Breast cancer is a malignant tumor that occurs in the glandular epithelium of the breast, and it is one of the most common tumors that seriously affect the physical and mental health of women. With the aggravation of population aging, the incidence of breast cancer in the elderly has increased year by year in recent years. Elderly patients with breast cancer often have a variety of underlying diseases, and their prognosis is usually related to many factors such as cancer staging, cancer classification, treatment status and health status, with a significant difference in survival rate among patients. Due to the unique clinical and pathological characteristics of elderly patients with breast cancer compared to young and middle-aged patients, there are many studies on the treatment of elderly breast cancer patients in the past, and there are few reviews on the influencing factors of prognosis in elderly patients. This paper reviews the research progress of influencing factors of prognosis in elderly patients with breast cancer from the aspects of clinicopathological factors, treatment options and prognosis factors, in order to provide a reference for clinical determination of treatment options for elderly patients with breast cancer in the future.

BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

The KCNQ potassium channels play a crucial role in modulating neural excitability, and their dysfunction is closely associated with epileptic disorders. While variants in KCNQ2 have been extensively studied, KCNQ3-related disorders have rarely been reported. With advances in next-generation sequencing technologies, an increasing number of cases of KCNQ3-related disorders have been identified. However, the correlation between genotype and phenotype remains poorly understood. In this study, we established a variant library consisting of 24 missense mutations in KCNQ3 and introduced these mutations into three different template types: KCNQ3, KCNQ3-A315T (Q3*), and KCNQ3-KCNQ2 tandem (Q3-Q2). We then analyzed the effects of these mutations on the KCNQ3 channel function using patch-clamp recording. The most informative parameter across all three backgrounds was the current density of the mutant channels. The current density patterns in the Q3* and Q3-Q2 backgrounds were similar, with most mutations resulting in an almost complete loss of function (LOF), they were concentrated in the pore-forming domain of KCNQ3. In contrast, mutations in the voltage-sensing domain or C-terminus did not show significant differences from the wild-type channel. Interestingly, these LOF mutations were typically associated with self-limited familial neonatal epilepsy, while neurodevelopmental disorders (NDD) were more closely associated with mutations that did not significantly differ from the wild-type. V_1/2, another important parameter of the electrophysiological properties, could not be accurately determined in the majority of KCNQ3 mutations due to its nearly complete LOF in the Q3* and Q3-Q2 backgrounds. Intriguingly, the V_1/2 of functional mutations were primarily leftward shifted, indicating a gain-of-function (GOF) effect, which was typically associated with NDD. In addition to previously reported mutations, we identified G553R as a novel GOF mutation. In the co-transfection background, parameters such as V_1/2 could be determined, but the dysfunctional effects of these mutations were mitigated by the co-expression of wild-type KCNQ3 and KCNQ2 subunits, resulting in no significant differences between most mutations and the wild-type channel. Furthermore, we applied KCNQ modulators to reverse the electrophysiological abnormalities caused by KCNQ3 variants. The LOF mutations were reversed by the application of Pynegabine (HN37), a KCNQ opener, while the GOF mutation responded well to Amitriptyline (AMI), a KCNQ inhibitor. These findings provide essential insights into the pathogenic mechanisms underlying KCNQ3-related disorders and may inform clinical decision-making.
KCNQ3 Potassium Channel/genetics* ; Humans ; Mutation, Missense/genetics* ; KCNQ2 Potassium Channel/genetics* ; Patch-Clamp Techniques ; HEK293 Cells ; Animals ; Phenylenediamines/pharmacology* ; Carbamates

Objective:To analyze the physical activity level of patients treated with a percutaneous coronary intervention (PCI) for coronary artery disease in the early out-of-hospital recovery phase, and the factors influencing it.Methods:Patients who had been discharged within the previous 6 months after their first PCI treatment were surveyed using a general information questionnaire, the long form of the International Physical Activity Questionnaire (IPAQ), the Chinese version of the Tilburg Frailty Scale, the Social Support Rating Scale, and for their ability in the activities of daily living. Epidemiological descriptive methods were used to analyze the reported physical activity levels, and multifactoral logistic regression was applied to explore the influencing factors. The receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of the risk factors.Results:A total of 394 former patients were surveyed, including 117 (30%) reporting a low level of physical activity, 202 (51%) describing a moderate level and 75 (19%) claiming a high level. The univariate analysis revealed significant differences in physical activity levels among those of different ages, with different chronic co-morbidities, and with different frailty and self-care ability. Multifactoral logistic regression analysis showed that advanced age, chronic co-morbidities, frailty and little self-care ability are significant predictors of a low level of physical activity. The area under the ROC curve for predicting the physical activity level by combining those four factors was 0.89 (95% CI 0.84-0.94), with a sensitivity of 0.89 and a specificity of 0.80. Conclusions:The physical activity level of patients treated with PCI for coronary disease is moderately low early after their release from the hospital. Targeted intervention to increase it is called for.

Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.

Objective:To analyze the relationship between folate and thyroid antibody in early pregnancy and adverse pregnancy outcome in pregnant women with hypothyroidism during pregnancy.Methods:The data of 97 pregnant women with hypothyroidism from Jul. 2020 to Mar. 2023 in the Obstetrics Department of Liaocheng Second People’s Hospital were retrospectively analyzed. The levels of folate, thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were detected in the first trimester. According to whether adverse pregnancy outcome occurred in pregnant women with hypothyroidism during pregnancy, they were divided into occurrence group and non-occurrence group. The clinical data of the occurrence group and the non-occurrence group were compared. Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of folic acid, TGAb, TPOAb and their combination on adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy.Results:Among 97 pregnant women, the incidence of adverse pregnancy outcome was 14.43% (14/97) .The folate level in the occurrence group was lower than non-occurrence group ( P<0.05) , and the TGAb and TPOAb levels in the occurrence group were higher than non-occurrence group ( P<0.05) . The occurrence group with alanine aminotransferase (ALT) , glutamine transpeptidase (GGT) and aspartate aminotransferase (AST) were all higher than non-occurrence group ( P<0.05) .The folate, TGAb, and TPOAb levels were factors influencing adverse pregnancy outcomes in pregnant women with hypothyroidism ( P<0.05) . The area under the curve (AUC) values of folate, TGAb, TPOAb and their combined prediction of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy were 0.804, 0.843, 0.799, 0.909 ( P<0.05) , while the combined three with AUC values were higher ( P<0.05) . Conclusion:The folate, TGAb and TPOAb levels in early pregnancy can be used to evaluate adverse pregnancy outcomes in hypothyroidism pregnant women, and the combination of the three has a higher evaluation value.

Objective:To analyze the relationship between folate and thyroid antibody in early pregnancy and adverse pregnancy outcome in pregnant women with hypothyroidism during pregnancy.Methods:The data of 97 pregnant women with hypothyroidism from Jul. 2020 to Mar. 2023 in the Obstetrics Department of Liaocheng Second People’s Hospital were retrospectively analyzed. The levels of folate, thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were detected in the first trimester. According to whether adverse pregnancy outcome occurred in pregnant women with hypothyroidism during pregnancy, they were divided into occurrence group and non-occurrence group. The clinical data of the occurrence group and the non-occurrence group were compared. Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of folic acid, TGAb, TPOAb and their combination on adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy.Results:Among 97 pregnant women, the incidence of adverse pregnancy outcome was 14.43% (14/97) .The folate level in the occurrence group was lower than non-occurrence group ( P<0.05) , and the TGAb and TPOAb levels in the occurrence group were higher than non-occurrence group ( P<0.05) . The occurrence group with alanine aminotransferase (ALT) , glutamine transpeptidase (GGT) and aspartate aminotransferase (AST) were all higher than non-occurrence group ( P<0.05) .The folate, TGAb, and TPOAb levels were factors influencing adverse pregnancy outcomes in pregnant women with hypothyroidism ( P<0.05) . The area under the curve (AUC) values of folate, TGAb, TPOAb and their combined prediction of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy were 0.804, 0.843, 0.799, 0.909 ( P<0.05) , while the combined three with AUC values were higher ( P<0.05) . Conclusion:The folate, TGAb and TPOAb levels in early pregnancy can be used to evaluate adverse pregnancy outcomes in hypothyroidism pregnant women, and the combination of the three has a higher evaluation value.

Objective To investigate the predictive value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)radiomics combined with Magee equation 3(ME3)for pathological response following neoadjuvant chemotherapy(NAC)in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)breast cancer.Methods A ret-rospective analysis was performed on 325 breast cancer patients diagnosed with HR+/HER2-in two hospitals.Patients from the first hospital were randomly divided into training and internal validation sets at a ratio of 7∶3.Patients from the second hospital served as external validation set.The volume of interest(VOI)of breast cancer was delineated on DCE-MRI images.Then the rele-vant radiomics features were extracted and selected,and the Radiomics score(Radscore)was calculated.The statistically significant clinical and pathological features and Radscore were incorporated into a multivariate analysis.The combined radiomics-clinical model and nomogram were established,and the prediction performance was evaluated by using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results In the training set,seven radiomics features were selected to construct the radiomics model.ME3 score emerged as the independent factor for pathological complete response(pCR)(P＜0.001).By integrating ME3 score and Radscore,a combined radiomics-clinical model was developed.This model demonstrated robust predictive accuracy,with area under the curve(AUC)of 0.88[95％confidence interval(CI)0.80-0.95],0.90(95％CI 0.82-0.98),and 0.82(95％CI 0.70-0.93)in the training,internal validation,and external validation sets,respectively.The nomogram construc-ted from the combined model exhibited excellent discrimination and calibration,with P-values of 0.455,0.312 and 0.062 in the train-ing,internal validation,and external validation sets.Conclusion DCE-MRI radiomics combined with ME3 can be used to predict the pathological response of NAC in HR+/HER2-breast cancer.