Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To analyze the dynamic changes in serum adiponectin (APN) levels after acute myocardial infarction (AMI) and its relationship with heart failure (HF) and major adverse cardiovascular events (MACE). Methods A total of 124 AMI patients who underwent percutaneous coronary intervention (PCI) in our hospital from January 2021 to December 2023 were enrolled as AMI group. Additionally, 30 patients with non-AMI coronary artery disease and 30 healthy individuals were included in non-AMI coronary artery disease group and healthy group, respectively. General information such as age, gender, smoking, alcohol consumption, hypertension, diabetes, and blood lipids were recorded for all subjects. Serum APN levels were measured using the enzyme-linked immunosorbent assay (ELISA) method; plasma brain natriuretic peptide (BNP) levels were determined by immunofluorescence; and left ventricular ejection fraction (LVEF) was assessed using echocardiography. Changes in serum APN levels and its relationship with BNP, LVEF, and MACE were recorded during a one-year follow-up period. Results AMI patients had lower serum APN levels than those in the non-AMI coronary artery disease group and the healthy group, while levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C); Lipoprotein-associated phospholipase A2 (Lp-PLA2), and the proportions of smokers and diabetics were higher(P < 0.05). A one-year follow-up of AMI patients revealed an upward trend in serum APN and BNP levels and a downward trend in LVEF levels at one week, one month, three months, six months, and one year postoperatively (P < 0.05). APN and BNP levels peaked one month after PCI, while LVEF reached its lowest level at the same time point. However, there were no statistically significant changes in these indicators in the subsequent 11 months (P>0.05). The incidence of MACE in AMI patients at one, three, six, and twelve months postoperatively was 2.8%, 3.2%, 4.6%, and 8.8%, respectively. Both preoperative and one-month postoperative serum APN levels had high predictive value for the occurrence of HF and MACE within one year in AMI patients, and the area under the curve for predicting HF and MACE one month postoperatively was larger than that preoperatively (P < 0.05). Conclusion Serum APN levels in AMI patients show an upward trend after PCI, peaking one month postoperatively. At this time point, serum APN levels have the highest predictive value for the occurrence of HF and MACE.

Objective To verify the applicability of serum creatinine(Cr)reference interval and the distri-bution characteristics of Cr under different influencing factors,and to explore the difference of different for-mulas for estimating glomerular filtration rate(eGFR)in chronic kidney disease and to validate the new for-mula.Methods Data from the laboratory information system of the hospital on September 1,2022 to August 31,2023 on healthy examinees were retrieved.The Skewness-Kurtosis method was used to determine the nor-mality of data,Box-Cox method was used to convert skewed data,and interquartile range method was used to remove outliers.Mann-Whitney U test,Kruskal-Wallis one-way ANOVA,and covariance analysis were used to compare differences in Cr by gender,age,and season.The applicability of the current Cr reference range was verified based on industry standards in China.Data of chronic kidney disease patients hospitalized during the same period were selected and the CKD-EPICr2009 formula currently in use in the laboratory was used as the standard to validate the newly developed MMB-eGFR formula in France.Spearman correlation,Deming re-gression,and Bland-Altman plot were used to analyze the correlation,linear relationship,and consistency of the results of two estimation formulas.Results Data of 54 710 healthy subjects who underwent the physical examination were included.There were statistically significant differences in Cr between genders,ages,and seasons.Cr level in males was significantly higher than that in females(P＜0.001).There were statistically significant differences among the age groups except for the age range of 20-＜30 and 30-＜40(P＜0.001),and Cr level increased with age.The Cr levels in males and females varied in a"checkmark"and"inverted trapezoidal"pattern between the four seasons.The above data were all used for the applicability verification of the Cr reference interval,and the pass rates of each subgroup were greater than 90％.336 patients with chronic kidney disease were screened and included in the study for comparison between CKD-EPICr2009 and MMB-eGFR results.There was a significant correlation between the results of two estimation formulas(r=0.943,P＜0.001),and there was a linear relationship with a consistency of 92.86％.Conclusion There are statistically significant differences in serum Cr levels in terms of age,gender,and season.The Cr reference range provided in the industry standards is applicable to the local area.The MMB-eGFR and CKD-EPICr2009 formulas have high consistency and are suitable for the local area.

Osteosarcopenia(OS) is the coexistence of sarcopenia(SP) and osteoporosis(OP). SP is a decrease in the number and strength of muscle fibers, causing impaired skeletal muscle function, and OP manifests itself as bone loss, decreased density, and degradation of bone microarchitecture. Mechanical loading is an important factor in maintaining the skeletal muscle-skeletal units in the interaction between skeletal muscle and bone. Increased muscle mass promotes bone growth and development and improves bone density and strength. As we age, skeletal muscle mass progressively decreases, leading to reduced skeletal loading which triggers wasting atrophy of the skeleton. Hormonal imbalance, chronic inflammation, oxidative stress, imbalance between protein degradation and synthesis, decreased physical activity and malnutrition are all closely associated with the development of OS. Interleukin(IL)-6 and tumor necrosis factor α(TNF-α)are important regulators of bone metabolism, and their elevated levels are negatively correlated with bone mineral density. IL-6 and TNF-α also inhibit protein synthesis in muscle by interfering with PI3K/Akt signaling pathways. NOD-like receptor protein 3(NLRP3) causes up-regulation of the NF-κB(nuclear factor-kappa B) pathway by activating damage-related molecules, and NLRP3 recruits pro-Caspase-1 to promote the release of IL-1β and IL-18, leading to increased chronic inflammation and inducing OS. The interdependence between skeletal muscle and bone and the interaction of multiple biological factors combine to contribute to the development of OS. As global aging increases, the incidence of OS will continue to rise, and in-depth investigation of its mechanisms is urgently needed to provide a theoretical basis for OS prevention and treatment.

With the development of techniques for rapid microbial identification, MALDI-TOF MS has become an important tool for clinical identification of fungi. Problems such as the applicability and standardization of protein extraction methods have hindered the development of MALDI-TOF MS technology in the fungal field. This paper analyzed the complex structure of fungal cell walls, introduced the protein extraction methods recommended by MALDI-TOF MS commercial mass spectrometry systems, discussed the protein extraction methods for the identification of various genera of yeast-like fungi and filamentous fungi by MALDI-TOF MS, such as direct smear method, formic acid acetonitrile extraction method and magnetic bead grinding method, and summarized the current status and drawbacks of protein extraction methods in fungal identification by MALDI-TOF MS with a view to providing theoretical reference for subsequent research.

Objective:To assess the combination of conventional ultrasound with contrast-enhanced ultrasound(CEUS)in the diagnosis of urothelial carcinoma(UC)of the renal pelvis in elderly patients.Methods:Sixty-seven elderly patients with a histopathologic diagnosis of UC of the renal pelvis and surgically treated at our hospital between April 2015 and March 2023 were retrospectively analyzed.Characteristics of regular preoperative 2D ultrasound, color Doppler flow imaging(CDFI)and CEUS were examined.Results:Of 67 patients, 49(73.13%)were found to have localized lesions in the renal pelvis and renal calyces.Lesions in 53 patients(79.10%)could be clearly identified by conventional ultrasound, with 46(86.79%)being isoechoic or hypoechoic, and 7(13.21%)being hyperechoic.Analysis of tumor blood flow by CDFI found 22 cases(41.51%)with avascular lesions, 21(39.62%)with hypovascular lesions and 10(18.87%)with hypervascular lesions.The average value of the resistance index(RI)was 0.64.Enhancement was seen in 62 lesions(92.54%)by CEUS after injection of SonoVue.Compared with the cortex of the ipsilateral kidney, a slow enhancement pattern was observed in 46(74.19%), 14(22.58%)showed simultaneous enhancement, and 2(3.23%)showed fast enhancement.At peak enhancement, 43 lesions(69.35%)had hypo-enhancement, 10(16.13%)had iso-enhancement, and 9(14.52%)had hyper-enhancement, compared with the cortex.Concerning the homogeneity of enhancement, 16(25.81%)displayed heterogeneous enhancement, with tumor necrosis or hemorrhage, and 46(74.19%)had homogeneous enhancement.When the contrast agent washout rate was assessed, a fast washout pattern was observed in 53(85.48%), synchronous washout in 6(9.68%), and slow washout in 3(4.84%).Conclusions:UC of the renal pelvis mostly shows isoechoic and hypoechoic lesions on conventional ultrasound, avascular or hypo-vascular lesions on CDFI, and slow-in, fast-out and hypo-enhancement on CEUS, compared with the cortex.Conventional ultrasound combined with CEUS can help improve the diagnostic accuracy of UC of the renal pelvis.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.