Steroid-induced osteonecrosis of the femoral head (SONFH) is a challenging and debilitating orthopedic condition with a rising incidence in recent years. Shuanghe Decoction (SHD), a traditional Chinese medicine formula, has shown significant efficacy in treating SONFH, though its underlying mechanisms remain unclear. This study aims to elucidate the therapeutic effects and potential mechanisms of SHD on SONFH through in vivo experiments, combined with network pharmacology, metabolomics, and gut microbiota analysis. Forty male Sprague-Dawley rats (300 ± 20 g) were randomly assigned to four groups: Control, Model, SHD-L, and SHD-H, with 10 rats each. SONFH was induced in all groups except the Control group using lipopolysaccharide and methylprednisolone. The SHD-L and SHD-H groups were treated with Shuanghe decoction at doses of 4.86 g/kg/day and 9.72 g/kg/day, respectively, for eight weeks. Bone morphology, pathological changes, and osteogenic factors were evaluated using Micro-CT, histological staining, and immunohistochemistry. Network pharmacology, metabolomics, and gut microbiota analyses were conducted to explore SHD’s mechanisms. SHD improved bone morphology and increased osteogenic factor expression (RUNX2, OCN, COL-I). Network pharmacology indicated that metabolic pathways play a key role in SHD’s therapeutic effects. Metabolomic analysis identified 14 differential metabolites, including 21-hydroxypregnenolone and tyramine, which were restored to normal levels by SHD. Gut microbiota analysis revealed that SHD modulated bacterial abundance, particularly Verrucomicrobia, Allobaculum, and Burkholderiales. A comprehensive network identified two key metabolites (tyramine, 21-hydroxypregnenolone), seven targets (CYP19A1, CYP1A2, CYP1B1, CYP2C9, CYP3A4, MIF, and HSD11B1), two metabolic pathways (tyrosine metabolism, steroid hormone biosynthesis), and four bacterial taxa (Jeotgalicoccus, Clostridium, Corynebacterium, rc4-4) as central to SHD against SONFH. SHD alleviates SONFH by reshaping gut microbiota, reversing metabolic imbalances, and enhancing osteogenesis. Our findings provide novel insights into the pharmacological mechanisms of SHD, laying a foundation for its clinical application in treating SONFH.

Background: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Methods: Se@SiO₂ NPs were synthesized using a mixture of Cu_2-x Se nanocrystals, and the mechanism of action of Se@SiO₂ NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO₂ NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO₂ NPs for peripheral nerve regeneration were determined. Results: Porous Se@SiO₂ was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H₂O₂ and 200 μg/mL Se@SiO₂, and RNA-seq revealed that porous Se@SiO₂ was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO₂ could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO₂. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO₂. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO₂ group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO₂. Conclusion: Se@SiO₂ NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.

Objectives: To understand factors associated with senior high school students’ willingness to apply for pediatrics in order to inform recruitment strategies. Methods: An anonymous questionnaire was distributed to 9,574 high school students. The questions covered the following topics: students’ intention to apply for pediatrics, personal and family information, factors impacting a student’s choice of major, and cognizance of the state of pediatrics (including education and working conditions). univariate and multivariate logistic regression analysis and chi-square tests were used to compare students with and without a clear pediatric intention and to explore influencing factors. Results: Only 6.4% (513/8,050) of senior high school students had intention to apply for pediatrics (IAP). The goal was directly tied to private and family information. Students’ IAP is favorably connected with their interests and well-defined career objectives, particularly when considering COVID-19. The way that students view pediatric illnesses has an impact on their willingness as well. Students’ significant decisions are influenced by their understanding of pediatrics; the more positive their perceptions are of the remuneration and working circumstances for physicians, the more probable it is that they will have an IAP. Conclusion: This survey reveals the hesitancy of high school students in selecting pediatrics as their career path and explores potential contributing factors. Furthermore, these findings offer insights into the development of healthcare services in emerging economies.

Background: Nephrolithiasis seriously affects people’s health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO₂ nanocomposites as described in Zhu’s study. The size and morphology of the Se@SiO₂ nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO₂ group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO₂ group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO₂ nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO₂ groups (Se@SiO₂ 6.905±0.074 mg/kg; GAM + Se@SiO₂ 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO₂ nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO₂ nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.