ObjectiveStroke poses a heavy burden due to its high mortality and morbidity rates. Accurate and real-time detection of lesions is pivotal for prompt clinical intervention and favorable prognosis. Electrical impedance tomography (EIT) and microwave tomography (MWT) have emerged as compelling alternatives for stroke screening, owing to their non-ionizing, non-invasive and portable nature. EIT provides information on tissue conductivity, and MWT offers high sensitivity to changes in dielectric properties. However, single-modality imaging is inherently limited, EIT suffers from low sensitivity to deep-seated tissues and severe ill-posedness of inverse problems, whereas MWT is challenged by strong nonlinearity in inverse scattering and susceptibility to modeling errors. Consequently, the clinical utility of standalone EIT or MWT for stroke diagnosis remains constrained by poor spatial resolution and imaging artifacts. To improve the accuracy and robustness of stroke imaging, a dual-modality fusion conditional denoising diffusion probabilistic model (DM-DDPM) was proposed for high-precision dual-modality image reconstruction. MethodsA dual-encoder network with a symmetric architecture and independently trained parameters was constructed to extract heterogeneous features separately from EIT boundary voltage measurements and MWT scattered field signals. Attentional feature fusion (AFF) is employed to integrate complementary information from the two modalities adaptively, generating robust fused priors that suppress redundant noise while preserving key physical characteristics. Subsequently, the fused priors are embedded into a Transformer-based diffusion model via a cross attention mechanism to guide the reverse denoising process. This approach effectively reduces artifacts and enhances the stability of conductivity distribution reconstruction. Time step embedding is introduced to enable the network to perceive the diffusion stage and further improve the accuracy of noise prediction. ResultsSimulated experiments demonstrated that DM-DDPM significantly outperforms single-modality and multi-modality networks under various noise levels. A head model simulation dataset was constructed based on COMSOL Multiphysics, and tests were carried out under 50 dB, 40 dB and 30 dB signal-to-noise ratio levels. At 30 dB, the average relative error (RE) was below 0.20, while the structural similarity index measure (SSIM) and correlation coefficient (CC) remained above 0.90 and 0.89, respectively. Compared with single-modality and multi-modality networks, artifacts were significantly reduced, lesion edges were clearer, and localization was more accurate. The model maintains high reconstruction quality and strong robustness for single, double, and triple lesions simultaneously. Furthermore, physical experiments were conducted using a 16-electrode EIT system and a 16-antenna MWT system with asynchronous data acquisition. These experiments confirmed the feasibility of the method in real-world scenarios and demonstrated that it can robustly reconstruct simulated lesions despite environmental interference and measurement noise, validating its reliability for practical clinical applications. ConclusionThe proposed method effectively combines complementary dual-modality information with a conditional diffusion model. Low accuracy and poor noise resistance in single-modality imaging were effectively addressed, while the noise amplification issue caused by direct multimodal data fusion was avoided. The proposed algorithm exhibits strong anti-noise interference ability and high imaging stability in both simulation and physical experiments. Precise localization of stroke lesions with different quantities was achieved, providing a high-precision, and practical technical support for clinical stroke detection.

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

Objective To investigate the efficacy and influencing factors of programmed death-1(PD-1)inhibitors in neoadjuvant chemotherapy for triple-negative breast cancer(TNBC).Methods A total of 86 patients with TNBC who received neoadjuvant therapy in The Fifth Medical Center,PLA General Hospital between Jan.1,2018,and Jan.1,2024 and met the inclusion criteria were enrolled,and their clinicopathological data were collected.Based on the neoadjuvant treatment regimens,40 patients who received TP+PD-1 inhibitor(paclitaxel+carboplatin+pembrolizumab)were assigned to TP+PD-1 inhibitor group,and 46 patients who received TP(paclitaxel+carboplatin)were assigned to TP group.The efficacy and incidence of adverse events were compared between the 2 groups after 6 cycles of neoadjuvant therapy.According to the efficacy of neoadjuvant therapy,the patients were further categorized into pathological complete response(pCR)group and non-pCR group.Multivariate logistic stepwise regression analysis was performed to identify independent factors influencing neoadjuvant treatment efficacy.Patients were followed up until Dec.31,2024,and survival analysis was conducted using Kaplan-Meier method.Results There was no significant difference in the objective response rates between the TP+PD-1 inhibitor group and TP group after neoadjuvant therapy(95.0%[38/40]vs 91.3%[42/46],P=0.351].However,the pCR rate was significantly higher in the TP+PD-1 inhibitor group compared with the TP group(65.0%[26/40]vs 43.5%[20/46],P=0.047).There were no significant differences between the 2 groups in terms of disease-free survival,overall survival,or incidence of adverse events(all P＞0.05).Multivariate logistic stepwise regression analysis revealed that the expression of Ki-67 and treatment regimen were influencing factors of pCR after neoadjuvant therapy(odds ratio[OR]=3.382,95%confidence interval[95%CI]1.290-8.868,P=0.013;OR=2.524,95%CI 1.013-6.285,P=0.047).One case of distant metastasis and death occurred in the pCR group,while 8 cases of distant metastasis and 4 deaths occurred in the non-pCR group.The disease-free survival was significantly longer in the pCR group than in the non-pCR group(P=0.031),while the overall survival was similar between the 2 groups(P=0.087).Conclusion Compared with the 6-cycle TP regimen,the 6-cycle TP combined with PD-1 inhibitor regimen can improve the pCR rate in the neoadjuvant treatment of TNBC,with manageable adverse events,suggesting it may serve as a preferred option for TNBC neoadjuvant therapy.Ki-67 expression may serve as a predictive biomarker for achieving pCR.TNBC patients who achieved pCR have better disease-free survival than those who did not.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

Objective:To investigate the clinicopathological characteristics and prognostic influencing factors in young breast cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 408 young patients with breast cancer in the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2020 were retrospectively analyzed. The clinical characteristics and prognostic influencing factors of patients were observed. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS) of patients. Univariate analysis of prognostic factors was conducted by using the log-rank test, and multivariate analysis was performed by using Cox proportional risk model.Results:The median age [ M ( Q1, Q3)] of 408 young female patients with breast cancer was 36 (33, 39) years; the 5-year OS and 5-year DFS rates were 89.9%, 84.0% of 387 breast cancer patients in early and middle stage (except for stage Ⅳ). There were statistically significant differences in the 5-year OS and 5-year DFS rates (excluding stage Ⅳ of DFS) of patients with different clinical staging and molecular subtypes (all P < 0.05). The differences were statistically significant in the 5-year DFS rate of patients with different pathological types and histological grades (all P < 0.05). There were no statistically significant differences in the 5-year OS and DFS rates between the patients receiving breast-conserving surgery or mastectomy (all P > 0.05). The results of multivariate Cox regression analysis indicated that clinical staging ( HR = 3.121, 95% CI: 2.301-4.233, P < 0.001) and molecular classification ( HR = 1.441, 95% CI: 1.126-1.845, P = 0.004) were independent prognostic factors for OS. Additionally, clinical staging ( HR = 3.001, 95% CI: 2.174-4.141, P < 0.001) was identified as an independent prognostic factor for DFS. Conclusions:The prognosis of young breast cancer patients is closely related to clinical staging and molecular subtype. The later the clinical stage is, the poorer prognosis is. Luminal-type breast cancer has a better prognosis than other subtypes. For early-stage breast cancer patients who meet the criteria for breast-conserving surgery, breast-conserving surgery is the first-choice alternative.

Objective To investigate the correlation between cognitive impairment of cerebral small vessel disease(CSVD)and white matter hyperintensity grade and cerebral atrophy grade.Methods The data of 213 patients with CSVD were analyzed retro-spectively.The semi-quantitative Fazekas visual score of brain MR was used to evaluate the white matter hyperintensity,and cerebral atrophy was evaluated by the whole cerebral cortex atrophy grade.Mini-mental state examination(MMSE)and Montreal cognitive assessment(Mo CA)were used to evaluate each patient and to classify according to the results.Results There was a statistically sig-nificant difference in age between male and female patients with CSVD(P=0.04,t=4.288).The mean age of males[(66.5±10.3)years]was less than females[(69.5±10.0)years].There was significant difference between patients with different gender and history of hypertension(P=0.02,t=5.424).There were statistical differences between white matter hyperintensity Fazekes grade and MMSE and Mo CA scores(P<0.001,χ2=5.639;P<0.001,χ2=5.843),and there were statistical differences between whole cerebral cortex atrophy grade and MMSE score(P=0.036,χ2=2.895).Conclusion There is a certain correlation between cognitive impairment of CSVD and head MR imaging evaluation grade.

Objective To identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.