Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.
Humans ; Hypotension/complications* ; Cognitive Dysfunction/etiology* ; Alzheimer Disease/epidemiology* ; Cerebrovascular Circulation/physiology* ; Cognition Disorders/etiology*

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

Objective:To conduct a meta-analysis of clinical data to investigate the relationship between incretins and fracture in order to provide individualized hypoglycemic agents for type 2 diabetic patients with osteoporosis.Methods:PubMed, Embase, Web of Science, and Cochrane databases were searched up to January 1, 2018 for randomized controlled trials(RCTs)and the relationship between incretins and fracture was explored by meta-analysis.Results:The meta-analysis showed that the use of incretin was not associated with fracture risk compared with placebo or other positive hypoglycemic agents( OR 0.972, 95% CI 0.876-1.079). But in the subgroup analysis, 100 mg/d sitagliptin( OR 0.495, 95% CI 0.304-0.806)or 1.8 mg/d liraglutide( OR 0.621, 95% CI 0.413-0.933)reduced fracture risk. Conclusions:Meta-analysis shows no increase in the incidence of fracture events after the use of incretin. 100 mg/d sitagliptin or 1.8 mg/d liraglutide may exert protective effects on bone metabolism. However, the included data are from the reports of fracture adverse reactions in RCT studies, and large-scale clinical studies are needed to confirm these findings.

Objective To explore the effect of psoralen on topoisomerase IIα(TopoIIα) expression of breast cancer stem cells.Methods CD44+CD24-/low breast cancer stem cells were sorted from MCF-7/ADR by magnetic-activated cell sorting(MACS).We observed the growth characteristics of these stem cells through optical microscope and detected the growth-inhibitory effects of psoralen on breast cancer stem cells by CCK-8 assay and IC50 of adriamycin and adriamycin combined with psoralen to calculate the reversal index.The mRNA and protein expressions of Topo IIα were detected using RT-PCR and Western blot, respectively.Results Under the optical microscope, breast cancer stem cells presented spheres.IC10 and IC20 of psoralen on breast cancer stem cells were (6.77±0.23)μg/mL and (10.36±0.21)μg/mL.IC50 of adriamycin and adriamycin combined with psoralen on breast cancer stem cells was (90.03±3.56)μg/mL and (21.47±0.82)μg/mL, the reversal index was 4.19.Psoralen significantly raised the expressions of Topo Ⅱα at mRNA and protein levels.Conclusion Psoralen reversed the resistance of adriamycin by increasing the gene and protein expressions of breast cancer stem cells Topo Ⅱα and the drug targets.

BACKGROUND:Breast cancer stem cells not only lead to theoccurrence of breast cancer, but also may cause breast cancer metastasis and recurrence. The relationship between stem cells and cell resistance is also gaining increasing attentions, and the focus on the stem cell treatment may result in unexpected results.OBJECTIVE:To explore the reversal effect of psoralen on glutathione-S-transferase π (GST-π) in human breast cancer MCF-7/ADR cells and its mechanism.METHODS:MCF-7/ADR cells were cultured and enriched in serum-free medium to obtain breast cancer stem cells.RT-PCR and western blot were used to detect the expression of GST-π at the levels of gene and protein in the MCF-7/ADR cells after treatment with 0, 4, 8, 12, 16 mg/L psoralen. To observe the activation of nuclear factor-κB,western blot was used. The expression of GST-π was detected by RT-PCR in 18 μmol/L SN50 group and 8 mg/L psoralen group. Cell counting kit-8 assay was used to detect the effect of doxorubicin on cell proliferation.RESULTS AND CONCLUSION:Compared with the control group, psoralen reduced the expression of GST-π at the mRNA and protein levels, and significantly inhibited the activation of nuclear factor-κB. It was suggested that psoralen could reverse the multidrug resistance of human breast cancer MCF-7/ADR stem cells by decreasing the expression level of GST-π. The mechanism may be achieved by inhibiting the nuclear factor-κB signal pathway.