Latest ArticlesTo discuss the effects of acacetin on lung injury in Mycoplasma pneumoniae pneumonia (MPP) mice and analyze the relationship between its mechanism and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
A MPP mouse model was constructed, and successfully modeled mice were stochastically divided into model group, low, medium and high dose acacetin experimental groups (acacetin-L, M, and H groups: 12.5, 25.0, and 50.0 mg·kg-1 acacetin) and high-dose acacetin-H+JAK2 activator coumarin group (acacetin-H+coumarin 50 mg·kg-1 acacetin-L and 2 mg·kg-1 coumarin), each with 12 mice. Twelve normal healthy mice were intranasally instilled with an equal amount of physiological saline as the control group. Blood gas analyzer was used to detect arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) of mice, oxygen concentration analyzer was used to detect fraction of inspired oxygen (FiO2), and the oxygenation index (OI) was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factors. Biochemical method was used to detect oxidative stress indicators. The lung index and lung wet dry ratio were weighed and calculated. Hematoxylin-eosin (HE) staining was employed to evaluate the pathological lesions in lung tissue. Western blot assay was performed to detect the protein expression of JAK2/STAT3 signaling pathway-related molecules.
The OI value of the acacetin-L, -M, -H groups, control group, model group, and acacetin-H+coumamycin group were (274.63±30.02), (320.16±35.79), (374.55±39.88), (403.57±43.61), (220.31±26.78) and (241.03±29.14)mmHg, respectively; the IL-6 levels were (124.56±13.27), (87.61±9.23), (56.34±6.77), (36.50±4.15), (172.59±18.24) and (149.33±16.05)pg·mL-1, respectively; the MDA contents were (4.06±0.45), (2.97±0.31), (1.93±0.22), (1.82±0.20), (5.31±0.58) and (4.69±0.49) nmol·mL-1, respectively; the lung index was 1.31±0.15, 0.99±0.11, 0.57±0.07, 0.52±0.06, 1.78±0.19, and 1.54±0.17, respectively; the lung wet/dry weight ratio was (6.83±0.73)%, (5.61±0.58)%, (4.35±0.49)%, (4.10±0.45)%, (7.86±0.86)% and (7.33±0.81)%, respectively; the phosphorylated(p)-JAK2/JAK2 ratio were 0.71±0.08, 0.56±0.06, 0.43±0.05, 0.39±0.04, 0.86±0.09 and 0.79±0.08, respectively; the p-STAT3/STAT3 ratio were 0.67±0.07, 0.46±0.06, 0.30±0.04, 0.16±0.02, 0.83±0.09 and 0.74±0.08, respectively. There were statistically significant differences in the above indicators between the model group and the control group, between the acacetin-H group and the model group, and between the acacetin-H+coumarin group and the acacetin-H group (all P<0.05).
Acacetin can effectively improve lung injury in MPP mice, possibly by inhibiting the JAK2/STAT3 signaling pathway.
In the context of "internet plus health care", the annual internet outpatient prescriptions of a tertiary children′s hospital (Beijing Children′s Hospital affiliated to Capital Medical University, hereinafter referred to as the hospital) were taken as the objects, and the rationality of prescriptions was analyzed based on the rational drug use system, and the types, causes and drug characteristics of unreasonable treatments were identified to provide data support for the rational drug use management of pediatric Internet outpatient.
All prescriptions from the hospital′s internet outpatient hospital information system (HIS) in 2024 were collected and summarized. Review results were obtained by relying on the Puhua Hecheng Rational Drug Use System, and true positive irrational prescriptions were determined by combining with pharmacists′ manual re-evaluation. Statistical analysis was performed using Excel software.
A total of 58 560 internet outpatient prescriptions were included. The rational drug use software reviewed 1 334 machine-screened positive irrational prescriptions, and 438 true-positive irrational prescriptions were confirmed after manual re-evaluation, with an overall irrational rate of 0.75%. Among the 438 prescriptions, 93.61% involved only one irrational drug item, and a total of 559 medication problems were detected. Among these, inappropriate indication accounted for the highest proportion (63.51%), which was identified as the primary factor by Pareto analysis. Among the problems of inappropriate dosage and usage, 80.22% involved two combined issues (primarily single-dose overdose and daily-dose overdose, accounting for 61.54%). Inappropriate administration route was mainly attributed to non-standard labeling of "as needed" (70.00%), primarily involving nebulized drugs and nutritional supplements. The top three medications involved in irrational prescriptions were all nutritional supplements and vitamins, with this category ranking first among medication classifications.
The overall rationality of prescriptions in the hospital's pediatric internet-based outpatient service is relatively high. However, inappropriate indications and non-standard dosage and usage remain core issues. Targeted optimization of rational drug use system rules, enhanced pharmaceutical intervention, strengthened physician training, and improved remote consultation processes are needed to enhance medication safety and achieve continuous improvement.
To summarize and analyze clinical development strategy and the key considerations of clinical trial design of drugs for the treatment of corona virus disease 2019 (COVID-19) at home and abroad in recent years, including ribonucleic acid (RNA) polymerase inhibitors, 3CL protease inhibitors, and neutralizing antibodies, etc. In general, the confirmatory clinical trials for therapeutic drugs for COVID-19 typically adopt a randomized, double blind, placebo-controlled clinical trials using a superiority design. Based on their therapeutic positioning, most trials mainly enroll patients with mild to moderate COVID-19, with or without high-risk of complications, and the primary efficacy endpoints are the proportion of patients hospitalized or mortality by an appropriate time point, or the time to sustained clinical recovery assessed over an appropriate duration. Through reviewing drug development during the COVID-19 pandemic, this paper summarized the considerations and changes for clinical research and development, as well as the focus of clinical trial design for new drugs in the treatment of COVID-19, in the context of emerging and sudden major infectious diseases, hoping to provide references for drug research and development.
To discuss the effects of esculetin on myocardial ischemia-reperfusion injury in rats by regulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
A total of 60 rats were randomly divided into control group, model group, low-dose (L)-esculetin (20 mg·kg-1) experimental group, high-dose (H)-esculetin (40 mg·kg-1) experimental group, and H-esculetin+inhibitor (40 mg·kg-1 esculetin and 20 mg·kg-1 JAK2/STAT3 inhibitor WP1066) group, with 12 rats in each group. Except for the control group, rats in all other groups were subjected to myocardial ischemia-reperfusion modeling. Triphenyltetrazolium chloride (TTC) staining was used to evaluate infarct size; hematoxylin-eosin staining (HE) staining was used to observe histopathological changes; TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to observe myocardial apoptosis; enzyme linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines; Western blot was used to detect protein expression of JAK2/STAT3 pathway in rat myocardium.
The cardiomyocytes of the rats in the model group were enlarged and arranged in a disorderly manner, while the myocardial damage of rats in the L-esculetin group and the H-esculetin experimental group was reduced. The myocardial infarction areas of the rats in the control group, model group, L-esculetin experimental group, H-esculetin experimental group and H-esculetin+inhibitor group were (3.24±0.35)%, (31.36±3.51)%, (20.75±2.37)%, (10.48±1.16)% and (29.56±3.27)%, respectively; the cardiomyocyte apoptosis rates were (6.37±0.75)%, (56.24±6.03)%, (38.72±3.94)%, (21.46±2.37)% and (51.05±5.28)%, respectively, the levels of interleukin-1β (IL-1β) were (9.34±1.02), (158.95±16.83), (125.49±13.26), (94.83±10.54) and (151.27±16.42) pg·mL-1, respectively; the levels of interleukin-18 (IL-18) were (13.27±1.46), (568.93±59.95), (486.38±51.32), (312.63±33.41) and (527.46±56.25) pg·mL-1, respectively; the levels of tumor necrosis factor-α (TNF-α) were (7.85±0.98), (124.84±14.64), (88.95±9.63), (53.58±5.97) and (116.32±13.27) pg·mL-1, respectively; the relative expression levels of pentraxin 3 (PTX3) protein were 0.86±0.11, 0.32±0.04, 0.53±0.07, 0.71±0.08 and 0.69±0.08, respectively; the relative expression levels of phospho-JAK2 (p-JAK2) protein were 0.81±0.09, 0.36±0.05, 0.54±0.07, 0.73±0.08 and 0.39±0.05, respectively; the relative expression levels of phospho-STAT3 (p-STAT3) protein were 0.78±0.09, 0.29±0.04, 0.52±0.06, 0.74± 0.09 and 0.33±0.04, respectively. Comparing the control group with the model group, the model group with the L-phenithin experimental group, the L-phenithin group with the H-phenithin experimenal group, and the H-phenithin experimental group with the H-phenithin+inhibitor group, there were statistically significant differences in the above indicators (all P<0.05).
Esculetin alleviates myocardial ischemia-reperfusion injury in rats by activating the JAK2/STAT3 signaling pathway.
Thioctic acid is widely used in clinical treatment of diabetic peripheral neuropathy. The human bioequivalence (BE) study of thioctic acid tablet should follow the relevant regulations and guidelines, and fully consider the particularity of the clinical use of this product. It is recommended to adopt a single dose, two preparations, two sequences, partial or complete repeated crossover study design, and select the reference preparations that have been publicly released for the fasting test. In addition, researchers should pay attention to the Chinese version of The Internationevl Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M13A and its Q&A document, as well as the BE study ideas of similar drugs. This article takes the BE study of thioctic acid tablet as an example to provide in-depth guidance for the research.
The prevention and treatment of perioperative myocardial injury primarily rely on hemodynamic management and conventional cardiovascular medications, yet limitations remain, such as constraints in intervention timing, significant individual response variability, and the irreversible effects or notable adverse reactions associated with some drugs. As an ultra-short-acting, highly selective β1-receptor blocker, esmolol offers rapid onset, a short half-life, and precise controllability. It not only effectively stabilizes heart rate and blood pressure but may also exert myocardial protective effects through multiple pathways, including regulating myocardial oxygen supply-demand balance, suppressing inflammatory responses, and mitigating cellular apoptosis. This article reviews recent domestic and international studies, summarizing the mechanisms of perioperative myocardial injury, the myocardial protective effects of esmolol, and its potential molecular pathways. The aim is to provide new perspectives and a theoretical basis for optimizing perioperative cardiac protection strategies.
To give patients a more scientific instruction of prescription drugs, drug regulatory authorities in developed countries such as Europe, the United States, and Japan are actively promoting the establishment of patient labeling system. Unlike professional labeling, patient labeling uses easy-to-understand language to help patients understand the most critical information about the drug, thereby enabling safer use of prescription drugs. This article focuses on the U.S. Food and Drug Administration(FDA)′s patient labeling system, briefly introducing the main content and relevant requirements of different types of patient labeling, such as the medication guides (MG), patient package inserts (PPI), instructions for use (IFU), and consumer medication information (CMI). It also provides a detailed introduction to the scope of application, specific content, and format requirements of the patient medication information (PMI) that the FDA is currently promoting, while giving a brief explanation of the patient labeling systems of other drug regulatory authorities (such as the European Union and Japan). PMI is a new form of patient labeling further optimized by the FDA based on previous experience in patient labeling work, and it plans to gradually unify and replace the original MG and PPI. In China, the State Council issued and implemented the Law of the People′s Republic of China on the Construction of Accessible Environments in 2023, requiring drug manufacturers and operators to provide labels and instructions in accessible formats such as audio, large print, braille, and electronic versions. In the same year, the National Medical Products Administration (NMPA) issued a public notice to promote the pilot work on aging-friendly labeling. By sorting out and summarizing the practical experience of the FDA′s patient labeling system and comparing it with the current pilot work on aging-friendly labeling in China, this article provides insights and references for promoting the establishment of a patient labeling system in China.
Signal transducer and activator of transcription 3 (Stat3), as a crucial transcription factor, plays a core regulatory role in regulating the cell cycle and various cellular processes such as proliferation, survival, differentiation, and inflammatory responses. Aberrant activation of Stat3 is closely related to the occurrence and development of many tumors. Meanwhile, the activity and stability of Stat3 are influenced by its post-translational modifications, including phosphorylation, acetylation, methylation, etc., among which phosphorylation is one of the most critical regulatory mechanisms. Under pathological and physiological stimuli, phosphorylation modifications can alter the structure of Stat3 in different cells, thereby determining specific gene programs. This process leads to the activation of Stat3 and promotes tumor cell proliferation, etc. This article focuses on the phosphorylation modification of Stat3, systematically elaborating on the regulatory mechanisms of its main phosphorylation sites (tyrosine 705 site and serine 727 site), as well as its roles in tumor cell cycle regulation, apoptosis inhibition, angiogenesis, invasion and metastasis, and tumor microenvironment remodeling. At the same time, it explores tumor treatment strategies targeting Stat3 phosphorylation, providing theoretical references for tumor mechanism research and clinical treatment.
Drug safety spans the full lifecycle of drug research and development, manufacture, distribution and usage, serving as both the cornerstone of public health maintenance and a core issue in regulatory science. Traditional drug safety monitoring models face numerous challenges regarding data processing efficiency, agility in risk identification and comprehensiveness. However, the advancement of artificial intelligence (AI) technologies offers unprecedented opportunities for this field. From a full lifecycle perspective, this paper systematically reviews and analyzes the key technologies and application progress of AI in safety assessment across three stages: preclinical research, clinical trials, and post-marketing pharmacovigilance. Currently, AI technologies, represented by machine learning and natural language processing, have demonstrated significant potential in drug toxicity prediction, the automated identification of adverse events, and real-time safety monitoring. Nevertheless, uneven data quality, insufficient model interpretability, and imperfect regulatory compliance remain the primary bottlenecks hindering the widespread application of AI in the field of drug safety. Future development will focus on the fusion of multi-modal data, the enhancement of model interpretability, and the application of federated learning for privacy protection, with the aim of constructing a more precise and reliable intelligent drug safety monitoring system.
This article aimed to explore the targets of the innovative drug HSK31679 in treating metabolic dysfunction-associated steatohepatitis (MASH), and to validate the changes in drug efficacy before and after target knockout through in vivo experiments.
Using the drug and disease databases, HSK31679 and MASH related targets were identified. The core targets were further determined by Cytoscape software. Auto Dock predicted the binding affinity of corresponding proteins to HSK31679. MASH mouse models of wild-type and liver caspase 8 (CASP8) knockout were constructed. Mice were divided into control group (normal feeding of mice + 0.5 mL saline administration), model group (modeling of mice + 0.5 mL saline administration), experimental group (modeling of mice + 3 mg·kg-1 HSK31679 administration), ΔCASP8 model group (modeling of CASP8 knockout mice + 0.5 mL saline administration) and ΔCASP8 experimental group (modeling of CASP8 knockout mice + 3 mg·kg-1 HSK31679 administration), with 8 mice in each group. Serum biochemical indicators were measured using an enzyme-linked immunosorbent assay (ELISA) after treatment, and liver sections were stained with HE to velidate the role of core targets of HSK31679′s treatment of MASH.
HE staining revealed significant and typical MASH-associated cellular damage in hepatocytes of the model group, indicating successful model establishment. Five major core targets associated with both HSK31679 and MASH were identified, and HSK31679 exhibited favorable binding activity with the CASP8 protein among them. In animal experiments, the serum triglyceride (TG) levels in the blank group, model group, experimental group, ΔCASP8 model group, and ΔCASP8 experimental group were (0.61±0.05), (1.01±0.15), (0.66±0.13), (0.62±0.09), and (0.63±0.12) mmol·L-1, respectively; the total cholesterol (TC) levels were (1.24±0.13), (2.88±0.32), (1.60±0.29), (1.30±0.35), and (1.32±0.10) mmol·L-1, respectively; the alanine aminotransferase (ALT) levels were (74.64±9.31), (140.20±23.74), (88.67±13.67), (78.18±17.66), and (73.58±16.15) IU·L-1, respectively; the aspartate aminotransferase (AST) levels were (106.33±26.77), (227.32±20.51), (124.58±13.63), (138.37±18.08), and (115.54±27.14) IU·L-1, respectively. Compared with the model group, the differences of above indicators in the experimental group were all statistically significant (all P<0.01). In HE staining, hepatocytes were arranged in a relatively orderly and dense manner, with a significant reduction in cytoplasmic vacuoles. The aforementioned indicators in the ΔCASP8 experimental group showed no statistically significant differences compared to the ΔCASP8 model group (all P>0.05). There was also no significant difference in the degree of hepatocyte degeneration between the two groups.
CASP8 protein is the key target of HSK31679 in the treatment of MASH. HSK31679 alleviated MASH-related hepatic inflammatory symptoms by binding to CASP8 protein and reducing its activity.
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