Latest ArticlesTo investigate the effects of paeoniflorin on insulin resistance and myocardial injury in rats with gestational diabetes mellitus and its mechanism.
Female rats were randomly divided into control group (normal diet), model group [male rats fed with high-fat diet and intraperitoneally injected 30 mg·kg-1 streptozotocin (STZ) after close cages], experimental group (after modeling, 50 mg·kg-1 paeoniflorin was given by gavage), si-NC group (50 mg·kg-1 paeoniflorin + si-NC plasmid injected into tail vein after modeling), si-IGFBP2 group (50 mg·kg-1 paeoniflorin + si-IGFBP2 plasmid injected into tail vein after modeling), each group of 10 rats. After 2 weeks of continuous treatment, fasting blood glucose (FBG) was measured with a glucose meter. Serum insulin-like growth factor binding protein 2 (IGFBP2), fasting insulin (FINS), cardiac troponin Ⅰ (cTnⅠ), creatine kinase isoenzyme MB (CK-MB) related factors were detected by enzyme-linked immunosorbent assay (ELISA), insulin resistance index (HOMA-IRI) was calculated, and the expression of signal pathway-related proteins was detected by Western blot assay.
The levels of FBG in control group, model group, experimental group, si-NC group and si-IGFBP2 group were: (5.62±0.56), (18.10±1.76), (9.81±1.46), (10.02±1.38) and (16.32±1.87) mmol·L-1, respectively; IGFBP2 levels were (39.47±2.64), (20.65±1.86), (27.18±1.85), (27.95±1.74) and (15.28±1.22) ng·mL-1, respectively; FINS levels were (8.72±0.75), (21.11±2.50), (16.88±1.86), (16.06±1.39) and (20.01±2.94) mU·L-1, respectively; cTnⅠ levels were (406.04±29.98), (788.11±84.43), (513.70±57.62), (526.85±38.03) and (756.51±63.88) pg·mL-1, respectively; CK-MB levels were (7.98±0.07), (15.15±1.26), (11.59±1.23), (11.37±1.79) and (13.49±1.54) U·L-1, respectively; HOMA-IRI levels were 2.17±0.26, 16.92±2.12, 6.24±0.95, 6.60±1.10 and 12.83±1.68, respectively; the relative expression levels of phosphorylate-phosphatidylinositol 3-kinase (p-PI3K) protein were 0.68±0.11, 0.39±0.04, 0.53±0.05, 0.51±0.06 and 0.43±0.04, respectively; the above indexes in the model group were compared with the control group, the experimental group were compared with the model group, and the si-IGFBP2 group were compared with the si-NC group, the differences were statistically significant (all P<0.05).
Paeoniflorin may improve insulin resistance and myocardium injury in gestational diabetes mellitus rats by up-regulating IGFBP2 expression.
To evaluate the impact of stage assessment nursing mode on the psychological state of healthy participants in Phase I clinical trials of new drugs based on psychological questionnaire.
This was a randomized, single blind, controlled clinical research. Healthy participants were randomly divided into treatment and control group. According to the impact of anxiety and depression on healthy participants, the treatment group was given a stage evaluation nursing model, while the control group received routine nursing measures. Both groups were evaluated using the self rating depression scale (SDS) and self rating anxiety scale (SAS) questionnaires before administration, on the day of administration, after administration (mid-term of the trial), on the day of discharge, and on the day of withdrawal, and their effectiveness was observed.
A total of 159 healthy participants were included in the study, with 83 cases in the treatment group and 76 cases in the control group. SDS scores of treatment group and control group were (54.93±4.62) and (54.87±4.89) points before administration, (52.17±6.55) and (53.95±7.03) points on the administration day, (49.94±7.35) and (51.69±9.16) points at the mid-term of the trial, (52.13±6.70) and (53.85±6.76) points on the discharge day, (51.33±7.99) and (52.60±7.39) points on the day of withdrawal, respectively. Compared with before administration, there was statistically significant difference in treatment group during administration day and the day of withdrawal, as well as in the mid-term of trial in the control group (all P<0.01). SAS scores for treatment group and control group were (36.08±6.45) and (37.04±6.87) points before administration, (36.18±7.79) and (37.43±8.53) points on administration day, (35.04±7.09) and (36.86±9.55) points at the mid-term of the trial, (35.82±7.75) and (37.68±8.78) points on discharge day, (39.29±9.17) and (36.47±7.91) points on the day of withdrawal, respectively. No statistical significance of SAS scores was observed (all P>0.05).
Use of psychological questionnaires and stage nursing assessment forms for evaluation and nursing intervention can alleviate the levels of depression and anxiety in healthy participants.
Osteonrosis of the femoral head (ONFH) is an intractable orthopaedic disease caused by insufficient blood supply to the femoral head. As a highly vascularised tissue, vascular microcirculatory dysfunction can lead to increased apoptosis of bone cells and inadequate blood supply to the femoral head. Vascular endothelial cells are the main constituent cells of the vascular wall, which are crucial for maintaining the normal state of blood vessels, when inflammation, oxidative stress and other risk factors cause vascular endothelial cell dysfunction, it can disrupt vascular homeostasis and normal blood flow to the bone tissue, leading to inhibition of angiogenesis-osteogenesis coupling function, and ultimately resulting in necrosis due to insufficient osteogenesis and haematological transport to the femoral head. Traditional Chinese medicine can promote angiogenesis and reduce apoptosis of vascular endothelial cells by promoting the expression of vascular endothelial cytogenesis-related factors, and enhance the blood supply of the femoral head. Therefore, this article reviews the effects of vascular endothelial cell dysfunction on the blood supply of the femoral head and the mechanism of action of traditional Chinese medicine in promoting angiogenesis, with a view to providing ideas for the treatment of ONFH.
To explore the effect of Wuzi Yanzong pill on testicular dysfunction in subacute aging rats through metabolomics.
Forty-two rats were subcutaneously injected with 200 mg·kg-1 D-galactose (D-Gal) to induce a subacute aging model. After successful modeling, the rats were randomly divided into four groups: model group, control group, exprimental-L group, exprimental-H group, each with 9 rats. Eight normal rats without D-Gal treatment were used as the normal group. The exprimental-L,-H groups were administered Wuzi Yanzong pill at doses of 0.54 and 2.16 g·kg-1 by gavage, respectively, while the control group was given 300 mg·kg-1 metformin by gavage. The normal and model groups were treated with an equal volume of distilled water by gavage. All rats were dosed once daily for 4 weeks. During this period, the each group (except for the normal group) was continued injected 200 mg·kg-1 D-Gal injections. The levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum were measured using enzyme-linked immunosorbent assay (ELISA). The relative expression of proteins involved in testicular secretory function [hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1), steroidogenic acute regulatory protein (STAR)] was determined by Western blot. Metabolomics analysis was performed to study metabolic changes in the testicular tissue.
The serum T levels in the normal, model, control, experimental-L, and experimental-H groups were (8.67±1.71), (1.95±0.46), (6.50±1.15), (2.45±0.49) and (5.81±0.96) pg·mL-1, respectively; the FSH levels were (28.53±4.16), (46.73±3.72), (30.18±5.17), (35.35±1.90) and (30.31±4.35) mU·mL-1, respectively; the LH levels were (22.66±3.97), (37.89±4.16), (24.28±3.75), (37.09±3.98) and (28.35±4.38) mU·mL-1, respectively; the relative protein expression levels of HSD17B3 were 1.04±0.05, 0.29±0.14, 0.78±0.18, 0.71±0.13 and 0.85±0.18; the relative protein expression levels of CYP11A1 were 1.23±0.15, 0.62±0.08, 1.01±0.05, 0.77±0.15 and 1.24±0.09; the relative protein expression levels of STAR were 0.97±0.12, 0.21±0.05, 0.79±0.19, 0.62±0.23 and 0.96±0.25, respectively. The model group showed significant differences in these indicators when compared with the control and experimental-H groups (all P<0.05). Metabolomics analysis identified six differential metabolites in the experimental-H group compared to the model group. These metabolites were mainly involved in steroid hormone biosynthesis, ovarian steroidogenesis, lipid metabolism, and biotin metabolism.
In vivo and metabolomics studies show that Wuzi Yanzong pill improves antioxidant capacity in the testes, reduces oxidative stress damage, delays aging, and effectively treats testicular dysfunction, thereby improving testicular function.
To explore the therapeutic effect of hydroxysafflor yellow A (HSYA) on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) mice and its mechanism of action.
Mice were randomly divided into control group, model group and experimental -L, -M, -H groups, with 20 mice per group. The control group was raised normally, and the other groups were exposed to cigarette smoke (CS) and non-typeable Haemophilus influenzae (NTHi) infection to establish an AECOPD mouse model. Starting from the 12th week of CS exposure, experimental -L, -M, -H groups were administered 25, 50 and 100 mg·kg-1·d-1 HSYA by gavage, and control and model groups were given 0.9% NaCl by gavage. Five groups were administered once a day for 2 weeks. The functional residual capacity (FRC) of the mice was measured using the Buxco lung function test system. The percentage of neutrophils in bronchoalveolar lavage fluid (BALF) was measured using flow cytometry. The expression levels of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (Akt) in lung tissues were detected by Western blot.
The FRC of experimental -M, -H groups, model group and control group were (0.31±0.01), (0.27±0.01), (0.37±0.02) and (0.25±0.01) L; the neutrophil percentages were (37.96±2.88)%, (28.41±1.64)%, (60.27±2.12)% and (11.33±0.31)%; the phosphorylated PI3K/PI3K ratios were 1.59±0.08, 1.30±0.06, 2.28±0.08 and 1.00±0.06; the phosphorylated Akt/Akt ratios were 1.33±0.11, 1.15±0.03, 1.76±0.11 and 1.00±0.06, respectively. Compared with model group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).
HSYA may reduce neutrophil activity by inhibiting the PI3K/Akt pathway, thereby inhibiting inflammatory responses and alleviating lung injury.
This study examines the practical value of regulatory science action plans in identifying strategic regulatory trends. By analyzing real-world research initiatives from leading international drug regulatory agencies through three dimensions—data platform development, regulatory science implementation, and international harmonization—this paper provides critical references for researchers and regulatory practitioners. Internationally, regulatory authorities have established robust data platforms such as Sentinel, DARWIN EU, and MID-NET. Collaborative partnerships with academic institutions have been formed to advance frontier research topics, while concerted efforts toward international coordination aim to standardize real-world evidence (RWE) applications. Current technical priorities focus on innovations in data infrastructure and research paradigms, particularly methodological advancements in bias mitigation and causal inference frameworks. The expanding application of RWE across the entire drug lifecycle marks a pivotal trend in global pharmaceutical regulation. These developments offer strategic insights for China to accelerate the construction of integrated data platforms and cultivate an innovation-driven regulatory ecosystem.
To study the possible mechanism and related signaling pathway of cell senescence in hypertensive nephropathy with the help of bioinformatics.
The microarray data GSE37455 was downloaded from the gene expression database, and the data was merged with R software to remove the batch effect, so as to obtain differentially expressed genes. Cell aging genes were obtained from the CellAge database, and differential genes related to cell aging were obtained through R package “ggVennDiagram”. Gene interaction network string database was imported to obtain protein protein interaction (PPI) network map, and Cytoscape3.8.0 software was used to mine core differential genes. The function and pathway of core differential genes were analyzed by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA).
A total of 41 differential genes were obtained, including 32 up-regulated genes and 9 down-regulated genes. Four differential genes related to cell senescence were obtained after intersection. The core differential gene-activated transcription factor 3(ATF3) was obtained by PPI analysis and Cytoscape treatment. GSEA analysis showed that cell senescence might play a role in hypertensive nephropathy through the thermogenesis of mitochondrial uncoupling protein 1 and the signal transduction of type Ⅰ interferon response (TYPE-Ⅰ-IFN).
Cellular senescence may play a role in hypertensive nephropathy through pathways such as mitochondrial uncoupling protein-1 thermogenesis and TYPE-Ⅰ-IFN signaling, which provides a therapeutic target for the study of hypertensive nephropathy.
To analyze the antimicrobial sensitivity against clinical isolates in the first affiliated hospital of air force medical university in the past three years.
The nonduplicate clinical isolates were collected in 2021—2023, identification and drug sensitivity test were performed by using VITEK2-compact automatic bacteria identification system. The data was analyzed using WHONET 5.6 software and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) 2023 breakpoints.
A total of 20 536 clinical isolates were collected, of which 28.78% were gram-positive, 58.64% were gram-negative, 11.94% were fungi and 0.64% were anaerobe. The prevalence of methicillin-resistant strains in Staphylococcus aureus and coagulase-negative Staphylococcus were 49.11% and 73.06%, respectively. No Staphylococcus resistant to vancomycin, linezolid, or tigecycline was detected. The resistance rates of Enterococcus faecium to most antimicrobial agents were much higher than Enterococcus faecalis. 8 strains of vancomycin-resistant Enterococcus faecium were isolated, and a few linezolid-resistant strains were identiffed in both species. The prevalence of penicillin-susceptible Streptococcus pneumoniae (PSSP) was 95.85%. The resistance rate to carbapenems was 0.2% to 12.8% in Enterobacterales species, and the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 6.6%, with Klebsiella pneumoniae accounting for 66.53%. The resistance rates of Acinetobacter spp to imipenem and meropenem were 75.3% and 76.7%, respectively. Meanwhile, the rates of Pseudomonas aeruginosa were 22.9% and 19.9% respectively.
The antimicrobial resistance of clinical isolates in our hospital is still serious. All relevant departments should strengthen the monitoring of bacterial resistance in order to curb the development and spread of bacterial resistance.
To investigate the effect of Acorus calamus L. on wound healing of radioactive skin injury in rats based on the mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB) signaling pathway.
A rat model of radioactive skin injury was induced by the radionuclide irradiation, the successful model rats were randomly divided into the model group, the control group, and the experimental -H, -M, -L groups with 12 rats in each group, and another 12 normal rats were taken as the normal group. Experimental-H, -M, -L goups was applied with Acorus calamus L. 600, 400, 200 g·kg-1, respectively. Control group was applied with triethanolamine cream 400 g·kg-1 on rat wounds; normal and model groups were treated with 0.9% NaCl. Six groups were treated once a day for 45 days. The healing rate of wounds was compared among the six groups. The levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in serum and hydroxyproline (HYP) in wound tissue were measured by enzyme linked immunosorbent assay. The protein levels of IL-1β, IL-6, TNF-α, mitogen-activated protein kinase (p38) and nuclear factor κB p65 subunit (p65) were detected by Western blot.
The wound healing rates of experimental-H, -M, -L groups, control group and model group were (70.24±3.17)%, (62.41±4.52)%, (49.89±4.61)%, (50.35±2.44)% and (29.42±4.23)%, respectively. The levels of IL-1β in experimental-H, -M, -L groups, control group, model group and normal group were (41.22±2.98), (52.35±1.69), (61.32±2.74), (45.26±3.12), (79.24±5.64) and (28.85±2.11) pg·L-1; the levels of IL-6 were (25.68±1.65), (32.55±2.64), (51.23±2.34), (32.32±1.56), (61.12±2.35) and (18.88±1.12) pg·L-1; the levels of TNF-α were (62.38±5.66), (73.56±4.52), (88.63±5.68), (68.33±4.32), (112.48±6.52) and (55.21±3.89) pg·L-1; the levels of HYPs of (3.77±0.41), (3.51±0.26), (2.98±0.39), (3.62±0.37), (2.21±0.48) and (4.22±0.55) μg·mg-1; the relative expression levels of IL-1β were 0.31±0.04, 0.43±0.07, 0.60±0.03, 0.51±0.04, 0.69±0.06 and 0.11±0.07; the relative expression levels of IL-6 were 0.50±0.03, 0.60±0.04, 0.69±0.04, 0.62±0.07, 0.83±0.08 and 0.28±0.06; the relative expression levels of TNF-α were 0.49±0.06, 0.61±0.03, 0.73±0.06, 0.59±0.04, 0.83±0.05 and 0.28±0.04; the phosphorylated p38/p38 ratios were 0.46±0.06, 0.56±0.04, 0.67±0.03, 0.56±0.05, 0.84±0.04 and 0.34±0.08; the phosphorylated p65/p65 ratios were 0.37±0.06, 0.54±0.03, 0.63±0.04, 0.47±0.05, 0.79±0.04, and 0.32±0.06, respectively. Compared with model group, the above indexes in the experimental-H, -M groups were statistically significant (all P<0.05).
Acorus calamus L. can promote the healing of radioactive skin injury in rats, inhibit the inflammation level of the wound tissue, and promote collagen deposition, and its mechanism may be related to the regulation of MAPK/NF-κB pathway.
To explore the mechanism of prasugrel (PRAS) in alleviating oxidative stress of myocardial ischemia reperfusion (IR) by inducing pyroptosis of rat cardiomyocytes based on nuclear factor erythroid derived 2-like 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway.
SD rats were randomly divided into sham operation group (only the heart was exposed, no IR model was constructed, and the same amount of normal saline was injected into the stomach), model group (IR rat model was constructed, and the stomach was given an equal amount of 0.9% NaCl), the experimental-L group (model group rats were intragastric with 5 mg·kg-1 PRAS), the experimental-M group (model group rats were intragastric with 10 mg·kg-1 PRAS), and experimental-H group (model group rats were intragastric with 15 mg·kg-1 PRAS). The serum levels of myocardial injury markers and oxidative stress factors were detected by enzyme-linked immunosorbent assay. The relative expression levels of pyroptosis-related proteins and Nrf2/HO-1/NQO1 signaling pathway-related proteins in myocardial tissue were detected by Western blot.
The contents of cardiac troponin Ⅰ (cTnⅠ) in sham operation group, model group, experimental-L group, experimental-M group and experimental-H group were (264.52±39.04), (558.40±101.68), (477.65±64.33), (429.71±75.94) and (313.84±52.26) pg·mL-1, respectively; the creatine kinase isoenzyme (CK-MB) levels were (0.68±0.11), (2.76±0.45), (1.92±0.27), (1.53±0.23) and (1.11±0.19) U·L-1, respectively; the levels of malondialdehyde (MDA) were (4.05±0.68), (10.12±1.74), (8.44±1.26), (6.79±1.05) and (5.47±1.02) nmol·L-1, respectively; the relative expression levels of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) were 1.00±0.14, 2.16±0.32, 1.72±0.25, 1.54±0.28 and 1.28±0.21, respectively; the relative expression levels of Nrf2 were 1.00±0.15, 0.32±0.04, 0.39±0.05, 0.61±0.10 and 0.80±0.13, respectively. The above indexes of model group were compared with those of sham-operation group, and those of experimental-L, experimental-M and experimental-H groups were compared with those of model group (P<0.05, P<0.01, P<0.001).
PRAS may resist oxidative stress and reduce pyroptosis and apoptosis of myocardial cells by activating Nrf2/HO-1/NQO1 signaling pathway, thereby alleviating IR injury and protecting cardiac function.