At present, the listed antidepressants have certain limitations, and the different mechanisms of which are closely related to their efficacy and safety. Therefore, the discovery of antidepressants with novel mechanisms is an important research direction in the field of antidepressants. This paper reviews some major antidepressants currently under clinical research stage, and analyzes their mechanisms of action, so as to provide reference for the development of antidepressants with new mechanisms of action.

Recently, radioimmunotherapy (RIT) has attracted much attention because of its precision targeted therapy. It is a therapeutic mode with great clinical application value to select an appropriate target molecule for radioimmunotherapy. B7-H3, also known as CD276, is an immune checkpoint molecule belonging to the B7 immunoglobin superfamily, which makes it an ideal candidate for RIT agents due to its unique expression characteristics and biological functions. Herein, we summarize the expression characteristics and biological functions of B7-H3. We also review the latest developments in radioimmunotherapy targeting B7-H3 in the context of cancer therapeutic.

Cichorium glandulosum is a special medicinal and edible plant in Xinjiang of China, which contains polysaccharides, flavonoids, terpenoids as the main active ingredients. The significant pharmacological activities include liver protection, lipids reduction, anti-inflammatory and so on. It is a traditional medicine commonly used by people of all ethnic groups in Xinjiang of China. C.glandulosum was searched as the key word in CNKI, WANFANG and PubMed database as the search platform, using search items of keywords and full text. The research hotspots of C.glandulosum was statistically analyzed in recent years. The paper reports and patent of C.glandulosum were retrieved, 100 papers and 15 patents were included, among which studies of pharmacognosy, chemical composition, and pharmacological activity were involved, and the patents mainly relate to its biomedicine, health care products, and preparation techniques. In this paper, cultivation, pharmacognosy, pharmacological activities, and patent application of C.glandulosum are reviewed and prospected, in order to provide reference for the development and utilization of C.glandulosum. It is suggested that C.glandulosum had potential research value in medicine, health care products, food and other industries.

2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) is a natural product of chalcone type isolated from diverse plants with a variety of great pharmacological properties. This article reviews the research progress from physicochemical properties, sources, extraction and detection, chemical synthesis, and pharmacological activities, in order to provide a theoretical basis for the development or prodrug design of DMC.

Objective: To evaluate the tolerability and pharmacokinetics of sitafloxacin fumarate injection in healthy Chinese volunteers.Methods:A total of 40 volunteers, half male and half female, were enrolled for single administration and multiple administrations of sitafloxacin fumarate injection. The single dose groups were further divided into 400 mg group and 500 mg group, and the tolerance was investigated. Multiple dose groups were divided into 300 mg (qd) group and 400 mg (qd) group to investigate the tolerability and pharmacokinetics. Adverse reactions were observed during the trial, and changes in vital signs, laboratory tests and other data were monitored to evaluate the safety and tolerability of the drug. The plasma concentrations of sitafloxacin were determined using HPLC-MS/MS, and its pharmacokinetic parameters were calculated and statistically analyzed.Results:No serious adverse events occurred during the trial. Main pharmacokinetic parameters of sitafloxacin after repeated administration are as follows: C_max, AUC_0-t, and AUC_0-∞ are (2 913.00±436.63) μg·L^-1, (18 368.93±4 141.28) h·μg·L^-1 and (19 662.17±4 820.31) h·μg·L^-1 in 300 mg (qd) group on day 1 of repeated administration; while (3 080.00±695.11) μg·L^-1, (22 625.89±5 729.43) h·μg·L^-1, and (22 990.68±5 866.94) h·μg·L^-1 on day 7. The corresponding values are (4 590.00±894.67) μg·L^-1, (24 113.91±5 030.12) h·μg·L^-1 and (25 277.71±5 159.69) h·μg·L^-1 in 400 mg (qd) group on day 1 of repeated administration; while (4 570.00±1 230.04) μg·L^-1, (30 280.20±7 007.20) h·μg·L^-1 and (30 586.30±7 055.85) h·μg·L^-1 on day 7.Conclusion:Sitafloxacin fumarate injection is safe and well tolerated in Chinese healthy volunteers. The dynamic characteristics of multipledoses were nonlinear, without significant accumulation in patients of once-daily administration. There was no statistical significance in gender difference of main pharmacokinetic parameters within the same dose group.

The concept of patient-focused drug development has been paid increasing attention by researchers in China and abroad. Patient-reported outcome (PRO) has gradually become one of the endpoints in clinical trials. PRO provides health information directly from the patient and plays an important role in the clinical decision making by physicians. However, the use of PRO assessment and data interpretation in oncology clinical trials are still waiting for further improvement. The selection of core PRO indicators is critical to the consistency of PRO assessment criteria. In 2021, U.S. FDA issued the "Core Patient-Reported Outcomes in Cancer Clinical Trials Guidance for Industry (draft)" for drug development in cancer clinical trials, providing guidance for sponsors on core PRO collection, PRO assessment tool selection, and standardized trial design. This paper interprets the systematic assessment and application of core PRO in the guideline, helps practitioners of new drug clinical trials to further understand PRO and promotes the implement of PROs in new drug clinical trials in a good way.

In the ethical review of the qualification of principal investigators, some problems such as insufficient certification materials to fully reflect the qualification of principal investigator, lack of qualification standard system of principal investigator, simple review method and single form, insufficient attention, weak awareness and low degree of independence were found. To further standardize the operation of the ethics committee and to improve the comprehensive review capacity, it is suggested to clearly specify the certification materials for qualification submission, building a comprehensive evaluation index system of qualification, taking a variety of review forms and strengthening the capacity-building of the ethics committee, so as to provide experience and reference.

Objective: Three kinds of paclitaxel saturated fatty acid ester liposomes were prepared to preliminarily compare the difference between them in anti-tumor, and to explore the reasons for the difference of efficacy by the study of tissue distribution.Methods:Three kinds of paclitaxel fatty acid ester liposomes were prepared by thin film dispersion method, and the particle size, potential, encapsulation efficiency and drug loading were measured, respectively. A mouse model of breast cancer was established, and paclitaxel injection (Taxol), paclitaxel myristate liposome (PTX-MA-L), paclitaxel palmitate liposome (PTX-PA-L) and paclitaxel stearate liposome (PTX-SA-L) were injected via the tail vein, respectively. The anti-tumor effects of the two preparations were investigated, and the safety of the preparations was evaluated by routine blood tests. Finally, the prodrug metabolism for three prodrug liposomes was evaluated by in vivo tissue distribution.Results:Three taxol saturated fatty acid ester liposomes were successfully constructed. The particle sizes of PTX-MA-L, PTX-PA-L and PTX-SA-L are (69.56±1.08), (72±0.86) and (75±1.02) nm; Polymer dispersity index (PDI) are (0.185±0.009), (0.165±0.012), (0.171±0.024); Zeta potentials are -(11.26±1.37), -(12.18±1.86), -(13.92±0.59) mV, respectively. Encapsulation rates are (95±0.39)%, (97±0.28)% and (98±0.19)%, respectively. In pharmacodynamic evaluation in 4T1 breast cancer transplanted tumor model, the pharmacodynamic of PTX-PA-L at equal dose was stronger than that of taxol, PTX-MA-L and PTX-SA-L. The results of routine blood test showed that the blood cell level of paclitaxel fatty acid ester liposome was significantly higher than that of paclitaxel injection. The tissue distribution results showed that PTX-MA-L was metabolized to PTX at a fast rate, short half-life and fast elimination rate. PTX metabolized from PTX-PA-L increases slowly with time. Its half-life is the longest among the three prodrug liposomes, the area under the drug-time curve is the largest, and the clearance rate is the lowest. PTX-SA-L was metabolized to PTX the most slowly, and the maximum plasma concentration was the lowest in tumors.Conclusion:The paclitaxel prodrug liposome modified with saturated fatty acid has better tumor treatment effect and alleviates the toxic and side effects caused by traditional paclitaxel dosage forms. Among them, the antitumor effect of PTX-PA-L is better than that of PTX-MA-L and PTX-SA-L, which may be related to the metabolism of fatty acid prodrugs in vivo.

Objective: To investigate the mechanism of inhibitory effect of hydroxy-γ-isosanshool on estrogen synthesis in human ovarian granulosa cells.Methods:The effects of four kinds of sanshool on the proliferation of human ovarian granulosa cell line (KGN cell line) were detected by CCK-8. The effects of four kinds of sanshool on estradiol synthesis in KGN cells were detected by Elisa. Aromatase gene in KGN cells was detected by RT-qPCR, and aromatase protein and related pathway proteins were detected by Western Blot.Results:Hydroxy-γ-isosanshool had the strongest inhibitory effect on estradiol biosynthesis [IC₅₀=(16.63±0.39) μmol·L^-1], while had no significant inhibitory effect on the proliferation of KGN cells at the same concentration. The expression levels of aromatase gene and protein decreased significantly after the intervention of hydroxy-γ-isosanshool (P<0.05), and the activity of aromatase was not significantly affected. Hydroxy-γ-isosanshool significantly reduced the protein expressions of P-CERB, P-AKT and P-p38 (P<0.05).Conclusion:Hydroxy-γ-isosanshool may inhibit aromatase transcription and estrogen biosynthesis in KGN cells by inhibiting the activation of p38/MAPK and PI3K/AKT pathways and reducing the level of CREB phosphorylation, inhibit aromatase transcription, and ultimately inhibit the estrogen biosynthesis of KGN cells.

Objective: To eatablish a UPLC-MS/MS method for determination of three azide-type genotoxics, 5-(4′-(azidomethyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole (MB-X), 4′-(azidomethyl)-[1,1′-bihenyl]-2-carbonitrile (AZBC), and 5-(4′-((5-azido-2-butyl-4-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole (LADX), in active pharmaceutical ingredients (API) of irbesartan and losartan potassium.Methods:The separation was performed on a ACQUITY UPLC HSS T3 column(100 mm×2.1 mm, 1.8 μm) with the mobile phases consisting of 0.1% formic acid aqueous solution (mobile phase A) and 0.1% formic acid methanol solution (mobile phase B) using a gradient elution at a flow rate of 0.35 mL·min^-1. The column temperature was set at 50 ℃. Multiplereaction monitoring (MRM) was performed on a triple quadripole mass spectrometer equipped with a APCI source in positive/negative mode.Results:the calibration curve was linear for three compounds in the range of 0.5~100 ng·mL^-1. The recoveries (n=3) in irbesartan of low, middle, high concentration-spiked samples are 94.5%~103.5% with RSD<3.88%. The recoveries (n=3) in losartan potassium of low, middle, high concentration-spiked samples are 93.8%~100.9% with RSD<4.25%. The limits of detection are 0.05, 0.03, 0.02 ng·mL^-1 and the limits of quantification are 0.15, 0.11, 0.08 ng·mL^-1, respectively.Conclusion:The method is sensitive and accurate, which is applicable for quantification of three azide-type genotoxic impurities in irbesartan API and losartan potassium API. The method can provide reference for quality control of irbesartan and losartan potassium.