Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Objective:To establish a model of reactive Th17 cells proliferation induced by collagen type Ⅱ(C Ⅱ)in vitro and investigate its influencing factors.Methods:The splenic lymphocytes of normal and CIA mice were isolated and divided into groups.They were given inactivated or non-inactivated C Ⅱ or different concentrations of IL-23(2,10,50 ng/mL),or IL-23p19 antibody.Culturing for 60 hours,the ratio of CD4+RORγt+Th17 cells was detected by flow cytometry.Then,the results obtained are ana lyzed,and the corresponding conclusions are drawn.Results:After 60 hours of culture in vitro,the ratio of Th 17 cells stimulated by inactivated or non-inactivated C Ⅱ in normal mouse spleen lymphocytes was significantly lower than that before culture,and the ratio of Th17 cells not stimulated by C Ⅱ in CIA mouse spleen lymphocytes was also significantly lower than that before culture,while the ratio of Th17 cells stimulated by inactivated C Ⅱ or non-inactivated C Ⅱ in CIA mouse spleen lymphocytes was significantly higher than that before culture,and there was a significant difference compared with the CIA control group(P＜0.05).However,there was no statistical difference in the ratio of Th17 cells between the two groups without inactivated C Ⅱ and inactivated C Ⅱ(P=0.44).After the analysis of the data obtained from the study,it was further concluded that different concentrations of IL-23 did not affect the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro,but after adding IL-23p19 antibody neutralization reagent,the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro decreased significantly,with a statistical difference compared with the blank control group(P＜0.01).Conclusions:This study established an in vitro Th17 cell proliferation model induced by type Ⅱ collagen,exploring the effects of IL-23 and collagen activity on Th17 cell proliferation.The results showed that CⅡ stimulation significantly promoted Th17 cell proliferation in CIA mice,with both active and inactivated CⅡ inducing proliferation.IL-23 was found to be essential for the maintenance of Th17 cells,although its direct proliferative effect was limited.These findings provide new experimental evidence and theoretical support for the mechanism research of rheumatic diseases and IL-23/IL-17 pathway-targeted therapies,with important implications for immune regulation and drug development.

Objective:To establish a model of reactive Th17 cells proliferation induced by collagen type Ⅱ(C Ⅱ)in vitro and investigate its influencing factors.Methods:The splenic lymphocytes of normal and CIA mice were isolated and divided into groups.They were given inactivated or non-inactivated C Ⅱ or different concentrations of IL-23(2,10,50 ng/mL),or IL-23p19 antibody.Culturing for 60 hours,the ratio of CD4+RORγt+Th17 cells was detected by flow cytometry.Then,the results obtained are ana lyzed,and the corresponding conclusions are drawn.Results:After 60 hours of culture in vitro,the ratio of Th 17 cells stimulated by inactivated or non-inactivated C Ⅱ in normal mouse spleen lymphocytes was significantly lower than that before culture,and the ratio of Th17 cells not stimulated by C Ⅱ in CIA mouse spleen lymphocytes was also significantly lower than that before culture,while the ratio of Th17 cells stimulated by inactivated C Ⅱ or non-inactivated C Ⅱ in CIA mouse spleen lymphocytes was significantly higher than that before culture,and there was a significant difference compared with the CIA control group(P＜0.05).However,there was no statistical difference in the ratio of Th17 cells between the two groups without inactivated C Ⅱ and inactivated C Ⅱ(P=0.44).After the analysis of the data obtained from the study,it was further concluded that different concentrations of IL-23 did not affect the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro,but after adding IL-23p19 antibody neutralization reagent,the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro decreased significantly,with a statistical difference compared with the blank control group(P＜0.01).Conclusions:This study established an in vitro Th17 cell proliferation model induced by type Ⅱ collagen,exploring the effects of IL-23 and collagen activity on Th17 cell proliferation.The results showed that CⅡ stimulation significantly promoted Th17 cell proliferation in CIA mice,with both active and inactivated CⅡ inducing proliferation.IL-23 was found to be essential for the maintenance of Th17 cells,although its direct proliferative effect was limited.These findings provide new experimental evidence and theoretical support for the mechanism research of rheumatic diseases and IL-23/IL-17 pathway-targeted therapies,with important implications for immune regulation and drug development.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.