Based on the similar structure of adrenaline shared by higenamine (HI), salsolinol (SA) and coryneine (CO), a photochemical colorimetric sensor based on the displacement reaction of o-diphenol hydroxyl group and alizarin red S-phenylboric acid system was constructed to quickly distinguish and identify the cardiac strength of Shengfupian. The results show that the optimal condition of the sensor is: the molar ratio of alizarin red S (ARS) to phenylboric acid (PA) is 1:3, reaction temperature is 0℃; The preparation method of the sample solution is optimized as follows: 2.5 g of Shengfupian powder was taken, 10 times the amount of methanol was added, and 300 W, 40 kHz ultrasound was carried out for 15 min; methodological studies showed that the method had good precision, repeatability and stability. The|△G|value (G is green, |△G|=|G after-G before|) of each sample was obtained by response values determination of 14 batches of Shengfupian. LC-MS/MS was used to determine the contents of three cardiac components in Shengfupian. It was found that the order of the total contents of cardiotonic components was basically consistent with|△G|. Then the correlation was analyzed, and the correlation coefficient R² was as high as 0.87, which proved the scientificity and accuracy of this method. This study fills the methodological gap of rapid evaluation of the quality of Shengfupian, and provides the key technical support for the high quality and good price of Shengfupian in the market circulation and clinical application.

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12Cinhibitor resistance, so as to provide the clues for the combat of drug resistance.

In this study, nrDNA ITS sequences of Lycium cultivars were sequenced and used to test the existence of incomplete concerted evolution and pseudogenes. Together with 44 ITS sequences retrieved from GenBank, the pattern of base substitutions, GC content, 5.8S conserved motifs, the minimum free energy of secondary structures, nucleotide diversity and phylogenetic relationship of the samples were analyzed. While 83 of the 144 sequences were identified as pseudogenes, the results suggested a high degree of polymorphism and putative pseudogenes in Lycium, suggesting an incomplete concerted evolution of the ITS region. ITS polymorphism and pseudogene of Lycium were systematically tested for the first time. This research provides a references for ITS sequence to be used in the study of Lycium germplasm resources and DNA barcode identification.

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

Rhei Rhizoma is commonly used as a traditional Chinese medicine with multiple botanical origins. Different botanical sources may have different pharmacological activities. The germplasm resources of commercial Rhei Rhizoma were determined based on the chloroplast gene matK, and the anthraquinone and free anthraquinone content was determined by UPLC to analyze quality of commercial Rhei Rhizoma. Eighty-nine commercial Rhei Rhizoma samples were collected from 40 cities in 27 provinces. DNA was extracted and the matK gene was amplified by PCR. Results indicated that the collected samples were from the same botanical origin, Rheum palmatum, and 8 genotypes were identified, including Rp1, Rp2, Rp3, Rp4, Rp5, Rp6, Rp10 and Rp12. Rp4 and Rp6, cultivated in Gansu, Sichuan and Yunnan provinces were the main circulating genotypes, representing 40.45% and 37.08% of the total samples, respectively. Phylogenetic tree analysis showed that the eight genotypes were mainly divided into two branches, of which the main genotypes Rp4 and Rp6 were in one branch. Genetic distance analysis indicated that the genetic separation of the eight genotypes was between 0.001 and 0.010. UPLC analysis indicated that 93.26% of the samples met the Pharmacopoeia standards. There were significant differences in the content of total anthraquinone and free anthraquinone among the samples, in which the difference in free anthraquinone was 1.01% and the difference in total anthraquinone content was 3.79%, indicating that the quality of commercial Rhei Rhizoma samples varies considerably. There was no significant difference in the content of total anthraquinone and free anthraquinone in commercial Rhei Rhizoma among different collection provinces and genotypes. This study will help guide the circulation of Rhei Rhizoma in the market and provides valuable insights for molecular identification and quality analysis of other traditional Chinese medicines.

To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.

Progesterone is currently the first-line drug for the treatment and prevention of threatened abortion and habitual abortion. With the gradual liberalization of China's childbirth policy, the number of elderly parturients has increased significantly. As a result, the market demand for progesterone and the individual requirements have been continuously improved. Clinical studies have found that the indications of progesterone are not limited to gynecological diseases, but can also be used for the treatment of renal colic, traumatic brain injury and other diseases. Existing progesterone preparations include oral capsules, intramuscular injections, vaginal gels, etc., but they can no longer meet the current market situation and the increase of indications. Improving existing preparations, developing new preparations, and opening up new routes of administration have become one of the directions of progesterone drug research. This article will review the research progress of new dosage forms in existing administration, new routes of administration and related preparation methods of progesterone.

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide-arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2±7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17±1.88)%, an encapsulation rate (5.85±0.72)%, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

As one of the "Three Drugs Three Prescriptions" anti-COVID-19 traditional Chinese medicine, Jinhua Qinggan granules (JHQG) has been proved to have clear clinical effects. With complex medicinal flavors and ingredients, there is no systematic research report on chemical composition in vivo or in vitro. An ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) method was developed in this study to identify the components of the anti-COVID-19 traditional Chinese medicine JHQG granules. Analyze the collected rat plasma samples after administration and explore the exposed components in rats within 8 hours after intragastric administration. Preliminary pharmacokinetic analysis was then performed on this basis. Through UPLC-QTOF/MS analysis and verification by standard products, a total of 77 chemical components in JHQG formula have been identified, among which 22 compounds were highly exposed in vivo, mainly derived from three medicinal materials of honeysuckle, scutellaria and forsythia. Through the assessment of the blood drug concentration by the compartment model, 6 PK parameters of 4 high-exposure chemical components have been obtained, clarifying the metabolic characteristics of the main exposed components in JHQG briefly. The method is simple, efficient, sensitive and accurate and provides research basis to the clarification of the pharmacodynamics material basis and mechanism of JHQG, which has certain reference significance for the basics and applications research of the traditional Chinese medicine prescriptions in fighting the SARS-CoV-2.