Associations of screen-based sedentary activities with all cause dementia, Alzheimer's disease, vascular dementia: a longitudinal study based on 462,524 participants from the UK Biobank.

BACKGROUND: Current drug treatments for dementia aren't effective. Studying gene-environment interactions can help develop personalized early intervention strategies for Alzheimer's disease (AD). However, no studies have examined the relationship between screen-based sedentary activities and genetic susceptibility to AD risk, and further understanding of the causal relationship is also crucial. METHODS: This study included 462,524 participants from the UK Biobank with a follow-up of 13.6 years. Participants' screen-based sedentary activities time was categorized into three groups based on recorded time: ≥ 4 h/day, 2-3 h/day, and ≤ 1 h/day. Cox proportional risk models were used to analyze the association between computer use/TV viewing groups and the risk of all-cause dementia, AD and vascular dementia (VD). Generalized linear model (GLM) were used to examine the relationship between screen-based sedentary activities and brain structure. Bidirectional Mendelian randomization (MR) was used to validate the causal relationship between TV viewing and AD. RESULTS: Compared to TV viewing ≤ 1 h/day, 1)TV viewing 2-3 h/day was correlated with a higher risk of all-cause dementia (HR = 1.09, 95% CI:1.01-1.18, P < 0.05), and TV viewing ≥ 4 h/day was associated with a higher risk of all-cause dementia (HR = 1.29, 95% CI: 1.19-1.40, P < 0.001), AD (HR = 1.25, 95% CI:1.1-1.42, P < 0.001), and VD (HR = 1.24, 95% CI: 1.04-1.49, P < 0.05); 2) TV viewing ≥ 4 h/day was correlated with a higher AD risk at intermediate (HR = 1.34, 95% CI: 1.03-1.75, P < 0.001) and high AD genetic risk score (AD-GRS) (HR = 2.18, 95% CI: 1.65-2.87, P < 0.001);3) TV viewing 2-3 h/day [ß = (-94.8), 95% CI: (-37.9) -(-151.7), P < 0.01] and TV viewing ≥ 4 h/day [ß = (-92.94), 95% CI: (-17.42) -(-168.46), P < 0.05] were correlated with a less hippocampus volume. In addition, a causal effect of TV viewing times was observed on AD analyzed using MR Egger (OR = 5.618, 95%CI:1.502-21.013, P < 0.05). CONCLUSIONS: There was a causal effect between TV viewing time and AD analyzed using bidirectional MR, and more TV viewing time exposure was correlated with a higher AD risk. Therefore, it is recommended that people with intermediate and high AD-GRS should control their TV viewing time to be less than 4 h/ day or even less than 1 h/day.

[Platycladi Semen oil ameliorates Aß_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota].

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aß_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aß_(25-35), 200 µmol·L~(-1), 0.15 µL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aß_(1-42)/Aß_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aß_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aß_(1-42)/Aß_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aß_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

Recent Estimates and Predictions of 5-Year Survival in Patients with Gastric Cancer: A Model-Based Period Analysis.

BACKGROUND: The overall incidence and mortality of gastric cancer have steadily declined in the United States over the past few decades, but it is still a serious disease burden for patients. Therefore, it is of great significance to evaluate the latest survival rate of gastric cancer. METHODS: Based on the Surveillance, Epidemiology, and End Results database, this study analyzed the age-standardized relative survival rates and survival trends of gastric cancer cases in 2007-2011 and 2012-2016 using period analysis, and the survival rate 2017-2021 was predicted using a generalized linear model based on the period analysis. RESULTS: During 2007-2016, the 5-year relative survival rate of patients with gastric cancer continued to rise, and the same trend was observed in 2017-2021. The 5-year overall age-standardized relative survival rates in 2007-2011, 2012-2016, and 2017-2021 were 38.3%, 40.6%, and 42.9%, respectively. However, despite these favorable trends, the overall relative survival of patients with gastric cancer remains at a low level. There were significant differences in the relative survival rates of patients with gastric cancer in terms of age, sex, race, primary site, stage, and socioeconomic status. Notably, the survival rate of patients with distant-stage gastric cancer remains very low (10%). CONCLUSION: We found that the survival rate of patients with gastric cancer showed different degrees of improvement in each subgroup. However, the overall relative survival rate of patients with gastric cancer remains low. Analyzing the changes of patients with gastric cancer in the last 10 years will be helpful in predicting the changing trend of cancer in the future. It also provides a scientific basis for relevant departments to formulate effective tumor prevention and control measures.

Influence of ambulatory blood pressure-related indicators within 24 h on in-hospital death in sepsis patients.

Background: Sepsis is a serious public health problem worldwide. Blood pressure is one of the indicators that is closely monitored in intensive-care units, and it reflects complex interactions between the internal cardiovascular control mechanism and the external environment. We aimed to determine the impact of indicators related to the ambulatory blood pressure on the prognosis of sepsis patients. Methods: This retrospective study was based on the Medical Information Mart for Intensive Care IV database. Relevant information about sepsis patients was extracted according to specific inclusion and exclusion criteria. Examined parameters included the average blood pressure, blood pressure variability (BPV), and circadian rhythm, and the study outcome was in-hospital death. We investigated the effects of these indicators on the risk of in-hospital death among sepsis patients using Cox proportional-hazards models, restricted cubic splines analysis, and subgroup analysis. Results: This study enrolled 10,316 sepsis patients, among whom 2,117 died during hospitalization. All parameters except the nighttime variation coefficient of the diastolic blood pressure (DBP) were associated with in-hospital death of sepsis patients. All parameters except for fluctuations in DBP exhibited nonlinear correlations with the outcome. The subgroup analysis revealed that some of the examined parameters were associated with in-hospital death only in certain subgroups. Conclusion: Indicators related to the ambulatory blood pressure within 24 h are related to the prognosis of sepsis patients. When treating sepsis, in addition to blood pressure, attention should also be paid to BPV and the circadian rhythm in order to improve the prognosis and the survival rate.

Deep transfer learning to quantify pleural effusion severity in chest X-rays.

PURPOSE: The detection of pleural effusion in chest radiography is crucial for doctors to make timely treatment decisions for patients with chronic obstructive pulmonary disease. We used the MIMIC-CXR database to develop a deep learning model to quantify pleural effusion severity in chest radiographs. METHODS: The Medical Information Mart for Intensive Care Chest X-ray (MIMIC-CXR) dataset was divided into patients 'with' or 'without' chronic obstructive pulmonary disease (COPD). The label of pleural effusion severity was obtained from the extracted COPD radiology reports and classified into four categories: no effusion, small effusion, moderate effusion, and large effusion. A total of 200 datasets were randomly sampled to manually check each item and determine whether the tags are correct. A professional doctor re-tagged these items as a verification cohort without knowing their previous tags. The learning models include eight common network structures including Resnet, DenseNet, and GoogleNET. Three data processing methods (no sampling, downsampling, and upsampling) and two loss algorithms (focal loss and cross-entropy loss) were used for unbalanced data. The Neural Network Intelligence tool was applied to train the model. Receiver operating characteristic curves, Area under the curve, and confusion matrix were employed to evaluate the model results. Grad-CAM was used for model interpretation. RESULTS: Among the 8533 patients, 15,620 chest X-rays with clearly marked pleural effusion severity were obtained (no effusion, 5685; small effusion, 4877; moderate effusion, 3657; and large effusion, 1401). The error rate of the manual check label was 6.5%, and the error rate of the doctor's relabeling was 11.0%. The highest accuracy rate of the optimized model was 73.07. The micro-average AUCs of the testing and validation cohorts was 0.89 and 0.90, respectively, and their macro-average AUCs were 0.86 and 0.89, respectively. The AUC of the distinguishing results of each class and the other three classes were 0.95 and 0.94, 0.76 and 0.83, 0.85 and 0.83, and 0.87 and 0.93. CONCLUSION: The deep transfer learning model can grade the severity of pleural effusion.

A Novel Risk-Prediction Scoring System for Sepsis among Patients with Acute Pancreatitis: A Retrospective Analysis of a Large Clinical Database.

Background: The prognosis is poor when acute pancreatitis (AP) progresses to sepsis; therefore, it is necessary to accurately predict the probability of sepsis and develop a personalized treatment plan to reduce the disease burden of AP patients. Methods: A total of 1295 patients with AP and 43 variables were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV database. The included patients were randomly assigned to the training set and to the validation set at a ratio of 7 : 3. The chi-square test or Fisher's exact test was used to test the distribution of categorical variables, and Student's t-test was used for continuous variables. Multivariate logistic regression was used to establish a prognostic model for predicting the occurrence of sepsis in AP patients. The indicators to verify the overall performance of the model included the area under the receiver operating characteristic curve (AUC), calibration curves, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results: The multifactor analysis results showed that temperature, phosphate, calcium, lactate, the mean blood pressure (MBP), urinary output, Glasgow Coma Scale (GCS), Charlson Comorbidity Index (CCI), sodium, platelet count, and albumin were independent risk factors. All of the indicators proved that the prediction performance and clinical profitability of the newly established nomogram were better than those of other common indicators (including SIRS, BISAP, SOFA, and qSOFA). Conclusions: The new risk-prediction system that was established in this research can accurately predict the probability of sepsis in patients with acute pancreatitis, and this helps clinicians formulate personalized treatment plans for patients. The new model can reduce the disease burden of patients and can contribute to the reasonable allocation of medical resources, which is significant for tertiary prevention.

The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells.

BACKGROUND: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). METHODS: A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines. RESULTS: Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) decreased. CONCLUSIONS: The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression.

A ratiometric electrochemical biosensor based on ARGET ATRP for detection of HER2 gene.

Human epidermal growth factor receptor 2 (HER2), a common proto-oncogene, is overexpressed in a subset of breast cancer patients. It is essential to track HER2 expression for early breast cancer diagnosis. Herein, a ratiometric electrochemical biosensor for detection of HER2 based on activators generated by electron transfer for atom transfer radical polymerisation (AGET ATRP) and hairpin DNA was developed. Specifically, hairpin DNA was first self-assembled on the gold electrode by Au-S bond. Upon capturing HER2, the stem-loop structure of hairpin DNA was unfolded, the signal value of methylene blue (MB) decreased as it moved away from the electrode surface. cDNA was linked with HER2 by complementary base pairing to introduce amino group. Then, the initiator 2-bromo-2-methylpropionic acid (BMP) were connected to the amino group on the cDNA to activate ARGET ATRP. The detection performance of biosensors for HER2 was explored by the ratio signal between two signal molecules. Under optimal conditions, this ratiometric electrochemical biosensor shows good selectivity and stability with a wide detection range of 1-1 × 106 pM and a detection limit of 78.47 fM. Furthermore, the biosensor exhibits satisfactory anti-interference ability due to the hairpin DNA and dual signal system, and has promising application prospects in the detection of other DNA disease markers.

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016.

OBJECTIVE: To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers). DESIGN: Cross-sectional analysis. SETTING: US National Health and Nutrition Examination Survey, 2013-2016. OUTCOME MEASURES: Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL. PARTICIPANTS: A total of 622 female participants aged ≥20 years were included in the analysis. RESULTS: For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1. CONCLUSION: SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.

Salvia miltiorrhiza Bunge extract and Przewalskin ameliorate Bleomycin-induced pulmonary fibrosis by inhibition of apoptosis, oxidative stress and collagen deposition via the TGF-ß1 pathway.

BACKGROUND: Salvia miltiorrhiza Bunge (Labiatae) (DS) is a key part of the traditional Chinese medicine, whose roots are used to remove blood stasis, relieve pain, eliminate carbuncle and calm the nerves. Our research team found that the DS extract could significantly reverse LPS-induced lung injury, and five new diterpenoid quinones in DS extract with excellent lung protective activity for the first time. However, the material basis and mechanism of DS on pulmonary fibrosis (PF) needs to be explored in depth. OBJECTIVE: Bleomycin (BLM) was employed to establish the PF model, and Transcriptome and Surface plasmon resonance (SPR) ligand fishing technology were used to explore the material basis and mechanism of DS on PF, and provided theoretical research for clinical treatment of PF. METHODS: DS extract (24.58 or 49.16 mg/kg, i.g.) was administered daily from Day 8 to Day 28, followed by intratracheal BLM drip (5 mg/kg) to induce PF. Data about the influences of DS on PF were collected by transcriptome sequencing technology. Pulmonary ultrasound, airway responsiveness, lung damage, collagen deposition, and the levels of TNF-α, IL-1ß, apoptosis, oxidative stress (OS), immune cells, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ were examined. The affinity component (Przewalskin) in DS extract targeted by TGF-ß1 was fished by SPR ligand fishing technology. Furthermore, an in vivo PF mouse model and an in vitro TGF-ß1 induced BEAS-2B cell model were established, to explore the mechanism of Przewalskin on PF from the apoptosis, OS and epithelial mesenchymal transformation pathway. RESULTS: DS extract improved pulmonary ultrasound, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ, transformed immune cells following Bleomycin challenge. Furthermore, affinity component (Przewalskin) also improved pulmonary ultrasound and airway responsiveness, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS in vivo and in vitro. CONCLUSION: Analysis using a mouse model revealed that DS extract and Przewalskin can relieve clinical symptoms of PF, reduce lung injury and improve lung function. Meanwhile, DS extract and Przewalskin can improve BLM-induced PF by inhibition of, OS, apoptosis and collagen deposition might via the TGF-ß1 pathway. This study provides references to identification of novel therapeutic targets, thereby facilitating drug development for PF.

Indole-3-carboxaldehyde alleviates cisplatin-induced acute kidney injury in mice by improving mitochondrial dysfunction via PKA activation.

Cisplatin (DDP) is widely used in the treatment of cancer as a chemotherapeutic drug. However, its severe nephrotoxicity limits the extensive application of cisplatin, which is characterized by injury and apoptosis of renal tubular epithelial cells. This study aimed to reveal the protective effect and its underlying mechanism of Indole-3-carboxaldehyde (IC) against DDP-induced AKI in mice and NRK-52E cells pretreated with PKA antagonist (H-89). Here, we reported that IC improved renal artery blood flow velocity and renal function related indicators, attenuated renal pathological changes, which were confirmed by the results of HE staining and PASM staining. Meanwhile, IC inhibited the levels of inflammatory factors, oxidative stress, CTR1, OCT2, and the levels of autophagy and apoptosis. Mitochondrial dysfunction was significantly improved as observed by TEM. To clarify the potential mechanism, NRK-52E cells induced by DDP was used and the results proved that H-89 could blocked the improvement with IC effectively in vitro. Our findings showed that IC has the potential to treat cisplatin-induced AKI, and its role in protecting the kidney was closely related to activating PKA, inhibiting autophagy and apoptosis, improving mitochondrial function, which could provide a theoretical basis for the development of new clinical drugs.

Aralia saponin A isolated from Achyranthes bidentata Bl. ameliorates LPS/D-GalN induced acute liver injury via SPHK1/S1P/S1PR1 pathway in vivo and in vitro.

OBJECTIVE: Acute liver injury (ALI) refers to a disease in which the liver is affected by factors such as chemical substances, alcohol, and virus infection in a short time, resulting in damage to liver cells. Achyranthes bidentata Bl. with the hepatoprotective activity has attracted great attention. In this study, a pentacyclic triterpenoid (Aralia saponin A, AsA) was isolated from roots of Achyranthes bidentata Bl. and its anti-ALI activity, as well as the mechanisms, were investigated for the first time. METHODS: AsA (10 or 20 mg/kg, i.g.) was administered over a period of 1 weeks, following which liver injury was induced by LPS (10 µg/kg)/D-GalN (700 mg/kg). H&E staining of liver, Aspartate amino transferase (AST), Alanine transaminase (ALT) and cytokines was employed to investigate ALI relevant features. The mitochondrial morphology and levels of mitochondrial membrane potential (MMP), oxidative stress balance, apoptosis, average fluorescence intensity of 2-DG, natural killer (NK) cells in liver tissues were determined to assess the oxidative stress damage and inflammatory injury. Transcriptomics and metabonomics analysis were employed to clarify the mechanisms. Additionally, the mRNA and protein expression levels of Sphingosine 1-phosphate (S1P), Sphingosine kinase-1 (SPKH1), Sphingosine 1 phosphate receptor 1 (S1PR1), Sphingosine 1 phosphate receptor 3 (S1PR3), TNF receptor associated factor 2 (TRAF-2), Phospho-NF- kappaB p65 (p-P65), NF- kappaB p65 (P65), Proto-oncogene ras (Ras), Ras-related C3 botulinum toxin substrate (Rac), Phospholipase C (PLC), Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), Interleukin 1ß (IL-1ß), Vascular cell adhesion molecule 1 (Vcam1), CC chemokine ligand-2 (Ccl2) were analyzed. The mediating role of SPHK1 in the observed effects caused by AsA was assessed by investigatin SPHK1 transfection silencing/overexpression against AsA in AML12 cells induced by LPS/D-GalN. RESULTS: AsA can ameliorate liver function, inflammation, mitochondrial structure and oxidative stress in the ALI model. Meanwhile, AsA led to downregulated expression of proteins associated with sphingolipid signaling pathway. Silencing of SPHK1 led to enhanced protective effects of AsA, while over-expression of SPHK1 led to degraded protective effects of AsA in LPS/D-GalN-induced AML12 cells, suggesting that ALI is regulated by active molecules of AsA by means of SPHK1 mediation. CONCLUSIONS: AsA can ameliorate LPS/D-GalN-induced ALI by inhibiting inflammation and oxidative stress via the SPHK1/S1P/S1PR1 pathway. In this way, a molecular justification is provided for AsA application in ALI treatment.

Pharmacoeconomic evaluation of stroke and myocardial infarction prevention in hypertensive patients: Markov model based on the ACCOMPLISH trial.

OBJECTIVE: We evaluated the pharmacoeconomics of amlodipine combined with benazepril and hydrochlorothiazide combined with benazepril in the treatment of hypertension using a Markov model to provide an evidence-based reference for clinical drug use. METHODS: In this retrospective study, we constructed two types of Markov model using data from the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial to dynamically simulate the development of hypertension. The models were subjected to rollback analysis and cohort analysis to obtain the cost and effectiveness of the two drug regimens in preventing stroke and myocardial infarction in hypertensive patients. We conducted sensitivity analysis to determine the stability of the results. RESULTS: The cost-effectiveness of amlodipine combined with benazepril was 66,196.97 RMB with 6.59 QALYs and that of hydrochlorothiazide combined with benazepril was 74,588.50 RMB with 6.46 QALYs. The incremental cost-effectiveness ratio of hydrochlorothiazide + benazepril was -64,550.23 compared with amlodipine + benazepril. The amlodipine + benazepril regimen was therefore more cost-effective than hydrochlorothiazide combined with benazepril. The sensitivity analysis results showed that the model was robust. CONCLUSION: Compared with the hydrochlorothiazide + benazepril treatment regimen, the amlodipine + benazepril regimen showed greater economic benefits.

The role of hypertension in bone mineral density among males older than 50 years and postmenopausal females: evidence from the US National Health and Nutrition Examination Survey, 2005-2010.

Background: Hypertension is a significant chronic disease that has been linked with bone mineral density (BMD) in various studies. However, the conclusions are contradictory. The purpose of our study was to identify the bone mineral density (BMD) of postmenopausal females and males older than 50 years with hypertension. Methods: This cross-sectional study of 4,306 participants from the 2005-2010 US National Health and Nutrition Examination Survey explored the relationship between BMD and hypertension. Participants who had a mean systolic blood pressure (SBP) ≥140 mmHg, or a mean diastolic blood pressure (DBP) ≥90 mmHg, or were taking any prescribed medicine for high blood pressure were defined as having hypertension. BMD values were measured at the femoral neck and lumbar vertebrae as the primary outcome. Weight general linear model was used to describe the status of BMD in patients with hypertension. Weighted multivariate regression analysis was conducted to demonstrate the association between hypertension and BMD. Weighted restricted cubic spline (RCS) was used to assess the relationship between BMD and SBP and DBP. Results: Our study found that there was a positive association between hypertension and lumbar BMD and the lumbar BMD was significantly higher in the presence of hypertension than in the control group in both males (1.072 vs. 1.047 g/cm2) and females (0.967 vs. 0.938 g/cm2; both p < 0.05), but a similar pattern was not found in the femoral neck. Meanwhile, lumbar BMD was positively associated with SBP and negatively associated with DBP both in males and females. The prevalence of low bone mass and osteoporosis at the lumbar vertebrae was lower in male patients with hypertension than in the control group. However, no difference was observed among postmenopausal females between the hypertension and control groups. Conclusions: Hypertension was associated with higher BMD at the lumbar vertebrae in both males older than 50 years and postmenopausal females.

Differentiating glioblastoma from primary central nervous system lymphoma of atypical manifestation using multiparametric magnetic resonance imaging: A comparative study.

Background: The aim of this study is to evaluate the diagnostic efficiency of magnetic resonance imaging (MRI) of single parameters, unimodality, and bimodality in distinguishing glioblastoma (GBM) from atypical primary central nervous system lymphoma (PCNSL) based on diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC) enhancement, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) findings. Methods: The cohort included 108 patients pathologically diagnosed with GBM and 54 patients pathologically diagnosed with PCNSL. Pretreatment morphological MRI, DWI, DSC, DTI and MRS were all performed on each patient. The quantitative parameters of multimodal MRI were measured and compared between the patients in the GBM and atypical PCNSL groups, and those parameters showing a significant difference (p < 0.05) between patients in the GBM and atypical PCNSL groups were used to develop one-parameters, unimodality, and bimodality models. We evaluated the efficiency of different models in distinguishing GBM from atypical PCNSL by performing receiver operating characteristic analysis (ROC). Results: Atypical PCNSL had lower minimum apparent diffusion coefficient (ADCmin), mean ADC (ADCmean), relative ADC (rADC), mean relative cerebral blood volume (rCBVmean), maximum rCBV (rCBVmax), fractional anisotropy (FA), axial diffusion coefficient (DA) and radial diffusion coefficient (DR) values and higher choline/creatine (Cho/Cr) and lipid/creatine (Lip/Cr) ratios than GBM (all p < 0.05). The rCBVmax, DTI and DSC + DTI data were optimal models of single-parameter, unimodality and bimodality for differentiation of GBM from atypical PCNSL, yielding areas under the curves (AUCs) of 0.905, 0.954, and 0.992, respectively. Conclusions: Models of single-parameter, unimodality and bimodality based on muti multiparameter functional MRI may help to discriminate GBM from atypical PCNSL.

Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes.

BACKGROUND: The role of nonalcoholic fatty liver disease (NAFLD) as a mediator in the association between various unhealthy lifestyles and major adverse cardiovascular events and all-cause death remains unclear. METHODS AND RESULTS: This study used data from the UK Biobank, with follow-up until the end of 2021. It involved the calculation of unweighted and weighted lifestyle scores using the Cox model to classify participants on the basis of these scores. Additionally, the research assessed the mediation effect proportion of NAFLD using the difference method and examined the interaction and joint effects of lifestyle and NAFLD on health outcomes. Among the 134 616 enrolled participants, 4024 had records of major adverse cardiovascular events, while among the 130 144 participants included in the analysis of all-cause death, 6697 deaths occurred. The proportions of the association between overall lifestyle and major adverse cardiovascular events mediated by NAFLD were 19.4% and 21.7% (95% CI, 16.2-22.6 and 17.8-25.7) for scores 1 and 2, respectively, and those for all-cause death were 14.1% and 10.1% (95% CI, 11.3-17.1 and 7.9-12.2). After fully adjusting for traditional cardiovascular risk factors, the mediating effects declined across both outcomes. The associations between overall lifestyle and outcomes were stronger among those of the non-NAFLD group, and significant interactions were observed between overall lifestyle and NAFLD status. The joint analysis revealed that patients with NAFLD with unhealthy lifestyle had the highest risk of major adverse cardiovascular events and all-cause death. CONCLUSIONS: Improving lifestyle and addressing metabolic risk factors are essential for cardiovascular risk management in patients with NAFLD.

Distinguishing Tumor Recurrence From Radiation Necrosis in Treated Glioblastoma Using Multiparametric MRI.

PURPOSE: The purpose of this study was to evaluate the diagnostic performance of single-parameter, unimodal and bimodal magnetic resonance imaging (MRI) in differentiating tumor recurrence (TR) from radiation necrosis (RN) in patients with glioblastoma (GBM) after treatment using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic susceptibility contrast enhancement-perfusion weighted imaging (DSC-PWI), and proton magnetic resonance spectroscopy (1H-MRS). MATERIALS AND METHODS: Patients with histologically proven GBM who underwent surgical intervention followed by chemoradiotherapy and developed a new, progressively enhanced lesion on follow-up MRI were included in our study. Subsequently, DWI, DTI, DSC-PWI, and 1H-MRS were performed. Then, these patients underwent a second surgical operation or follow-up MRI to prove TR or RN. MRI metrics include apparent diffusion coefficient (ADC) and relative ADC (rADC) values derived from DWI; fractional anisotropy (FA), axial diffusion coefficient (DA) and radial diffusion coefficient (DR) values derived from DTI; and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) derived from DSC-PWI. Spectral metabolites such as choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lactate (Lac), and lipids (Lip) were derived from MRS, and the ratios of these metabolites were calculated, including Cho/NAA, Cho/Cr, NAA/Cr, Lac/Cr, and Lip/Cr. These indices were compared between the TR group and RN group, and the receiver operating characteristic (ROC) curve was used to evaluate the performance in distinguishing TR from RN by using single-parameter, unimodal and bimodal MRI. RESULTS: There were significant differences between the TR and RN groups in terms of ADC (p = 0.001), rADC (p < 0.001), FA (p = 0.001), DA (p = 0.003), DR (p = 0.003), rCBV (p < 0.001), rCBF (p < 0.001), Cho/NAA (p < 0.001), Lac/Cr (p < 0.001) and Lip/Cr (p < 0.001). ROC analysis suggested that rCBV, MRS, and DSC + MRS were the optimal single-parameter, unimodal, and bimodal MRI classifiers for distinguishing TR from RN, with AUC values of 0.909, 0.940, and 0.994, respectively. CONCLUSION: The combination of parameters based on multiparametric MRI in the region of enhanced lesions is a valuable noninvasive tool for discriminating TR from RN.

Analysis and prediction of relative survival trends in patients with non-Hodgkin lymphoma in the United States using a model-based period analysis method.

Background: Survival rates are usually used to evaluate the effect of cancer treatment and prevention. This study aims to analyze the 5-year relative survival of non-Hodgkin lymphoma (NHL) in United States using population-based cancer registry data. Methods: A period analysis was used to evaluate the improvement in long-term prognosis of patients with NHL from 2004 to 2018, and a generalized linear model was developed to predict the 5-year relative survival rates of patients during 2019-2023 based on data from the SEER database stratified by age, sex, race and subtype. Results: In this study, relative survival improved for all NHL, although the extent of improvement varied by sex, age group and lymphoma subtype. Survival improvement was also noted for NHL subtypes, although the extent varied, with marginal-zone lymphoma having the highest 5-year relative survival rate (92.5%) followed by follicular lymphoma (91.6%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (87.3%). Across all subtypes, survival rates were slightly higher in females than in males. Survival rates are lower in the elderly than in the young. Furthermore, the study demonstrated that black patients had lower NHL survival rates than white patients. Survival rates for NHL were higher in rural areas than in urban areas. Patients with extra-nodal NHL had a higher survival rate than patients with nodal NHL. Conclusion: Overall, patient survival rates for NHL gradually improved during 2004-2018. The trend continues with a survival rate of 75.2% for the period 2019-2023. Analysis by NHL subtype and subgroups indicating that etiology and risk factors may differ by subtype. Identification of population-specific prevention strategies and treatments for each subtype can be aided by understanding these variations.

Machine learning models for predicting survival in patients with ampullary adenocarcinoma.

Objective: The aim of this study was to predict the long-term survival probability of patients with ampullary adenocarcinoma (AAC), which would provide a theoretical basis for the long-term care of these patients. Methods: Data on patients with AAC during 2004-2015 were obtained from the Surveillance, Epidemiology, and End Results database, which were split at a 7:3 ratio into two independent cohorts: training and testing cohorts. Differences in survival between the two groups were tested using the Kaplan-Meier estimator and log-rank test methods. We constructed six survival analysis methods: the American Joint Committee on Cancer TNM stage, Cox Proportional Hazards regression, CoxTime, DeepSurv, XGBoost Survival Embeddings, and Random Survival Forest. The performances of these models were evaluated using the C-index, receiver operating characteristic (ROC), and calibration curves. Results: This study included 2,935 patients with AAC. Univariate Cox regression analyses of the training cohort indicated that race, marital status at diagnosis, scope of regional lymph node surgery, tumor grade, summary stage, American Joint Committee on Cancer stage, TNM stage T, and TNM stage N were important factors affecting survival (P â€‹< â€‹0.05). The results of the C-index indicated that DeepSurv performed the best among the six models, with the highest C-index of 0.731. The areas under the ROC curves of the DeepSurv model at the 1-year, 3-year, 5-year, and 10-year time points were 0.823, 0.786, 0.803, and 0.813, respectively. The calibration curve indicated that DeepSurv performed well, with good calibration. Conclusions: Machine learning models such as DeepSurv have a stronger performance in the survival analysis of patients with AAC.

Factors Associated With Lymph Node Yield and Effects of Lymph Node Density on Survival of Patients With Pulmonary Sarcomatoid Carcinoma.

OBJECTIVE: The objective of this study was to identify factors associated with lymph node yield (LNY) during surgeries for pulmonary sarcomatoid carcinoma (PSC) and to determine effects of lymph node density (LND) on the overall survival (OS) of patients with PSC. MATERIALS AND METHODS: The SEER Research Plus database was searched for data on patients with PSC from 1988 to 2018. Poisson regression was used of all patients with PSC to identify relevant factors associated with LNY. Univariate and multivariate Cox regression analyses were adopted for lymph node (LN)-positive patients to evaluate the impact of LND on OS. The 5-year OS rates of patients with PSC were compared based on their LN status and LND. RESULTS: There were 545 eligible patients in the study sample, 175 of which were LN-positive. These patients had significantly lower 5-year OS than those with no positive LNs ( P <0.001). Poisson regression analysis indicated relevant factors increasing LNY included higher diagnosis age, non-Hispanic American Indian or Alaska Native races, larger tumor, pleomorphic carcinoma histology, and more advanced disease stages. The Cox regression analysis indicated higher LND ( P =0.022) was probably associated with a worse prognosis for LN-positive patients. The group with LND ≥0.12 had a higher risk of death than the group with LND <0.12 ( P <0.001) among LN-positive patients with PSC. CONCLUSIONS: Patients with PSC with high LND experienced worse outcomes than those with low LND. Further risk stratification of patients with PSC may help to improve survival benefits based on prognostic indicators of LND.