Current Medical Science最新文献

Objective: This study aimed to explore a novel method that integrates the segmentation guidance classification and the diffusion model augmentation to realize the automatic classification for tibial plateau fractures (TPFs).

Methods: YOLOv8n-cls was used to construct a baseline model on the data of 3781 patients from the Orthopedic Trauma Center of Wuhan Union Hospital. Additionally, a segmentation-guided classification approach was proposed. To enhance the dataset, a diffusion model was further demonstrated for data augmentation.

Results: The novel method that integrated the segmentation-guided classification and diffusion model augmentation significantly improved the accuracy and robustness of fracture classification. The average accuracy of classification for TPFs rose from 0.844 to 0.896. The comprehensive performance of the dual-stream model was also significantly enhanced after many rounds of training, with both the macro-area under the curve (AUC) and the micro-AUC increasing from 0.94 to 0.97. By utilizing diffusion model augmentation and segmentation map integration, the model demonstrated superior efficacy in identifying Schatzker I, achieving an accuracy of 0.880. It yielded an accuracy of 0.898 for Schatzker II and III and 0.913 for Schatzker IV; for Schatzker V and VI, the accuracy was 0.887; and for intercondylar ridge fracture, the accuracy was 0.923.

Conclusion: The dual-stream attention-based classification network, which has been verified by many experiments, exhibited great potential in predicting the classification of TPFs. This method facilitates automatic TPF assessment and may assist surgeons in the rapid formulation of surgical plans.

Objective: This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.

Methods: A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018. The quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment of β-cell function (HOMA-β) were used as independent variables. The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable, with other potential confounding factors considered. Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.

Results: A total of 2128 patients, comprising 1191 men and 937 women, were included in our analysis. The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic cardiovascular event [β = - 8.85, CI (- 15.77, - 1.93)] after adjusting for age, race, body mass index, systolic blood pressure, diastolic blood pressure, hypertension treatment, smoking, diabetes, and low-density lipoprotein cholesterol. Conversely, an increase in HOMA-β was associated with 10-year risk [β =  6.84, CI (0.45, 13.23)]. Gender-specific subgroup analysis indicated that the QUICKI had a β value of 0.077 (0.046, 0.108) for men and 0.080 (0.061, 0.094) for women.

Conclusion: This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.

Objective: Stroke is a main cause of disability and mortality worldwide. It has been reported that ischemic preconditioning (IP) has neuroprotective effects against stroke. This study aimed to verify the mechanism by which calcium-sensing receptor (Casr) inhibition-mediated M2 microglial transformation in the IP protects against stroke, which will provide a potential therapeutic target for stroke.

Methods: Middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD) neurons were used in this study. IP was induced via the transient MCAO and OGD methods. RNA sequencing (RNA-Seq) was used to explore the underlying key molecules. Western blotting and immunohistochemistry were performed to detect the expression of Casr and the M1 and M2 microglial markers. CCK8 was used to detect cell viability. The calcium concentration was detected via the use of Fluo-4 AM, a fluorescence probe. The Casr inhibitor NPS2143 and the Casr activator R568 were used to explore the role of Casr in M2 microglial transformation and neuroprotection.

Results: We first revealed that IP induced M2 microglial transformation in ischemic injury. In addition, MCAO injury increased Casr expression and the calcium concentration, which was inhibited by IP. Furthermore, Casr activation inhibited the M2 microglial transformation induced by IP. Finally, we found that Casr inhibition improved the survival rate, alleviated neurological deficits, and reduced the infarct volume induced by MCAO.

Conclusions: We confirmed that Casr-related neuroprotection induced by IP is associated with the transformation of M2 microglia. These findings can be used to understand the protective mechanisms of IP against ischemic stroke.

Objective: Tumour cells in a hypoxic state are more invasive, have stronger self-renewal capabilities, and are difficult to treat because of their ability to promote tumour recurrence and metastasis. The glycolysis inhibitor 3-bromopyruvic acid (3-BrPA) can completely inactivate glycolytic enzymes at extremely low drug concentrations, thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells. Therefore, we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells (HepG2) in vitro; then, we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.

Methods: In vitro, a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells, and light microscopy confirmed that the HepG2 cells were completely dead. Western blotting was used to detect the expression of key proteins involved in apoptosis. A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment: the control group was perfused with saline in the hepatic artery; the transcatheter arterial embolization (TAE) group was given TAE; and the experimental group was perfused with 3-BrPA combined with TAE. The tumor-bearing rabbits were killed one week after surgery. The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.

Results: In vitro, the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration. 3-BrPA (100 μmol/L) could induce the necrosis of HepG2 cells. Stimulation with 50 μmol/L 3-BrPA could activate the tumor cell apoptosis pathway. 3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.

Conclusion: 3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.

Objective: Hypoxia plays a critical role in the pathophysiology of cardiomyopathy, myocardial infarction, and heart failure. Promoting ketone metabolism has been shown to be beneficial for myocardial cells under hypoxic conditions. However, the expression and regulatory mechanisms of key enzymes in the ketone pathway under hypoxic conditions are still unclear. This study aimed to investigate the effects of hypoxia on the expression of key enzymes in the ketone metabolic pathway and the underlying regulatory mechanisms involved.

Methods: H9C2 myocardial cells were cultured for 6 h in an oxygen-glucose-deprived state, and the expression of various genes was detected by quantitative real-time PCR. ELISA and lactate dehydrogenase (LDH) cytotoxicity assay were used to measure CoAs, itaconic acid, and LDH levels, respectively, and the dependence of gene expression on hypoxia-inducible factor-1 alpha (HIF-1α) was evaluated using the inhibitor LW6.

Results: H9C2 cardiomyocytes exhibited increased ketone body metabolism in response to hypoxia. Hypoxia induced the expression of the ketone body enzymes succinyl-CoA:3-oxoacid CoA transferase (SCOT/OXCT1), 3-hydroxybutyrate dehydrogenase 2 (BDH2), and acyl-CoA: cholesterol acyltransferase 1 (ACAT1) in cardiomyocytes, with a concomitant increase in the level of acyl-CoA and a decrease in the level of succinyl-CoA. The HIF-1α inhibitor LW6 could partially reverse the expression of BDH2 and ACAT1, as well as the levels of succinyl-CoA. Interestingly, however, hypoxia-induced SCOT/OXCT1 expression was not regulated by the HIF-1α inhibitor. In addition, hypoxia promoted the expression of inflammatory factors.

Conclusion: These data confirm the critical role of ketone metabolism in myocardial hypoxia and help to elucidate the pathophysiology of cardiomyopathy, myocardial infarction and heart failure.

Objective: This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.

Methods: In this hospital-based retrospective study, we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders (schizophrenia, depressive episode, bipolar disorder, pervasive developmental disorder, and unspecified mood disorder) that accounted for the overall proportion of patients admitted. The rank and proportion of these mental disorders, demographic characteristics and disease indicators were analysed.

Results: There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years, with a sharp decline in 2020 due to the COVID-19 pandemic, followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022. The average age of hospitalization decreased significantly from 20.7 to 16.2 years, with a marked increase in the 12-17-year-old age group. The proportion of female hospitalizations increased from 39.2% to 55.2%, with a corresponding decrease in male hospitalizations. There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.

Conclusion: This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.

Objective: The objective of this study was to explore the therapeutic effects of kaempferol (Kae) on rheumatoid arthritis (RA) and to elucidate the underlying mechanisms.

Methods: The collagen-induced arthritis (CIA) model was established using collagen II to induce RA. Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage. Pathological changes in the ankle joint were analyzed. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of inflammatory factors. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of genes associated with the balance of regulatory T (Treg)/T helper 17 (Th17) cells. Flow cytometry was utilized to determine the Treg/Th17 ratio. Furthermore, these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae. Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.

Results: Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t (RORγt) and IL-17 expression, and an upregulation of Foxp3, IL-10, and TGF-β expression in CIA mice. Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines. Furthermore, Kae treatment suppressed the expression of miR-34a, which was identified as a target of miR-34a. Finally, Kae regulated Treg/ Th17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.

Conclusion: The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis. These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.

Objective: Alternative splicing affects gene expression during placental development. The present study aimed to identify poly (ADP-ribose) polymerase 1 (PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.

Methods: Decidual tissues were collected from women with induced abortion and spontaneous abortion. PARP1 transcription was quantified by RT-qPCR. Small interfering RNA (siRNA) was used to knock down the PARP1 expression in HTR-8/Svneo cells. The transfection efficiency was verified by RT-qPCR and Western blotting. Total RNA was extracted, and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes. The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR. Functional analysis, which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, was performed.

Results: The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group, when compared to the induced abortion group. However, the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells. Furthermore, 227 genes that underwent alternative splicing were identified, and these were differentially expressed in siPARP1 cells, when compared to siNC cells.

Conclusion: The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts. Furthermore, the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.