Prognostic significance and value of further classification of lymphovascular invasion in invasive breast cancer: a retrospective observational study.

PURPOSE: To investigate the prognostic significance of lymphovascular invasion in invasive breast cancer and the value of using specific vascular endothelial markers to further classify lymphovascular invasion. METHODS: We collected 2124 patients with invasive breast cancer who were hospitalized at the First Hospital of Dalian Medical University from 2012 to 2020. Statistical methods were used to investigate the relationship between lymphovascular invasion and clinicopathological characteristics of breast cancer, and the correlation between lymphovascular invasion on overall survival (OS) and disease-free survival (DFS) of various categories of breast cancers. Immunohistochemical staining of breast cancer samples containing lymphovascular invasion using specific vascular endothelial markers D2-40 and CD34 was used to classify lymphovascular invasion and to investigate the relationship between lymphovascular invasion and breast cancer progression. RESULTS: There was a high correlation between lymphovascular invasion and T stage, N stage and nerve invasion. Survival analyses showed that patients with lymphovascular invasion, especially luminal B, triple-negative, and Her-2 overexpression breast cancer patients, had poorer OS and DFS prognosis, and that lymphovascular invasion was an independent prognostic factor affecting OS and DFS in breast cancer. The immunohistochemical staining results showed that positive D2-40 staining of lymphovascular invasion was linked to the N stage and localized recurrence of breast cancer. CONCLUSION: Lymphovascular invasion is associated with aggressive clinicopathological features and is an independent poor prognostic factor in invasive breast cancer. Breast cancer localized recurrence rate and lymph node metastases are influenced by lymphatic vessel invasion. Immunohistochemical techniques should be added to the routine diagnosis of lymphovascular invasion.

Co-occurrence of depressive and anxious symptoms and their influence on self-rated health: a national representative survey among Chinese older adults.

OBJECTIVES: The prevalence of the co-occurrence of depressive and anxious symptoms (CO) and their influence on perceived overall health were not clear in community dwelling Chinese older adults. The aims of the study were to investigate the prevalence of CO and to explore its influence on self-rated health (SRH). METHOD: This study included 12301 individuals aged ≥65 years from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationally representative survey of older adults in mainland China. Participants received face-to-face interviews and assessments of depressive symptoms and anxious symptoms via 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), respectively. SRH was measured by self-reported. A logistic regression model was used to examine the association between CO and SRH after adjusting for confounding variables. RESULTS: The average age was 83.4 (SD: 11.0) years and there were 6576 (53.5%) females. The age- and sex-standardized prevalence of depressive symptoms only (DSO) was 38.6%, anxious symptoms only (ASO) was 1.5%, and CO was 10.8%. Compared with those without depressive and anxious symptoms, the older adults with DSO or ASO were more likely to have significant influence on SRH. And particularly, CO was likely to produce the greatest decrement in the level of SRH. CONCLUSION: CO was not rare in Chinese older adults nationwide. The older adults having CO had increased risk for lower level of SRH than having DSO or ASO. More attention should be given to CO among the older adults.

Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey.

OBJECTIVES: To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories. METHODS: The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10 years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes. RESULTS: Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9 h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline. CONCLUSIONS: The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

The Segmentation of Multiple Types of Uterine Lesions in Magnetic Resonance Images Using a Sequential Deep Learning Method with Image-Level Annotations.

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods.

Practical application of the patient data-based quality control method: the potassium example.

Introduction: Internal quality control (IQC) is a core pillar of laboratory quality control strategies. Internal quality control commercial materials lack the same characteristics as patient samples and IQC contributes to the costs of laboratory testing. Patient data-based quality control (PDB-QC) may be a valuable supplement to IQC; the smaller the biological variation, the stronger the ability to detect errors. Using the potassium concentration in serum as an example study compared error detection effectiveness between PDB-QC and IQC. Materials and methods: Serum potassium concentrations were measured by using an indirect ion-selective electrode method. For the training database, 23,772 patient-generated data and 366 IQC data from April 2022 to September 2022 were used; 15,351 patient-generated data and 246 IQC data from October 2022 to January 2023 were used as the testing database. For both PDB-QC and IQC, average values and standard deviations were calculated, and z-score charts were plotted for comparison purposes. Results: Five systematic and three random errors were detected using IQC. Nine systematic errors but no random errors were detected in PDB-QC. The PDB-QC showed systematic error warnings earlier than the IQC. Conclusions: The daily average value of patient-generated data was superior to IQC in terms of the efficiency and timeliness of detecting systematic errors but inferior to IQC in detecting random errors.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Biological variation in the estimated glomerular filtration rate of healthy individuals within 24 h calculated using 2021CKD-EPI equations.

BACKGROUND AND AIMS: Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24 h in a healthy population to help explain future studies using eGFR in the context of a known BV. METHODS: Blood samples were collected from 30 healthy subjects at six time points within 24 h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data. RESULTS: The eGFR CVI for the four equations (MDRD, CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCVpos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCVpos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCVpos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPICrea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively. CONCLUSIONS: We present data on the 24 h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCVpos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCVpos/neg values before interpreting the results.

Early prediction of pathological response to neoadjuvant chemotherapy of breast tumors: a comparative study using amide proton transfer-weighted, diffusion weighted and dynamic contrast enhanced MRI.

Objective: To examine amide proton transfer-weighted (APTw) combined with diffusion weighed (DWI) and dynamic contrast enhanced (DCE) MRI for early prediction of pathological response to neoadjuvant chemotherapy in invasive breast cancer. Materials: In this prospective study, 50 female breast cancer patients (49.58 ± 10.62 years old) administered neoadjuvant chemotherapy (NAC) were enrolled with MRI carried out both before NAC (T0) and at the end of the second cycle of NAC (T1). The patients were divided into 2 groups based on tumor response according to the Miller-Payne Grading (MPG) system. Group 1 included patients with a greater degree of decrease in major histologic responder (MHR, Miller-Payne G4-5), while group 2 included non-MHR cases (Miller-Payne G1-3). Traditional imaging protocols (T1 weighted, T2 weighted, diffusion weighted, and DCE-MRI) and APTw imaging were scanned for each subject before and after treatment. APTw value (APTw0 and APTw1), Dmax (maximum diameter, Dmax0 and Dmax1), V (3D tumor volume, V0 and V1), and ADC (apparent diffusion coefficient, ADC0 and ADC1) before and after treatment, as well as changes between the two times points (ΔAPT, ΔDmax, ΔV, ΔADC) for breast tumors were compared between the two groups. Results: APT0 and APT1 values significantly differed between the two groups (p = 0.034 and 0.01). ΔAPTw values were significantly lower in non-MHR tumors compared with MHR tumors (p = 0.015). ΔDmax values were significantly higher in MHR tumors compared with non-MHR tumors (p = 0.005). ADC0 and ADC1 values were significantly higher in MHR tumors than in non-MHR tumors (p = 0.038 and 0.035). AUC (Dmax+DWI + APTw) = AUC (Dmax+APTw) > AUC (APTw) > AUC (Dmax+DWI) > AUC (Dmax). Conclusion: APTw imaging along with change of tumor size showed a significant potential in early prediction of MHR for NAC treatment in breast cancer, which might allow timely regimen refinement before definitive surgical treatment.

A novel immune-related gene signature for diagnosis and potential immunotherapy of microsatellite stable endometrial carcinoma.

An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P < 0.05). Besides, patients in MSS group were more FIGO stages II-IV (42.7% vs. 26%), serous histology (35.7% vs. 5.3%) and with higher IRGS risk score (1.51 ± 3.11 vs. 1.02 ± 0.67) (P < 0.05) than patients in MSI group. Furthermore, patients in IRGS high-risk group had higher tumor purity, more Macrophages M1 and Macrophages M2 infiltrating, higher proportion of Macrophages M2 and Dendritic cells activated, lower proportion of T cells regulatory (Tregs), lower tumor mutation burden (TMB). Correspondingly, subjects in IRGS low-risk group had higher immunphenoscores than IRGS high-risk group. The relative mRNA level of AGTR1 and HTR3C were gradually increase, while CD3E and SERPIND1 were reversed in rt-qPCR. Through IHC experiments, AGTR1(69.2% vs 30%, P = 0.074) and HTR3C (76.9% vs 30%, P = 0.024) had higher positive staining rates in ECs than non-ECs. While SERPIND1 (84.6% vs 20%, P = 0.003) and CD3E (61.5% vs 40%, P = 0.000) had higher positive staining rates in non-ECs. IRGS is a potential diagnostic and prognostic biomarker for EC. IRGS low risk group might benefit from immune checkpoint inhibitors, while IRGS high risk group deserve other potential immunotherapy.

The olfactory working memory capacity paradigm: A more sensitive and robust method of assessing cognitive function in male 5XFAD mice.

The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of ß-amyloid (Aß). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.

Improvement of oxidized myofibrillar protein gel properties by black rice extract.

In order to investigate the effects of black rice extract (BE) on the composition of oxidized myofibrillar protein (MP) gel, different concentrations of BE (0, 10, 20, 50 mg g-1) were analyzed experimentally. Results revealed that the addition of small doses of BE significantly inhibited the formation of carbonyl groups in oxidized MP, and improved surface hydrophobicity and gel water holding capacity. Additionally, 10 and 20 mg g-1 BE increased the ordered structure of oxidized MP. Furthermore, dynamic rheometer results showed a significant increase in the storage modulus (G') of oxidized MP with 10 and 20 mg g-1 BE during heating. Scanning Electron Microscopy (SEM) showed that MP formed a denser network structure with addition of 10 and 20 mg g-1 BE. Low-Field Nuclear Magnetic Resonance (LF-NMR) and magnetic resonance imaging (MRI) showed that there is a significant increase in immobile water in MP gel and a decrease in free water within the 20 mg g-1 BE group. In conclusion, 20 mg g-1 supplemented BE significantly improved the structure order and hardness of oxidized MP gel, increased its structure density and water holding capacity, and it provides a theoretical basis for the application of antioxidants in meat products.

Genetic associations with longevity are on average stronger in females than in males.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels.

Background and aims: Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Methods: Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. Results: One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045-1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138-2.014, P = 0.004) were independent factors associated with advanced inflammation. Conclusions: High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

Factors associated with health-seeking for urinary incontinence in Hong Kong Chinese women: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: To explore levels of urinary incontinence (UI) knowledge among Hong Kong Chinese women and the factors affecting patients' help-seeking behavior. METHODS: Chinese women with age ≥ 40 years who attended General Out-patient Clinics between May 1 and June 30, 2022, were invited to complete the questionnaire. The questionnaire consisted of four sections: (1) demographic data, (2) knowledge of UI (UI quiz), (3) severity of UI (UDI-6) and impairment of quality of life (QOL) (IIQ-7), and (4) barriers to seeking medical help. Severity of UI, impairment of QOL, knowledge of UI, and sociodemographic characteristics were analyzed regarding their relationship with help-seeking behavior. RESULTS: Of 351 women, 53.2% had symptoms of UI but only 25.0% symptomatic patients had consulted a doctor. The UI quiz score was 6.82 ± 2.76 (total 14) and the highest incorrect item was "Urinary incontinence is the normal aging" (incorrect rate 86.3%). The most frequent barrier for help-seeking was "The symptoms are not severe and do not affect me." Logistic regression analysis showed that UDI-6 score (adjusted OR = 1.06, P < 0.0001) and UI quiz score (adjusted OR = 1.30, P = 0.001) were the independent impact factors of patient's help-seeking behavior. CONCLUSIONS: Hong Kong Chinese women's knowledge toward UI is not sufficient, and the consultation rate is low. Besides symptom severity, the knowledge level of UI is the other independent factor affecting patients' help-seeking behavior. Community education on UI may encourage women to seek early help.

Interference of MDM2 attenuates vascular endothelial dysfunction in hypertension partly through blocking Notch1/NLRP3 inflammasome pathway.

BACKGROUND: Hypertension is a life-threatening disease mainly featured as vascular endothelial dysfunction. This study aims to explore the regulatory role of murine double minute 2 (MDM2) in hypertension and vascular damage. METHODS: Mice were infused with angiotensin II (AngII) to establish a hypertension mouse model in vivo and AngII-stimulated HUVECs were constructed to simulate the damage of vascular endothelial cells in hypertension in vitro. The plasmids targeting to MDM2 was injected to mice or transfected to HUVECs. qRT-PCR and western blot were performed to detect corresponding gene expression in mice aorta. Blood pressure was measured. H&E and Masson staining were conducted to evaluate histological changes of aorta. Responses to the acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in aorta. ZO-1 expression and cell apoptosis were detected by immunofluorescence and TUNEL, respectively. Network formation ability was determined employing a tube formation. RESULTS: MDM2 was upregulated in hypertensive mice. Knockdown of MDM2 inhibited AngII-induced high BP, histological damage, vascular relaxation to Ach, and promoted the levels of p-eNOS and ZO-1 in the aorta in hypertensive mice. MDM2 knockdown inactivated Notch1 signaling and NLRP3 inflammasome, while the inhibitory effect of MDM2 knockdown on NLRP3 inflammasome activation was partly restored by the activation of Notch1. Furthermore, knockdown of MDM2 relieved AngII-induced endothelial dysfunction in HUVECs, as well as suppressing AngII-promoted cell apoptosis. Whereas, the impacts generated by MDM2 knockdown were partly weakened by the activation of Notch1 signaling or NLRP3 inflammasome. CONCLUSION: In summary, knockdown of MDM2 can attenuate vascular endothelial dysfunction in hypertension, which may be achieved through inhibiting the activation of Notch1 and NLRP3 inflammasome.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

Cerebral dominance representation of directed connectivity within and between left-right hemispheres and frontal-posterior lobes in mild cognitive impairment.

Electroencephalography can assess connectivity between brain hemispheres, potentially influencing cognitive functions. Much of the existing electroencephalography research primarily focuses on undirected connectivity, leaving uncertainties about directed connectivity alterations between left-right brain hemispheres or frontal-posterior lobes in mild cognitive impairment. We analyzed resting-state electroencephalography data from 34 mild cognitive impairment individuals and 23 normal controls using directed transfer function and graph theory for directed network analysis. Concerning the dominance within left-right hemispheres or frontal-posterior lobes, the mild cognitive impairment group exhibited decreased connectivity within the frontal compared with posterior brain regions in the delta and theta bands. Regarding the dominance between the brain hemispheres or lobes, the mild cognitive impairment group showed reduced connectivity from the posterior to the frontal regions versus the reverse direction in the same bands. Among all participants, the intra-lobe frontal-posterior dominance correlated positively with executive function in the delta and alpha bands. Inter-lobe dominance between frontal and posterior regions also positively correlated with executive function, attention, and language in the delta band. Additionally, interhemispheric dominance between the left and right hemispheres positively correlated with attention in delta and theta bands. These findings suggest altered cerebral dominance in mild cognitive impairment, potentially serving as electrophysiological markers for neurocognitive disorders.

A novel web-based online nomogram to predict advanced liver fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

Background: Patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome. Methods: A total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score. Results: The median age of patients was 53.0 years (IQR: 46.0-63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754-0.936) and 0.843 (95 % CI: 0.705-0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility. Conclusion: This novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.