BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective : To explore the expression of prohibitin2(PHB2) in breast cancer and its effect on the biological behaviors of tumor cells. Methods : Immunohistochemistry was used to detect the expression of PHB2 protein in breast cancer tissues and its relationship with clinicopathologic features. Breast cancer stable transient cell lines were constructed with knockdown and overexpression ofPHB2, respectively. The effects of PHB2 on cell proliferation, migration and invasion ability were detected by clone formation assay, scratch assay and Transwell assay. Western blot(WB) was used to detect the effects of PHB2 on the expression of epithelial-mesenchymal transition(EMT)-related markers, including E-cadherin, N-cadherin, Snail family transcriptional repressor 1(Snail) protein, Vimentin, and Claudin-1. The effect of PHB2 on tumorigenicityin vivowas detected by subcutaneous tumor formation assay in nude mice. Results: The result of immunohistochemical showed that PHB2 was highly expressed in breast cancer and the expression of PHB2 was significantly positive correlated with tumor size, human epidermal growth factor receptor-2(HER-2) status and proliferation index Ki-67 levels(P<0.05). Clone formation assay, scratch assay and Transwell assay revealed that knockdown ofPBH2significantly inhibited the proliferation, migration and invasion ability of breast cancer cells(P<0.01), while the overexpression ofPHB2significantly promoted cell proliferation, migration and invasion(P<0.01). The result of subcutaneous tumor formation experiment in nude mice revealed a significant decrease in tumor volume and weight in knockdownPHB2mice(P<0.000 1), whilePHB2overexpression tumors significantly increased in volume and weight(P<0.001).WB assay showed that the protein expression of epithelial marker E-cadherin increased, while the expressions of mesenchymal markers N-cadherin, Snail and Vimentin decreased significantly afterPHB2knockdown with them in control cells(P<0.01). The expression of Claudin-1 decreased, while the expressions of N-cadherin, Snail and Vimentin increased significantly inPHB2overexpression cells(P<0.05). Conclusion PHB2 is highly expressed in breast cancer and promotes multiple malignant biological behaviors in tumor cells, suggesting PHB2 may be a potential target for breast cancer diagnosis and treatment.

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective:To summarize the evidence on self-management in patients with chronic low back pain.Methods:The literature on self-management of patients with chronic low back pain was electronically retrieved from websites and databases such as the National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Medlive, UpToDate, British Medical Journal Best Practice, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data. The search period was from October 1, 2014 to October 1, 2024. Two researchers conducted literature quality evaluation, extracted and summarized evidence.Results:A total of 17 articles were included, including three guidelines, eight systematic reviews, two expert consensus, and four evidence summaries. Twenty-eight pieces of evidence were summarized from six aspects of health education, self-monitoring, exercise management, psychological and emotional management, lifestyle habits, and support management.Conclusions:This study summarizes the best evidence for self-management in patients with chronic low back pain. Healthcare professionals can apply evidence based on clinical scenarios and patient preferences.

Objective:To investigate the pattern of Mesothelin(MSLN)-specific T-cell(CTLs)immune reconstitution after allogeneic hematopoietic stem cell transplantation.Methods:Two cases of Mesothelin-positive patients with acute myeloid leukemia(AML)were screened,and the number of MSLN-CTLs and its subpopulations,the expression of surface PD-1/CTLA-4/TIM-3 im-mune exhaustion molecules,and the functions of secreted cytokines TNF-α and IFN-γ were monitored by flow cytometry after trans-plantation.They were compared with WT1-CTLs and cytomegalovirus(CMV)CTLs.Meanwhile,the relationship between CTL recon-stitution and Minimal residual disease(MRD)and leukemia recurrence was analyzed.Results:After transplantation,MSLN-CTLs,WT1-CTLs and CMV-CTLs can be detected,and intracellular factors were secreted.The phenotypes of WT1 specific CD8+T cells,MSLN specific CD8+T cells and CMV specific CD8+T cells were mainly TEM subsets and TEMRA subsets,and the TEM subsets of CMV specific CD8+T cells were more obvious.Compared with CMV-CTLs,the proportions of T Naive,TCM and TEMRA subsets were relatively higher in MSLN-specific CD8+T cells and WT1-specific CD8+T cells,and the expression levels of PD-1,CTLA-4 and TIM-3 were higher in MSLN-CTLs and WT1-CTLs.The dynamic changes of MSLN-CTLs and WT1-CTLs after transplantation were related to leukemia load and the chimerism rate of donor and recipient.Conclusion:After allogeneic hematopoietic stem cell transplantation,im-mune recovery to MSLN is found,which is different from WT1-CTLs and CMV-CTLs.

Objective To construct a mammography image classification assistant system suitable for Chinese population,and explore the potential of artificial intelligence technology to assist early screening of breast cancer in China.Methods Curated breast imaging subset of digital database for screening mammography(CBIS-DDSM),Mammographic image analysis society database(MIAS)and other international open datasets were used to conduct model training respectively in order to reproduce the mainstream in-depth learning methods in the current literature.The model was also tested on the Chinese breast mammography database(CBMD)provided by Huajiao Technology Co.,Ltd,and the performance was compared.Aiming at the problem that the Chinese population data are not ideal in the performance test of the open dataset training model,an optimization strategy based on the sliding window adjustment mechanism was implemented in combination with the characteristics of Chinese population data.Then a two-stage migration learning method was designed to improve the overall performance of the model,and then development of our system was carried out.Results With the sliding window adjustment mechanism and the CBMD training model after two-stage transfer learning,the accuracy of our developed system was improved from 0.50 of the open datasets to 0.80,precision from 0.54 to 0.82,sensitivity from 0.52 to 0.80,F1 value from 0.52 to 0.80,and AUC value from 0.51 to 0.89 based on the Chinese population dataset as the test set.Conclusion Through the introduction of sliding window adjustment mechanism and two-stage migration learning strategy,the performance of the breast molybdenum target image classification model has been significantly improved in the Chinese population dataset,and our system primarily achieves the purpose of assisting the classification of breast molybdenum target images for the Chinese population.

Objective:To explore the association between healthy lifestyle and co-morbidity of overweight/obesity and myopia in adolescents.Methods:Based on the Shanghai Municipal Dynamic Cohort of Student Common Diseases, we used the group-based trajectory model (GBTM) to establish a model for the development of adolescents' healthy lifestyle trajectories aged 11-14 years and the Cox proportional hazard regression model to assess the effects of different healthy lifestyles on the co-morbidity of overweight/obesity and myopia in adolescents.Results:A total of 2 331 adolescents were included in the analysis. The average follow-up time was 1.87 years, with age of (11.44±0.45) years at the initial follow-up, among 1 106 boys and 1 225 girls. During the 2-year follow-up period, the incidence rates of overweight/obesity, myopia, and co-occurrence of overweight/obesity and myopia were 25.9%, 77.0%, and 13.7%, respectively. GBTM identified 3 healthy lifestyles: the unhealthy group (7.3%), the relatively healthy group (50.2%), and the healthy group (42.5%). The risk of overweight/obesity was lower in the relatively healthy group than in the unhealthy group ( HR=0.694, 95% CI: 0.508-0.947). There was no statistically significant association between the GBTM lifestyle subgroups and myopia ( P>0.05). The risk of co-occurrence of overweight/obesity and myopia was lower in both relatively healthy group and healthy group than in the unhealthy group (relatively healthy group: HR=0.515, 95% CI: 0.348-0.763; healthy group: HR=0.571, 95% CI: 0.384-0.849). Sensitivity analyses showed this result to be stable for myopia, overweight/obesity and myopia co-morbidities. Conclusion:Persistent unhealthy lifestyle increases the risk of overweight/obesity and myopia co-occurrence in adolescents.

Objective:To analyze the risk factors for human cytomegalovirus (HCMV) infection in pediatric recipients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of children who underwent first allo-HSCT were retrospectively analyzed from March 2017 to November 2024. A total of 259 pediatric allo-HSCT recipients were analyzed through comparing HCMV infection group (n=115) and Non-HCMV infection group (n=144). Clinical characteristics were compared, and risk factors for HCMV infection were analyzed using univariate and multivariate logistic regression.Results:The result of univariate analysis showed that adrenoleukodystrophy (ALD), length of hospitalization, duration of antiviral therapy, and bacterial infection were significantly associated with HCMV infection in pediatric allo-HSCT recipients ( P<0.05). The result of multivariate analysis showed that ALD was an independent protective factor against HCMV infection of allo-HSCT recipients ( P<0.05) [OR=0.22, 95% CI: 0.06-0.86], while umbilical cord blood transplantation (UCBT) was an independent risk factor for HCMV infection in allo-HSCT recipients ( P<0.05) [OR=6.13, 95% CI: 1.34-28.04]. When the area under the ROC curve (AUC) for predicting post-transplant relapse based on HCMV viral load was 0.75 (95% CI: 0.55-0.94, P=0.014) and at the cutoff value of 3×10 3 copies/ml, the sensitivity and specificity for predicting relapse were 81.13% and 66.67%, respectively. Conclusions:HCMV infection in pediatric allo-HSCT recipients may lead to longer hospitalization and increased risk of relapse.