Latest ArticlesSodium-glucose cotransporter 2 (SGLT2) inhibitors, as a new class of oral antidiabetic drugs, have gained attention in the cardiovascular and metabolic fields due to their non-dependent hypoglycemic effects and cardioprotective effects. Studies have confirmed that these drugs protect myocardial cells by reconstructing the mitochondrial metabolic network in cardiomyocytes. They are widely used in patients with cardiovascular diseases and show significant efficacy. This article integrates recent research findings, systematically reviewing the mechanisms of myocardial cell protection under multidimensional regulation of mitochondrial metabolism by SGLT2 inhibitors. It expands the theoretical support for their use in cardiovascular therapy and provides references for related research directions.
To characterize clinical features, identify risk factors, and propose risk management strategies for drug-induced liver injury (DILI) in clinical trials.
260 drug-induced liver injury suspected unexpected serious adverse reaction (SUSAR) reports were systematically extracted from China’s National Medical Products Administration Pharmacovigilance System in Clinical Trials (January 2020-February 2025).
Key risk profiles included anticancer drug trials (86.92%), combination therapies (48.85%), elderly participants (≥50 years, 76.89%), phase Ⅲ studies (45.00%). Hospitalization/prolonged hospitalization occurred in 75.00% of cases. Sponsor-investigator causality assessments showed 91.54% concordance. Outcomes remained unresolved in 44.62% of cases, while permanent treatment discontinuation was the least frequent intervention (8.08%).
Implementation of early-warning systems, dynamic liver monitoring, standardized causality assessment, and personalized risk control should be enforced in clinical trial safety information risk management.
To explore the effects of sleep cognitive behavioral therapy combined with escitalopram tablets on negative emotions and sleep function of patients with depression and anxiety in our hospital.
From April 2021 to May 2023, patients with depression complicated with anxiety in our hospital were divided into control group and experimental group according to treatment methods. The control group was given escitalopram orally, 10 mg each time, qd for 8 weeks; in the experimental group, CBT-I (including sleep health education, stimulation control and other modules) was added on the basis of the control group, once a week for 60-90 min, and the course of treatment was 8 weeks. The clinical efficacy, negative emotional scores [using Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD)], sleep quality [using Pittsburgh Sleep Quality Index (PSQI)], social function [using Social Disability Screening Scale (SDSS)], cognitive function [using Mini-Mental State Examination (MMSE)], serum neuron-specific enolase (NSE) and neuropeptide Y (NPY) levels, medication compliance (using Morisky medication compliance questionnaire), and recurrence rate were compared between the two groups.
A total of 126 patients with depression and anxiety were screened and 100 patients were enrolled, including 48 patients in the control group and 52 patients in the experimental group. After treatment, the total effective rate of the treatment group was 82.69% (43 cases /52 cases), which was significantly higher than that of the control group 62.50% (30 cases/48 cases) (P<0.05). The HAMA scores in the treatment group and control group were (8.33±4.61) and (14.66 ±5.29) scores, respectively; the HAMD scores were (6.87±2.42) and (10.76±2.63), respectively; the PSQI scores were (7.06±1.11) and (10.69±1.03), respectively; the serum NSE levels were (10.35±1.46) and (12.26±1.55) μg·L-1; the NPY levels were (431.55±97.22) and (314.22±41.38) μg·L-1, respectively. The above indexes in the treatment group were significantly lower than those in the control group (all P<0.05). The recurrence rate of the treatment group and control group was 3.85% (2 cases /52 cases) and 16.67% (8 cases /48 cases), respectively, without statistically significant difference (P>0.05). No serious adverse events occurred during the intervention period in both groups, and there was no significant difference in the incidence of adverse events (P>0.05).
Cognitive behavioral therapy for insomnia combined with escitalopram tablets can effectively alleviate negative emotions, improve sleep function and reduce recurrence rate in patients with depression complicated with anxiety in our hospital, with good clinical efficacy.
To establish a high performance liquid chromatography method for the determination of arecoline in rat plasma, to study the pharmacokinetic behavior of arecoline in rats, and to provide a scientific basis for the pharmacodynamic substance basis of arecoline.
SD rats were given low, medium and high (10, 20 and 30 mg·kg-1) aqueous solutions of arecine by gavage, and blood was collected from the fundus venous plexus at different time points, and the supernatant was extracted by ethyl acetate and then injected for analysis. Puerarin was used as the internal standard to detect the content of arecine in plasma by HPLC, the mobile phase was acetonitrile-methanol-0.1% triethylamine aqueous solution (6∶16∶78, pH=4.5), isocratic elution, flow rate 1.0 mL·min-1, detection wavelength 215 nm, column temperature 30 ℃, and the pharmacokinetic parameters were calculated by DAS2.0 software.
The linear relationship between arecaine in 0.5-32.0 μg·mL-1 was good, the standard curve was y=0.0512x-0.0326(r=0.9960), the lower limit of quantification was 0.5 μg·mL-1, and the precision, repeatability, stability and recovery test results were good. The main pharmacokinetic parameters of arecaine in the low-, medium-, and high-dose groups were (1.36±0.21), (2.15±0.72) and (2.75±0.69) mg·L-1, and the area under the curve (AUC0-t) was (3.04±0.24), (3.87±1.02) and (4.49±0.76) mg·L-1·h, and the elimination half-lives (t1/2) were (3.67±1.73), (2.88±1.66) and (3.12±1.86) h.
The method is simple and rapid, suitable for the pharmacokinetic study of arecoline in rat plasma.
Dry eye disease causes eye discomfort in patients due to lack of tears or instability of the tear film and has a prevalence of 30%-50% in Asia. Conventional therapies suffer from limited efficacy and frequent drug administration, leading to continued active research and development of new drugs. This research explores the development process of 12 new dry eye drugs from 2003 to 2023, and analyzes the key successes and failures of these drugs in the context of U.S. Food and Drug Administration(FDA) guidelines. The study found that the core strategies of successful drugs included flexible adjustment of phase Ⅲ endpoints, strict adherence to one of the three FDA efficacy targets, and consistency between phase Ⅱ and phase Ⅲ trial designs. Failure cases were mostly due to deficiencies in the design of phase Ⅱ trials, such as overestimation of the efficacy of the drug due to small samples and lack of a placebo control, which led to an insufficient sample size for phase Ⅲ trials, and also due to the failure of the drug because of failure of endpoints to be adjusted in a timely manner. Dry eye drug development should be based on rigorous phase Ⅱ clinical trials, prioritize objective endpoint indicators such as the Schirmer test in phase Ⅲ studies, and set up an run-in period to reduce the placebo effect, as well as to meet the FDA's requirements on sample size and endpoint indicators, so as to effectively reduce the risk of research and development and improve the success rate of drug marketing.
To investigate the effect of β-sitosterol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by regulating the transforming growth factor β1 (TGF-β1)/mothers against decapentaplegic drosophila homolog 3 (Smad3) pathway.
BMSCs were randomly assigned into control group, low-dose β-sitosterol (β-sitosterol-L) group, medium-dose β-sitosterol group (β-sitosterol-M), and high-dose β-sitosterol group (β-sitosterol-H). Control group was cultured normally and β-sitosterol-L, -M and -H group was intervened by 1.5、3.0、6.0 μg·mL-1 β-sitosterol. BMSCs were randomly divided into control group (normal culture), β-sitosterol group (6 μg·mL-1 β-sitosterol), SIS3 group (5 μmol·L-1 SIS3), and β-sitosterol+SIS3 group (6 μg·mL-1 β-sitosterol+5 μmol·L-1 SIS3). Enzyme-linked immunosorbent assay (ELISA) was used to detect the alkaline phosphatase (ALP) activity was measured in each group. Alizarin red staining was used to determine the calcium deposition rate of each group, and then the osteogenic differentiation of BMSCs in each group was detected. Western blot was used to detect the osteogenic differentiation of BMSCs and the expression of TGF-β1/Smad3 pathway related proteins in each group.
The ALP activities of the β-sitosterol-L, β-sitosterol-M, β-sitosterol-H and the control groups were (1.24±0.10), (1.53±0.08), (1.84±0.11) and (0.95±0.09) U·mg prot-1, respectively; the calcium deposition rates were (196.21±13.67)%, (301.73±16.90)%, (423.60±20.25)% and (100.00±0)%, respectively; the relative expression levels of bone morphogenetic protein 2 (BMP-2) protein were 0.49±0.05, 0.89±0.07, 1.30±0.09 and 0.13±0.02, respectively; the relative protein expression of TGF-β 1 were 0.47±0.04, 0.85±0.07, 1.26±0.09 and 0.10±0.01, respectively; the p-Smad3/Smad3 values were 0.32±0.03, 0.59±0.06, 0.94±0.05 and 0.08±0.02, respectively. Compared with the control group, the above indicators of the β-sitosterol-L, β-sitosterol-M and β-sitosterol-H groups showed an increase in a dose-dependent manner, and the differences were statistically significant (all P<0.05). The ALP activities of the β-sitosterol group, SIS3 group, β-sitosterol+SIS3 group and the control group were (1.78±0.14), (0.43±0.08), (0.97±0.13) and (0.91±0.10) U·mg prot-1, respectively; the calcium deposition rates were (410.35±19.72)%, (45.62±13.91)%, (109.14±16.53)% and (100.00±0)%, respectively; the relative expression levels of BMP-2 protein were 1.79±0.16, 0.27±0.07, 0.87±0.10 and 0.85±0.11, respectively; the relative protein expression levels of TGF-β1 were 1.47±0.10, 0.11±0.03, 0.56±0.09 and 0.55±0.06, respectively; The p-Smad3/Smad3 values were 0.94±0.06, 0.09±0.02, 0.45±0.05 and 0.43±0.04, respectively. Compared with the control group, the above indicators were all increased in the β-sitosterol group, while they were all decreased in the SIS3 group, and the differences were statistically significant (all P<0.05). Compared with the β-sitostero group, the above indicators were all decreased in the β-sitosterol+SIS3 group, and the differences were statistically significant (all P<0.05).
β-sitosterol can promote osteogenic differentiation of BMSCs by activating the TGF-β1/Smad3 pathway.
To systematically screen potential antioxidant targets for the treatment of Alzheimer’s disease (AD) based on network pharmacology strategy.
Firstly, the structure-data file (SDF) of the antioxidant compound library was converted into the standard simplified molecular input line entry system (SMILES) molecular structure format usingrational discovery kit (RDKit), and then the potential targets of antioxidant compounds were predicted using the SwissTargetPrediction platform. After the obtained targets were analyzed with the differentially expressed genes of AD, a protein interaction network (PPI network) was constructed, and the functional interaction relationship was mined based on the STRING database. Further, the "compound-disease target-signaling pathway" network diagram was established with the help of Cytoscape software to screen key therapeutic targets. Finally, the core targets were annotated with Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the DAVID database.
Finally, 10 core targets with potential anti-Alzheimer’s disease effects were screened. Among them, the top three key nodes in degree value were heat shock protein 90α family class B member 1 (HSP90AB1), catenin β1 (CTNNB1) and proto-oncogene tyrosine protein kinase (SRC). Enrichment analysis suggested that these core targets may be mainly involved in the pathogenesis and intervention of Alzheimer’s disease through calcium signaling pathway and phosphatidyqinositol-3 kinase/protein kinase B (PI3K-Akt) signaling pathway, and had important therapeutic potential.
This study systematically identified the core antioxidant targets and key pathways for the treatment of Alzheimer’s disease from the perspective of network pharmacology, providing theoretical support for further research on antioxidant drugs.
To investigate the bioequivalence of oral torasemide tablets in healthy subjects under fasting and postprandial states.
A single-center, randomized, open-label, single-dose, double-period, double-cross study design was adopted. Each period involved a single oral administration of 10 mg of torasemide under fasting or postprandial conditions. The plasma drug concentration of torasemide was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic data were calculated and bioequivalence evaluation was performed.
The pharmacokinetic parameters of the test formulation and reference formulation in the fasting group were as follows: Cmax were (1 664.91±353.89) and (1 645.29±363.80) ng·mL-1, AUC0-t were (3 459.38±659.07) and (3 468.21±616.06) h·ng·mL-1, AUC0-∞ were (3 637.12±700.25) and (3 644.48±651.24) h·ng·mL-1. The pharmacokinetic parameters of the test formulation and reference formulation in the postprandial group were as follows: Cmax were (1 018.18±336.79) and (883.97±172.43) ng·mL-1, AUC0-t were (3 974.56±963.76) and (3 924.70±943.83) h·ng·mL-1, AUC0-∞ were (4 192.17±1081.81) and (4 143.90±1068.71) h·ng·mL-1; the 90% confidence intervals of the ratios of the pharmacokinetic parameters of the test formulation and reference formulation (test formulation/reference formulation) under fasting and postprandial conditions were all within the statistically equivalent range.
Torasemide tablets test formulation and the reference formulation have bioequivalence under both fasting and postprandial administration conditions.
In recent years, there has been an increasing trend in poisoning cases caused by improper use of sedative-hypnotic drugs, with related fatalities also rising annually. The dual characteristics of significant therapeutic effects and abuse potential have made these drugs a critical issue in global public health and clinical diagnosis and treatment. As a classic category of sedative-hypnotic agents, benzodiazepines are widely used in clinical departments such as emergency medicine, psychiatry, and cardiology. However, long-term use may lead to drug accumulation, tolerance, and dependence risks. Due to increasing social stress and accelerated population aging, the illicit use and recreational abuse of benzodiazepines persist. A growing number of individuals attempt to use these drugs to improve sleep quality or seek psychological euphoria, resulting in a significant rise in abuse and poisoning risks. This article outlines the monitoring requirements for benzodiazepines in clinical medication, introduces the latest sample pretreatment techniques, and reviews the current commonly used analytical technology systems, including the development trends of chromatography, mass spectrometry, and their hyphenated techniques. It focuses on the application value of different detection technologies in clinical monitoring, emergency treatment, and drug abuse prevention. By summarizing the development trends of emerging detection technologies, this study provides a theoretical basis and practical reference for technological advancements in clinical drug monitoring and public health regulation.
To explore the protective effects and potential mechanism of bifendate against methionine-choline-deficient (MCD) diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) in mice.
A total of 24 male C57BL/6J mice were randomly divided into control group, model group, and experimental group. The model group was fed with MCD diet to establish the MASLD model, while the experimental group received bifendate (300 mg·kg-1) in addition to the MCD diet. After 6 weeks, liver pathology was assessed using Hematoxylin-Eosin (H&E) and Oil Red O staining. Hepatic triglyceride (TG) content, serum lipopolysaccharide (LPS) and serum alanine aminotransferase (ALT) levels were measured using assay kits. Gut microbiota composition and diversity were analyzed by high-throughput sequencing. The relative expression levels of the intestinal tight junction protein ZO-1 and Occludin were detected by Western blot.
Oil Red O staining revealed that the number and degree of hepatocellular steatosis were significantly reduced in the experimental group compared to the model group. The MCD diet successfully induced steatohepatitis in mice, characterized by significantly increased hepatic TG, serum ALT, and marked hepatocellular steatosis. Hepatic TG contents were (66.43±14.58), (231.29±20.26), and (190.39±29.33) μmol·g-1 for the control, model and experimental groups, respectively; serum ALT levels were (52.04±16.80), (219.74±123.37) and (31.68±10.70) IU·L-1, respectively; serum LPS levels were (0.89±0.57), (4.01±0.65) and (0.52±0.25) EU·mL-1, respectively. The relative expression levels of ZO-1 were 1.00±0.94, 0.06±0.03 and 0.25±0.27, respectively, and for Occludin were 1.00±0.57, 0.06±0.03 and 0.15±0.15, respectively. Compared with the model group, the experimental group showed statistically significant differences in all the aforementioned indicators (P<0.05, P<0.001). Bifendate intervention significantly reduced serum ALT and hepatic TG levels and markedly alleviated the extent and severity of hepatocellular steatosis. Regarding the gut-liver axis, bifendate significantly improved the diversity and richness of the gut microbiota in model mice, particularly increasing the relative abundance of Bilophila and Desulfovibrio, genera closely related to bile acid metabolism. Furthermore, bifendate intervention significantly up-regulated the expression of intestinal tight junction proteins and decreased serum LPS levels.
Bifendate can effectively ameliorate MCD diet-induced steatohepatitis in mice. Its protective mechanism is closely related to the regulation of the gut-liver axis, including remodeling the intestinal flora structure (increasing the relative abundance of Bilophila and Desulfovibrio), enhancing intestinal barrier function (upregulating tight junction proteins, reducing serum LPS), and potentially affecting bile acid metabolism.
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