Conjugated estrogens (CE) are widely used in menopausal hormone therapy (MHT) for the relief of menopause-related symptoms (e.g., vasodilatory symptoms, neuropsychiatric symptoms, genitourinary atrophy symptoms, etc.) and the prevention of postmenopausal osteoporosis. This article reviews the characteristics, pharmacological effects, and practical applications of different dosage forms of CE (tablets, creams, and injections) in clinical practice. It has been shown that tablet CE effectively regulates the body's temperature center through systemic treatment, reduces hot flashes and night sweats, promotes bone formation, and increases bone density. Cream CE is used for local treatment to improve the genitourinary syndrome of menopause (GSM). Injectable CE is used for the treatment of abnormal uterine bleeding caused by hormonal imbalance without organ pathology. CE administered intravenously is indicated only for short-term use to rapidly and temporarily increase estrogen levels. Additionally, CE plays an important role in metabolism by improving insulin clearance and sensitivity and potentially protecting the nervous and cardiovascular systems, demonstrating a wide range of therapeutic potential. This paper provides new ideas for the design and development of drug dosage forms by exploring the formulation and application of CE.

The study of micromechanical behavior during tablet pressing is often limited to phenomenological studies, accurate calibration of the discrete element model parameters of binary particles is a prerequisite for conducting modeling research on tablet compression. In this study, we take pregelatinized starch and microcrystalline cellulose as the research objects, and apply the Edinburgh elasto-plastic adhesion (EEPA) contact model to establish a discrete elemental simulation model for binary material pressing. Taking tablet force-hardness and force-volume reduction as response values, the optimal values of the discrete meta-parameters that significantly affect tablet pressing are obtained by applying Plackett-Burman design, Latin hypercubic sampling, Kriging model, and Non-dominated Sorting Genetic Algorithm (NSGA-Ⅱ) calibration. The results obtained the optimum combination of discrete element method (DEM) parameters for pregelatinized starch, Poisson's ratio 0.257, shear modulus 1×10⁹ Pa, granule-particle static friction coefficient 0.165, unit normal stiffness 2.419 2×10⁹ N·m^-3, unit tangential stiffness 7.954 6×10⁹ N·m^-3, and strength of adhesive force -0.009 155 8 N. For microcrystalline cellulose, Poisson's ratio 0.381, shear modulus 1.04×10⁹ Pa, particle-particle static friction coefficient 0.719, unit normal stiffness 3.171 5×10⁹ N·m^-3, unit tangential stiffness 6.746 2×10⁹ N·m^-3, and strength of adhesion -0.038 7 N. For optimum combinations of the DEM parameters for the binary blend of excipients, particle-particle collision recovery coefficient 0.1, unit normal stiffness 9.947 1×10⁹ N·m^-3, unit tangential stiffness 1.994 5×10⁹ N·m^-3, and adhesion force strength -0.060 35. The simulation results under the optimal parameter combination are similar to the experimental results, indicating that the calibrated parameters can be used for discrete element simulation research and provide theoretical basis and data support for the subsequent intelligent and continuous production of tablets.

Synthetic cannabinoid N-(1-carbamoyl-2, 2-dimethylpropyl)-1-butylazole-3-formamide (ADB-BUTINACA), as a new psychoactive substance, shows strong stimulant and hallucinogenic effects. It can cause cardiovascular, renal and gastrointestinal diseases, and in severe cases, it can lead to death. However, there are few reports on toxicology studies of the ADB-BUTINACA metabolic pathway and its long-term effects on the organism and the molecular mechanisms behind it. In this study, the metabolic profile of rat serum after low, medium and high doses of ADB-BUTINACA (0.1, 1, and 5 mg·kg^-1) intervention were analyzed using UHPLC coupled with a Q-Orbitrap-MS (UHPLC-Q-Orbitrap-HRMS). The results showed that the intervention of ADB-BUTINACA could cause significant changes of 50 metabolites such as L-glutamate and 3-hydroxybutyrate, and nine metabolic pathways including alanine, aspartate and glutamate metabolism, retinol metabolism, and TCA cycle were disturbed. These findings provide a novel experimental and theoretical framework for further investigation of the toxicological mechanisms underlying ADB-BUTINACA-induced dysregulation of lipid and energy metabolism. Furthermore, they offer valuable insights that could facilitate the diagnosis and prevention of ADB-BUTINACA toxicity, thereby underscoring their significant implications for public health. The study was conducted in adherence to both the Declaration of Helsinki and the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals, and received approval from the animal experimental center at the Zhejiang Chinese Medical University (Ethical number: 20220718-11).

The study aims to establish HPLC fingerprint and multi-index content determination method of Guanxin Qiwei tablets and provide scientific basis for its quality control. The fingerprints of 18 batches of Guanxin Qiwei tablets were established by Shim-pack GGIST HP C₁₈ chromatographic column, and analyzed comprehensively in combination with the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition). Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for stoichiometric study. HPLC-MS/MS method was established for simultaneous determination of 9 components. A total of 22 common peaks were identified in 18 batches of Guanxin Qiwei tablets fingerprint, and the similarity was 0.952-0.998, 9 common peaks were identified. They were No. 1 gallic acid, No. 3 protocatechuic acid, No. 8 ellagic acid, No. 9 salvianolic acid B, No. 12 luteolin, No. 13 apigenin, No. 19 dehydrodiisoeugenol, No. 20 cryptotanshinone and No. 21 tanshinone ⅡA. CA and PCA analysis grouped 18 batches of Guanxin Qiwei tablets into 3 categories: S1-S4 (manufacturer A) was grouped into one category, S5-S8 (manufacturer B) was grouped into one category, and S9-S18 (manufacturer C and D) was grouped into one category. Under OPLS-DA analysis mode, 14 quality differentiators were selected with the variable important projection (VIP) greater than 1 as the standard, and all of them had significant differences. The linear relationship of the 9 components was good in their respective ranges, and the linear correlation coefficient r was greater than or equal to 0.099 9. Precision RSDS were all lower than 3.00%. The stability and repeatability were good, RSD lower than 5.00%; The average recoveries were 96.58%-106.28%, RSD was 2.68%-6.45%. This method is efficient and stable, and can be used for quality control of Guanxin Qiwei tablets.

Human influenza is mainly caused by influenza A virus and influenza B virus, and it is one of the most serious infectious diseases that pose a serious threat to human health. Currently, there are few marketed drugs for influenza viruses, and the existing drugs are faced with problems such as drug resistance. The development and research of combinations of anti-influenza drugs have gradually attracted people's attention. At present, certain progress has been made in aspects such as the discovery of anti-influenza drug combinations and the evaluation of drug effects. Discovering effective combination drugs is an ideal method for repurposing old drugs. That can be used to improve therapeutic effects and delay or reduce the occurrence of drug resistance. Herein, this article introduces the evaluation methods, models of combinations of anti-influenza drugs, as well as available data resources and tools, and summarizes the latest progress in the current research on combinations of anti-influenza drugs, with the aim of providing a reference for the research and development of the combined application of anti-influenza virus drugs.

Exosomes are small vesicles secreted by cells that contain important bioactive molecules such as nucleic acids and proteins. Increasing research indicates that exosomes play a unique and crucial role as signal molecule carriers in various diseases, and they exhibit great potential in disease diagnosis and treatment. Recent studies have shown that exosomes play an important role in immune regulation. The NOD (nucleotide binding oligomerization domain)-like receptors protein 3 (NLRP3), an essential component of the innate immune system, plays a key role in the occurrence and development of various diseases including autoimmune diseases, metabolic diseases, and neurodegenerative diseases. Its activation and regulatory mechanisms are complex and diverse. However, the regulatory mechanisms associated with exosomes and NLRP3 inflammasome have not yet been fully elucidated. This article reviews the regulatory effects of exosomes from different sources on the NLRP3 inflammasome and summarizes the therapeutic potential of exosomes in diseases associated with the NLRP3 inflammasome, aiming to provide new ideas for the prevention and treatment of diseases related to the NLRP3 inflammasome.

Radiopharmaceuticals play a crucial role in nuclear medicine, with the development of radioligands being a key focus in this field. Peptide-based radiopharmaceuticals have shown significant advantages in clinical applications, with the majority of FDA-approved targeting radiopharmaceuticals since 2018 being derived from peptides or peptidomimetics. Bicyclic peptides have emerged as a promising targeting moiety in radioligands, offering improved biophysical properties compared to linear or monocyclic peptide ligands. This article provides an overview of the methods for obtaining bicyclic peptide ligands, as well as highlighting the major clinical and preclinical advancements in bicyclic peptide-based radiopharmaceuticals. The review also discusses the future prospects of bicyclic peptide-based radiopharmaceuticals, offering insights for practitioners in the field of pharmaceutical science and nuclear medicine to keep up with the latest developments in radiopharmaceutical innovation.

Liver fibrosis is a common stage in the progression of chronic liver diseases, yet there is a lack of clinical drugs against liver fibrosis globally. Gynostemma pentaphyllum has the name of "Southern ginseng", commonly used in folk prevention and treatment of a variety of chronic liver disease, there are also reports of its anti-hepatic fibrosis. However, there are fewer relevant scientific studies. In this study, we used LC-MS metabolomics analysis to investigate the effects of Gynostemma pentaphyllum ethanol extract (GPE) on liver fibrosis in carbon tetrachloride (CCl₄)-induced mouse models and its potential mechanisms. All animal experiments were approved by the experimental animal ethics committee of Capital Medical University (DWLLGZR202202204). The results showed that GPE could significantly reduce the inflammatory cell infiltration and collagen accumulation in the liver of model mice, significantly reduce serum alanine transaminase and aspartate transaminase activity and hypoxanthine levels in mice, and could effectively inhibit the gene transcription and protein expression of collagen 1A1 (COL 1A1) and α-smooth muscle actin (α-SMA). Non-targeted metabolomics analysis of the liver showed that GPE mainly affected 47 differential metabolites; KEGG pathway enrichment analysis indicated that the differential metabolites were mainly enriched in the fructose/mannose metabolism and aromatic amino acid metabolism pathways. The targeted metabolomic assay was further used to validate a total of 13 differential metabolites of D-mannose, mannose 6-phosphate, D-fructose, fructose 2-phosphate, D-sucrose, trehalose, glutamate, phenylalanine, tyrosine, L-2-amino-3-oxobutyric acid, lactate, 2-hydroxybutyrate, and taurine, which may be important metabolites related to GPE's anti-fibrotic effects. This confirms that GPE's anti-liver fibrosis effects may be closely related to the regulation of the fructose/mannose metabolism pathway and the aromatic amino acid metabolism pathway.

Five sesquiterpenoids were isolated from a 50% acetone extract of Cornus officinalis leaves, a traditional non-medicinal part of Cornus officinalis, using modern column chromatographic techniques such as macroporous adsorbent resins colum, silica gel colum, chromatography gel colum and semi-preparative liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as cornurtone A (1), cornucadinoside B (2), lacinilene C (3), 3, 12-dihydroxycadalene (4), cornucadinoside C (5). Compound 1 was new compound and compounds 2-5 were first isolated from leaves of Cornus officinalis. Compounds 2 and 3 had potential neuroprotective activities.

Severe alcoholic hepatitis (SAH) represents the most extreme form of alcoholic liver disease (ALD), accompanied by an extremely high mortality rate. Currently, there is a dearth of appropriate animal models for related research. The objective of this study is to establish a mouse model of SAH, thereby providing a preclinical animal model for subsequent research on SAH. This study is based on the NIAAA (National Institute on Alcohol Abuse and Alcoholism) model and constructs a mouse model by combining bacterial endotoxins. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-102). The model emulates the pathological processes of clinical SAH in terms of mouse mortality, liver tissue damage, and inflammatory markers, thereby establishing the model. Ultimately, it is ascertained that the optimal conditions for SAH mouse modeling based on the NIAAA model are the last intragastric administration of alcohol at a concentration of 7.5 g·kg^-1 in combination with intraperitoneal injection of lipopolysaccharide at a dose of 5 mg·kg^-1 for a period of 12 h. Under these conditions, the mouse model effectively simulates the high mortality and liver dysfunction seen in clinical SAH, with pathological staining results closely mirroring clinical findings. Additionally, it demonstrates a significant infiltration of neutrophils in the liver, indicative of an excessive inflammatory response. This model provides an ideal platform for preclinical research on SAH.