OBJECTIVE: To explore the mechanism by which ω-3 polyunsaturated fatty acids (hereinafter referred to as "ω-3") exert antioxidant stress protection and promote osteogenic differentiation in MC3T3-E1 cells, and to reveal the relationship between ω-3 and the key antioxidant stress pathway involving nuclear factor E2-related factor 2 (Nrf2) and NAD (P) H quinone oxidoreductase 1 (NQO1) in MC3T3-E1 cells. METHODS: The optimal concentration of H ₂O ₂ (used to establish the oxidative stress model of MC3T3-E1 cells in vitro) and the optimal intervention concentrations of ω-3 were screened by cell counting kit 8. MC3T3-E1 cells were divided into blank control group, oxidative stress group (H ₂O ₂), low-dose ω-3 group (H ₂O ₂+low-dose ω-3), and high-dose ω-3 group (H ₂O ₂+high-dose ω-3). After osteoblastic differentiation for 7 or 14 days, the intracellular reactive oxygen species (ROS) level was measured by fluorescence staining and flow cytometry, and the mitochondrial morphological changes were observed by biological transmission electron microscope; the expression levels of Nrf2, NQO1, heme oxygenase 1 (HO-1), Mitofusin 1 (Mfn1), and Mfn2 were detected by Western blot to evaluate the cells' antioxidant stress capacity; the expression levels of Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were detected by immunofluorescence staining and Western blot; osteogenic potential of MC3T3-E1 cells was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining. RESULTS: Compared with the oxidative stress group, the content of ROS in the low and high dose ω-3 groups significantly decreased, and the protein expressions of Nrf2, NQO1, and HO-1 significantly increased ( P<0.05). At the same time, the mitochondrial morphology of MC3T3-E1 cells improved, and the expressions of mitochondrial morphology-related proteins Mfn1 and Mfn2 significantly increased ( P<0.05). ALP staining and alizarin red staining showed that the low-dose and high-dose ω-3 groups showed stronger osteogenic ability, and the expressions of osteogenesis-related proteins RUNX2 and OCN significantly increased ( P<0.05). And the above results showed a dose-dependence in the two ω-3 treatment groups ( P<0.05). CONCLUSION ω-3 can enhance the antioxidant capacity of MC3T3-E1 cells under oxidative stress conditions and upregulate their osteogenic activity, possibly through the Nrf2/NQO1 signaling pathway.
Oxidative Stress/drug effects* ; NF-E2-Related Factor 2/metabolism* ; NAD(P)H Dehydrogenase (Quinone)/metabolism* ; Animals ; Mice ; Osteogenesis/drug effects* ; Cell Differentiation/drug effects* ; Fatty Acids, Omega-3/pharmacology* ; Signal Transduction/drug effects* ; Osteoblasts/drug effects* ; Reactive Oxygen Species/metabolism* ; Cell Line ; Hydrogen Peroxide/pharmacology* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Antioxidants/pharmacology* ; Heme Oxygenase-1/metabolism*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective:To explore the short-term oncological efficacy of the total prostatic urethra preservation（TPUP）technique in laparoscopic radical prostatectomy and its impact on postoperative urinary continence rate.Methods:The clinical data of 17 prostate cancer patients admitted to Shaoxing People’s Hospital from July 2023 to July 2024 were retrospectively analyzed. The age was（70.5 ± 6.5）years，the body mass index was（23.6 ± 2.5）kg/m 2，and the prostate-specific antigen（PSA）level was（7.845 ± 3.929）ng/ml. The preoperative biopsy pathological Gleason score were 6 in 8 cases，and 7 in 9 cases. All patients underwent laparoscopic radical prostatectomy，and the TPUP technique was used during the operation. The integrity of the preserved urethra was improved by preserving the prostatic surgical capsule closely attached to the corpus spongiosum of the urethra. During the operation，the urethra was completely preserved in 2 cases，nearly completely preserved in 14 cases，and partially preserved in 1 case. The recovery of urinary continence on the day of catheter removal and at 1 and 3 months after the operation was recorded. Recovery of urinary continence was defined as pad within 24 hours. PSA was re - examined at 6 weeks and 3 months after the operation. Results:All 17 operations in this study were successfully completed. The operation time was（143.6 ± 31.6）minutes，and the intraoperative blood loss was 50.0（20.0，50.0）ml. None of the cases was converted to open surgery，and no Clavien - Dindo grade ≥ 2 complications such as blood transfusion or intestinal injury occurred during the peri-operative period. The PSA levels at 6 weeks and 3 months after the operation were 0.054（0.008，0.215）ng/ml and 0.008（0.005，0.037）ng/ml，respectively. The indwelling catheter time after the operation was（13.4 ± 2.1）days. The number of cases with recovered urinary continence on the day of catheter removal and at 1 and 3 months after the operation was 10，15，and 17，respectively.Conclusions:The TPUP technique in laparoscopic radical prostatectomy leads to good recovery of postoperative urinary continence，and there is a slowly PSA decrease in the short term.

Objective:To explore the short-term oncological efficacy of the total prostatic urethra preservation（TPUP）technique in laparoscopic radical prostatectomy and its impact on postoperative urinary continence rate.Methods:The clinical data of 17 prostate cancer patients admitted to Shaoxing People’s Hospital from July 2023 to July 2024 were retrospectively analyzed. The age was（70.5 ± 6.5）years，the body mass index was（23.6 ± 2.5）kg/m 2，and the prostate-specific antigen（PSA）level was（7.845 ± 3.929）ng/ml. The preoperative biopsy pathological Gleason score were 6 in 8 cases，and 7 in 9 cases. All patients underwent laparoscopic radical prostatectomy，and the TPUP technique was used during the operation. The integrity of the preserved urethra was improved by preserving the prostatic surgical capsule closely attached to the corpus spongiosum of the urethra. During the operation，the urethra was completely preserved in 2 cases，nearly completely preserved in 14 cases，and partially preserved in 1 case. The recovery of urinary continence on the day of catheter removal and at 1 and 3 months after the operation was recorded. Recovery of urinary continence was defined as pad within 24 hours. PSA was re - examined at 6 weeks and 3 months after the operation. Results:All 17 operations in this study were successfully completed. The operation time was（143.6 ± 31.6）minutes，and the intraoperative blood loss was 50.0（20.0，50.0）ml. None of the cases was converted to open surgery，and no Clavien - Dindo grade ≥ 2 complications such as blood transfusion or intestinal injury occurred during the peri-operative period. The PSA levels at 6 weeks and 3 months after the operation were 0.054（0.008，0.215）ng/ml and 0.008（0.005，0.037）ng/ml，respectively. The indwelling catheter time after the operation was（13.4 ± 2.1）days. The number of cases with recovered urinary continence on the day of catheter removal and at 1 and 3 months after the operation was 10，15，and 17，respectively.Conclusions:The TPUP technique in laparoscopic radical prostatectomy leads to good recovery of postoperative urinary continence，and there is a slowly PSA decrease in the short term.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.

Preoperative planning,intraoperative navigation,and postoperative rehabilitation of total hip arthroplasty(THA)have been significantly enhanced by the integration of artificial intelligence(AI)technology.This review summarizes the latest advancements in AI technology for medical image segmentation and registration,with a particular focus on its application in THA.The notable differences between medical and natural images present challenges for the design of AI algorithms.Deep learning techniques,especially CNN,U-Net,and Transformer models,have demonstrated an outstanding performance in various medical image segmentation and registration tasks.The AI technology,through deep learning analysis of CT images,has significantly improved the accuracy of identifying hip pathologies.In terms of intraoperative guidance,AI systems provide real-time navigation and precise positioning for surgeries by utilizing intelligent segmentation and motion state simulation,effectively enhancing surgical efficiency.AI technology also encompasses surgical cost prediction and postoperative recovery,offering robust data support for medical decision-making through method such as Markov models.As deep learning technology continues to advance,the analysis of medical images is progressively achieving automation and intelligence,which has significant clinical implications for improving patients'overall surgical experiences and outcomes,suggesting potential new breakthroughs in the field of medical imaging in the future.

Objective:To search for potential synergistic drugs that can enhance the inhibitory effect of lenvatinib on the proliferation of hepatocellular carcinoma cells by compound screening and explore the underlying molecular mechanisms.Methods:The impact of lenvatinib on the proliferation of Huh7 cells was detected using CCK-8 assay and long-term cell proliferation assays.The potential synergistic drugs for lenvatinib in Huh7 cells was screened using an FDA-approved compound library.Subsequently,the inhibitory effect of lenvatinib combined with zinc pyrithione on the proliferation of Huh7 cells was assessed using CCK-8 assay and long-term cell proliferation assay.Furthermore,RNA-sequencing was utilized to investigate the changes in gene expression profiles following the combined action of zinc pyrithione and lenvatinib,exploring the potential molecular mechanisms.The impact of combination therapy on signaling pathways was investigated through Gene Set Enrichment Analysis(GSEA)and Gene Ontology Analysis(GO).Results:Lenvatinib exerts dose-dependent inhibition on the proliferation of Huh7 in vitro(IC50 value=0.190 μmol/L).Screening of compound libraries identified zinc pyrithione as a compound that synergistically promotes the inhibition of Huh7 cell proliferation by lenvatinib.This result was further validated through CCK-8 assay(P<0.05)and long-term cell proliferation experiments.Compared to treatment with lenvatinib alone,the combination treatment of zinc pyrithione and lenvatinib upregulated signaling pathways related to oxidative stress response,apoptosis,and cellular responses to copper ions in Huh7 cells,with Gene Set Enrichment Analysis(GSEA)showing significant enrichment of the oxidative phosphorylation pathway.Conclusion:Lenvatinib can inhibit the proliferation of Huh7 cells in vitro,while Zinc Pyrithione can synergize with lenvatinib to exert a more significant inhibitory effect on the Huh7 cells.The molecular mechanism of this synergistic effect may involve generation of a large amount of reactive oxygen species(ROS)to induce apoptosis of liver cancer cells through oxidative stress response,as well as promoting the death of hepatocellular carcinoma cells by disrupting copper homeostasis.

Objective:To explore the relationship between platform leadership, perceived overqualification, job crafting and career calling of clinical nurses, and provide references for formulating occupational calling strategies for clinical nurses.Methods:A total of 488 clinical nurses from Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital), Shandong University Qilu Hospital, and Qingdao Municipal Hospital were selected as the study subjects by the convenience sampling method from April to May 2023. A general data questionnaire, Platform Leadership Scale, Perceived Overqualification Scale, Job Crafting Scale, and Career Calling Scale were used to conduct a cross-sectional investigation on the research objects, and the relationship and mediating effect between platform leadership, perceived overqualification, job crafting, and career calling were analyzed.Results:Among the 488 clinical nurses, 79 were males and 409 were females, aged 23-51 (30.37 ± 6.40) years old. The scores of platform leadership, perceived overqualification, job crafting and career calling of clinical nurses were (86.12 ± 9.99), (21.79 ± 7.29), (70.61 ± 14.54) and (38.70 ± 7.54) points, respectively. The total effect of platform leadership on work engagement was 0.316. The mediating path of platform leadership to career calling included platform leadership→perceived overqualification→career calling; platform leadership→job crafting→career calling; platform leadership→perceived overqualification→job crafting→career calling. Three mediating effects accounted for 17.99%, 9.50% and 4.56% of the total effect, respectively.Conclusions:There is a chain-mediating effect of perceived overqualification and work remodeling on the relationship between platform leadership and the career calling of clinical nurses. Nursing managers should implement platform leadership to alleviate clinical nurses ′ perceived overqualification, improve job crafting, and then improve the level of clinical nurses ′ career calling.

Preoperative planning,intraoperative navigation,and postoperative rehabilitation of total hip arthroplasty(THA)have been significantly enhanced by the integration of artificial intelligence(AI)technology.This review summarizes the latest advancements in AI technology for medical image segmentation and registration,with a particular focus on its application in THA.The notable differences between medical and natural images present challenges for the design of AI algorithms.Deep learning techniques,especially CNN,U-Net,and Transformer models,have demonstrated an outstanding performance in various medical image segmentation and registration tasks.The AI technology,through deep learning analysis of CT images,has significantly improved the accuracy of identifying hip pathologies.In terms of intraoperative guidance,AI systems provide real-time navigation and precise positioning for surgeries by utilizing intelligent segmentation and motion state simulation,effectively enhancing surgical efficiency.AI technology also encompasses surgical cost prediction and postoperative recovery,offering robust data support for medical decision-making through method such as Markov models.As deep learning technology continues to advance,the analysis of medical images is progressively achieving automation and intelligence,which has significant clinical implications for improving patients'overall surgical experiences and outcomes,suggesting potential new breakthroughs in the field of medical imaging in the future.

Objective:To search for potential synergistic drugs that can enhance the inhibitory effect of lenvatinib on the proliferation of hepatocellular carcinoma cells by compound screening and explore the underlying molecular mechanisms.Methods:The impact of lenvatinib on the proliferation of Huh7 cells was detected using CCK-8 assay and long-term cell proliferation assays.The potential synergistic drugs for lenvatinib in Huh7 cells was screened using an FDA-approved compound library.Subsequently,the inhibitory effect of lenvatinib combined with zinc pyrithione on the proliferation of Huh7 cells was assessed using CCK-8 assay and long-term cell proliferation assay.Furthermore,RNA-sequencing was utilized to investigate the changes in gene expression profiles following the combined action of zinc pyrithione and lenvatinib,exploring the potential molecular mechanisms.The impact of combination therapy on signaling pathways was investigated through Gene Set Enrichment Analysis(GSEA)and Gene Ontology Analysis(GO).Results:Lenvatinib exerts dose-dependent inhibition on the proliferation of Huh7 in vitro(IC50 value=0.190 μmol/L).Screening of compound libraries identified zinc pyrithione as a compound that synergistically promotes the inhibition of Huh7 cell proliferation by lenvatinib.This result was further validated through CCK-8 assay(P<0.05)and long-term cell proliferation experiments.Compared to treatment with lenvatinib alone,the combination treatment of zinc pyrithione and lenvatinib upregulated signaling pathways related to oxidative stress response,apoptosis,and cellular responses to copper ions in Huh7 cells,with Gene Set Enrichment Analysis(GSEA)showing significant enrichment of the oxidative phosphorylation pathway.Conclusion:Lenvatinib can inhibit the proliferation of Huh7 cells in vitro,while Zinc Pyrithione can synergize with lenvatinib to exert a more significant inhibitory effect on the Huh7 cells.The molecular mechanism of this synergistic effect may involve generation of a large amount of reactive oxygen species(ROS)to induce apoptosis of liver cancer cells through oxidative stress response,as well as promoting the death of hepatocellular carcinoma cells by disrupting copper homeostasis.