sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-ß via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from Brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

Enhancing prognostic accuracy: a SEER-based analysis for overall and cancer-specific survival prediction in cervical adenocarcinoma patients.

BACKGROUND: Cervical adenocarcinoma (CA) is the second most prevalent histological subtype of cervical cancer, following cervical squamous cell carcinoma (CSCC). As stated in the guidelines provided by the National Comprehensive Cancer Network, they are staged and treated similarly. However, compared with CSCC patients, CA patients are more prone to lymph node metastasis and recurrence with a poorer prognosis. The objective of this research was to discover prognostic indicators and develop nomograms that can be utilized to anticipate the overall survival (OS) and cancer-specific survival (CSS) of patients diagnosed with CA. METHODS: Using the Surveillance, Epidemiology, and End Result (SEER) database, individuals with CA who received their diagnosis between 2004 and 2015 were identified. A total cohort (n = 4485) was randomly classified into two separate groups in a 3:2 ratio, to form a training cohort (n = 2679) and a testing cohort (n = 1806). Overall survival (OS) was the primary outcome measure and cancer-specific survival (CSS) was the secondary outcome measure. Univariate and multivariate Cox analyses were employed to select significant independent factors and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized to develop predictive nomogram models. The predictive accuracy and discriminatory ability of the nomogram were assessed by employing metrics such as the calibration curve, receiver operating characteristic (ROC) curve, and the concordance index (C-index). RESULTS: Age, Tumor Node Metastasis stages (T, N, and M), SEER stage, grade, and tumor size were assessed as common independent predictors of both OS and CSS. The C-index value of the nomograms for predicting OS was 0.832 (95% CI 0.817-0.847) in the training cohort and 0.823 (95% CI 0.805-0.841) in the testing cohort. CONCLUSION: We developed and verified nomogram models for predicting 1-, 3- and 5-year OS and CSS among patients with cervical adenocarcinoma. These models exhibited excellent performance in prognostic prediction, providing support and assisting clinicians in assessing survival prognosis and devising personalized treatments for CA patients.

Trends and Disparities in Stage-Specific Incidence of Hepatocellular Carcinoma among US Adults, 2004-2019.

Introduction: The aim of this study was to determine the stage-specific incidence trend of hepatocellular carcinoma (HCC) among US adults. Methods: The age-adjusted incidence rate was extracted from Surveillance, Epidemiology, and End Results database for localized, regional, and distant HCC. Trend analyses were conducted in the overall population and stratified by demographic and sociodemographic variables. The annual percentage change (APC) in 2014-2019 was estimated to determine the stage-specific incidence trend. Results: Although the incidence of localized HCC significantly declined, the incidence for regional and distant HCC plateaued in 2014-2019 (APCs, 4.4% [95% CI, -0.2% to 9.3%] and -0.7% [95% CI, -1.8% to 0.5%], respectively) with age and race/ethnicity disparities. More pronounced increases for regional and distant HCC were observed among the elderly (APCs, 8.4% [95% CI, 4.8-12.2%] and 2.2% [95% CI, 1.7-2.7%] for regional and distant HCC, respectively), non-Hispanic white individuals (APCs, 4.0% [95% CI, 2.9-5.1%] and 1.5% [95% CI, 0.7-2.4%] for regional and distant HCC, respectively). Conclusions: Disparities in incidence trends may reflect the inequalities in access to primary health care. More efforts are still in great demand for the vulnerable population.

Development and validation of a copper-related gene prognostic signature in hepatocellular carcinoma.

Introduction: Reliable biomarkers are in need to predict the prognosis of hepatocellular carcinoma (HCC). Whilst recent evidence has established the critical role of copper homeostasis in tumor growth and progression, no previous studies have dealt with the copper-related genes (CRGs) signature with prognostic potential in HCC. Methods: To develop and validate a CRGs prognostic signature for HCC, we retrospectively included 353 and 142 patients as the development and validation cohort, respectively. Copper-related Prognostic Signature (Copper-PSHC) was developed using differentially expressed CRGs with prognostic value. The hazard ratio (HR) and the area under the time-dependent receiver operating characteristic curve (AUC) during 3-year follow-up were utilized to evaluate the performance. Additionally, the Copper-PSHC was combined with age, sex, and cancer stage to construct a Copper-clinical-related Prognostic Signature (Copper-CPSHC), by multivariate Cox regression. We further explored the underlying mechanism of Copper-PSHC by analyzing the somatic mutation, functional enrichment, and tumor microenvironment. Potential drugs for the high-risk group were screened. Results: The Copper-PSHC was constructed with nine CRGs. Patients in the high-risk group demonstrated a significantly reduced overall survival (OS) (adjusted HR, 2.65 [95% CI, 1.83-3.84] and 3.30, [95% CI, 1.27-8.60] in the development and validation cohort, respectively). The Copper-PSHC achieved a 3-year AUC of 0.74 [95% CI, 0.67-0.82] and 0.71 [95% CI, 0.56-0.86] for OS in the development and validation cohort, respectively. Copper-CPSHC yield a 3-year AUC of 0.73 [95% CI, 0.66-0.80] and 0.72 [95% CI, 0.56-0.87] for OS in the development and validation cohort, respectively. Higher tumor mutation burden, downregulated metabolic processes, hypoxia status and infiltrated stroma cells were found for the high-risk group. Six small molecular drugs were screened for the treatment of the high-risk group. Conclusion: Copper-PSHC services as a promising tool to identify HCC with poor prognosis and to improve disease outcomes by providing potential clinical decision support in treatment.

Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States.

Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis. Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community.

Comparison of the prevalence of opioid use among U.S. adults with cardiac conditions before and during the COVID-19 pandemic.

Limited data are available on the prevalence of prescription opioid use among patients with cardiac conditions who were exposed to increased risks of cardiac events including myocardial failure and cardiac arrest. According to the U.S. National Health Interview Survey, we evaluated the prevalence of opioid use in patients with cardiac conditions who reported prescription opioid use in the past 12 months and 3 months in 2019 and 2020, respectively, and further estimated the prevalence of opioid use for acute pain or chronic pain. We also analyzed the stratified prevalence by demographical characteristics. Our results showed that there was no statistically significant change in the prevalence of opioid use in the past 12 months (26.5% in 2019 vs. 25.7% in 2020) or the past 3 months (66.6% in 2019 vs. 62.5% in 2020) before and during the COVID-19 pandemic. However, there was a significant decline in the prevalence of opioid use for acute pain, from 64.2% (95% confidence interval [CI] 57.6% to 70.3%) in 2019 to 49.6% (95% CI 40.1% to 59.0%) in 2020 (P = 0.012), particularly in the subgroups of men, non-Hispanic white people, adults with education below high school, those with an income-to-poverty ratio ranging from 1.0 to 1.9, and those covered with health insurance. Our findings suggest that monitoring opioid use in the era of living with COVID-19 is important, which will help inform healthcare providers to develop care strategies to reduce health loss for vulnerable individuals.

Effect and Mechanism of Soluble Starch on Bovine Serum Albumin Cold-Set Gel Induced by Microbial Transglutaminase: A Significantly Improved Carrier for Active Substances.

Soluble starch (SS) could significantly accelerate the process of bovine serum albumin (BSA) cold-set gelation by glucono-δ-lactone (GDL) and microbial transglutaminase (MTGase) coupling inducers, and enhance the mechanical properties. Hardness, WHC, loss modulus (G″) and storage modulus (G') of the gel increased significantly, along with the addition of SS, and gelation time was also shortened from 41 min (SS free) to 9 min (containing 4.0% SS); the microstructure also became more and more dense. The results from FTIR, fluorescence quenching and circular dichroism (CD) suggested that SS could bind to BSA to form their composites, and the hydrogen bond was probably the dominant force. Moreover, the ability of SS to bind the original free water in BSA gel was relatively strong, thereby indirectly increasing the concentration of BSA and improving the texture properties of the gel. The acceleration of gelling could also be attributed to the fact that SS reduced the negative charge of BSA aggregates and further promoted the rapid formation of the gel. The embedding efficiency (EE) of quercetin in BSA-SS cold-set gel increased from 68.3% (SS free) to 87.45% (containing 4.0% SS), and a controlled-released effect was detected by simulated gastrointestinal digestion tests. The work could put forward new insights into protein gelation accelerated by polysaccharide, and provide a candidate for the structural design of new products in the food and pharmaceutical fields.

Incidence trends and disparities in Helicobacter pylori related malignancy among US adults, 2000-2019.

Background: Helicobacter pylori (H. pylori) is closely related to the carcinogenesis of gastric cancer (GC) and gastric non-Hodgkin lymphoma (NHL). However, the systemic trend analysis in H. pylori-related malignancy is limited. We aimed to determine the national incidence trend in non-cardia GC, cardia GC, and gastric NHL in the US during 2000-2019. Method: In this population-based study, we included 186,769 patients with a newly diagnosed H. pylori-related malignancy, including non-cardia GC, cardia GC, and gastric NHL from the Surveillance, Epidemiology, and End Results (SEER) Registry from January 1, 2000 to December 31, 2019. We determined the age-adjusted incidence of three H. pylori-related malignancies respectively. Average annual percentage change (AAPC) in 2000-2019 was calculated to describe the incidence trends. Analyses were stratified by sex, age, race and ethnicity, geographic location and SEER registries. We also determined the 5-year incidence (during 2015-2019) by SEER registries to examine the geographic variance. Results: The incidence in non-cardia GC and gastric NHL significantly decreased during 2000-2019, while the rate plateaued for cardia GC (AAPCs, -1.0% [95% CI, -1.1%-0.9%], -2.6% [95% CI, -2.9%-2.3%], and -0.2% [95% CI, -0.7%-0.3%], respectively). For non-cardia GC, the incidence significantly increased among individuals aged 20-64 years (AAPC, 0.8% [95% CI, 0.6-1.0%]). A relative slower decline in incidence was also observed for women (AAPC, -0.4% [95% CI, -0.6%-0.2%], P for interaction < 0.05). The incidence of cardia GC reduced dramatically among Hispanics (AAPC, -0.8% [95% CI, -1.4%-0.3%]), however it increased significantly among nonmetropolitan residents (AAPC, 0.8% [95% CI, 0.4-1.3%]). For gastric NHL, the decreasing incidence were significantly slower for those aged 20-64 years (AAPC, -1.5% [95% CI, -1.9-1.1%]) and Black individuals (AAPC, -1.3% [95% CI, -1.9-1.1%]). Additionally, the highest incidence was observed among Asian and the Black for non-cardia GC, while Whites had the highest incidence of cardia GC and Hispanics had the highest incidence of gastric NHL (incidence rate, 8.0, 8.0, 3.1, and 1.2, respectively) in 2019. Geographic variance in incidence rates and trends were observed for all three H. pylori-related malignancies. The geographic disparities were more pronounced for non-cardia GC, with the most rapid decline occurring in Hawaii (AAPC, -4.5% [95% CI, -5.5-3.6%]) and a constant trend in New York (AAPC 0.0% [95% CI, -0.4-0.4%]), the highest incidence in Alaska Natives, and the lowest incidence among Iowans (14.3 and 2.3, respectively). Conclusion: The incidence of H. pylori-related cancer declined dramatically in the US between 2000 and 2019, with the exception of cardia GC. For young people, a rising trend in non-cardia GC was noted. Existence of racial/ethnic difference and geographic diversity persists. More cost-effective strategies of detection and management for H. pylori are still in demand.

Excess deaths from Alzheimer's disease and Parkinson's disease during the COVID-19 pandemic in the USA.

BACKGROUND: COVID-19 pandemic has indirect impacts on patients with chronic medical conditions, which may increase mortality risks for various non-COVID-19 causes. This study updates excess death statistics for Alzheimer's disease (AD) and Parkinson's disease (PD) up to 2022 and evaluates their demographic and spatial disparities in the USA. METHODS: This is an ecological time-series analysis of AD and PD mortality in the USA from January 2018 to March 2022. Poisson log-linear regressions were utilised to fit the weekly death data. Excess deaths were calculated with the difference between the observed and expected deaths under a counterfactual scenario of pandemic absence. RESULTS: From March 2020 to March 2022, we observed 41,115 and 10,328 excess deaths for AD and PD, respectively. The largest percentage increases in excess AD and PD deaths were found in the initial pandemic wave. For people aged ≥85 years, excess mortalities of AD and PD (per million persons) were 3946.0 (95% confidence interval [CI]: 2954.3, 4892.3) and 624.3 (95% CI: 369.4, 862.5), which were about 23 and 9 times higher than those aged 55-84 years, respectively. Females had a three-time higher excess mortality of AD than males (182.6 vs. 67.7 per million persons). The non-Hispanic Black people experienced larger increases in AD or PD deaths (excess percentage: 31.8% for AD and 34.6% for PD) than the non-Hispanic White population (17.1% for AD and 14.7% for PD). CONCLUSION: Under the continuing threats of COVID-19, efforts should be made to optimise health care capacity for patients with AD and PD.

MRI-based texture analysis for differentiate between pediatric posterior fossa ependymoma type A and B.

PURPOSE: The aim of the study was to evaluate the feasibility of texture analysis in differentiating between posterior fossa ependymoma type A (PF-EPN-A) and type B (PF-EPN-B) among children. MATERIALS AND METHODS: Our retrospective study included 43 patients (37 PF-EPN-A and 6 PF-EPN-B) who were pathologically diagnosed with ependymomas in the posterior fossa. The texture features were extracted automatically from the volume of interests (VOIs), which were manually delineated on fluid-attenuated inversion recovery (FLAIR), contrast-enhanced T1-weighted (T1C), and diffusion-weighted imaging (DWI) MRI sequences. A receiver operating characteristic curve (ROC) was built to assess the diagnostic value of the texture parameters, and the prognostic value was evaluated by survival analysis. RESULTS: Texture parameter [Wavelet-LHH (H: High pass filter, L: Low pass. filter)_glcm (gray-level co-occurrence matrix)_Idn (Inverse difference normalized)] provides valuable information in distinguishing subgroups of ependymomas with higher specificity and positive predictive value (PPV). A total of 27 patients were divided into a high-risk group (IDN value＞0.916) and a low-risk group (IDN value＜0.916) with the most optimistic cut-off value (0.916). The Kaplan-Meier analysis of the survival curves showed significantly longer disease-free survival for low-risk groups compared to high-risk groups [hazard ratio (HR): 0.28, 95% confidence interval (CI): 0.11-0.69; p = 0.017]. CONCLUSION: Our results suggested that the texture parameters based on DWI images can be used to differentiate PF-EPN-A from PF-EPN-B. Texture analysis could be used as a noninvasive tool in distinguishing subgroup pediatric posterior fossa ependymomas and provide reliable prognostic information upon the verification of its reproducibility and feasibility by further studies.