on carbapenem consumption DDDs in the whole hospital decreased from the 8th place in 2019 to the 12th place in 2022. At the same time, the incidence of urinary tract lithotripsy postoperative infection showed a decreasing trend year by year, from 0.84% in 2019 to 0.49% in 2022.   Conclusion  Positive control measures can promote the rational use of prophylactic antibiotics for urinary system lithotripsy.
Clinical curative effect of Pingchuan prescription combined with montelukast sodium on patients with bronchial asthma
CHEN Chunjuan, ZHENG Zhixin, LI Li
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202405035
Abstract(1402) HTML(491) PDF (875KB)(6)
Abstract:
  Objective  To explore the clinical curative effect of Pingchuan prescription combined with montelukast sodium on patients with bronchial asthma.   Methods  A total of 102 patients with bronchial asthma admitted to the hospital were enrolled between May 2022 and December 2023. According to simple randomization method, they were divided into control 1 group (n=34, montelukast sodium), control 2 group (n=34, Pingchuan prescription) and observation group (n=51, Pingchuan prescription combined with montelukast sodium). All patients were treated for 21d. The clinical curative effect in the three groups was evaluated. The scores of TCM syndromes, inflammatory factors [interleukin(IL)-4, IL-17, interferon(IFN)-γ, transforming growth factor-β1(TGF-β1), immunoglobulin(Ig)E] and scores of the test for respiratory and asthma control in kids (TRACK) in the three groups were compared before and after treatment. The adverse reactions were recorded.   Results  Compared with control 1 group and control 2 group, total response rate was higher in observation group (P<0.05). After treatment, scores of TCM syndromes (wheezing due to phlegm in throat, tachypnea, choking)in observation group were lower than those in control 1 group and control 2 group (P<0.05). After treatment, levels of IL-4, IL-17, TGF-β1 and IgE in observation group were lower than those in control 1 group and control 2 group, while IFN-γ level and TRACK score were higher than those in control 1 group and control 2 group (P<0.05). There was no difference in adverse reactions among the three groups (P>0.05).   Conclusion  Pingchuan prescription combined with montelukast sodium could improve clinical curative effect in patients with bronchial asthma, which was beneficial to alleviate inflammatory response and disease severity, with certain safety.
Correlation between plasma concentration of voriconazole and polymorphisms in CYP2C19, CYP2C9 and CYP3A5 genes in children
GUI Mingzhu, LI Jing, LI Zhiling
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202402020
Abstract(1298) HTML(1390) PDF (842KB)(5)
Abstract:
  Objective  To explore the effects of CYP2C19, CYP2C9 and CYP3A5 genotypes on the plasma concentration of voriconazole in children.   Methods  Collected blood samples from 50 hospitalized children with invasive fungal infections who received intravenous voriconazole from January 2020 to December 2020. High performance liquid chromatography was used to detect the blood trough concentration of voriconazole, and the time-of-flight mass spectrometry detection system was used to detect the genotypes of CYP2C19, CYP2C9 and CYP3A5, and the effects of children’s genotyping on the plasma concentration, efficacy and adverse reactions of voriconazole were analyzed.   Results  The total effective rate of 50 children with IFI was 84% (42/50) after voriconazole treatment. The incidence of adverse reactions was 20% (10/50 cases). The measured plasma concentration of voriconazole ranged from 0.56~7.62 μg/ml. Combined with the different mutation types of CYP2C19 gene loci, three metabolic activities were produced: fast, medium and slow, and the test results showed that there were 16 cases of fast metabolism, 27 cases of intermediate metabolism and 7 cases of slow metabolism. There was a significant difference in plasma concentrations between the three groups (F=15.359, P< 0.001), and the drug concentrations in the fast metabolic group were significantly lower than those in the intermediate metabolic and slow metabolic groups. The mutations of CYP2C9 and CYP3A5 had no significant effect on the plasma concentrations of the drugs, which were (F=2.213, P=0.086)and (F=0.757, P=0.475).   Conclusion  Voriconazole had significant efficacy in the treatment of invasive fungal infections in children, and the adverse reactions were mild. CYP2C19 genotype was significantly related to the rate of drug metabolism and was an important factor affecting blood drug concentration, the detection of drug concentration and genotype of voriconazole was helpful to adjust the effective drug dose clinically and achieve more scientific and individualized treatment.
Study on the efficacy and mechanism of Tongbianling capsule in the treatment of constipation
CHEN Ying, XU Zihua, HU Bei, CUI Yaling, GAO Huan, WU Qiong
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404008
Abstract(3540) HTML(1559) PDF (4039KB)(13)
Abstract:
  Object   To study the efficacy and potential mechanism of Tongbianling capsule in constipation.   Methods   To observe the effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot.   Results   The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group.   Conclusion   Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.
Skin pharmacokinetics of inositol nicotinate in heparin sodium inositol nicotinate cream
CUI Yaling, WU Qiong, MA Liangyu, HU Bei, YAO Dong, XU Zihua
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404006
Abstract(2611) HTML(644) PDF (965KB)(9)
Abstract:
  Objective  To establish an HPLC method to determine the concentration of inositol nicotinate(IN) in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream(GJR) in rats.   Methods  HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of GJR in rats, and the pharmacokinetic parameters were fitted with DAS software.   Results  The linearity of the analytical method was good in the concentration range of 0.25~20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of GJR in rats were as follows: t1/2 was (4.555±2.054) h, Tmax was (6±0)h, Cmax was (16.929±2.153)mg/L, AUC0−t was (150.665±16.568) mg·h /L ,AUC0−∞ was (161.074±23.917) mg·h /L, MRT(0−t) was (9.044±0.618)h, MRT(0−∞) was (10.444±1.91) h, CLz/F was (0.19±0.03) L/(h·kg), and Vz/F was (1.19±0.437) L/(h·kg).   Conclusion  IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method was simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.
Anti-frostbite effect of miglitol on cold-exposed mice through UCP1-mediated thermogenic activation
LI Xiang, LU Hongyuan, ZHANG Mingyu, GAO Huan, YAO Dong, XU Zihua
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404005
Abstract(2430) HTML(845) PDF (1670KB)(16)
Abstract:
  Objective  To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and improving cold injury in mice after cold exposure.   Methods  Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting.   Results  Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling.   Conclusion  Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.
Study on the synergistic antifungal effects of Caspofungin Acetate loaded glyceryl monostearate nanoparticle on Candida albicans
GUO Lingyi, LIU Yanchao, GAO LU, LIU Ruiyao, LV Quanzhen, YU Yuan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202310043
Abstract(3440) HTML(814) PDF (0KB)(4)
Abstract:
  Objective   To prepare and characterize caspofungin acetate-loaded solid lipid nanoparticles using glycerol monostearate (CAS-SLNs), and investigate the antifungal effect of potentiation on Candida albicans in vitro and in vivo.   Methods  A high performance liquid chromatography method was established for the determination of caspofungin acetate (CAS). CAS-SLNs were prepared by the melt-emulsification method and characterized. The minimum inhibitory concentration (MIC)and the inhibitory effect on Candida albicans biofilm were determined. A systemic infection model of Candida albicans was established in mice, and the growth curve models for body weight and fungal load of kidneys of the animals were investigated after intravenous infection.   Results  The retention time of CAS was 6.8 min. The calibration curve showed good linearity, and the precision and stability met the requirements of the assay. Transmission electron microscopy revealed that CAS-SLNs were spherical, with a particle size of 135.97±1.73 nm. The Zeta potential was 19.33±0.37 mV, drug loading was 7.55±0.68%, and encapsulation efficiency was 67.71±1.74%. CAS-SLNs showed significant in vitro antifungal inhibition with a MIC of 9.78×10−4 g/ml, which was significantly better than CAS group and the physical mixture group of CAS and GMS, as well as the same biofilm inhibition was observed(P<0.001, P<0.001). Pharmacodynamic studies demonstrated that CAS-SLNs maintained stable body weight gain compared to the control(P<0.01)and CAS groups in Candida albicans invasive infection model, and that CAS-SLNs significantly reduced renal fungal burden load relative to the CAS group (P<0.05). In vivo study revealed that a stable body weight was maintained in CAS-SLNs group compared to the control group (P<0.01)in Candida albicans invasive infection model. CAS-SLNs also significantly reduced renal fungal load compared to the CAS group(P<0.05).   Conclusion  CAS-SLNs significantly enhanced the antifungal effects of CAS in vitro and in vivo, which provided a valuable insight for the research of new formulation of CAS.
Rapid determination of tramadol in urine by surface-enhanced Raman spectroscopy
YAO Xiaojing, JI Peiying, LU Feng, SHI Guorong, FU Xiang
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202401072
Abstract(5349) HTML(1386) PDF (1577KB)(12)
Abstract:
  Objective  To establish a method for rapid detection of tramadol in urine by liquid-liquid extraction(LLE)-surface-enhanced Raman spectroscopy (SERS).   Methods  Tramadol was extracted from urine with chloroform: isopropyl alcohol (9∶1)extractant and detected in urine samples by enhanced Raman spectroscopy (wavelength 785 nm).   Results  The quantitative curve of tramadol was Y=204.35X−465.62, r=0.9952, and the linear range was 1-100 μg/ml. The detection limit of tramadol by this method (S/N=3)was 0.53 μg/ml. The sensitivity of SERS was higher than that of conventional methods, and it had reasonable reproducibility.   Conclusion  This method is simple, efficient and economical, and can be used for qualitative and quantitative analysis of tramadol personalized medicine.
Comprehensive evaluation of powder-liquid double-chamber bag products : a systematic review
SHU Fei, SUN Rui, SONG Kai, ZHANG Yuanlin, YAN Jiaming, SHU Lixin
In Press  doi: 10.12206/j.issn.2097-2024.202312009
Abstract(5796) HTML(1971) PDF (998KB)(49)
Abstract:
  Objective   Compared with traditional powder injection, the advantages of powder-liquid double-chamber bag products were comprehensively evaluated.   Methods   The systematic review method was used to collect the literature on powder-liquid double-chamber bag, extract common evaluation indicators, evaluate the use value of powder-liquid double-chamber bag products, and conduct a comprehensive comparison with traditional powder injection products.   Results   A total of 23 articles were included in the literature. The effectiveness indicators used for evaluation were the stability of the liquid medicine, the accuracy of the preparation concentration, and the residual amount of the liquid medicine; the safety indicators were the incidence of insoluble particles and the incidence of punctures and scratches. The economic indicators were preparation cost, occupied volume of preparation supplies, waste weight, hospitalization cost and incidence of blood infection. The applicability indicators were preparation time, average occupation of medical staff, packaging weight and storage and transportation volume, environmental adaptability, and ease of waste disposal. Accessibility indicators are the number of manufacturers, raw material supply capacity, and patient affordability. Through the rapid evaluation of literature evidence, it was found that the stability and concentration accuracy of the powder-liquid double-chamber bag were higher than those of the traditional powder injection, and the domestic supply had been achieved. The double-chamber bag method can reduce the infusion reaction and shorten the preparation time of the liquid medicine.   Conclusion   Compared with traditional powder injectabler products, powder-liquid double-chamber bags have advantages in the dimensions of effectiveness, safety, economy, suitability and innovation, and the accessibility dimension meets the requirements.
Analysis of characteristics of adverse drug reactions in our hospital from 2021 to 2023
SONG Hongwei, WANG Yan, FANG Ming, MA Yunpeng, ZHONG Chao, XU Yixin, XU Feng, ZHOU Ting
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202404041
Abstract(4315) HTML(1331) PDF (885KB)(21)
Abstract:
  Objective  To analyze the characteristics of adverse drug reactions (ADR) reported in our hospital from 2021-2023, to provide reference for promoting rational clinical drug use.   Methods  ADR data reported in our hospital were collected retrospectively, including patients' basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data.   Results  A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients (63.5%). The top five drugs involved with adverse reactions were antibiotics (48.8%), Chinese medicine injections, vitamins, Chinese patent medicine, equine tetanus immunoglobulin. Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage (55.4%). The clinical manifestations were rash, itching, and maculopapular rash.   Conclusion  From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital are still mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be paid attention to.
Research and Application Progress on Recognition Components for Surface Plasmon Resonance Sensors in the Pharmaceutical Field
WANG Xiaofei, ZHANG Ying, GU Jiayu, HU Xiner, ZHANG Hai, CAO Yan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309014
Abstract(6849) HTML(2314) PDF (1525KB)(12)
Abstract:
Surface plasmonresonance (SPR) sensoris anoptical detection technique enables real-time and dynamic monitoring of biological samples. SPR-based biosensors have remarkable characteristics such as label-free detection and high sensitivity, making them important tools for studying molecular interactions. The recognition element, which plays a critical role in SPR sensors, allows for specific identification and capture of target analytes, closely influencing the selectivity performance of the sensor. The progress on SPR sensors in pharmaceutical research were reviewed, which focused on the application of recognition elements such as antibodies, aptamers, molecularly imprinted polymers, and metal nanoparticles.
Determination of Lamotrigine in Human Plasma by Central cutting two-dimensional liquid Chromatography
LIN Junrong, ZHANG Minxin, ZHAO Xuemei, HUANG Aiwen
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202306020
Abstract(4072) HTML(995) PDF (1115KB)(4)
Abstract:
Objective To establish a central cutting two-dimensional liquid chromatography for the determination of lamotrigine in human plasma. Methods External standard method was used. The first dimensional chromatographic column: SNCB(T)-1A(silica gel, 4.6 mm×50 mm, 5 μm), mobile phase A:VCV-1D mobile phase, flow rate: 0.4 ml/min; mobile phase B: water, flow rate: 1.0 ml/min; second dimensional chromatographic column: Symmetry C18 (4.6 mm×250 mm, 5 μm), mobile phase: acetonitrile-10 mmol/L ammonium acetate solution(V/V=25∶75), flow rate: 1.0 ml/min; Intermediate column: SBX 4-MA(resin, 3.0 mm×10 mm, 5µm). The UV detection wavelength: 306 nm, the column temperature: 45 ℃, and the injection volume: 200 μl. Results The linear range of lamotrigine was 1.24-39.50 μg/ml, the lower limit of quantification was 1.24 μg/ml, the detection limit was 0.02 μg/ml, the intra-day precision RSD was less than 5%, the day-to-day precision RSD was less than 10%, the variation of intra-day accuracy ranged from 102.17% to 111.17%, and the daytime accuracy variation ranged from 99.80% to 107.31% the recovery RSD was less than 5%, and the variation range was 89.95% -96.16%. After 24 hours storage at room temperature, repeated freezing and thawing for 3 times and storage at-40 ℃ for 2 weeks, the ratio of the measured value / labeled value ranged from 87.01% to 115.88%. Conclusion In this study, a method with simple operation, good stability, high sensitivity and good reproducibility was established, which could be suitable for clinical monitoring of blood concentration of lamotrigine and provides reliable monitoring data support for clinical individualized medication guidance.
Study on quality standard of Andrographis paniculata standard decoction based on UPLC characteristic chromatogram and quantitative analysis of multi-components by single marker
MA Zhiling, WANG Xiaoya, DU Weibo, ZHANG Zhiqiang, SHEN Jianmei, LIU Yan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202310021
Abstract(3673) HTML(981) PDF (1585KB)(8)
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  Objective  To establish quality evaluation method of Andrographis paniculata standard decoction by UPLC.   Methods  21 batches of Andrographis paniculata standard decoctions were prepared according to the standardization method of TCM decoction pieces. The UPLC characteristic chromatograms analysis method was established. With andrographolide as a reference, quantitative analysis of multi-components by single marker(QAMS)was established for new neoandrographolide, 14 deoxyandrographolide and dehydrated andrographolide and the results were compared with the external standard method(ESM)to determine the accuracy of the method.   Results  Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 edition)was used to analyze and compare the characteristic chromatograms, and seven common peaks were determined and five were identified including luteolin-7-O-β-D-glucuronide, andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide. The RSDs of content results of each component by QAMS and ESM were all within 3%.   Conclusion  The determination method is reliable and accurate, which can be used to reflect the intrinsic quality of Andrographis paniculata standard decoction more comprehensively and provide the basis for the quality evaluation of Andrographis paniculata formula granules and other preparations.
Clinical research progress on RRx-001
GONG Yangyang, LOU Chunyang, ZHANG Huojun, MIAO Zhenyuan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202402028
Abstract(4534) HTML(1754) PDF (1796KB)(16)
Abstract:
It is difficult to treat malignant tumors, neurodegenerative diseases, and vascular diseases. For pathogenesis complexity of these diseases, researchers have focused on finding more drugs with high efficacy and low side effects. As a potential first-in-class drug, RRx-001 is expected to be an important first-line drug in tumor immunology, radiosensitizer and radio protecter. Currently, RRx-001 entered phase III clinical trials. The data of the phase II clinical trials demonstrated its safety and effectivity as a single agent and in combination with first-line clinical drugs. The novel mechanisms of RRx-001 and the result of main clinical trials were summarized, which could be valuable to further optimization and clinical application.
Application of eliminating flatulence and laxative cream in advanced hepatocellular carcinoma patients with opioid-associated constipation
HE Yalun, QI Zhi, CHANG Jie
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309009
Abstract(4529) HTML(1200) PDF (879KB)(12)
Abstract:
  Objective  To evaluate the curative effect of anti-flatulence laxative cream on patients with advanced hepatocellular carcinoma and opioid-associated constipation(OIC).   Methods  120 patients with advanced liver cancer complicated with OIC who were treated at the Third Affiliated Hospital of Naval Medical University from June 2021 to December 2022 were selected as the study subjects. The patients were divided into a control group(lactulose + conventional treatment)and an experimental group(anti-flatulence and laxative cream + conventional treatment)using a randomized numerical table method. Two groups were compared in terms of defecation, quality of life, and comprehensive post-treatment evaluation(economic cost, number of occurrences of diarrhea, and whether or not there was a change in the dosage of opioids used).   Results  After 28 days of intervention, both groups showed better results in relieving OIC(P < 0.05), and the experimental group was significantly better than the control group in terms of the quality of life of patients with advanced hepatocellular carcinoma, the economic cost and the number of diarrhea(P < 0.05).   Conclusion  In the treatment of OIC in patients with advanced hepatocellular carcinoma, constipation could be relieved by using both topical decongestant laxative cream and oral lactulose solution. Among them, anti-stagnation and laxative cream was more acceptable to patients and superior in terms of quality of life and economic cost, which could be a better choice for improving patient satisfaction and safety.
Research on the chemical compositions and their biological activities of Piper nigrum L.
GAO Xing, ZHAO Fengping, WANG Wentao, TIAN Wei, ZHENG Canhui, CHEN Xin
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202308065
Abstract(6143) HTML(4092) PDF (1638KB)(50)
Abstract:
Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.
Effects and mechanism of Triptolide on cerebral ischemia-reperfusion injury in rats
ZHU Dongjie, HE Xinzheng, ZOU Jie, YU Shidan, LI Hongxia
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202311021
Abstract(4808) HTML(1751) PDF (1393KB)(24)
Abstract:
  Objective  To investigate the effect of Triptolide on cerebral ischemia- reperfusion injury (CIRI) and explore its molecular mechanism.   Methods  One hundred and forty-four Wistar rats were randomly divided into sham operation group, model group, low, medium, high dose of triptolide group and butylphthalide group, with 24 rats in each group. The CIRI rat model was established by blocking the middle cerebral artery for 2 hours. 3 days before modeling, the rats in each group were ip administration once a day. 24 hours after reperfusion, the neurological deficit score was detected, the rate of cerebral infarction was measured by TTC staining, the blood brain barrier (BBB) permeability was detected by EB penetration test. The pathological changes neurons in the ischemic penumbra cortex were observed by HE and TUNEL staining. The content of inflammatory factors in ischemic cerebral cortex were detected by ELISA method. The expression of TLR4/NF-κB pathway related proteins were detected by Western blot.   Results  Compared with the model group, the neurological deficit score, cerebral infarction rate and EB content in the Triptolide middle, high dose groups and the Butylphthalide group were significantly decreased (P<0.05). The pathological changes of cortical neurons in the ischemic penumbra were significantly improved, and the apoptosis rate of neurons was significantly decreased (P<0.05). The content of TNF-α, IL-1β and the expression of TLR4, p-NF-κB, cleaved Caspase-3, Bax were significantly decreased, the expression of Bcl-2 was significantly increased, the ratio of p-NF-κB/NF-κB and Bax/Bcl-2 were significantly decreased (P<0.05). The regulatory effect of the high dose triptolide group on various detection indexes were better than that of the Butylphthalide group (P<0.05).   Conclusion  Triptolide could protect the permeability of BBB, improve the neurological deficit and neuropathy in CIRI rats, and reduce the rate of cerebral infarction, its mechanism may be related to the inhibition of TLR4/NF-κB pathway and which mediated inflammatory response and neuronal apoptosis.
Flavonoids from Corn Silk (Zea mays L.) and its pharmacological effects
ZHOU Licheng, OU Yiming
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309037
Abstract(6365) HTML(2221) PDF (1084KB)(23)
Abstract:
Corn silk, a Traditional Chinese Medicine, has the effect of calming liver, cholagogue, detumescence and diuresis. Corn silk is also widely used as tea and functional food. Natural flavonoids have multiple biological activities, which are also the main bioactive components of corn silk. In the past decade, many new advances have been made in the chemistry, analysis, pharmacology, pharmacokinetics, and safety evaluation of corn silk flavonoids. The chemical composition research of flavonoids has enriched the quantity of flavonoids in corn silk. Pharmacological studies have confirmed and expanded the efficacy of corn silk flavonoids. And safety evaluation has provided a theoretical basis for the safe application of corn silk flavonoids. Through literature search, the extraction, separation, compositional analysis, content determination, pharmacological effect, pharmacokinetics, and safety research progress of corn silk flavonoids in the past ten years were reviewed in this paper.
Effect of Hypoproteinemia on Cefoperazone Plasma Concentration
ZHAN Ji-hua, YAN Ying
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309040
Abstract(3843) HTML(947) PDF (833KB)(7)
Abstract:
  Objective   To analyze the effect of hypoproteinemia on the use of cefoperazone in patients, and provide references for the rational use of cefoperazone in clinical practice.   Methods   Clinical data of patients with cefoperazone blood concentration monitoring in our hospital from July 2021 to March 2022 were collected, and divided into low albumin group and normal albumin group according to different albumin concentration. Statistical analysis were conducted based on gender, age, laboratory examination, cefoperazone valley concentration and clinical efficacy of the two groups.   Results   Age, gender, inflammation and liver function of two groups had not shown statistical difference (P>0.05). Low protein group had significantly higher levels of creatinine than those in group with normal albumin (P<0.05). The trough concentration of cefoperazone in the low protein group was 46.29±36.94 mg/L, and that in the normal albumin group was 38.18±33.79 mg/L. Among the low protein patient group, the plasma concentration of cefoperazone in those treated with human albumin was significantly higher than that in the patients without human albumin treatment (P<0.05). Comparison of the clinical efficacy of the two groups revealed that the low protein group had a lower clinical response rate (P<0.05).   Conclusion   Supplementation of human serum albumin in patients with hypoproteinemia could increase the plasma concentration of cefoperazone, and correcting hypoproteinemia could be helpful for anti-infection treatment.
Effect of Huoxin Pill (concentrated pill) combined with Baduanjin on prognosis after interventional operation of acute myocardial infarction complicated with heart failure
WANG Peng, WU Zonggui, ZHANG Zhengyan
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202308034
Abstract(3935) HTML(1291) PDF (890KB)(15)
Abstract:
  Objective  To observe the effect of Huoxin Pill (concentrated pill) combined with Baduanjin on the prognosis of patients with acute myocardial infarction complicated by Percutaneous Coronary Intervention (PCI).   Methods  120 Patients with acute myocardial infarction complicated with heart failure who received emergency interventional treatment in our hospital from January 2022 to January 2023 were randomly divided into Western medicine treatment group and Traditional Chinese Medicine (TCM)comprehensive treatment group. Western medicine treatment: standard Western medicine treatment + five prescriptions for cardiac rehabilitation; Based on Western medicine treatment, Huaxin pill (concentrated pill) combined with Baduanjin therapy was added to the TCM comprehensive treatment group, and the follow-up was 6 months. The observed indexes were exertion angina pectoris scale, Chinese Medicine Syndrome Scale, Chinese medicine syndrome treatment effect evaluation, 6-minute walking test (6MWT), left ventricular ejection fraction (LVEF), and brain natriuretic peptide precursor (pro-BNP).   Results  Sixty patients were enrolled in the two groups respectively. During the treatment, 2 cases fell off in the Western medicine treatment group and 8 cases fell off in the TCM comprehensive treatment group, and a total of 110 cases were enrolled in the group. Compared with the western treatment group, TCM combined therapy significantly improved angina pectoris scale score, TCM Syndrome Scale score, pro-BNP, LVEF and 6MWT (P < 0.001). There were no significant differences in blood routine, liver and kidney function, potassium, blood glucose, blood lipids and cardiac Troponin I (cTnI) between the two groups (P > 0.05). No adverse cardiovascular events occurred during the entire treatment period in both groups.   Conclusion  Huaxin Pill (concentrated pill) combined with Baduanjin was more effective than Western therapy in improving LVEF, 6MWT distance, exercise tolerance and cardiac function in patients with acute myocardial infarction complicated with heart failure.
The protective effect of Rongmu Fugan Formula on ANIT induced liver injury in mice with cholestasis
YANG Nian, YANG Liu, ZHENG Sijia, ZHANG Junxia, XU Huaming
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202305008
Abstract(4513) HTML(1631) PDF (1663KB)(21)
Abstract:
  Objective  To explore the protective effect of Rongmu Fugan Formula on ANIT induced cholestasis liver injury in mice.   Methods  8-week old SPF Kunming mice were randomly divided into 6 groups, 10 mice in each group which were the blank control group (normal saline gavage), the model control group (normal saline gavage), the low (gavage dose:5.25 g/kg ) group, the medium (11.25 g/kg) group and the high (20.25 g/kg) group of Rongmu Fugan Formula, the positive control (Ursodeoxycholic acid, UDCA,0.1 g/kg). Mice were administered with continuous gavage once a day, for 7 consecutive days. On the 5th day, the blank normal control group was given an equal amount of olive oil by gavage, all other groups were given ANIT (65 mg/kg) by gavage for modeling. After 48 hours of modeling, 30 minutes after the last administration of each group of mice, blood and liver tissue samples were collected for testing of various indicators. The corresponding kits were used to detect the content of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bile acid (TBA),γ-glutamyl transpeptidase(γ-GT), total bilirubin (TBIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in peripheral blood of mice, respectively. HE staining was used to observe the pathological changes in the liver of mice.   Results  Compared with the model group, each dose group of Rongmu Fugan Formula reduced the levels of ALT, AST, AKP, TBA, TBIL,γ-GT and MDA (P<0.05) significantly, markedly increased the levels of SOD and GSH-PX (P<0.05). Compared with the model group, the low-dose and high-dose groups of Rongmu Fugan Formula showed a decrease in liver cell vacuolar degeneration and reduction in inflammatory infiltration. In the medium dose group, the vacuolar degeneration of liver cells was significantly reduced, the inflammatory infiltration was significantly improved, the liver cells were arranged in cords, and the structure of lobules of liver was intact.   Conclusion  Rongmu Fugan Formula could improve serum biochemical indicators of liver injury, reduce jaundice and eliminate oxidative free radicals, thereby exerting a protective effect against ANIT-induced cholestatic liver injury in mice.
Study of 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
In Press  doi: 10.12206/j.issn.2097-2024.202204094
Abstract(5168) HTML(2724) PDF (839KB)(43)
Abstract:
  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 Luodian Hospital of Baoshan District of Shanghai from June to December of 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(COPD assessment test)≥10 points, used 2 inhalation devices and inhalation technique score ≥8 points had better compliance when compared with other patients (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 devices should be strengthened and regularly follow-up evaluation should be carried out.
Analysis of the chemical constituents of Maxing Shigan decoction by UPLC-Q-TOF/MS
ZHAO Xue, GU Yanqiu, CHU Haowen, WU Caisheng, LI Gao, CHEN Xiaofei
In Press  doi: 10.12206/j.issn.2097-2024.202306028
Abstract(5427) HTML(1578) PDF (1510KB)(20)
Abstract:
  Objective  To analyze chemical constituents of compound Maxing Shigan decoction by ultra-high perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS).   Methods  The separation was performed on a UPLC BEH C18 column (2.1 mm×100 mm, 2.5 µm), with a gradient elution applying 0.1% aqueous formic acid solution and 0.1% formic acid acetonitrile as a mobile phase. The column temperature was 40 °C. The flow rate was 0.4 ml/min and the analysis time was 15 min. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes.   Results  Through UPLC-QTOF/MS analysis and reference validation, a total of 59 chemical components in Maxing Shigan decoction were identified.   Conclusion  In this study, an ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method was established to identify the chemical components of Maxing Shigan decoction. This method is simple, efficient, sensitive and accurate, and provides a basis for the elucidation of the pharmacodynamic material basis and mechanism of Maxing Shigan decoction. It can provide data reference for the optimization of the compatibility of traditional Chinese medicine in the treatment of COVID-19.
Molecular mechanism of Shenling Baizhu powder in treatment of cancer cachexia based on network pharmacology
KE Gang, DONG Qingke, XIAO Shirong, GONG Qian, LI Rong, WANG Daijie
In Press  doi: 10.12206/j.issn.2097-2024.202208115
Abstract(6846) HTML(1864) PDF (3143KB)(35)
Abstract:
  Objective   To analyze the pharmacological mechanism of Shenling Baizhu powder in the treatment of cancer cachexia based on the network pharmacological method and provide a reference for the clinical application of classical traditional Chinese medicine(TCM) prescriptions.   Methods   Through TCMSP and BATMAN-TCM databases, the main chemical components and their targets of the TCM prescription of Shenling Baizhu powder were obtained, and the active components of the TCM were screened according to ADME. The main targets of cancer cachexia were obtained through OMIM, Genecards, Disgenet and DRUGBANK databases, and protein interaction analysis was conducted using String platform to build a PPI network. The “drug active ingredient target” network of Shenling Baizhu powder was constructed by Cytoscape 3.7.2 software, and then the biological processes and pathways involved were analyzed by using Metascape platform. Finally, molecular docking verification was conducted by Discovery Studio.   Results  The core active ingredients of Shenling Baizhu powder in the treatment of cancer cachexia are quercetin, kaempferol, pyrolignous acid, stigmasterol, luteolin, β-sitosterol, etc. The core targets are AKT1, TP53, TNF, IL-6, MAPK3, CASP3, JUN, CTNNB1, HIF1A, EGFR, etc. The molecular docking test also showed that the top 10 active ingredients, such as pyrolignous acid, stigmasterol and β-sitosterol, had good binding activities with most of the target sites. The biological pathway of Shenling Baizhu powder in treating cancer cachexia is mainly to regulate tumor related pathway, metabolism related pathway, inflammatory factors and appetite related pathway.  Conclusion  This study preliminarily revealed the mechanism of action of Shenling Baizhu powder in treating cancer cachexia with multi components, multi targets and multi pathways, which provided a basis for the clinical development and utilization of Shenling Baizhu powder.
The mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics technology
WAN Lizhi, WANG Jinghan, WU Chunrong, LI Ling
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202307034
Abstract(4818) HTML(1308) PDF (1598KB)(26)
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  Objective   To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics.   Methods  The intracellular metabolites of C. albicans intervened by different drugs including NAM, AmB, and their combination with a proper concentration were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database.   Results   Compared with the control group, the NAM intervention group was hardly separated from it, while the AmB group and NAM+AmB group showed a clear trend separation. Under the intervention of AmB, 23 metabolites significantly changed compared with the control group, and 28 metabolites remarkably changed after NAM+AmB intervention, including amino acids, organic acids, sugars and other components.   Conclusion  NAM, as an endogenous metabolite of C. albicans, combined with AmB could enhance the effects of AmB in the original metabolic pathway and changed it to a certain extent. It is speculated that AmB combined with NAM may pose more antifungal effect on Candida albicans by regulating the tricarboxylic acid cycle, interfering with amino acid metabolism and influencing polyamine synthesis.
In Press
Abstract(5713) HTML(1284) PDF (699KB)(89)
Abstract:
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.
Abstract(2965) HTML(900) PDF (0KB)(326)
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Lactic acid bacteria as recombinant protein drug delivery carrier
WANG Xufang, WANG Yanting, YAO Chunmeng, LU Bin
Accepted Manuscript  doi: 10.12206/j.issn.2097-2024.202309021
Abstract(6873) HTML(2235) PDF (863KB)(67)
Abstract:
Lactic acid bacteria is a good candidate in living drug delivery system for its safety, beneficial nature, and intestinal colonizability. At present, most studies use it as a protein drug delivery carrier for disease treatment. As a model organism, a variety of gene modification schemes enable it to be applied to various diseases and can play a significant therapeutic effect. Lactic acid bacteria drug carrier has many advantages, including non-invasive drug delivery, gene editing, large-scale production Therefore, the use of lactic acid bacteria as recombinant protein expression vector has attracted global attention. In this review, the application basis, bioavailability improvement, gene editing strategy and research and application status of lactobacillus drug delivery system were summarized.
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(6252) HTML(1415) PDF (2083KB)(24)
Abstract:
  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.
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(5602) HTML(1627) PDF (999KB)(22)
Abstract:
  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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Progress on the treatment of sepsis
SONG Zecheng, CHEN Linlin, LU Renyi, LIU Mengxiao, WANG Yan
2024, 42(11): 457-460, 502.   doi: 10.12206/j.issn.2097-2024.202405059
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Sepsis is a severe and life-threatening symptom that poses a significant risk to human health. Treatment mainly involves supportive care, but research on new drugs is ongoing. Advancements have been achieved in the management of immune function, inflammatory pathway, blood coagulation, and vascular endothelial homeostasis in sepsis. The advances in the treatment of sepsis in recent years were these reviewed in this article.
Original articles
Identification and expression pattern analysis of FBXL gene family in Salvia miltiorrhiza
YAO Ruiyang, YU Haizheng, LI Yaoxin, ZHANG Lei
2024, 42(11): 461-470.   doi: 10.12206/j.issn.2097-2024.202407034
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  Objective   To identify and analyze the bioinformatics and expression patterns of the F-box-LRR(FBXL) gene family of Salvia miltiorrhiza based on genomic data, and provide a foundation for further elucidating its gene functions.   Methods  The SmFBXL gene was identified from the Salvia miltiorrhiza genomic database. Its gene structure features, promoter cis-acting elements, physicochemical properties of encoded proteins, evolutionary relationships, and tissue expression were analyzed by bioinformatics methods and online tools.   Results  A total of 104 SmFBXL genes were identified from the Salvia miltiorrhiza genome, unevenly distributed on 8 chromosomes, with upstream promoters containing cis-acting elements related to plant stress resistance, growth and development, and hormone response. A phylogenetic tree of the FBXL family members of Salvia miltiorrhiza, Arabidopsis thaliana, and Glycine max was constructed, dividing the 104 SmFBXL genes into 7 subfamilies. Through homologous evolution analysis, it was speculated that SmFBXL36 might be involved in defense against pathogen invasion, SmFBXL86 and SmFBXL79 might play important roles in regulating lateral root growth in Salvia miltiorrhiza, and SmFBXL11 and SmFBXL40 might regulate hypocotyl growth. Transcriptome data showed differential expression of SmFBXL genes in different tissues of Salvia miltiorrhiza, with 13 SmFBXL genes showing higher expression levels in roots and leaves, serving as candidate genes for further research on the SmFBXL gene family.   Conclusion  The research results provided a reference for further elucidating the regulatory mechanisms of SmFBXL genes in stress response and secondary metabolite biosynthesis in Salvia miltiorrhiza.
Study on the potential mechanism of JQQSG for the treatment of CAP based on network pharmacology and molecular docking technology
CHEN Jintao, QIAO Ziying, MA Minghua, ZHANG Ruoxi, WANG Zhenwei, NIAN Hua
2024, 42(11): 471-478.   doi: 10.12206/j.issn.2097-2024.202312014
Abstract(5605) HTML(2009) PDF (2177KB)(69)
Abstract:
  Objective  To investigate the possible mechanism of action of Jinqi Qingshu granules (JQQSG) in the treatment of community-acquired pneumonia (CAP) by network pharmacology and molecular docking technology.   Methods  The TCMSP database and SwissTargetPrediction database were used to obtain and screen the active ingredients and targets of JQQSG, and GeneCards, OMIM, TTD, and DisGeNET databases were used to search for the predicted targets of CAP, and the two targets were mapped and then imported into STRING database to construct a PPI network to screen the key targets, and then the GO and KEGG pathway enrichment were analyzed by the DAVID database, and molecular docking was carried out by the AutoDock Tools software.   Results  209 active ingredients and 1041 targets of JQQSG were obtained after screening; 312 targets were co-activated with CAP, and 64 core targets were obtained after PPI network screening. 571 biological processes, 68 cellular components, and 199 molecular functions were analyzed by GO enrichment, and 165 KEGG pathways were analyzed by KEGG pathway enrichment, mainly involved in protein action, apoptosis and MAPK signaling pathway. Molecular docking suggests that the core target and the core components all have good binding ability.   Conclusion  The mechanism of action of JQQSG in the treatment of CAP may be related to its regulation of Akt, MAPK signaling pathway, improvement of oxidative stress, and other pathways to exert anti-inflammatory and antioxidant effects, which could lay the foundation for further in-depth study of its specific mechanism of action.
Mechanism of effective ingredients of Dingqing tablets in the treatment of leukemia based on network pharmacology and molecular docking technology
CHEN Jing, HE Ruihua, WENG Yue, XU Yi, LIU Jing, HUANG Jin
2024, 42(11): 479-486.   doi: 10.12206/j.issn.2097-2024.202401073
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  Objective  To explore the material basis and mechanism of the Chinese medicine Dingqing tablets in the treatment of leukemia.   Methods  The potential active ingredients of Dingqing tablets were retrieved through TCMSP and HERB Database and the targets of herbs were screened by Swiss TargetPrediction databases. The treatment targets of leukemia were searched from the GeneCards, OMIM and Disgenet databases. The protein-protein interaction network was used to construct the interactive target regulation function of Dingqing tablets and leukemia by STRING software, and the core subnetworks were filtered by the MCODE plug-in. A component-target pathway network was constructed by GO and KEGG enrichment analysis of the highest scoring Gene cluster 1 gene in the DAVID database. Molecular docking of the active components and core targets of Dingqing tablets was performed by AutoDock and the results were visualized.   Results  A total of 82 active ingredients and 439 targets of action of Dingqing tablets, and 1 878 leukemia-related targets were obtained through database retrieval, in which 169 common targets of active ingredients and diseases were mapped. Based on the degree values, the main active ingredients were determined as quercetin, luteolin, kaempferol, etc. The PPI core network indicated that the key targets for treating leukemia included TP53, MMP9, TNF, AKT1, CASP3, etc. The gene enrichment analysis of sub-networks and the component-target pathway network diagram showed that Dingqing tablets might exert therapeutic effects on leukemia by regulating signaling pathways such as TNF and IL-17. The molecular docking results showed fairly strong binding activity between the active ingredients and the targets.  Conclusion  The active ingredients of Dingqing tablets may participate in TNF, IL-17, and other signaling pathways by regulating genes such as TP53, AKT1, and CASP3, thereby exerting therapeutic effects on leukemia.
Effects of MT-1207 on blood glucose, blood lipids and atherosclerosis in mice
ZHANG Xiuping, TIAN Jiasheng, WANG Daoxin, LI Jiaxin, WANG Pin, MIAO Chaoyu
2024, 42(11): 487-494.   doi: 10.12206/j.issn.2097-2024.202306011
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  Objective  To study the effect of MT-1207 on blood glucose, blood lipids and atherosclerosis in mice.   Methods  The apolipoprotein E knockout (ApoE-/-) mice were fed with normal feed, drug feed containing losartan and drug feed containing MT-1207 at a dosage of 30 mg/kg. The body weight, blood glucose and blood lipids were detected, and the plaque area of atherosclerotic was evaluated. 8-week-old male C57 mice were fed a high fat diet and given intragastric administration of MT-1207 and losartan at a dose of 30 mg/kg per day. The body weight, blood glucose and lipids levels were also examined to further evaluate the effects of MT-1207 on blood glucose and lipids levels.   Results  ApoE-/- mice treated with MT-1207 and losartan gained weight faster. There was no significant improvement in blood glucose and lipid levels, and no significant change in atherosclerotic plaque area. MT-1207 and losartan had no significant improvement effect on blood glucose and blood lipids of C57 mice.   Conclusion  MT-1207 and losartan couldn’t improve the levels of blood glucose, blood lipids and atherosclerosis, and couldn’t aggravate atherosclerosis.
Optimization of the preparation process for lenvatinib mixed micelles by central composite design-response surface methodology
KAILIBINUER Aobuliaisan, LI Qian, XIE Zhi, JIA Wenyan, YIN Dongfeng
2024, 42(11): 495-502.   doi: 10.12206/j.issn.2097-2024.202403019
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Abstract:
  Objective  To optimize the formulation and preparation process of lenvatinib mixed micelles.   Methods  Hybrid micelles of lenvatinib were prepared by film hydration method, with Pluronic P123 and F127 as carrier materials. Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology, and preliminary characterization of its physical properties was conducted.   Results  The optimized formulation and process conditions were identified as follows: P123 mass percentage of 80%, carrier material amount of 90 mg, drug loading of 10 mg, hydration volume of 6 ml, hydration time of 45 min, and rotary evaporation temperature of 55℃. The resulting lenvatinib mixed micelles had an average particle size of (104.0±0.32) nm, a polydispersity index (PDI) of 0.22±1.19, and a Zeta potential of (−2.56±0.81) mV. The average encapsulation efficiency was 83.33%±0.30% and the average drug loading was 8.67%±0.07%. The micelles displayed a uniform spherical morphology with a certain sustained-release capability.   Conclusion  The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates, and stable release, which could provide valuable insights for further research and development of lenvatinib mixed micelles.
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ISSN 2097-2024   CN  31-2185/R

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