Clinical Effects of Ultrasound-Guided Acupotomy in Knee Osteoarthritis Treatment.

The protocol presented here demonstrates the operation method of ultrasound-guided acupotomy for knee osteoarthritis (KOA), including patient recruitment, preoperative preparation, manual operation, and postoperative care. The purpose of this protocol is to relieve pain and improve knee function in patients with KOA. A total of 60 patients with KOA admitted between June 2022 and June 2023 were treated with ultrasound-guided acupotomy. Pathological changes and knee function scores were compared before and after the treatment. After 1 week of treatment, the synovial thickness of the suprapatellar bursae was significantly lesser than before treatment (p < 0.05), the Hospital for Special Surgery Knee Score (HSS) was significantly higher than before treatment (p < 0.05), the Visual analogue scale (VAS) was significantly lower than those of the control group (p < 0.05) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were significantly lower than those of the control group (p < 0.05). Therefore, ultrasound-guided acupotomy for the treatment of KOA can reduce synovial thickness, relieve pain, improve knee joint function, and have a remarkable curative effect.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Foreground Capture Feature Pyramid Network-Oriented Object Detection in Complex Backgrounds.

Feature pyramids are widely adopted in visual detection models for capturing multiscale features of objects. However, the utilization of feature pyramids in practical object detection tasks is prone to complex background interference, resulting in suboptimal capture of discriminative multiscale foreground semantic features. In this article, a foreground capture feature pyramid network (FCFPN) for multiscale object detection is proposed, to address the problem of inadequate feature learning in complex backgrounds. FCFPN consists of a foreground dual attention (FDA) module and a pathway aggregation (PA) structure. Specifically, the FDA mechanism activates top-down foreground channel responses and lateral spatial foreground location features, so that channel and spatial foreground features are adequately captured. Then, the PA module adaptively learns the fusion weights of multiscale features at different levels of the feature pyramid, which enhances the complementarity of semantic information between different levels of the foreground feature maps. Since the fusion weights are learned adaptively based on different pyramid levels, the detection model accordingly retains the gained information of feature sizes and suppresses the conflicting information. The evaluations on public datasets and the self-built complex background dataset demonstrate that the detection average precision (AP) and the feature learning performance of the proposed method are superior compared with other FPNs, which proves the effectiveness of the proposed FCFPN.

Unmasking the sky: high-resolution PM2.5 prediction in Texas using machine learning techniques.

BACKGROUND: Although PM2.5 (fine particulate matter with an aerodynamic diameter less than 2.5 µm) is an air pollutant of great concern in Texas, limited regulatory monitors pose a significant challenge for decision-making and environmental studies. OBJECTIVE: This study aimed to predict PM2.5 concentrations at a fine spatial scale on a daily basis by using novel machine learning approaches and incorporating satellite-derived Aerosol Optical Depth (AOD) and a variety of weather and land use variables. METHODS: We compiled a comprehensive dataset in Texas from 2013 to 2017, including ground-level PM2.5 concentrations from regulatory monitors; AOD values at 1-km resolution based on images retrieved from the MODIS satellite; and weather, land-use, population density, among others. We built predictive models for each year separately to estimate PM2.5 concentrations using two machine learning approaches called gradient boosted trees and random forest. We evaluated the model prediction performance using in-sample and out-of-sample validations. RESULTS: Our predictive models demonstrate excellent in-sample model performance, as indicated by high R2 values generated from the gradient boosting models (0.94-0.97) and random forest models (0.81-0.90). However, the out-of-sample R2 values fall within a range of 0.52-0.75 for gradient boosting models and 0.44-0.69 for random forest models. Model performance varies slightly across years. A generally decreasing trend in predicted PM2.5 concentrations over time is observed in Eastern Texas. IMPACT STATEMENT: We utilized machine learning approaches to predict PM2.5 levels in Texas. Both gradient boosting and random forest models perform well. Gradient boosting models perform slightly better than random forest models. Our models showed excellent in-sample prediction performance (R2 > 0.9).

A Retrospective Analysis of Azvudine in Patients with COVID-19 and Pre-existing Cancer.

Objectives: Azvudine has been recommended as a potential treatment for the recently discovered Coronavirus disease (COVID-19) in 2019. However, the effectiveness of Azvudine in individuals who have both COVID-19 and pre-existing cancer remains uncertain. Consequently, we undertook a retrospective analysis to evaluate the clinical efficacy of Azvudine therapy in hospitalized patients with COVID-19 and pre-existing cancer. Methods: This is a single-center retrospective analysis of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, selected from patients admitted to a specialist oncology hospital between June 1, 2022 to June 31, 2023 with positive RT-PCR and pre-existing cancer. After exclusion and propensity score matching, patients in the test group treated with Azvudine and control patients treated with standard antiviral therapy were included. The primary outcome is the interval time from the first dose of Azvudine to the attainment of the first negative result for nucleic acid. Secondary outcomes included the rate of nucleic acid conversion, the duration of hospitalization, and the admission to the intensive care unit (ICU). Cox proportional hazards models were used to analyze the hazard ratio (HR) of event outcomes and to assess whether cancer types and Azvudine treatment will affect the course of COVID-19, specifically the time it takes for primary symptoms to alleviate. Results: In this study, a total of 84 patients were included for analysis. Among them, 42 patients received Azvudine treatment after hospitalization, and the rest were treated with standard antiviral therapy. The results expressed that the time taken for the first negative nucleic acid test was significantly shorter in the Azvudine group compared to the control group [5 (IQR3-7) d vs 12 (IQR9-15) d], p<0.0001. This difference was statistically significant. Furthermore, a multivariate COX analysis indicated that Azvudine treatment could effectively reduce the time required for nucleic acid conversion in cancer patients (HR 1.994, 95% CI 1.064-3.736, p=0.031). And the type of cancer also had an impact on the course of COVID-19 in patients. (HR 3.442, 95%CI 1.214-9.756, p=0.020; HR 3.246, 95% CI 1.925-7.209, p=0.036). Conclusion: Azvudine was correlated with a reduced duration for achieving nucleic acid conversion in individuals diagnosed with cancer. And different types of cancer have a certain impact on the course of COVID-19 for patients.

Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Biomarker Changes during 20 Years Preceding Alzheimer's Disease.

BACKGROUND: Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies. METHODS: We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups. RESULTS: The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aß)42, 18 years; the ratio of Aß42 to Aß40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed. CONCLUSIONS: In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).

ACE2 Regulates Glycolipid Metabolism in Multiple Tissues.

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotensin system (RAS), which was once considered a linear cascade. ACE2 mainly functions to convert AngiotensinⅡ (AngⅡ) to Angiotensin1-7 (A1-7). The biologically active product A1-7 then binds to the Mas receptor to form the ACE2/A1-7/Mas axis. In contrast to classic RAS, which plays a decisive role in regulation, the ACE2/A1-7/Mas axis effectively counteracts vasoconstriction, the inflammatory response, oxidative stress, and cell proliferation, and is thus a negative regulator of the RAS. ACE2 also functions as a chaperone to regulate intestinal amino acid uptake. It is widely expressed in the lungs, cardiovascular system, gastrointestinal tract, kidney, pancreas and adipose tissue. Previous studies have confirmed that ACE2 has a vital role in homeostasis. ACE2 also has a variety of other biological activities and plays a critical role in Type 2 diabetes (T2DM) and its complications, especially diabetic nephropathy, obesity, dyslipidemia and other diseases. In this review, we summarize the latest research on the regulation of glucose and lipid metabolism by ACE2 in different organs. Our focus was particularly on T2DM, with the aim of providing new clinical ideas for the use of ACE2 as an effective target in the prevention and treatment of metabolic diseases.

The Time-Dependent Association Between Irritable Bowel Syndrome and All-Cause and Cause-Specific Mortality: A Prospective Cohort Study Within the UK Biobank.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank. METHODS: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 years). RESULTS: A total of 25,697 participants (5.1%) had a history of IBS at baseline. After a median follow-up of 13.7 years, a total of 44,499 deaths occurred. Having an IBS diagnosis was strongly associated with lower risks of all-cause (HR = 0.70, 95% CI = 0.62-0.78) and all-cancer (HR = 0.69, 95% CI = 0.60-0.79) mortality in the first 5 years of follow-up. These associations were attenuated over follow-up, but even after 10 years of follow-up, associations remained inverse (all-cause: HR = 0.89, 95% CI = 0.84-0.96; all-cancer: HR = 0.87, 95% CI = 0.78-0.97) after full adjustment. Individuals with IBS had decreased risk of mortality from breast, prostate, and colorectal cancers in some of the follow-up time categories. DISCUSSION: We found that earlier during follow-up, having diagnosed IBS was associated with lower mortality risk, and the association attenuated over time. Additional studies to understand whether specific factors, such as lifestyle and healthcare access, explain the inverse association between IBS and mortality are needed.

Modulating a prebiotic food source influences inflammation and immune-regulating gut microbes and metabolites: insights from the BE GONE trial.

BACKGROUND: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention. METHODS: This low-risk, non-invasive dietary intervention trial was conducted at MD Anderson Cancer Center (Houston, TX, USA). Following a 4-week equilibration, patients were randomized to continue their usual diet without beans (control) or to add a daily cup of study beans to their usual diet (intervention) with immediate crossover at 8-weeks. Stool and fasting blood were collected every 4 weeks to assess the primary outcome of intra and inter-individual changes in the gut microbiome and in circulating markers and metabolites within 8 weeks. This study was registered on ClinicalTrials.gov as NCT02843425, recruitment is complete and long-term follow-up continues. FINDINGS: Of the 55 patients randomized by intervention sequence, 87% completed the 16-week trial, demonstrating an increase on-intervention in diversity [n = 48; linear mixed effect and 95% CI for inverse Simpson index: 0.16 (0.02, 0.30); p = 0.02] and shifts in multiple bacteria indicative of prebiotic efficacy, including increased Faecalibacterium, Eubacterium and Bifidobacterium (all p < 0.05). The circulating metabolome showed parallel shifts in nutrient and microbiome-derived metabolites, including increased pipecolic acid and decreased indole (all p < 0.002) that regressed upon returning to the usual diet. No significant changes were observed in circulating lipoproteins within 8 weeks; however, proteomic biomarkers of intestinal and systemic inflammatory response, fibroblast-growth factor-19 increased, and interleukin-10 receptor-α decreased (p = 0.01). INTERPRETATION: These findings underscore the prebiotic and potential therapeutic role of beans to enhance the gut microbiome and to regulate host markers associated with metabolic obesity and colorectal cancer, while further emphasizing the need for consistent and sustainable dietary adjustments in high-risk patients. FUNDING: This study was funded by the American Cancer Society.

The association between inflammatory bowel disease and all-cause and cause-specific mortality in the UK Biobank.

PURPOSE: Inflammatory bowel disease (IBD) has a rising global prevalence. However, the understanding of its impact on mortality remains inconsistent so we explored the association between IBD and all-cause and cause-specific mortality. METHODS: This study included 502,369 participants from the UK Biobank, a large, population-based, prospective cohort study with mortality data through 2022. IBD was defined by baseline self-report or from primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality in multivariable Cox proportional hazards regression models. RESULTS: A total of 5799 (1.2%) participants had a history of IBD at baseline. After a median follow-up of 13.7 years, 44,499 deaths occurred. Having IBD was associated with an increased risk of death from all causes (HR = 1.16, 95% CI = 1.07-1.24) and cancer (HR = 1.16, 95% CI = 1.05-1.30), particularly colorectal cancer (CRC) (HR = 1.56, 95% CI = 1.17-2.09). We observed elevated breast cancer mortality rates for individuals with Crohn's disease, and increased CRC mortality rates for individuals with ulcerative colitis. In stratified analyses of IBD and all-cause mortality, mortality risk differed by individuals' duration of IBD, age at IBD diagnosis, body mass index (BMI) (PHeterogeneity = 0.03) and smoking status (PHeterogeneity = 0.01). Positive associations between IBD and all-cause mortality were detected in individuals diagnosed with IBD for 10 years or longer, those diagnosed before the age of 50, all BMI subgroups except obese individuals, and in never or current, but not former smokers. CONCLUSIONS: We found that having IBD was associated with increased risks of mortality from all causes, all cancers, and CRC. This underscores the importance of enhanced patient management strategies and targeted prevention efforts in individuals with IBD.

The Relationship Between Physical Activity and All-Cause Mortality Among Older Adults - China, 1998-2018.

What is already known about this topic?: Previous research indicates that non-occupational physical activity can reduce mortality risk. Nevertheless, the relationship between occupational physical activity and health improvements has not been consistently established. What is added by this report?: The study found that regular exercise and leisure activities reduced the risk of all-cause mortality. However, the combination of exercise and leisure activities demonstrated more substantial benefits. Additionally, no meaningful association was identified between physical work and mortality risk within the older population. What are the implications for public health practice?: It may be beneficial to encourage older adults to engage in regular exercise and to partake actively in leisure activities. Combining these two elements might yield greater benefits than regular exercise alone.

Spatial oblivion channel attention targeting intra-class diversity feature learning.

Convolutional neural networks (CNNs) have successfully driven many visual recognition tasks including image classification. However, when dealing with classification tasks with intra-class sample style diversity, the network tends to be disturbed by more diverse features, resulting in limited feature learning. In this article, a spatial oblivion channel attention (SOCA) for intra-class diversity feature learning is proposed. Specifically, SOCA performs spatial structure oblivion in a progressive regularization for each channel after convolution, so that the network is not restricted to a limited feature learning, and pays attention to more regionally detailed features. Further, SOCA reassigns channel weights in the progressively oblivious feature space from top to bottom along the channel direction, to ensure the network learns more image details in an orderly manner while not falling into feature redundancy. Experiments are conducted on the standard classification dataset CIFAR-10/100 and two garbage datasets with intra-class diverse styles. SOCA improves SqueezeNet, MobileNet, BN-VGG-19, Inception and ResNet-50 in classification accuracy by 1.31%, 1.18%, 1.57%, 2.09% and 2.27% on average, respectively. The feasibility and effectiveness of intra-class diversity feature learning in SOCA-enhanced networks are verified. Besides, the class activation map shows that more local detail feature regions are activated by adding the SOCA module, which also demonstrates the interpretability of the method for intra-class diversity feature learning.

Characteristics and Mechanism of Acute Ischemic Stroke in NAVF Patients With Prior Oral Anticoagulant Therapy.

OBJECTIVES: We aimed to analyze the characteristics and mechanisms of acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (NVAF) who received prior anticoagulant therapy. METHODS: We retrospectively analyzed the data of patients with NVAF and AIS between January 2016 and December 2021. Patients were divided into non-anticoagulant, adequate anticoagulant, and insufficient anticoagulant groups according to their prior anticoagulant status. Patients with prior anticoagulant therapy were further divided into warfarin and direct oral anticoagulant groups. RESULTS: A total of 749 patients (661 without anticoagulants, 33 with adequate anticoagulants, and 55 with insufficient anticoagulants) were included. Patients with adequate anticoagulant had a milder National Institute of Health Stroke Scale at presentation ( P =0.001) and discharge ( P =0.003), a higher proportion of Modified Rankin Scale (mRS) ≤2 at discharge ( P =0.011), and lower rates of massive infarction ( P =0.008) than patients without anticoagulant. Compared with the non-anticoagulant group, the proportion of intravenous thrombolysis was significantly lower in the adequate anticoagulant ( P <0.001) and insufficient anticoagulant ( P =0.009) groups. Patients in the adequate anticoagulant group had higher rates of responsible cerebral atherosclerotic stenosis ( P =0.001 and 0.006, respectively) and competing large artery atherosclerotic mechanisms ( P =0.006 and 0.009, respectively) than those in the other 2 groups. Compared with warfarin, direct oral anticoagulant was associated with higher rates of Modified Rankin Scale ≤2 at discharge ( P =0.003). CONCLUSIONS: Adequate anticoagulant therapy may be associated with milder stroke severity and better outcomes at discharge in patients with NVAF. Competing large artery atherosclerotic mechanisms may be associated with anticoagulant failure in patients with NAVF with prior adequate anticoagulant therapy.

Associations of residential greenness and ambient air pollution with overweight and obesity in older adults.

OBJECTIVE: This study aimed to examine the impact of greenness and fine particulate matter <2.5 µm (PM2.5 ) on overweight/obesity among older adults in China. METHODS: A total of 21,355 participants aged ≥65 years were included from the Chinese Longitudinal Healthy Longevity Survey between 2000 and 2018. Normalized difference vegetation index (NDVI) with a radius of 250 m and PM2.5 in a 1 × 1-km grid resolution were calculated around each participant's residence. Cox proportional hazards models were used to estimate the effects of NDVI and PM2.5 on overweight/obesity. Interaction and mediation analyses were conducted to explore combined effects. RESULTS: The study observed 1895 incident cases of overweight/obesity over 109,566 person-years. For every 0.1-unit increase in NDVI the hazard ratio of overweight/obesity was 0.91 (95% CI: 0.88-0.95), and for every 10-µg/m3 increase in PM2.5 the hazard ratio was 1.11 (95% CI: 1.07-1.14). The effect of NDVI on overweight/obesity was partially mediated by PM2.5 , with a relative mediation proportion of 20.10% (95% CI: 1.63%-38.57%). CONCLUSIONS: Greenness exposure appears to lower the risk of overweight/obesity in older adults in China, whereas PM2.5 , acting as a mediator, partly mediated this protective effect.

A blood-based composite panel that screens Alzheimer's disease.

BACKGROUND: Blood tests would be much easier to implement in the clinical diagnosis of Alzheimer's disease (AD) as minimally invasive measurements. Multiple inspection technologies promoted AD-associated blood biomarkers' exploration. However, there was a lack of further screening and validation for these explored blood-based biomarkers. We selected four potential biomarkers to explore their plasma levels in AD and amnestic mild cognitive impairment (aMCI) and developed a composite panel for AD and aMCI screening. METHOD: The plasma concentrations of soluble low-density lipoprotein receptor-associated protein 1 (sLRP1), Gelsolin (GSN), Kallikrein 4 (KLK4) and Caspase 3 were measured in the discovery and validation cohort. The receiver operating characteristic (ROC) curve was generated to assess the classification panel with the area under the curve (AUC). RESULTS: A total of 233 participants (26 CN, 27 aMCI, and 26 AD in the discovery cohort, and 51 CN, 50 aMCI, and 53 AD in the validation cohort) with complete data were included in the study. The plasma concentrations of sLRP1 and Caspase 3 were significantly decreased in AD and aMCI when compared with those in the CN group. Compared with the CN group, the concentrations of KLK4 and GSN were increased in AD, but not in MCI. Interestingly, one of four proteins, sLRP1 in plasma level was higher in Apolipoprotein E (APOE) ε4 non-carriers than that in APOE ε4 carriers, especially among CN and MCI. No significant difference was found between females and males in the plasma levels of four proteins. The composite panel is based on four blood biomarkers accurately classifying AD from CN (AUC = 0.903-0.928), and MCI from CN (AUC = 0.846-0.865). Moreover, dynamic changes in the plasma levels of four proteins exhibited a significant correlation with cognitive assessment. CONCLUSIONS: Altogether, these findings indicate that the plasma levels of sLRP1, KLK4, GSN and Caspase 3 changed with the progression of AD. And their combination could be used to develop a panel for classifying AD and aMCI with high accuracy, which would provide an alternative approach for developing a blood-based test for AD and aMCI screening.

Unveiling and regulating the solvent-polarity-associated excited state intramolecular double proton transfer behavior for 1-bis(benzothiazolyl)naphthalene-diol fluorophore.

Inspired by the regulatory luminescence properties of HBT derivatives, in this work, we mainly conduct a detailed theoretical exploration on the photoinduced excitation behavior of a novel di-proton-transfer type HBT derivative 1-bis(benzothiazolyl)naphthalene-diol (1-BBTND). The intramolecular double hydrogen bonding interaction and the excited state intramolecular double proton transfer (ESDPT) behavior of 1-BBTND fluorophore are investigated in combination with different polar solvent environments. From the structural changes and charge recombination induced by photoexcitation, we can conclude that strong polar solvent environment promotes the excited state dynamical reaction for 1-BBTND compound. By constructing potential energy surfaces (PESs) in S0 and S1 states, we clarify that 1-BBTND fluorophore should undergo a stepwise ESDPT reaction after photoexcitation. Combined with the size of potential energy barriers along with reaction paths in different solvents, we finally propose a new solvent-polarity-dependent stepwise ESDPT for 1-BBTND fluorophore.

High prevalence and genomic characteristics of carbapenem-resistant Enterobacteriaceae and colistin-resistant Enterobacteriaceae from large-scale rivers in China.

The widespread presence of carbapenem-resistant Enterobacteriaceae (CRE) and mcr-positive Escherichia coli (MCREC) poses a huge threat to both animal and human health. River water environments are vital reservoirs of antibiotic resistance genes, however, the prevalence and characteristics of CRE and MCREC from large-scale rivers in China have not been reported. In the current study, we sampled 86 rivers from four cities in Shandong Province, China in 2021 and analyzed the prevalence of CRE and MCREC. The blaNDM/blaKPC-2/mcr-positive isolates were characterized with methods including PCR, antimicrobial susceptibility testing, conjugation, replicon typing, whole-genome sequencing and phylogenetic analysis. We found that the prevalence of CRE and MCREC in 86 rivers was 16.3% (14/86) and 27.9% (24/86), respectively and eight rivers carried both mcr-1 and blaNDM/blaKPC-2. A total of 48 Enterobacteriaceae isolates (10 ST11 Klebsiella pneumoniae with blaKPC-2, 12 blaNDM-positive E. coli and 26 MCREC carrying only mcr-1) were obtained in this study and 47 displayed multidrug resistance (MDR). Notably, 10 of the 12 blaNDM-positive E. coli isolates also harbored the mcr-1 gene. The blaKPC-2 gene was located within mobile element ISKpn27-blaKPC-2-ISKpn6 on novel F33:A-:B- non-conjugative MDR plasmids in ST11 K. pneumoniae. The dissemination of blaNDM was mediated by transferable MDR IncB/O plasmids or IncX3 plasmids while mcr-1 was primarily disseminated by highly similar IncI2 plasmids. Notably, these waterborne IncB/O, IncX3 and IncI2 plasmids were all highly similar to previously identified plasmids from animal and human isolates. A phylogenomic analysis revealed that the CRE and MCREC isolates from water environments might be derived from animals and trigger infections in humans. The high prevalence of CRE and MCREC in large-scale environmental rivers is alarming and needs sustained surveillance due to the potential risk for transmission to humans via the food chain (irrigation) or direct contact.

Effects of resistance and balance exercises for athletic ability and quality of life in people with osteoporotic vertebral fracture: Systematic review and meta-analysis of randomized control trials.

Purpose: This study aimed to use meta-analysis to determine the impact of resistance and balance training on athletic ability and quality of life for patients with osteoporotic vertebral fracture (OVF). Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria for systematic reviews and meta-analyzes. The PubMed, Web of science, Cochrane, Embase, and CNKI databases were searched for randomized controlled trials (RCTs) up to September 2022. The search strategy was related to the intervention measures, population, and results, and was structured around the search terms: "Exercise," "Osteoporotic vertebral fracture," and "activities of function." Two reviewers strictly implemented the inclusion and exclusion criteria. Subgroup analyzes of age and training duration were performed for the main outcomes. Results: We included 12 RCTs (n = 1,289) of resistance and balance training in patients with OVF. Compared with controls, the intervention group showed improvements on the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis, visual analog pain scale, Timed Up and Go, falls efficacy scale international (FES-I), kyphosis, and functional reach. On subgroup analysis, the effect was more significant when training continued >10 weeks. Conclusion: Resistance and balance exercise training improved function and balance, and reduced fall risk in patients with OVF. We recommend resistance and balance training for at least 10 weeks. Future multicenter, large sample trials are needed for more reliable conclusions.

The association between poor oral health and risk of breast cancer in the UK Biobank.

PURPOSE: Specific oral health conditions may be risk factors for breast cancer. This study aimed to investigate the associations of oral health conditions with breast cancer risk. METHODS: A total of 234,363 women from the UK Biobank prospective cohort were included in this study. We examined the association of self-reported painful/bleeding gums, loose teeth, mouth ulcers, toothache, and use of dentures with the risk of breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for multiple confounders. RESULTS: No associations of self-reported painful/bleeding gums (HR = 1.04, 95% CI 0.98-1.10), loose teeth (HR = 0.92, 95% CI 0.82-1.02), mouth ulcers (HR = 0.99, 95% CI 0.93-1.06), toothache (HR = 1.03, 95% CI 0.92-1.14), or denture use (HR = 0.96, 95% CI 0.91-1.02) with breast cancer risk were found. No statistical heterogeneity was observed in analyses stratified by baseline smoking and menopausal status. CONCLUSION: We observed no association between self-reported oral health conditions with the risk of breast cancer. Additional research with clinical examinations or oral health biomarkers in diverse populations is warranted.