ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

Objective: To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods: The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results: The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.

OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×10⁷ MM patient-derived mononuclear cells (MNCs), 2.0×10⁶ MM.1S cells and 2.0×10⁶ NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry and fluorescence in situ hybridization (FISH). The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation, apoptosis and in vitro and in vivo experiments. The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC, TUNEL staining and confocal fluorescence microscope. RESULTS: MM PDX model was successfully established by subcutaneously inoculating primary MNCs. The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells. MM PDX tumor cells positively expressed CD138 and CD38, which presented 1q21 amplification, deletion of Rb1 and IgH rearrangement, and had a lower proliferative activity than MM cell lines. in vitro, PDX, MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours, respectively. Cell viability assay showed that the IC₅₀ value of bortezomib were 5 716.486, 1.025 and 2.775 nmol/L, and IC₅₀ value of anlotinib were 5 5107.337, 0.706 and 5.13 μmol/L, respectively. Anlotinib treatment increased the apoptosis of MM.1S cells (P < 0.01), but did not affect PDX tumor cells (P >0.05). in vivo, there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group (P >0.05), while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth (both P < 0.05). The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group (both P < 0.01). The apoptotic cells in anlotinib treatment group were increased compared with those in control group (P < 0.05). CONCLUSION Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice. This PDX model, which retains the basic biological characteristics of MM cells, can be used to study the novel therapies.
Animals ; Bortezomib ; Humans ; Multiple Myeloma/pathology* ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Mice, Inbred NOD ; Disease Models, Animal ; Cell Proliferation ; Transplantation, Heterologous

OBJECTIVE: To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients. METHODS: The clinical data of 186 newly diagnosed AML patients (except M3 subtype) in the First People's Hospital of Changzhou were retrospectively analyzed, and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model. The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model. RESULTS: A total of 60 AML patients had IDH1/2 mutation at initial diagnosis. LASSO regression screened 9 predictive variables associated with IDH1/2 mutation, including CD7, CD56, CD11b, CD15, CD64, HLA-DR, platelet count≥50×10⁹/L, isolated +8 and normal karyotype. The nomogram and ROC curve were plotted based on the above 9 variables. The area under the ROC curve (AUC) of the training set and the validation set were 0.871 and 0.806, respectively. Internal validation showed that the nomogram had good predictive ability. CONCLUSION The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Retrospective Studies ; Nomograms ; Female ; Male ; ROC Curve ; Middle Aged

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Photothermal therapy,as a novel anti-tumor treatment strategy,faces many challenges such as insufficient targeting,limited penetration ability,and inability to achieve long-term inhibition when used alone for anti-tumor treatment.Based on this,in this study,macrophage extracellular vesicles(MEVs)were modified onto the surface of a vector carrying CSF1R-siRNA and photothermal agents to form a multifunctional gene delivery vector MEVs@RNPs.It could induce the macrophages to reprogram from M2 type to M1 type,so as to achieve efficient photothermal and immunotherapy for triple negative breast cancer(TNBC).The basic physicochemical properties of each nanocarrier were characterized using nanoparticle size analyzer,UV-vis spectrometer,fluorescence spectrometer,thermal imaging instrument,etc.TNBC cells 4T1,endothelial cells Bend3,and macrophages 264.7 were used as in vitro experimental subjects for measurement of MEVs@RNPs.The ability to target tumor cells,kill tumor cells,and induce macrophage reprogramming in vitro was investigated.With Balb/c mice as the in vivo research object,a subcutaneous transplant tumor model was established in mice,and the changes in tumor volume and body weight of mice in different treatment groups were measured.In addition,further isolation of mouse blood and tumor tissue was performed,and hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method,and enzyme-linked immunosorbent assay(ELISA)method were used to determine the apoptosis and cytokine secretion of tumor cells for comprehensive evaluation of MEVs@RNPs.The results showed that the MEVs@RNPs could preferentially target tumor cells and induce stronger TNBC cell killing effect under photothermal conditions.Meanwhile,the results of flow cytometry and ELISA analysis showed that the MEVs@RNPs could promote the transformation of macrophages from M2 type to anti-tumor M1 type,significantly enhancing the secretion levels of anti-tumor cytokines tumor necrosis factor-α(TNF-α)and interleukin-12(IL-12).The in vivo anti-tumor treatment effect assessment of the MEVs@RNPs showed that under laser processing conditions,the MEVs@RNPs could significantly induce pathological necrosis and apoptosis of tumor cells,promote macrophage reprogramming and infiltration of CD4+/CD8+T cells into the tumor site,and enhance the secretion levels of TNF-α and IL-12,thereby comprehensively improving the therapeutic effect of TNBC.

Accurate analysis of metal nanoparticles(MNPs)in sediments is a prerequisite for assessing the ecological risks of MNPs in aquatic environmental sediments.In this study,an analytical method for quantitative detection of concentration and particle size distribution of silver-containing nanoparticles(Ag-NPs),zinc-containing nanoparticles(Zn-NPs),cerium-containing nanoparticles(Ce-NPs),and titanium-containing nanoparticles(Ti-NPs)in sediments was established based on ultrasonic extraction-single particle inductively coupled plasma mass spectrometry(SP-ICP-MS).The effects of sample preparation conditions such as extraction solvent type,solid-liquid ratio,ultrasonic time,and settling time on the recovery of MNPs were investigated.The results showed that the extraction of MNPs from sediment by distilled water could effectively eliminate the high background signal interference introduced by the extractant under the conditions of solid-liquid ratio of 1∶400(g∶mL),ultrasonic extraction time of 1 h and settling time of 3 h.The detection limits for particle size of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 31,35,26 and 85 nm,respectively,while the detection limits of particle concentrations were 1.21×104,1.90×104,5.26×107 and 1.48×107 particles/g,respectively.The spiking recoveries of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 62.1％-108.7％,with relative standard deviations below 10％.This method could rapidly,accurately and simultaneously determine the concentration and particle size distribution of various MNPs in sediments,and was successfully applied to analysis of Ag-NPs,Zn-NPs,Ce-NPs,and Ti-NPs in authentic marine sediments.