In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

OBJECTIVE: To evaluate precise assessment methods for predicting the optimal acetabular cup size in total hip arthroplasty (THA). METHODS: A clinical data of 73 patients (80 hips) who underwent primary THA between December 2022 and July 2024 and met the inclusion criteria was analyzed. There were 39 males and 34 females with an average age of 66.3 years (range, 56-78 years). Among them, 66 cases were unilateral THA and 7 were bilateral THAs. There were 29 patients (34 hips) of osteoarthritis, 35 patients (35 hips) of femoral neck fractures, and 9 patients (11 hips) of osteonecrosis of the femoral head. Based on anteroposterior pelvic X-ray films, three methods were employed to predict acetabular cup size, including preoperative template planning, radiographic femoral head diameter (FHD) measurement, and intraoperative FHD measurement. The predicted acetabular cup sizes from these methods were compared with the actual implanted sizes. RESULTS: The predicted acetabular cup sizes using the preoperative template planning, radiographic FHD measurement, and intraoperative FHD measurement were (51.25±2.81), (49.72±3.11), and (49.90±2.74) mm, respectively, compared to the actual implanted cup size of (50.57±2.74) mm, with no significant difference ( P>0.05). Regarding agreement with the actual implanted cup size, the preoperative template planning achieved exact matches in 35 hips (43.75%), one-size deviation in 41 hips (51.25%), and two-size deviations in 4 hips (5%); the radiographic FHD measurement achieved exact matches in 12 hips (15%), one-size deviation in 57 hips (71.25%), and two-size deviations in 11 hips (13.75%); and the intraoperative FHD measurement achieved exact matches in 26 hips (32.5%), one-size deviation in 52 hips (65%), and two-size deviations in 2 hips (2.5%). There were significant differences in agreement distributions between the three methods and the actual implanted cup sizes ( H=18.579, P<0.001). CONCLUSION The intraoperative FHD measurement, as a simple, cost-effective, and accurate method, effectively guides acetabular cup selection, reduces the risk of prosthesis wear, enhances postoperative joint stability.
Humans ; Arthroplasty, Replacement, Hip/instrumentation* ; Male ; Female ; Middle Aged ; Acetabulum/diagnostic imaging* ; Aged ; Hip Prosthesis ; Prosthesis Design ; Femur Head/surgery* ; Osteoarthritis, Hip/surgery* ; Radiography ; Femoral Neck Fractures/surgery* ; Femur Head Necrosis/surgery*

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

OBJECTIVE: The relationship between non-high-density lipoprotein (NHDL) cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and stoke remains unknown. This study aimed to evaluate the association between the adult NHHR and stroke occurrence in the United States of America (USA). METHODS: To clarify the relationship between the NHHR and stroke risk, this study used a multivariable logistic regression model and a restricted cubic spline (RCS) model to investigate the association between the NHHR and stroke, and data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Subgroup and sensitivity analyses were conducted to test the robustness of the results. RESULTS: This study included 29,928 adult participants, of which 1,165 participants had a history of stroke. Logistic regression analysis of variables demonstrated a positive association between NHHR and stroke ( OR 1.24, 95% CI: 1.03-1.50, P = 0.026). Compared with the lowest reference group of NHHR, participants in the second, third, and fourth quartile had a significantly increased risk of stroke after full adjustments ( OR: 1.35, 95% CI: 1.08-1.69) ( OR: 1.83, 95% CI: 1.42-2.36) ( OR: 2.04, 95% CI: 1.50-2.79). In the total population, a nonlinear dose-response relationship was observed between the NHHR and stroke risk ( P non-linearity = 0.002). This association remained significant in several subgroup analyses. Further investigation of the NHHR may enhance our understanding of stroke prevention and treatment. CONCLUSION Our findings suggest a positive correlation between the NHHR and an increased prevalence of stroke, potentially serving as a novel predictive factor for stroke. Timely intervention and management of the NHHR may effectively mitigate stroke occurrence. Prospective studies are required to validate this association and further explore the underlying biological mechanisms.
Humans ; Stroke/blood* ; United States/epidemiology* ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Nutrition Surveys ; Adult ; Aged ; Cholesterol, HDL/blood* ; Cholesterol/blood* ; Risk Factors

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

OBJECTIVE To prepare tetrandrine （TET）-loaded chitosan（CS）-stearic acid （SA） nano micelles modified with folic acid （FA）（ FA-CS-SA/TET nano micelles）， characterize them and study the anti-inflammatory effect in vitro. METHODS FA- CS-SA/TET nano micelles were prepared by ultrasonic method； the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET， ultrasound power and ultrasound times as the factors， using the comprehensive score of entrapment efficiency （EE）， drug loading （DL） and particle size as evaluation index. FA-CS-SA/ TET nano micelles prepared by the optimal technology were characterized， and their release performance in vitro was investigated. RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro. RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1， ultrasonic power was 200 W， and the ultrasonic frequency was 200 times. The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was （98.86± 0.30）%， DL was （28.57±0.34）%， the average particle size was （227.0±9.4） nm， polydispersity index was 0.42±0.04， and the Zeta potential was（12.6±2.3）mV， respectively. The nano micelles were uniform in appearance and round in shape. The nano micelles were released quickly in 0.5% sodium dodecyl sulfate solution， with a cumulative release rate of （79.49±3.43）% within 72 hours， and its anti-inflammatory effect was stronger than that of TET raw materials. CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study， with good drug loading performance， uniform particle size， and good in vitro anti-inflammatory activity.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.