Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

BACKGROUND:At present,there is a main kind of operation,which is represented by the proximal femoral nail antirotation,to treat femoral intertrochanteric fractures,but some sequelae still occur such as internal fixation loosening,failure,and nail withdrawal.We designed a new femoral neck spiral blade system to solve this problem,so we analyze the mechanical structure by the finite element method that can be regard as the theoretical basis for the system.OBJECTIVE:To compare the mechanical properties of the new femoral neck spiral blade system and the proximal femoral nail antirotation in the treatment of femoral intertrochanteric fracture by the finite element method.METHODS:Based on the finite element model of the femur,the A1.2 and A2.2 femoral intertrochanteric fracture models were established according to the AO fracture classification principle of 2018 edition.The models were fixed with the proximal femoral nail antirotation and the new internal fixation system,applying an axial load of 700,1 400,and 2 100 N above the femoral head.The mechanical characteristics of the two internal fixation methods were respectively compared and analyzed by observing the maximum equivalent stress and the maximum deformation of each group.RESULTS AND CONCLUSION:(1)The maximum equivalent stress of the new internal fixation group under different compressive loads was smaller than that of the proximal femoral nail antirotation group.(2)In the A1.2 fracture model,under different compression loads,the deformation of the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.113 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 2.017 mm between the two.(3)In the A1.2 fracture model,under different compressive loads,the maximum deformation of the spiral blade fixed by the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.062 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 1.891 mm between the two.(4)The results indicate that the new femoral neck spiral blade system has a lower internal fixation stress value compared to the proximal femoral nail antirotation,and a smaller displacement value of the femur after fixation and internal fixation.It can more effectively fix fractures and prevent the spiral blade from retracting or cutting out in the femoral neck.

Objective:To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors in the treatment of acute severe ulcerative colitis (ASUC).Methods:A retrospective cohort study was conducted. Patients with ASUC treated with JAK inhibitors at the First Affiliated Hospital of Air Force Medical University between January 2021 and March 2024 were enrolled. The primary endpoints were clinical response rate at 1 week and colectomy rate at 90 days. The secondary endpoints were clinical response rate and clinical remission rate at 8 weeks, and adverse events rate at 90 days.Results:A total of 15 patients with ASUC (7 men, 8 women; mean age, 42.47±9.92 years) were included. Eight patients were treated with upadacitinib, and 7 with tofacitinib. The clinical response rate at 1 week was 53.3% (8/15), the colectomy rate at 90 days was 20.0% (3/15), the clinical response rate at 8 weeks was 60.0% (9/15), and the clinical remission rate at 8 weeks was 33.3% (5/15). During the 90-day follow-up, only 1 patient (6.7%) treated with tofacitinib experienced a mild leukopenia.Conclusion:JAK inhibitors are effective for ASUC with the high safety.

Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0％.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.

Objective:To explore the application value of radiomics, deep learning, and their combined models in predicting the efficacy of radioiodine adjuvant therapy in patients with papillary thyroid cancer (PTC).Methods:A retrospective analysis was conducted on the clinical and imaging data of 131 PTC patients (38 males, 93 females; age 41(33, 48) years) who received first 131I treatment at the Affiliated Hospital of Guilin Medical University from January 2018 to March 2023. Patients were randomly divided into a training set ( n=105) and a test set ( n=26) at the ratio of 8∶2. Multivariate logistic regression analysis was used to screen clinical features to determine independent predictors affecting the efficacy of 131I therapy. Radiomics and deep learning features were extracted from the enhanced CT scans and were combined by using the extremely randomized trees (ExtraTrees) algorithm to construct radiomics, deep learning, and combined models. The predictive abilities of the models were evaluated by AUC, and the Delong test was applied to compare the difference between AUCs. Results:Higher pre-ablation stimulated thyroglobulin (ps-Tg) levels (odds ratio( OR)=1.060, 95% CI: 1.025-1.095, P=0.004) and bilateral lesions ( OR=5.085, 95% CI: 1.452-17.814, P=0.033) were independent predictors of the efficacy of 131I therapy in intermediate to high-risk PTC patients. In the training set, the radiomics model (AUC=0.853) and combined model (AUC=0.880) significantly outperformed the deep learning model (AUC=0.711; Z values: 2.48, 3.09, P values: 0.013, 0.002), while there was no statistically significant difference between the radiomics and combined models ( Z=0.51, P=0.610). In the test set, AUCs of the radiomics, deep learning, and combined models were 0.746, 0.624, and 0.876, respectively, and the AUC of the combined model was higher than that of the radiomics model or deep learning model ( Z values: 2.05, 1.99, P values: 0.040, 0.047). Conclusion:The combined model demonstrates superior performance over the standalone radiomics model and deep learning model in predicting the efficacy of 131I treatment in PTC patients.

BACKGROUND:Degenerative diseases caused by bone and muscle degeneration are major reasons for the decline in physical function and mobility,increased fragility fractures,and high mortality rates in the elderly,significantly affecting their health and quality of life.OBJECTIVE:To review the research progress in the mechanisms of muscle-bone interaction and the etiology,prevention,and treatment of related diseases.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature published from 2014 to 2024.The search terms were"muscle-bone crosstalk,musculoskeletal system,inter-tissue communication,myokines,osteokines,osteosarcopenia,sarcopenia,osteoporosis,bone regeneration,fibro-adipogenic progenitors"in Chinese and English.By reading the articles,we eliminated irrelevant,outdated,and poorly focused literature,and finally 94 articles were included for review.RESULTS AND CONCLUSION:Mechanical interaction,secretion factor interaction,and stem cell interaction between muscle and bone are crucial for the metabolism and regeneration regulation of the musculoskeletal system.Systemic interventions targeting biochemical signals of muscle factors(such as myostatin and irisin)and bone factors(such as nuclear factor-κB receptor-activating factor ligand and sclerostin)can improve the quality and function of skeletal muscle and bone,and have positive effects on fracture healing.In recent years,it has been found that related stem cells in the musculoskeletal system can interact,with the activation of muscle progenitor cells(such as fibro-adipogenic progenitors)having a significant impact on bone growth,repair,and regeneration.Research on the mechanisms of muscle-bone interaction can provide insights into the etiology,prevention,and treatment of related diseases.However,there are currently no effective clinical treatments for muscle-bone comorbidities,with most research still at the cellular and animal experiment stage.Therefore,extensive research is needed in the future to gradually move from experiments to clinical applications,developing more targeted therapies and drugs to better serve clinical needs.

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.