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  • Xiao-dong LI, Xin-ci REN, Wei SUN, Guang-chuan WANG, Pian-pian SANG, Fang WANG, Wen QIAN, Jing WANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(9): 704-710.

    AIM To analytical hierarchy process (AHP) and technique for order preference by similarity to an ideal solution (TOPSIS) were used to evaluate the rationality of the use of sacubitril valsartan in the treatment of chronic heart failure, to provide a reference for clinical pharmacists to intervene and promote the rational use of clinical drugs. METHODS Based on the drug instruction of sacubitril valsartan, treatment guidelines, expert consensus and relevant literature, the evaluation criteria for the rational use of sacubitril valsartan in the treatment of chronic heart failure was established, and the AHP method was used to assign weights to the indicators and the TOPSIS method was used to evaluate the rational use of sacubitril valsartan in the treatment of chronic heart failure in our hospital records from January 2022 to June 2022. RESULTS The top 5 indicators with higher weight of the established evaluation criteria were 0.277 8 for indications, 0.199 6 for prohibited combination, 0.176 3 for combination therapy, 0.114 0 for dose administration and 0.081 5 for drug conversion. Ninety medical records were included, of which 22 cases (24%) were evaluated as reasonable medication use, 50 cases (56%) as basic reasonable medication use and 18 cases (20%) as unreasonable medication use. CONCLUSION The AHP-weighted TOPSIS method can be used to evaluate the rationality of sacubitril valsartan in the treatment of chronic heart failure, which can identify problems in clinical application, provide a basis for pharmacological intervention by clinical pharmacists and promote rational drug use in clinical departments.

  • Xiang CAI, Ling-hua LI, Zong-bi QIN, Bai-yi QIU, Ya-nan HE
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(9): 710-715.

    AIM To investigate the effects of salidroside ( Sal) on the proliferation, migration and collagen synthesis of human keloid fibroblasts ( HKF) by regulating Notch1/Hes1 pathway. METHODS HKF in logarithmic growth period was divided into control group ( NC group), Sal-L, Sal-M, Sal-H ( 10, 20, 40 μmol·L-1) group, Jagged1 group (Notch activator,5 mg·L-1), Sal ( 40 μmol·L-1) + Jagged1 (5 mg·L-1) group. MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration was detected by scratch test, and Western blot was used to detect the expression of collagen-Ⅰ, collagen-Ⅲ, proliferating cell nuclear antigen ( PCNA), matrix metalloproteinase-2 (MMP-2), Notch1 and Hes1 proteins. RESULTS Compared with the NC group, the A value, the proportion of cells in S phase and G2/M phase decreased, scratch healing rate decreased, the protein expression of collagen-Ⅰ, collagen-Ⅲ, PCNA, MMP-2, Notch1 and Hes1 decreased in the Sal-L, Sal-M and Sal-H group, the proportion of cells in G0/G1 phase and the rate of apoptosis increased, in a dose-dependent manner ( P<0.05), while the Jagged1 group showed the opposite change of the above indexes. Compared with the Sal-H group, the A value, the proportion of cells in S phase and G2/M phase, scratch healing rate, the protein expression of collagen-Ⅰ, collagen-Ⅲ, PCNA, MMP-2, Notch1 and Hes1 increased, the proportion of cells in G0/G1 phase and the rate of apoptosis decreased in the Sal group ( P<0.05). CONCLUSION Sal may inhibit the proliferation, migration and collagen synthesis of HKF by inhibiting Notch1/Hes1 pathway.

  • Yan-gai WANG, Xiang-rong BAI, Qing-xia ZHANG, Yan-qi CHU, Lan ZHANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(9): 716-720.

    AIM To investigate the clinical features of tacrolimus-related epilepsy, and provide reference for clinical rational antiepileptic drug use. METHODS Related domestic and foreign databases (both up to June 2023) were searched, and case-report literature on tacrolimus-related epilepsy were collected. Clinical information was extracted and analyzed by descriptive statistical method, including patient’s basic characteristics, tacrolimus application (such as indications, dose, route of administration, and blood concentration), and the occurrence time, clinical manifestation, imaging characteristics, intervention measures, and outcomes of epilepsy. RESULTS A total of 11 patients were enrolled in the study, including 6 males and 5 females, aged from 2 years 11 months to 63 years, with a median age of 44 years. In terms of indications, there were 2 cases of hematopoietic stem cell transplantation, 3 cases of kidney transplantation, 4 cases of liver transplantation,1 case of nephrotic syndrome, and 1 case of primary membranous nephropathy. Nine patients underwent tacrolimus plasma concentrations testing, and 3 of them exceed the upper limit of the treatment window when seizure occurred. Epilepsy mainly appeared in d1 to d44 of tacrolimus use. MRI examination in 4 patients showed abnormal signal shadows near the sickle, mild demyelinating of white matter, and patchy abnormal signals around the lateral ventricles. CONCLUSION Tacrolimus-related epilepsy are primarily caused by increased blood concentrations of tacrolimus. It is essential to strengthen the monitoring in clinical application of tacrolimus and provide active symptomatic treatment.

  • Group for Expert Consensus on Grading Criteria for Adverse Events of Phase Clinical Trials in Healthy Subjects, Drug Clinical Trial Committee of Shanghai Pharmacological Society
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 561-567.
  • Zhong-ling ZHU, Ye-hui SHI
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 568-573.

    Glutamine (Gln) is the key carbon and nitrogen donor and energy source of the body. It is not only a critical player in tumorigenesis but also involved in regulating the development and activation of immune cells. Rapidly proliferating tumor cells will obtain a large amount of nutrients from the tumor microenvironment, leading to depletion of Gln, which significantly inhibits the activity and function of T cells and induces T cell exhaustion. The proliferation of tumor cells was suppressed by Gln metabolism inhibitors, including Gln mimetics, glutaminase inhibitors,and Gln transporter inhibitors. Meanwhile, T cell depletion was not further aggravated. Instead, the tumor microenvironment was improved to enhance the antitumor immune response by regulating multiple mechanisms such as immune checkpoint molecule expression,extracellular matrix structure remodeling, and tumor-associated macrophage polarization. Combining Gln metabolic inhibitors with immune checkpoint inhibitors can also exert synergistic effects.

  • Wan MU, Ying-zhuo DING, Yu-fei XI, Shen-yu BEN, Bin CHEN, Ling GE
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 574-581.

    Glaucoma, a leading cause of irreversible blindness worldwide, primarily involves pathological elevation of intraocular pressure (IOP), which is its main risk factor, so the clinical goal in treating glaucoma is to reduce IOP to individual target levels. Currently, the classical local anti-glaucoma drugs include five categories: prostaglandin analogues(PGAs), β-adrenergic receptor blockers, α2- adrenergic receptor agonists, carbonic anhydrase inhibitors, and cholinergic receptor agonists. These drugs mainly work by reducing aqueous humor production, increasing aqueous outflow through the trabecular pathway and the uveal scleral pathway, and contracting the pupil sphincter to open the chamber angle. Among these, PGAs have become the preferred choice for controlling IOP in primary open-angle glaucoma patients due to their efficacy and safety. In recent years, the introduction of novel glaucoma medications, including Rho kinase inhibitors and nitric oxide-donating anti-glaucoma drugs, along with the development of related drug-releasing formulations (intraocular and extraocular drug delivery systems), offers new options for glaucoma treatment.

  • Na MOU, Yang ZHUO, Min-jie GAO
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 582-586.

    In order to establish a technical evaluation system in line with the characteristics of traditional Chinese medicine (TCM) and promote the inheritance and innovative development of TCM, China is building a TCM registration and evaluation evidence system combining TCM theory, human experience, and clinical trials. Human experience is of great significance to support the registration and evaluation of new drugs of TCM. Based on the survey of 20 medical institutions in Shanghai, this paper analyzed the current situation and common problems of human experience collection of TCM. It was found that medical institutions had been aware of carrying out human experience collection for the development of TCM preparations or new drugs. However, the hardware conditions, personnel capabilities, and the importance of medical institutions in collecting human experience were still not optimistic. There were difficulties in the collection process. 90%of institutions believed that the quality of collected data did not meet the requirements of drug registration. Regulators and medical institutions should work together to improve and standardize the collection of human experience of TCM by improving collection methods, increasing research capabilities, strengthening the construction of information systems, and enhancing research quality management according to GCP principles, so as to ultimately obtain high-quality evidence materials to support the innovation and transformation of TCM.

  • Jing LI, Xue TANG, Yong HUANG, Qiang WANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 587-594.

    Risk minimisation measure (RMM) is a critical step to maximize the benefit-risk ratio of a medicinal product in pharmacovigilance activities. Through literature review and consulting the websites of major healthcare authorities in Europe Union, the USA, and Japan, this paper reviewed the RMM regulatory requirements and implementation status of these countries and regions. It was found that Europe, the USA, and Japan established relevant regulations earlier and accumulated valuable experience, and the specific implementation and supervision intensity of RMM varied among regions due to differences in medical systems. For example, additional risk minimization measures in Japan and the European Union are presented as risk evaluation and mitigation strategies in the USA. It is suggested that RMM-related regulations and supervision system should be continuously improved, and the marketing authorization holders in China should develop RMM implementation plans that conform to the actual conditions of China based on foreign experience and combined with the current situation of local medical system, and conduct feasible and efficient RMM effectiveness assessment to ensure patient medication safety.

  • Shan WU, Guo-ting ZHAO, Zhen-yao DONG, Xiu-hua MA, Yi-zhang YAO
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 594-599.
    AIM

    To observe the influences of ginsenoside Rb1 (GsRb1) on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), and its molecular mechanism related to stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) pathway.

    METHODS

    hPDLSCs were isolated and cultured by enzyme digestion method. Cell morphology was observed under an inverted microscope. Flow cytometry was used to detect the proportion of stromal cell antigen 1 (STRO-1) and cluster of differentiation 146 (CD146) positive cells. hPDLSCs were treated with 0, 0.5, 1.0, 2.0, 4.0, 6.0 μmol·L-1 GsRb1, respectively, and the optimal concentration was screened by CCK-8 method. hPDLSCs were divided into control group, GsRb1 (4.0 μmol·L-1) group, AMD3100 (5 μg·mL-1) group, and GsRb1+AMD3100 group, the cell proliferation and alkaline phosphatase (ALP) activity of each group were compared, the mRNA expression of Runt-related gene 2 (Runx2), oxterix, and osteopontin (OPN) were detected by qRT-PCR, and the formation of mineralized nodules in hPDLSCs was detected by alizarin red staining and quantitative analysis. Western blot was used to detect the expression of SDF-1/CXCR4 signaling pathway-related proteins.

    RESULTS

    hPDLSCs were arranged radially, with long spindles, and the growth was relatively dense. The proportions of STRO-1 and CD146 positive cells were 97.19% and 98.01%, respectively. With the increase of GsRb1 concentration, the proliferation activity of hPDLSCs was enhanced in a dose-dependent manner (P<0.05). Compared with the control group, the cell viability and ALP activity in the GsRb1 group were enhanced, and the mRNA expression of Runx2, oxterix, OPN, the amount of mineralized nodules, and the protein expression of SDF-1 and CXCR4 were increased (P<0.05), while the AMD3100 group was the opposite (P<0.05).Compared with the GsRb1 group, the cell viability and ALP activity in the GsRb1+AMD3100 group were decreased, and the mRNA expression of Runx2, oxterix, OPN, the amount of mineralized nodules, and the protein expression of SDF-1 and CXCR4 were decreased (P<0.05).

    CONCLUSION

    GsRb1 can promote the proliferation and osteogenic differentiation of hPDLSCs, which may be related to the increased protein expression of SDF-1/CXCR4 signaling pathway.

  • Ting-ting WU, Fan YANG, Ke CHANG, Chun-xia REN, Zi-cheng YU
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(8): 600-606.
    AIM

    To study the anti-tumor effect of icotinib combined with metformin on non-small cell lung cancer (NSCLC) H1975 cells and its possible mechanism.

    METHODS

    CCK-8 assay was used to detect the proliferation inhibitory effect and combination index (CI) of icotinib monotherapy (0, 0.1, 1, 5, 10, 20, 40 μmol·mL-1), metformin monotherapy (0, 2, 4, 8, 16, 32, 64 mmol·mL-1), and icotinib (0, 0.125, 0.25, 0.5, 1 times of IC50) combined with metformin (0.5 times of IC50) on the H1975 cells. The migratory ability of the cells was detected by scratch test,and the invasive ability of the cells was detected by invasion test. Annexin V-FITC/PI flow cytometry was used to detect the rate of apoptosis. Western blot was used to detect the expression level of related proteins.

    RESULTS

    The IC50 of icotinib and metformin for the inhibition on H1975 cells after 48 h were (49.90±4.84) μmol·mL-1 and (13.20±1.27)mmol·mL-1, respectively. Icotinib and metformin produced a synergistic effect in H1975 cells(CI<1). Compared with the metformin group and the icotinib group, the migration rate and invasion ability of combination group were significantly decreased, and the apoptosis rate was significantly increased (P<0.05);the expression of p-Akt, p-mTOR and Bcl-2 were significantly decreased, while the expression of p-AMPK and Bax were significantly increased (P<0.05).

    CONCLUSION

    Icotinib and metformin have significant synergic antitumor effects and proapoptotic effects on non-small cell lung cancer H1975 cells, and the underlying mechanism may be related to enhancing activation of AMPK and inhibition of Akt/mTOR signaling pathway.