ObjectiveTo address the key challenges in breast electrical impedance tomography (EIT) reconstruction including the severe ill‑posedness of the inverse problem, limited measurement information from the electrodes, low contrast of small lesions, as well as the common drawbacks of traditional reconstruction methods such as boundary blurring, low spatial resolution, and weak small-target detection capability, and to overcome the limitations of existing deep learning approaches namely low training efficiency, insufficient physical consistency, and substantial information loss during the low‑to‑high dimensional mapping process, this study proposes a multi‑scale attention and dynamic sparse mask fusion network (MADS‑Net). The proposed method aims to enhance high‑resolution reconstruction accuracy, small-lesion detectability, noise robustness, and computational efficiency in breast‑screening-oriented EIT, thereby providing a feasible solution for the application of EIT in breast functional imaging. MethodsThe proposed network adopts a strategy of “locate first, reconstruct later”. It realizes adaptive allocation of computational resources through a dynamic mask module, alleviates information loss in the low-to-high dimensional mapping process via a multi-scale attention mechanism, and embeds physical constraints to improve the physical rationality of reconstruction results. The performance of the proposed method was validated through systematic numerical simulations, agar phantom experiments, and porcine tissue experiments. Comparisons were made with mainstream methods including the Gauss-Newton algorithm, convolutional neural networks, U-Net, and Deep D-Bar. The image correlation coefficient (ICC), root mean square error (RMSE), and peak signal-to-noise ratio (PSNR) were adopted as quantitative evaluation metrics. Furthermore, lesion‑level evaluation metrics were introduced to assess the capability of different methods in reconstructing abnormal target boundaries and small‑sized target regions. ResultsExperimental results demonstrate that MADS-Net outperforms all comparison methods across all test scenarios. In numerical simulations, it achieves higher accuracy in target morphology and spatial location recovery as well as better background suppression. In agar phantom experiments, its detection and imaging reliability for small targets is significantly superior to the comparison methods. In porcine tissue experiments, the model maintains good generalization performance and can adapt to complex biological tissue imaging scenarios. Quantitative results show that MADS-Net achieves an average ICC of 0.917 6±0.048 8, an RMSE as low as0.060 6±0.031 6, and a PSNR of (23.893 9±2.685 3) dB. It successfully detects tiny targets as small as 5 mm within a 100 mm diameter sensing field, reduces the total training duration by 23.5% compared with the baseline method, and maintains stable reconstruction performance even under strong noise interference. ConclusionThe results demonstrate that MADS-Net achieves favorable EIT reconstruction performance in numerical simulations, agar phantom experiments, and porcine tissue experiments, even under common practical imaging challenges including low signal-to-noise ratio and blurred tissue boundaries. This study provides a methodological reference for further research on EIT in breast-screening-related scenarios and other medical functional imaging tasks, and also offers a low-cost, radiation-free alternative for breast lesion screening that aligns with the clinical demand for non-invasive diagnostic tools. It should be noted that real clinical breast data have not yet been used for validation in this study, and the clinical applicability of the proposed method requires further investigation. Future work will prioritize collecting multi-center real clinical breast datasets, and further optimize the model’s generalization ability to adapt to individual differences in breast tissue composition to promote its clinical application.

ObjectiveTo evaluate the quality of clinical practice guidelines and expert consensus statements on knee osteoarthritis （KOA） based on the Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）， thus providing a new perspective for clinical selection as well as guideline development and updating. MethodsA systematic search was conducted for KOA-related guidelines and consensus statements published from November 1， 2019 to December 31， 2025. The databases and platforms searched included CNKI， VIP， Wanfang Data， PubMed， Web of Science， the National Institute for Health and Care Excellence （NICE）， SinoMed， Yimaitong， and relevant official websites. Two researchers independently screened the literature， and four researchers used AGREE Ⅱ to score the included documents and completed the quality appraisal after reaching a unified understanding. Subgroup analyses were further performed according to developing organization， document type， medical approach， funding status， and region of development， and longitudinal comparisons were conducted by year of publication. ResultsA total of 23 guidelines and consensus statements were included. The standardized scores of the six AGREE Ⅱ domains， from the highest to the lowest， were clarity of presentation ［（70.36±8.13）%］， scope and purpose ［（67.46 ± 11.44）%］， editorial independence ［（64.50±20.01）%］， rigor of development ［（62.24±15.26）%］， stakeholder involvement ［（55.73±10.29）%］， and applicability ［（53.89±13.17）%］. In terms of overall recommendation， 6 documents were rated as grade A and 17 as grade B. Stratified analyses showed that professional organizations scored higher than comprehensive organizations. The overall scores of traditional Chinese medicine/integrative medicine and Western medicine guidelines （or consensus statements） were similar. Guidelines scored higher than consensus statements. The overall scores were similar between documents with reported funding and those without reported funding. International guidelines scored higher than domestic guidelines. Longitudinal comparisons showed that the largest number of documents was published in 2021. The overall scores were higher in 2021—2022， and some domain scores declined in 2023—2024. Overall， the quality of recent guidelines and consensus statements for KOA showed slight fluctuations， without a clear linear trend. ConclusionThe included guidelines and consensus statements for KOA can generally serve as references for clinical practice. However， the quality across domains remains uneven， and stakeholder involvement and applicability are still weak domains. Future guideline development and updating should further improve methodological standardization and transparency in reporting.

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 In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

The main features of chronic obstructive pulmonary disease include chronic airway inflammation,persis-tent airflow limitation,progressive dyspnea,and impaired lung function.Acetylation is one of the most common post-translational modifications of proteins,which plays an important role in the pathogenesis of chronic obstructive pulmonary disease,such as oxidative stress,inflammatory reaction,and airway remodeling,by regulating gene ex-pression,cell signaling,and protein function.Therefore,exploring the regulatory mechanism of acetylating modifi-cation in chronic obstructive pulmonary disease can not only deeply understand the pathophysiological mechanism of the disease,but also provide a theoretical basis for the development of new treatment strategies.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

Objective To explore the acceptability of routine biochemical test results for serum samples with varying degrees of chylous high triglyceride(TG).Methods Blood samples of 69 patients with different degrees of lipids were collected,including 33 patients with mild to moderate lipids(1.7 mmol/L≤TG<5.6 mmol/L)and 36 patients with severe lipids(TG≥5.6 mmol/L).Twenty-nine biochemical tests were detected before and after high-speed centrifugation.The result acceptability before high speed centrifugation of serum was compared with the results after high speed centrifugation as the gold standard[TG and total cholesterol(TC)before centrifugation].The acceptable criteria were subject to the following three conditions at the same time.Firstly,correlation coefficient(R2)was greater than or equal to 0.95.Secondly,the slope of linear re-gression equation was 1.00±0.05.Thirdly,for the same index,the number of samples whose result bias be-fore and after centrifugation was less than 1/2 total allowable error(TEa)in more than 90%of the total sam-ple numbers.Results Firstly,in the mild to moderate lipemia group,22 tests met the criteria,7 tests did not,including total protein(TP),albumin(ALB),TG,aspartate aminotransferase(AST),carbon dioxide(CO2),α-L-fucosidase(AFU),lactate dehydrogenase(LDH)(bias<10%),and the coincidence rate was 75.9%.In the severe lipemia group,12 tests met the criteria,17 tests did not,including pre-albumin(PA),AFU,γ-glu-tamyltransferase(γ-GT),LDH,AST,TC,direct bilirubin(DBIL),CO2,5'-nucleotidase(5'-NT),small and low-density lipoprotein cholesterol(sd-LDL-C),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),adenosine deaminase(ADA),cystatin C(CysC),glycosylated albumin(GA),total bilirubin(TBIL)(bias>10%),the coincidence rate was 41.4%,and there was a statistically sig-nificant difference in the coincidence rate between the two groups(P<0.05).Secondly,there was no statisti-cally significant difference in the acceptability of results between continuous monitoring method and endpoint method detection methods(P>0.05).Conclusion Most test results of direct determination with mild or moderate lipemia samples are acceptable,and the bias of unacceptable tests is small(<10%),so it is recom-mended to issue a test report without further sample treatment.However,due to the large number of unacceptable tests and larger bias(>10%),severe lipemia samples should be determined after high-speed centrifugation.

[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62％(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15％,-2.49％,-4.31％and-2.23％,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50～59,60～69 and 70～79 years old showed a decreasing trend,the AAPC ranged from-9.06％to-4.14％(all P＜0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men＜30 years old increased yearly with an AAPC of 4.30％(P＜0.05).Compared with 2009,the com-position of incidence in men aged 15～39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60～79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42％(P＜0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.