Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

OBJECTIVE: To investigate the biological behavior, differentiation ability, and differential gene expression of lymph node mesenchymal stem cells (MSCs) in patients with diffuse large B-cell lymphoma (DLBCL) and reactive lymphoid hyperplasia (RLH), providing a theoretical basis for clinical chemotherapy resistance. METHODS: Lymph node MSCs from patients with DLBCL and RLH were separated, passaged and cultured. The cell morphology and growth status were observed. Flow cytometry was performed to detect the immune phenotype of MSCs. The in vitro directed differentiation ability of the two types of MSCs was observed. High-throughput sequencing was used to analyze the differential gene expression and enrichment of two groups of MSCs. RESULTS: The lymph node MSCs of patients with DLBCL and RLH had similar cell morphology and growth characteristics, and both groups of MSCs expressed CD90, CD105, and CD73 on the cell surface. Compared with lymph node MSCs derived from patients with RLH, lymph node MSCs derived from DLBCL patients showed stronger osteogenic and adipogenic differentiation abilities. High-throughput sequencing results displayed that lymph node MSCs derived from DLBCL patients significantly upregulated some genes such as TOP2A, LFNG, GRIA3, SEC14L2, SPON2, AURKA, LRRC15, FOXD1, HOXC9, CDC20 and remarkably downregulated some genes such as TBC1D8, LDLR, PCDHAC2, POLH, PKP2, ANKRD37, DMKN, HSD11B1, ARHGAP20, PTGS1,etc. CONCLUSION Lymph node MSCs in DLBCL patients exhibit unique biological behavior and gene expression profiles, which may be closely related to clinical chemotherapy resistance.
Humans ; Mesenchymal Stem Cells/cytology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Differentiation ; Lymph Nodes/pathology* ; Pseudolymphoma/pathology*

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

BackgroundThe existing tools in China for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint do not sufficiently consider the specialty in psychiatric practice， and the scale items are somewhat cumbersome to use， which together restrict their further promotion and application. Accordingly， there is an urgent need for developing a more scientific assessment tool. ObjectiveTo construct a scale for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint and to verify its reliability and validity， so as to provide a generic tool for the assessment. MethodsBased on the theoretical framework of the knowledge-attitude-practice model， the preliminary scale was formed through systematic literature review， qualitative interview and Delphi method. From July to December 2021， a stratified sampling was utilized to select 729 psychiatric nurses from tertiary， secondary and primary （including unclassified medical institutions and grassroots hospitals） psychiatric hospitals in Guangdong Province. The formal scale was developed through item analysis， exploratory factor analysis and confirmatory factor analysis. The validity of the scale was evaluated by content validity and structure validity， and the reliability was verified by procedures including Cronbach's α coefficient， test-retest reliability， and split-half reliability. ResultsA total of 12 items of three dimensions （knowledge， attitude， practice） were included in the scale for assessing psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint. The scale-level content validity index （S-CVI） was 0.941， and the item-level content validity index （I-CVI） ranged from 0.812 to 1.000. Exploratory factor analysis extracted three common factors， and the cumulative variance contribution rate was 62.948%. The confirmatory factor yielded adequate fit. Cronbach's α coefficient was found to be 0.887 for the scale， 0.819 for knowledge dimension， 0.842 for attitude dimension， and 0.831 for practice dimension. The split-half reliability and test-retest reliability for the scale were 0.712 and 0.922， respectively. ConclusionThe scale shows satisfactory reliability and validity， which can be used to assess psychiatric nurses' knowledge， attitude and practice towards the use of protective restraint. ［Funded by Guangdong Clinical Teaching Base Teaching Reform Research Project （number， 2021JD119）］