Latest ArticlesAcne vulgaris is one of the most common skin diseases in dermatology. Retinoids are commonly used in the treatment of this disease. Trifarotene is derived from CD437, a triaryl skeleton lead compound with retinoic acid receptor subtype selectivity, after the optimization of receptor structure. It is called the fourth generation retinoic acid anti-acne drug because of its high selectivity for retinoic acid γ receptor（RAR-γ）. In October 2019, trifarotene was approved by the U.S.Food and Drug Administration for the treatment of acne vulgaris in patients aged 9 and above. Clinical trials have shown that trifarotene is safe, effective and well tolerated in the treatment of acne vulgaris, which has a good clinical application prospect.
To investigate the role of miR-17-5p in mediating cisplatin（DDP）resistance in breast cancer cells by regulating the PTEN/Akt pathway.
MCF-7/DDP-resistant cell line was cultured with a gradient of increasing DDP concentrations. The content of miR-17-5p was detected in MCF-7 and MCF-7/DDP cells by RT-qPCR. MCF-7 cells were divided into miR-NC and miR-17-5p groups, and transfected with miR-NC and miR-17-5p mimics plasmids,respectively. MCF-7/DDP-resistant cells were divided into anti-miR-NC and anti-miR-17-5p groups, and transfected with anti-miR-NC and anti-miR-17-5p plasmids, respectively. Transfection efficiency was defined by RT-qPCR. The drug sensitivity of DDP in each group of transfected cells was evaluated by MTT. The direct effect of miR-17-5p on the invasive ability was obtained by Transwell assay. DDP-induced apoptosis of MCF-7 and MCF-7/DDP cells after transfection was analyzed by flow cytometry. The targeting relationship between miR-17-5p and PTEN was verified by double luciferase reporter gene assay. The changes of apoptosis and key proteins of PTEN/Akt pathway under the regulation of miR-17-5p were detected by Western blot.
Compared with MCF-7 cells, the miR-17-5p expression in MCF-7/DDP-resistant cells was abnormally increased, while the PTEN expression was reduced（P<0.01）. PTEN was regulated by miR-17-5p as a target gene. Compared with the miR-NC group, the proliferation inhibition rate in the miR-17-5p mimics group was significantly declined, the number of invaded cells was enhanced, and the apoptosis rate was also decreased（P<0.05）, and the expressions of tumor suppressor proteins PTEN, p21 and p27 in the PTEN/Akt pathway were decreased, and the expressions of p-Akt308, p-Akt473 and cyclin D1 were increased（P<0.01）. Compared with the anti-miR-NC group, the proliferation inhibition rate was increased in the anti-miR-17-5p group, the number of invaded cells was decreased, and the apoptosis rate was also increased（P<0.05）, and the expression of tumor suppressor proteins PTEN, p21 and p27 was increased, and the expression of p-Akt308, p-Akt473 and cyclin D1 was decreased（P<0.01）.
Knockdown of miR-17-5p can effectively improve the DDP sensitivity of breast cancer cells, attenuate the invasive ability, and induce further apoptosis,which may be related to the regulatory effect of miR-17-5p on the PTEN/Akt pathway.
To explore the current research progress, research status, and future development directions in the field of traditional Chinese medicine（TCM）innovation.
CiteSpace software was used to analyze the paper trends and keywords in domestic journal articles between 1999 and 2023, and keyword clustering analysis, drawing timeline mapping,and emergent word analysis were used to visualize the field of Chinese medicine innovation in China.
The number of TCM innovation-related publications showed a fluctuating upward trend year by year. The research is still dominated by the researchers’ respective teams and lacks relevant team cooperation. The development of TCM research has entered a rapid development stage, which has envolved from the traditional research direction such as prescription research and development,it has developed to the construction of TCM data platform and intelligent production in the industry.
Research in the field of TCM innovation in China is developing steadily and undergoing a transformation towards diversification,digitization, and intelligence.
Chinese materia medica genetic resources are important biological and health resources. With the increasing reliance on Chinese materia medica genetic resources in various fields, bio-piracy against Chinese materia medica genetic resources is becoming more and more frequent and has posed a threat to China’s ecological security and the rights of people’s lives and health. However, the system of the source disclosure of genetic resources established by China’s Patent Law, as well as the use of contractual mechanisms to achieve access to Chinese materia medica genetic resources and benefit-sharing, are both inadequate and unable to effectively deal with the problem of bio-piracy. Therefore, in order to safeguard the rights and interests，China, as a party to the Convention on Biological Diversity and the Nagoya Protocol, should formulate or improve the domestic laws following the legal rules established by the above-mentioned international treaties and China’s national conditions. Related initiatives may include taking the source disclosure as a formal condition for the patent grant, expanding the target and scope of the disclosure, and imposing legal liability for defect disclosure; clarifying the subjects of rights to Chinese materia medica genetic resources, and introducing public authority to “monitor” the signing and implementation of contracts to ensure fair and equitable benefit-sharing.
To evaluate the rationality of irinotecan application based on weighted TOPSIS method.
Based on the drug label of irinotecan, combined with relevant guidelines and literatures, weighted TOPSIS method was used to establish the evaluation criteria for the rationality of irinotecan clinical application, with “indications,contraindications, application and dosage, solvent selection, baseline examination, pretreatment, administration sequence,blood routine monitoring, dosage adjustment and ADR monitoring” as evaluation indicators. The archived medical records of inpatients who had used irinotecan in Binhu Hospital of Hefei from January 1, 2022 to May 31, 2023 were evaluated for the rationary of irinotecan administration.
Among the 10 evaluation indicators, the highest relative weighted index was indication（0.133 1）, while the lowest was pretreatment（0.084 9）. Among the included 97 cases, 10 cases（10%）had relative proximity（Ci）≥0.8, with the evaluation result as rational drug application; 79 cases（81%）had 0.6≤ Ci< 0.8,with the evaluation result as basic rational drug application; 8 cases（8%）had 0.4≤Ci < 0.6, with the evaluation result as irrational drug application.
The weighted TOPSIS method can be used to evaluate the rational usage of irinotecan. In our hospital, the use of irinotecan is basically reasonable, however, there are still some problems about baseline examination, blood routine monitoring and unreasonable indications.
To investigate the impact of erianin on the development of pancreatic cancer by regulating cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) signal pathway.
SW1990 cells were divided into control group, low-, medium- and high-concentration erianin groups (10, 20, 40 nmol·L-1), RU.521 (cGAS inhibitor)group (1 μmol·L-1), and erianin (40 nmol·L-1) +RU.521 (1 μmol·L-1) group. The proliferation was detected by CCK-8 method, and apoptosis was detected by flow cytometry. The migration and invasion of SW1990 cells were detected by scratch test and Transwell test, respectively. Western blot was applied to detect the protein expressions of cyclin D1, Bcl-2 associated X protein (Bax), matrix metalloproteinase (MMP)-2, MMP-9, cGAS and STING in SW1990 cells. SW1990 cells were co-cultured with NK cells for 48 hours, the levels of granzyme B and perforin (PF) in co-culture supernatant were detected by ELISA, and NK cell killing activity was detected.
Compared with the control group, the cell proliferation rate,the rate of scratch healing, the number of invasive cells were decreased in the low-, medium- and high-concentration erianin groups, the protein expressions of cyclin D1, MMP-2, MMP-9 were decreased, the apoptosis rate was increased, and the protein expressions of Bax, cGAS and STING were decreased in a concentration-dependent manner (P<0.05), while the change trends of the above indexes in the RU.521 group were opposite (P<0.05). Compared with the high-concentration erianin group, the cell proliferation rate, scratch healing rate, the number of invasive cells, and the protein expressions of cyclin D1,MMP-2, MMP-9, Bax, cGAS and STING in the erianin +RU.521 group were increased, and the apoptosis rate was decreased (P<0.05). In the co-culture experiment, compared with the control group, the levels of granzyme B and PF and NK cell killing activity in the cell supernatant of the low-, medium- and high-concentration erianin groups were increased in a concentration-dependent manner (P<0.05), while the change trends of corresponding indexes in the RU.521 group were opposite (P<0.05).Compared with the high-concentration erianin group, the levels of granzyme B and PF and NK cell killing activity in the erianin+RU.521 group were decreased (P<0.05).
Erianin may inhibit the proliferation, migration, invasion,and immune escape of pancreatic cancer cells and promote cell apoptosis by activating cGAS-STING signaling pathway.
To explore the research hotspots and development trends of global drug regulatory science, and to provide reference for promoting the sustainable development of drug regulatory science in China.
The literatures related to drug regulatory science published from 1991 to 2023 was searched from Web of Science database, and the contents of time distribution, author, institution, country / region and keywords were analyzed by CiteSpace 5.8.R3.
A total of 540 papers were included, and the annual number of published papers showed a stable growth trend. Foreign regulatory scientific research started early, and now it has formed a relatively complete regulatory scientific development system, and formed a relatively close cooperative relations among countries and institutions. Drug regulatory science research has evolved from an initial stage to a stage of refined research around new tools, standards, and methods; research hotspots include drug development, risk assessment, biomarkers, etc.
China’s drug regulatory authorities can increase policy guidance, strengthen basic theoretical research and applied capacity building, promote interdisciplinary joint research, and build a multidisciplinary academic exchange platform in order to accelerate the development of drug regulatory science.
The use of polyethylene glycol (PEG) modified drugs or nano-carriers is a widely accepted method that can effectively improve therapeutic effects of drugs in vivo. However, PEGylated drugs are usually immunogenic in vivo and can trigger the secretion of anti-PEG immunoglobulin IgG and IgM, leading to a significant increase in blood clearance efficiency of drugs and the occurrence of hypersensitivity reactions. The physicochemical properties of PEG molecules,drugs, or drug carriers will affect the secretion of anti-PEG antibodies, and the PEG modification density and administration frequency will also affect the immunogenicity of PEGylated drugs. Optimizing the causes and influencing factors is an effective method to improve the immunogenicity of PEGylated drugs in vivo. PEG alternative biomaterial is a new direction of drug research and development.
The efficacy of interleukin (IL)-2 in tumor immunotherapy is remarkable, but its adverse reactions greatly limit its further clinical application. In recent years, researchers have tried to improve or regulate the receptor selectivity of IL-2, that is, selectively bias the activation of IL-2Rβγ and reduce or even completely do not bind to IL-2Rα, so as to preferentially activate CD8+ T cells with tumor killing function and maximize the immune activation of IL-2. The main development strategies of receptor biased IL-2 include polyethylene glycol chemical modification and site-specific mutation technology. Currently, the drugs under research include NKTR-214, THOR-707, SHR-1916, TransConIL-2β/γ, 8MW2311,RG7461, FSD13, IBI363, etc. But none of them have been successfully developed yet. Further in-depth research on their mechanisms of action is required, or various drug development strategies need to be used in combination.
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