Depression is a heterogeneous mental disorder in which the interaction between genetic susceptibility and environ-mental factors plays a key role in its pathogenesis.Although the specific mechanisms of the disease still need to be thoroughly studied and elucidated,there is now a broad consensus that epi-genetic markers have a central influence on its mechanism of ac-tion.DNA methylation of brain-derived neurotrophic factor(BD-NF)is not only regarded as a promising epigenetic biomarker of pathology,but may also help predict the efficacy of antidepres-sants.In this paper we reviewed the gene structure of BDNF and its DNA methylation regulation mechanism,and also analyzed the changes of DNA methylation of this factor in depression pa-tients and animal models,aiming to provide new ideas and theo-retical support for clinical research.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P＜0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P＜0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P＜0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P＜0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.05,P＜0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.05,P＜0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.

Objective:To evaluate the feasibility of using the domestic ArcherQA system for fast and simplified independent verification of CyberKnife (CK) stereotactic radiotherapy (SRT) plans.Methods:SRT plans of 57 patients treated with CK at Tianjin Medical University Cancer Institute and Hospital from August 2021 to August 2022 were retrospectively analyzed, including 15 intracranial, 30 pulmonary, and 12 abdominal tumors cases. Point-dose and planar-dose verifications were performed using an ionization chamber and radiochromic films embedded in a homogeneous phantom, and the results were compared with those calculated by the treatment planning system (TPS). The localization CT images and corresponding SRT plans were imported into the ArcherQA system for independent dose verification and analysis. The correlation between ArcherQA results and phantom measurements was analyzed, with comparisons of target mean dose differences and γ pass rates.Results:Phantom measurement results showed, the measured point-dose differences for intracranial, lung, and abdominal plans were -0.94% ± 3.22%, 1.92% ± 2.05%, and 2.12% ± 0.77%, respectively. The mean dose differences in target dose calculation between ArcherQA and TPS: intracranial in the gross tumor volume (GTV) regions were 0.34% ± 2.21%, lung tumor GTV were -2.47% ± 2.46%, and abdominal tumor GTV were 0.80% ± 2.61%, respectively. Among them, the abdominal GTV region showed the highest correlation between ArcherQA and measured results ( r=0.78). The average two-dimensional γ pass rates (2 mm/2%, threshold=10%) measured using phantom films were 95.92% ± 2.35% for intracranial, 95.70% ± 2.74% for lung, and 96.74% ± 3.41% for abdominal tumors plans, respectively. The three-dimensional ArcherQA results showed comparable γ pass rates (1 mm/2%, threshold=10%) for lung and abdominal GTV and PTV regions, with similar medians and data dispersion to film measurements. Conclusions:The ArcherQA system enables rapid and efficient independent dose verification of CK SRT plans without the need for additional hardware. The verification results show good correlation with phantom measurements, supporting its potential as an auxiliary quality assurance tool in clinical CK SRT implementation.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To investigate the hemodynamic characteristics of intracranial collateral circulation assessed non-invasively by TCD and their correlation with clinical prognosis in patients with severe carotid stenosis or occlusion.Methods:A retrospective cohort study design was used to include 96 patients with severe stenosis(≥70％)or occlusion of the unilateral internal carotid artery admitted from March 2021 to March 2024,who were divided into a well-compensated group(58 patients)versus a poorly-compensated group(38 patients)based on the ASITN/SIR collateral branch score.Hemodynamic parameters(PSV,EDV,MFV,PI,RI)were measured using TCD,and collateral circulation status was validated by digital subtraction angiography(DSA).Prognosis was evaluated over a 12-month follow-up.Logistic regression was used to analyze risk factors for poor prognosis.Results:The good collateral group exhibited significantly higher PSV(82.32±18.51 vs.56.45±15.32 cm/s)and MFV(56.93±12.33 vs.35.89±9.83 cm/s),and significantly lower PI(0.64±0.15 vs.0.82±0.21)and RI(0.43±0.08 vs.0.51±0.11)compared to the poor collateral group(all P＜0.001).TCD parameters showed strong correlations with ASITN/SIR grades(PSV:r=0.62;PI:r=-0.61,all P＜0.001).Multivariate analysis identified age ≥65 years(OR=1.06),hypertension(OR=3.07),PI ≥ 1.00(OR=17.25),and PSV ≤ 60 cm/s(OR=1.96)as independent risk factors for poor prognosis(all P＜0.05).Conclusion:The TCD multi-parameter model enables quantitative assessment of collateral circulation function,with PI ≥ 1.00 and PSV ≤ 60 cm/s serving as key predictors of adverse outcomes.The non-invasive and dynamic monitoring advantages of TCD provide critical insights for hemodynamic stratification and personalized intervention in patients with carotid stenosis or occlusion.

Objective:This study aimed to evaluate the prognostic factors of clinical and histopathological parameters,including age,gender,tumor stage,tumor grade,tumor differentiation,lymph node metastasis(LNM),tumor frequency,and tumor count,in patients undergoing radical cystectomy(RC)combined with Mainz Pouch Ⅱ bladder reconstruction.Methods:A total of 237 bladder cancer patients(198 male and 39 female)who underwent RC combined with Mainz Pouch Ⅱ bladder reconstruction without chemotherapy or radiotherapy,from January 2004 to January 2023,were included in this study.Kaplan-Meier and Cox regression analyses were performed to assess the impact of age,tumor grade,tumor stage,tumor differentiation,LNM,tumor frequency,and tumor count on 5-year overall survival(OS)and 5-year cancer-specific survival(CSS).Results:The mean age at diagnosis was 59.8 years,with 198 male and 39 female patients.The mean follow-up duration was 47.8 months.In univariate analysis,patients younger than 65 years had significantly higher 5-year OS and 5-year CSS compared to those aged≥65 years.Patients with urothelial carcinoma showed better 5-year OS than those with non-urothelial carcinoma.Additionally,tumor stage,tumor grade,and LNM were negatively associated with 5-year OS and 5-year CSS.On multivariate analysis,only tumor grade and LNM remained statistically significant(P<0.05).Conclusions:Tumor grade and LNM were identified as independent prognostic risk factors for 5-year OS and 5-year CSS following RC combined with Mainz PouchⅡ bladder reconstruction.Moreover,the application of RC combined with Mainz Pouch Ⅱ bladder reconstruction should consider the patient's preferences and physical condition.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.